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Exploring the Scope of Nitrogen Acyclic Carbenes (NACs) in Gold-Catalyzed Reactions
Abstract
The catalytic activity of the recently reported nitrogen acyclic carbene (NAC) complexes of gold(I) has been investigated and compared with the reported activity of other gold(I) and gold(III) complexes. The complexes studied, [AuCl{C(NEt2)(NHTol-p)}], [AuCl{C(NEt2)(NHXylyl)}], and [Au(NTf2){C(NEt2)(NHXylyl)}], are very active in processes such as the rearrangement of homopropargylsulfoxides, the intramolecular hydroamination of N-allenyl carbamates, the intramolecular hydroalkoxylation of allenes, the hydroarylation of acetylenecarboxylic acid ester, and the benzylation of anisole. Although the NAC ligands have not been optimized for the reactions tested, the yields obtained are usually similar and sometimes better than those reported with other catalysts, showing that the presence of N−H bonds and the wider N−C−N angle in the NAC (as compared to the NHC) complexes are not detrimental for the catalysis. For the hydroarylation reaction (where two competing products can be formed), the NAC complexes allow favoring one over the other. For the benzylation of anisole the selectivity is complementary to that obtained using H[AuCl4] as catalyst, and depending on the substrate, the NAC gold(III) complexes outperform the activity of H[AuCl4]. On average, the reactivity found suggests that the basicity of NACs toward gold(I) is very similar to that of NHCs and higher than that of phosphines.
... As an alternative to conventional Au I NHCs, hydrogen-bond-supported heterocyclic carbenes (HBHCs) 44 are suitable ligands because they are easily achieved by a mere nucleophilic addition of primary amines to isocyanides, which shows a great advantage over the complicated preparation of NHCs obtained by transmetalation from Ag. In a comparative study, 45 it was observed that Nacyclic carbenes (NACs) 46 were also valid for the skeletal rearrangement of 1,6-enynes, similar to HBHCs, showing the advantage of an easy modulation of their steric and electronic characteristics, which has given rise to an intense search of Au I catalysts that can be obtained by employing these preparation methods. 47,48 Chart 1 shows the types of Au I carbene complexes. ...
... Subsequent work by our group [103] and others [104][105][106] has expanded on such reactions using well-defined gold catalysts. N-heterocyclic carbene (NHC) complexes of Au(I) are shown to catalyze Reaction 2 at low catalyst loadings (0.1 mol%) at room temperature. ...
An overview of the current state of mechanistic understanding of gold-catalyzed intermolecular alkyne hydrofunctionalization reactions is presented. Moving from the analysis of the main features of the by-now-generally accepted reaction mechanism, studies and evidences pointing out the mechanistic peculiarities of these reactions using different nucleophiles HNu that add to the alkyne triple bond are presented and discussed. The effects of the nature of the employed alkyne substrate and of the gold catalyst (employed ligands, counteranions, gold oxidation state), of additional additives and of the reaction conditions are also considered. Aim of this work is to provide the reader with a detailed mechanistic knowledge of this important reaction class, which will be invaluable for rapidly developing and optimizing synthetic protocols involving a gold-catalyzed alkyne hydrofunctionalization as a reaction step.
... We synthesized a variety of Au complexes both neutral and cationic and subsequently used these complexes as catalysts in a variety of reactions. High enantioselectivities were achieved in the asymmetric intramolecular hydroamination of allenes by using a variety of chiral phosphine-Au(I) complexes [57][58][59][60][61][62][63]. On the other hand, the intramolecular hydroamination of olefins is a more important reaction in organic synthesis and has been widely reported [64][65][66][67][68]. Recently, the enantioselective intramolecular hydroamination of olefins has also been significantly improved by using various transition metal complexes or other metal complexes [69][70][71][72][73][74][75][76][77]. ...
Several novel chiral N-heterocyclic carbene and phosphine ligands were prepared from (S)-BINOL. Moreover, their ligated Au complexes were also successfully synthesized and characterized by X-ray crystal diffraction. A weak gold-π interaction between the Au atom and the aromatic ring in these gold complexes was identified. Furthermore, we confirmed the formation of a pair of diastereomeric isomers in NHC gold complexes bearing an axially chiral binaphthyl moiety derived from the hindered rotation around C-C and C-N bonds. In the asymmetric intramolecular hydroamination reaction most of these chiral Au(I) complexes showed good catalytic activities towards olefins tethered with a NHTs functional group to give the corresponding product in moderate yields and up to 29% ee.
A variety of unsymmetric diaryl gold N‐acyclic carbene (NAC) complexes was synthesized via the isonitrile route by three different methods: (a) solvent free in a melt, (b) mechanochemically and (c) in THF at room temperature. The latter method can also be used to synthesize unsaturated gold NHC complexes. These methods overall offer access to a broad array of new complexes and remove one of the previous limitations of the isonitrile route to NAC and NHC complexes of gold, namely the inability to react with the less nucleophilic aromatic amines. The new complexes also proved to be successful as pre‐catalysts in the gold‐catalyzed phenol synthesis.
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In this chapter, the monocyclic, benzo and dibenzo-fused ring systems, thiepine, thiepane, 1-benzothiepine, 2-benzothiepine, 3-benzothiepine, dibenzo[b,d]thiepine, dibenzo[b,e]thiepine, dibenzo[b,f]thiepine, dibenzo[c,e]thiepine and their carbocycle and heterocycle-fused systems are included. Further dihydro, and tetrahydro derivatives and their bridged bicyclic analogs are also described, as well as the corresponding sulfoxides and sulfones. The present chapter is intended to update the previous work on thiepines and thiepanes, and covers literature published since 2008.
Theoretical studies on thiepine-benzene sulfide valence isomerization have been of continuous interest. In addition, the theoretical interest related to aromaticity and anti-aromaticity has been studied. Furthermore, fused systems, such as dibenzo[b,f]thiepines has become important structural motifs found in a diverse array of biologically active molecules. In the last decade, many reports on the synthesis and reactions of thiepines by transition-metal catalysts have appeared.
Benzoxazinone derivatives containing conjugated substituents have been synthesized through bromination of an benzoallene ether and the subsequent palladium‐catalyzed coupling reactions. Heck or Suzuki coupling reaction of the vinylbromide precursor provided resonable to good yields of the desired products. Bromoamination of the benzoallene ether with N‐bromosuccinimide in methylene chloride provided the benzoxazinone vinylbromide in 87% yield. The subsequent palladium‐catalyzed Heck reaction with ethyl acrylate yielded the conjugated diene substituent in 73%. The Suzuki coupling reaction of the benzoxazinone vinylbromide with arylboronic acids also afforded good yields of the benzoxazinone products attached by the corresponding styrene side chain.
This review describes the gold-catalyzed reactions of specially activated alkynes, allenes, and alkenes. Such species are characterized by the presence of either electron-donating or electron-withdrawing groups as substituents of the carbon π-system. They are intrinsically polarized, and when compared to their nonspecially activated counterparts can therefore be involved in gold-catalyzed transformations featuring increased regio-, stereo-, and chemoselectivities. The chemistry of specially activated carbon π-systems under homogeneous gold catalysis is extremely rich and varied. The reactivity observed with nonspecially activated unsaturated systems can often be transposed to specially activated ones without loss of efficiency. However, specially activated carbon π-systems also exhibit specific reactivities that cannot be attained with regular substrates. In this family of carbon π-systems, ynamides and their analogs, along with alkynyl carbonyl derivatives, are the classes of substrates that have retained the most attention. This review provides an overview of the chemistry developed with all classes of specially activated carbon π-systems by discussing their general and specific reactivities, presenting and commenting on their gold-catalyzed transformations as well as their applications.
This publication is a continuation of the series of reviews devoted to the state of the art of gold catalysis in organic chemistry. The third review covers gold-catalyzed reactions of compounds containing double bonds. The reactions of alkenes, cumulated and conjugated dienes and enynes with different types of nucleophiles, including those with heteroatoms (oxygen, nitrogen and sulfur), are considered.
The bibliography includes 355 references.
A series of gold(I) and gold(III) N‐acyclic diamino carbene (ADC) complexes with different ancillary ligands have been synthesized. The chloride carbene derivatives [Au{C(NHR)(NHCH2py)}Cl] (R = Cy, R = naphthyl, R = xylyl) have been obtained by reaction of 2‐picolylamine with the corresponding [AuCl(CNR)]. The gold(I) thiolate derivatives [Au{C(NHR)(NHCH2py)}(Spy)] were prepared by reaction of the chlorido complexes with 2‐mercaptopyridine (2‐HSpy) in presence of potassium carbonate. The phosphane derivative [Au(pyCH2NH2)(PPh3)](OTf) was obtained by reaction of freshly prepared [Au(OTf)(PPh3)] with 2‐picolylamine. The phosphane‐carbene complexes [Au{C(NHR)(NHCH2py}(PPh3)](OTf) were obtained from the reaction of picolylamino species with the isocyanide. The gold(III) derivative cis‐[Au(C6F5)2(pyCH2NH2)](ClO4) was obtained by the reaction of 2‐picolylamine with freshly [Au(C6F5)2(Et2O)2](ClO4). The reaction of the former with CNCy led to complex cis‐[Au(C6F5)2{C(NHCy)(NHCH2py)}]ClO4 by a nucleophilic attack of the isocyanide to the amine ligand, thus producing a bidentate C,N acyclic carbene ligand. Cytotoxic studies against the tumor human cell lines Jurkat (T‐cell leukaemia), MiaPaca2 (pancreatic carcinoma), A549 (lung carcinoma) and MDA‐MB‐231 (breast carcinoma) showed moderate to good cytotoxic activity for some of the complexes.
The first catalytic application of well‐defined (P,C) cyclometalated gold(III) complexes is reported. The bench‐stable bis(trifluoroacetyl) complexes 2a,b perform very well in the intermolecular hydroarylation of alkynes. The reaction is broad in scope, it proceeds within few hours at 25°C at catalytic loadings of 0.1‐5 mol%. The electron‐rich arene adds across the C≡C bond with complete regio‐ and stereo‐selectivity. The significance of well‐defined gold(III) complexes and ligand design are highlighted in a powerful but challenging catalytic transformation.
The first catalytic application of well‐defined (P,C) cyclometalated gold(III) complexes is reported. The bench‐stable bis(trifluoroacetyl) complexes 2a,b perform very well in the intermolecular hydroarylation of alkynes. The reaction is broad in scope, it proceeds within few hours at 25°C at catalytic loadings of 0.1‐5 mol%. The electron‐rich arene adds across the C≡C bond with complete regio‐ and stereo‐selectivity. The significance of well‐defined gold(III) complexes and ligand design are highlighted in a powerful but challenging catalytic transformation.
This chapter reviews the advancements made in the field of metal-catalyzed intramolecular and intermolecular hydroarylation of alkynes promoted by gold (Au), silver (Ag), and copper (Cu) salts. Within the context of these two different reactions, it discusses the reactivity of alkynes (activated or non-activated), the selectivity, and mechanism of the transformation. Indoles and pyrroles are excellent nucleophiles in alkyne hydroarylation reactions. Other electron-rich heteroarenes, such as furans and benzofurans, undergo facile intramolecular alkenylations with alkynes in the presence of π-Lewis acids. The alkyne hydroarylation promoted by π-acid catalysts is an efficient approach for the rapid generation of various structural motifs including simple alkenylated (hetero)arenes to functionalized polycyclic scaffolds, which are present in the complex architectures of some natural products. Although the gold-catalyzed hydroarylation has been widely used in the synthesis of natural products, silver and copper p-acid catalysts have been much less applied in target-oriented synthesis.
The addition of an amine NH‐functionality to alkenes (including vinyl arenes, conjugated dienes, allenes or ring‐strained alkenes), the so‐called hydroamination, represents a simple and highly atom‐economical approach for the synthesis of nitrogen‐containing products. A large variety of catalyst systems are available, ranging from alkali, alkaline earth, rare earth, Group 4 and Group 5 metals, to late transition metal catalysts, and, less prominent, Brønsted and Lewis acid‐based catalyst systems. The mode of operation of these catalyst systems can vary significantly and the different reaction mechanisms and the scope and limitations are discussed. While intramolecular hydroamination reactions can be readily achieved with a large number of catalyst systems, significantly fewer examples for the more challenging intermolecular hydroamination are known, especially for unactivated alkenes. The stereoselective hydroamination has also received significant attention due to the importance of chiral nitrogen‐containing molecules in pharmaceutical industry. A variety of highly selective chiral catalyst systems have been developed for intramolecular hydroaminations, while examples of intermolecular asymmetric hydroaminations are scarce.
Hydroamination in the context of this review article is defined as the addition of HNR 2 across a non‐activated, unsaturated carbon‐carbon multiple bond. This review focuses on the hydroamination reaction of simple, non‐activated alkenes. The addition of amines to slightly activated alkenes, such as vinyl arenes, 1,3‐dienes, strained alkenes (norbornene derivatives, methylenecyclopropenes) and allenes is closely related and is covered as well. However, hydroamination reactions of alkynes and Aza‐Michael reactions involving the addition of an N‐H fragment across the conjugated or otherwise activated double bond of a Michael acceptor are not covered. The scope of amine types includes ammonia, primary and secondary aliphatic and aromatic amines, azoles, and hydrazines. N ‐Protected amines, such as ureas, carboxamides, and sulfonamides are covered as well, as they are important substrates for metal‐free and late transition metal‐based catalysts. The literature through January 2011 will be covered with two selected references from 2012 (comprising Table 3D). A supplemental reference list is provided for reports appearing February 2011 through April 2015.
The chapter is organized by the nature of the carbon unsaturation to which the amine is added. Ranging from less reactive substrates such as ethylene and unactivated alkenes, to slightly activated substrates, such as vinyl arenes, and more activated substrates, including conjugated dienes, allenes and strained alkenes. Enantioselective hydroamination reactions, an area that has seen significant progress over the past decade, are discussed next. Finally, tandem hydroamination/carbocyclization reactions of aminodialkenes provide rapid access to complex alkaloidal skeletons.
The tables at the end of the chapter are separated into five main sections: achiral intermolecular hydroamination, achiral intramolecular hydroamination, enantioselective intermolecular hydroamination, enantioselective intramolecular hydroamination, and tandem hydroamination/carbocyclization. Within the first four sections the tables are further divided into subsections based on the participating alkene, i.e. alkenes, vinyl arenes, dienes, allenes, and strained alkenes.
The nucleophilic addition of protected and substituted hydrazine derivatives to isonitrile complexes of gold(I), platinum(II), palladium(II) and rhodium(III) provides the corresponding hydrazino amino acyclic carbene complexes. These are characterized by their spectroscopic data, four different X‐ray single crystal structure analyses and their catalytic activity in the gold(I)‐catalyzed cycloisomerization of N ‐propargylcarboxamides to alkylideneoxazolines is investigated.
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This study deals with two striking phenomena: the complete protection against decomposition of hypothetically monocoordinated AuI intermediates [AuL]Y (L = strongly coordinating ligand; Y⁻ = poorly coordinating anion) by addition of small substoichiometric amounts (5 mol % relative to Au) of not strongly coordinating ligands (e.g., AsPh3) and the fact that, in contrast, strongly coordinating ligands cannot provide this substoichiometric protection. The two phenomena are explained considering that (i) the existence of real monocoordinated [AuL]Y is negligible in condensed phases and the kinetically efficient existing species are dicoordinated [AuL(W)]Y (W = any very weakly coordinating ligand existing in solution, including OH2, the solvent, or the Y⁻ anion) and (ii) these [AuL(W)]Y intermediates give rise to decomposition by a disproportionation mechanism, via polynuclear intermediates formed by associative oligomerization with release of some W ligands. It is also shown that very small concentrations of [AuL(W)]Y are still catalytically efficient and can be stabilized by overstoichiometric adventitious water, so that full decomposition of the catalyst is hardly reached, although eventually the stabilized concentration can be kinetically inefficient for the catalysis. These results suggest that, in cases of gold catalysis requiring the use of a significant quantity of gold catalyst, the turnover numbers can be increased or the concentration of gold catalyst widely reduced, using substoichiometric protection properly tuned to the case.
The Pd-catalysed reactions of allenyl ethers and allenylamines derived from commercially available o-aminophenols and o-nitroaniline have been studied. Using a wide variety of aryl- and heteroaryl halides, carboamination of the allenes led to sequential C–C and C–N bond formation. Both carbo- and hydroamination processes resulted in the formation of nitrogen-containing benzo-fused rings. In the case of aminoallenes arising from o-phenylenediamine, the regioselectivity of the cyclization step was strongly dependent on the protecting group tethered to the nitrogen atoms, allowing the formation of five- and seven-membered rings.
The gold-catalyzed enantioselective hydroazidation and hydroamination reactions of allenes are presented herein. ADC gold(I) catalysts derived from BINAM were critical for achieving high levels of enantioselectivity in both transformations. The sense of enantioinduction is reversed for the two different nucleophiles, allowing access to both enantiomers of the corresponding allylic amines using the same catalyst enantiomer. Chiral allylic azides and amines are obtained by enantioselective hydroazidation and hydroamination of allenes catalyzed by acyclic diaminocarbene gold(I) catalysts derived from BINAM. The sense of enantioinduction is reversed for the two different nucleophiles, allowing easy access to both enantiomers with a single catalyst enantiomer.
Hydroarylations, also called alkenylations of (hetero)arenes are important transformations in organic chemistry. The recent development of gold-catalyzed processes to achieve such transformations has added a new tool in the chemist's toolbox. Thus, the hydroarylations of alkynes under gold catalysis are reviewed from a mechanistic and practical point of view. Both intramolecular and the more challenging intermolecular alkenylations are considered and described in a comprehensive account that includes detailed mechanisms as well as supporting theoretical calculations when relevant. This chapter also aims at illustrating the reactivity of internal and external alkynes which may differ in certain cases, as well as the various reactivities encountered with heteroarenes and arenes. The employment of supported gold catalysts to perform this type of transformations is also discussed in the last section of the chapter.
Keywords:
alkynes;
alkenylations;
catalysis;
gold;
hydroarylation
The intramolecular hydrofunctionalization of carbon–carbon multiple bonds has emerged as a powerful way to form cyclic structures. A particularly important class of reactions involves the use of amine or alcohol nucleophiles, and alkenes or allenes as electrophiles, to form pyrrolidine, piperidine, tetrahydrofuran, and tetrahydropyran heterocycles in a highly efficient manner using late transition metal catalysts. Asymmetric methods for hydroamination and hydroalkoxylation reactions have recently emerged, allowing for the enantioselective synthesis of such saturated heterocycles. This review covers recent developments (over the last 5–10 years) in late transition metal-catalyzed hydroamination and hydroalkoxylation reactions that generate saturated heterocycles.
The reaction of [PdI{C,N-C(=NHXy)C6H4NH2-2}CNXy]TfO with XyNC (1:2, TfO = CF3SO3, Xy = C6H3Me2-2,6) gives the cationic carbene complex [PdI{C,C-C(=NHXy)C6H4{NHC(NHXy)}-2}CNXy]TfO (4), while that of [PdCl2{C(=NHXy)C6H4NH2-2}] with isocyanides (1:1, 50-60 degrees C) gives the neutral carbene complexes [PdCl2{C,C-C(=NHXy)C6H4{NHC(NHR)}-2}] (R = Bu-t (8), Xy (9)), from which mono- and dicationic derivatives [PdCl{C,C-C(=NHXy)C6H4{NHC(NHXy)}-2}L]X (L = XyNC, X = TfO (10); L = PPh3, X = Cl (11)) and [Pd{C,C-C(=NHXy)C6H4{NHC(NHXy)}-2}(CNXy)(2)](TfO)(2) (12), respectively, have been isolated. Dehydrochlorination of complex 9 with TlTfO and NaOAc (1:2:2) or with NEt3 (1:1) affords the dinuclear complexes [(Pdx)(2){mu-N,C,C-C(=NXy)C6H4{NHC(NHXy)}-2}(2)] (X = OAc (13), Cl (14)), which in turn react with PPh3 to give [PdX{C,C-C(=NXy)C6H4(NHC(NHXy)}-2}PPh3] (X = OAc (15), Cl (16)). Oxidative addition of 2-iodobenzoic acid to 13 leads to the Pd(IV) complex [{PdI(C6H4CO2-2)}(2){mu-N,C,C-C(=NXy)C6H4{NHC(NHXy)}-2}(2)] (17), while the reaction of 14 with PhICl2 affords the Pd(III) derivative [(PdCl2)(2){mu-N,C,C-C(=NXy)C6H4{NHC(NHXy)}-2}(2)] (18). The crystal structures of 4, 9, and 12 have been determined, and the atomic connectivity in 18 has been established.
This chapter describes late transition metal complexes-catalyzed hydroamination, the formal addition of an H-N bond across a C-C multiple bond. Late transition metal catalysis has been intensely developed in the hydroamination and additions of various kinds of amines to C-C multiple bonds have been achieved. The reaction pathways strongly depend on the choice of metal complexes, substrates, and reaction conditions. This chapter is organized primarily based on the difference in the mechanisms of hydroamination reactions, and in the scope section concise summary of the hydroamination reaction is shown.
In recent years, gold‐electrophilic activation of allenes has unraveled a huge potential for new reactivities toward the synthesis of complex molecules with synthetic or biological importance.
Gold and allenes are a unique combination that has shown to be very versatile and give better reactivity, and in some cases is complementary to other metals. Coordination of gold to allenes is more complex than coordination to a simple olefin or alkyne, and several types of structures can be predicted depending on the atoms involved in the coordination. The nature of the gold–allene interaction defines the reactivity of these complexes, which can be modulated toward the desired product by slight changes in the catalysts or reaction conditions.
New reactions involving gold–allene complexes for the formation of carbon–heteroatom or carbon–carbon bond formation will be discussed in this chapter, including inter‐ and intramolecular examples of nucleophilic additions, and inter‐ and intramolecular cycloaddition and cycloisomerization reactions with alkenes, dienes, alkynes, and other allenes.
Underlying the growing interest in acyclic carbene ligands are their unique ligand properties, which differ substantially from those of cyclic carbenes. Data regarding donor ability and structural/steric features are of particular relevance for catalysis. However, these features have to be balanced against potential decomposition routes that do not affect N-heterocyclic carbenes (NHCs). Gradually, the focus has shifted toward identifying reactions that benefit from the distinct steric and electronic properties of acyclic carbenes. This chapter highlights key examples of catalysts that exhibit unusual stabilities, activities, or selectivities resulting from the presence of acyclic carbene ligands. It demonstrates the value of the isocyanide-based synthetic route for rapid catalyst optimization via ligand modification.
The catalytic system "PtBr2(0.3 mol%)/2P(OR)(3)/10nBu(4)PBr"(R = alkyl) discovered recently in our group, allows good to excellent catalytic activities for the intermolecular hydroamination of ethylene and higher alpha-olefins (1-hexene) with aniline type amines to give the expected N-ethyl- (1) and N,N-diethyl-anilines (2) along with 2-methyl-quinoline (3). A poisoning effect of alkyl and aromatic phosphines has been observed. This effect could be minimised using small amounts of molecular iodide which reacts with phosphorus ligands to form non-coordinating well-described ionic species. Interestingly, beneficial effects of added P(OR)(3) (R = alkyl) have been pointed out and further investigated. In this way, a new potential family of Arbuzov-type phosphorus-metal complexes has been suggested to be responsible for good catalytic activities found when using P(OR)(3) alkyl phosphites rather than PR3 (R = alkyl, aromatic) and P(OPh)(3) co-catalysts. [GRAPHICS]
Heterosubstituted aminoallenes underwent smooth ruthenium‐catalyzed intramolecular exo ‐hydroamination reactions yielding the corresponding five‐, six‐, or seven‐membered 1,3‐diaza‐ or 1,3‐oxaza‐heterocyclic structures. This procedure is a valuable and less expensive alternative to the already known transition metal‐catalyzed hydroamination reactions of aminoallenes.
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We elucidate the role of the ligand in determining the ion pair structure of the [(NAC)Au(η2-3-hexyne)]+ BF4‒ [(NAC = Nitrogen Acyclic Carbene, also known as ADC = Acyclic Diamino Carbene)] catalysts and how the position of the anion influences their catalytic performances, giving a detailed relationship between the ion pairs structure, determined by 19F, 1H-HOESY NMR experiments and DFT calculations, and the catalytic activity in the intermolecular alkoxylation of alkynes. From our results, it is evident that if the anion is forced to be far from the catalytic site by ancillary ligand-anion hydrogen bonding interactions, the reaction slows down. On the contrary if the anion is located near the alkynes the reaction is accelerated, coherently with the proposed active role of the anion in catalysis. These results open new opportunities in ligands design for the gold-mediated reactions in which the anion plays an important role during the catalysis.
Neutral gold complexes with hydrogen-bond-supported heterocyclic carbene (HBHC) and nitrogen acyclic carbene (NAC) ligands have been synthesized by the reactions of isocyanogold derivatives [AuCl(CNR)] with amines. Cationic [Au(carbene)(AsPh3)][SbF6] complexes have also been prepared. The catalytic activity of both types of complex (for the former, AgSbF6 is used to extract the halide ligand) in the skeletal rearrangement and methoxycyclization of enynes has been studied. The cationic complexes with AsPh3 are active but slower; advantageously, they do not decompose during the catalysis. In contrast, the catalysts formed in situ from the neutral halide complexes are very fast but undergo decomposition. An interesting trade-off was found by adding substoichiometric amounts of AsPh3 (e.g., 10 mol-%) relative to the gold catalyst {[Au(carbene)Cl] + AgSbF6}, which prevents or dramatically reduces the decomposition. This protecting ligand promises to prevent or minimize the undesired decomposition of gold catalysts.
Lucky bag: Suitably substituted acyclic diaminocarbene (ADC) ligands were demonstrated to generate a chiral pocket around linear gold(I) complexes. These new catalysts were used to perform the very first catalytic enantioselective cycloisomerization/ acetalization tandem reaction.
The intramolecular gold catalysed asymmetric hydroamination of alkenes was studied screening a series of mononuclear gold(I) and (III) complexes in combination with silver salts. Among the various chiral mono-phosphine and diaminocarbene ligands tried, the best catalysts arose from mononuclear gold(I) complexes synthesized from BINOL based phosphoramidite ligands. The latest were improved by addition of bulky substituents at specific positions of the BINOL scaffold. The resulting gold(I) complexes were combined with selected silver salts to afford efficient catalysts for intramolecular hydroamination of alkenes at mild temperatures, with good conversions and average enantioselectivities.
A combination of gold chloride organometallic complex and a silver salt was used to catalyze intermolecular hydroamination of activated alkenes, i.e aza-Michael reactions. The gold-catalyzed reactions of activated alkenes with nitrogen substrates were investigated and found to afford various mono- and dihydroamination products, the latter being rare and original. After flash chromatography, gold NHC catalyst could be recovered as a gold hydroxide NHC complex. When combined with a silver salt, the gold complex lead again to an active hydroamination catalyst.
Substituenten-Rochade: Eine neue Gold(I)-katalysierte Umlagerung wurde entwickelt, die unter milden Bedingungen abläuft und über eine unerwartete Substituenten-„Rochade“ (siehe rote und blaue Kreise im Schema) einen effizienten Zugang zu Benzo[b]furanen aus den einfachen, leicht zugänglichen 3-Silyloxy-1,5-eninen eröffnet (IPr=N,N′-Bis(2,6-diisopropylphenyl)imidazol-2-yliden, NTf2=Bis(trifluormethylsulfonyl)imid).
The intramolecular gold-catalyzed asymmetric hydroamination of allenes was studied by screening a series of mononuclear gold(I) and -(III) complexes in combination with silver salts. Among the various chiral monophosphine and diaminocarbene ligands tried, the best catalysts arose from mononuclear gold(I) complexes synthesized from BINOL-based phosphoramidite ligands. The latest were improved by addition of bulky substituents at specific positions of the BINOL scaffold. The resulting gold(I) complexes were combined with selected silver salts to afford efficient catalysts for intramolecular hydroamination of allenes at room temperature or below, with good conversions and enantioselectivities.
A series of three chiral, expanded six-membered NHC–palladium(II) complexes was prepared with successively increased sterical demand, while retaining natural d-(+)-camphor as a chiral motif. The catalysts showed different reaction profiles in the asymmetric, intramolecular α-arylation of amides. The molecular structure of two N-heterocyclic and one nitrogen acyclic carbene palladium isonitrile complex was unequivocally determined by X-ray crystallographic analysis. The results reported herein account for a correlation of catalytic activity and enantiodiscrimination in relation to the degree of chiral substitution and steric congestion at the metal center. The modular and convergent synthetic route of these air- and moisture-stable palladium isonitrile complexes underlines the usefulness of this approach.
A series of NAC− and their structurally related NHC−palladium(II) isonitrile complexes, including examples of dinuclear complexes, were prepared. In a second series, NHC−palladium complexes bearing an aryl group on one nitrogen of the NHC ring and different cycloalkyl groups ranging from six- to 15-membered rings have been synthesized. The good yields document the value of the very short route to new palladium(II) NHC complexes. The stuctures have been investigated by crystal structure analyses of some representatives; in addition conformational studies by NMR were conducted. The reactivity in Suzuki cross-coupling reactions was investigated, showing turnover frequencies of up to 18 050 h−1 and a clear correlation of the size of the cycloalkyl moiety with the turnover number achieved for the coupling of chlorobenzene and 2,5-dimethylphenylboronic acid.
A series of sterically demanding acyclic aminooxycarbenes (AAOCs) were prepared in good yields from chloroiminium salts and alkoxysilanes via the TMS-Cl elimination pathway. The steric profiles of bulky AAOCs were determined by X-ray crystallographic studies of the Au(I) complexes. The percent buried volume values (%VBur) of the AAOC ligands range from 35.8% to 47.9%. Acyclic aminooxycarbenes maintain coplanarity around the carbene center, in sharp contrast to the similarly bulky acyclic diaminocarbenes that show significant distortion from the coplanarity. The Au(I) complexes of AAOCs exhibited high efficiency in the hydroamination of alkenyl ureas. Bulkier AAOC–Au(I) complexes displayed faster reaction rates and higher conversions. The reaction rate, yield, and stereoselectivity observed with the AAOC–Au(I) catalyst were better than those with acyclic diaminocarbene Au catalysts and comparable to the best results reported to date.
Novel [Au(NHC)(DIC)]BF4 complexes (NHC = SIMes, IMes, SIPr, IPr; DIC = 2,6-dimethylphenyl isocyanide) were synthesized and characterized. These substrates react with secondary amines at room temperature under mild experimental conditions to give new bis-carbene NHC-NAC derivatives. The reaction of formation of the latter complexes with piperidine, morpholine, and diethylamine was studied by NMR and UV−vis spectrometry, and a mechanism involving a concomitant attack of the amine at the metal center and at the coordinated isocyanide was proposed on the basis of a detailed kinetic study. The mechanistic network was completely resolved by means of an independent determination of the equilibrium constant of formation of the adduct [Au(NHC)(DIC)(amine)]+, Keq, calculated from the absorbance vs amine concentration data obtained from direct spectrophotometric titration of the starting complex [Au(NHC)(DIC)]+ with the amine. The [Au(NHC){C(NHAr)(NC5H10)}]BF4 bis-carbene complexes obtained by attack of piperidine at the [Au(NHC)(DIC)] derivatives were isolated and fully characterized. The solid-state structures of the new complexes [Au(IMes)(DIC)]BF4 and [Au(IMes){C(NHAr)(NC5H10) }]BF4 were resolved and reported.
Acyclic aminocarbenes have received much less attention as ancillary ligands in homogeneous catalysis compared with their cyclic relatives (i.e., N-heterocyclic carbenes, NHCs), despite having a longer history and greater structural variety. Although these species are generally more fragile than NHCs, recent advances in the synthesis and catalytic application of metal complexes of acyclic carbenes have brought increased attention to these underutilized ligands. It is increasingly clear that acyclic carbenes possess unique properties that distinguish them from other ligand classes and make them potentially valuable for catalysis. These include exceptional donor ability, conformational flexibility, and wide N–C(carbene)–N angles that can place bulky or chiral substituents near catalytic substrate binding sites. This purpose of this Perspective is to review and critically assess recent progress in this forefront area of catalyst design. Syntheses and ligand properties of acyclic diaminocarbenes, aminooxycarbenes, and other aminocarbenes are reviewed with a view toward catalytic relevance. A special focus is to highlight catalytic reactions in which acyclic carbene ligands confer unusual selectivity or activity on metal catalysts compared with conventional ligand types. Particularly promising catalytic results have been obtained with acyclic carbene complexes of gold, including some highly enantioselective catalytic transformations.
A series of differently substituted Chugaev‐type palladium bis(acyclic diaminocarbene) complexes was screened to identify the most active catalyst for Mizoroki–Heck coupling reactions of aryl bromides with styrene. The best catalyst, which contains three methyl groups on the bis(carbene) ligand, gives excellent coupling yields at 120 °C for both activated and deactivated aryl bromides. However, activity with aryl chlorides is limited to electron‐deficient examples. The optimized catalyst demonstrates limited air and moisture stability, giving reduced yields in couplings of activated aryl bromides in open‐flask conditions. The modular synthesis of this class of catalysts should allow further fine‐tuning of activity in Mizoroki–Heck and related coupling reactions. Copyright © 2012 John Wiley & Sons, Ltd.
Catalytically active gold(I)–carbene complexes on a polystyrene backbone were synthesized by treating metal-coordinated isocyanides with the nitrogen nucleophile of a piperazine group bonded to the polystyrene. The local environment of the metal was readily tuned by variation of the functional group. This versatile synthesis procedure is not restricted to gold and can easily be extended to other metals such as Pd and Pt. The gold carbene complexes were extensively characterized, and resonant inelastic X-ray scattering identified the +1 oxidation state of the supported gold. This single-site catalyst catalyzed the synthesis of oxazoles, and the system could be used in continuous flow.
A gold(I)-catalysed regioselective method for the preparation of 3-fluoro-tetrahydropyran-4-one derivatives from homopropargyl acetal is reported. A one-pot procedure based on a gold(I)-catalysed Petasis-Ferrier rearrangement/cyclization and subsequent fluorination was developed. The 3-fluoropyran-4-one compound acts as a protected precursor of alkylfluoro-alpha,beta-(E)-unsaturated ketone, which was readily obtained by ring-cleavage. Corresponding hemiacetals were not suitable substrates for the formation of the 3-halo-pyran derivatives. The present transformation would represent a useful method to readily afford highly substituted 3-fluoro-tetrahydropyran-4-ones.
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We have synthesized and characterized several cationic complexes of gold(I) of the type [Au(L1)(L2)]+ (L1 = NHC, L2 = DIC; L1 = NHC, L2 = NAC; L1 = NAC, L2 = DIC; L1 = L2 = NAC; NHC = N-heterocyclic carbene; NAC = N-acyclic carbene, DIC = 2,6-dimethylphenylisocyanide).The complexes of type [Au(NHC)(DIC)]+ react with a slight excess of Br2 yielding the corresponding gold(III) species [Au(NHC)(DIC)Br2]+. The latter decompose with a rate that is modulated by the nature of the ancillary ligands. The oxidative addition of Br2 to complexes of the type [Au(NHC)(NAC)]+ and [Au(L)(NAC)]+ (L = DIC, NAC) has been also carried out and the ensuing gold(III) derivatives [Au(NHC)(NAC)Br2]+ and [Au(NAC)2Br2]+ are stable in solution whereas the complex [Au(NAC)(DIC)Br2]+ decomposes. Finally, on the basis of kinetic studies we have proposed propose a mechanism involving a fast pre-equilibrium forming an adduct containing the starting complex and Br2 followed by a slow rearrangement of the latter to yield the final gold(III) derivatives.
Starting from the first reported application of complexes bearing acyclic diaminocarbene (ADC) ligands as catalysts ca. 5 years ago, these compounds have been successfully employed for several useful organic transformations, viz. cross-coupling reactions (Suzuki–Miyaura, Heck, Sonogashira, Buchwald–Hartwig, and Kumada) and some cyclizations/additions to substrates having the CC and CC bonds. In these processes, ADC–metal complexes behave as an attractive alternative to extremely popular N-heterocyclic carbenes (NHCs). This review attempts to systematize studies published until now and to explain various observations and initial ideas on mechanisms and driving forces of ADC-based catalysts as well as to draw attention to the potential and the advantages that application of ADCs gives to synthetic organometallic and organic chemistry.
The field of nucleophilic carbenoid ligands in organometallic catalysis is continuously expanding with new chemical transformations and improved catalytic systems. This review highlights just few developments of the last year. Out of several hundred scientific papers that covered the subject last year, the authors limit themselves to the reports that present direct catalytic results and, at some extent, interesting stoichiometric reactions or mechanistic aspects with obvious applicability in catalysis.
With the suitable selection of a gold catalyst as well as the appropriate control of the reaction conditions, various new gold-catalyzed cyclizations of 2-alkynyl benzaldehyde with acyclic or cyclic vinyl ethers have been developed. Acetal-tethered dihydronaphthalene and isochromenes were obtained from the reactions of 2-alkynyl benzaldehydes with acyclic vinyl ethers under mild conditions. And, more interestingly, the gold-catalyzed reactions of 2-alkynyl benzaldehyde with a cyclic vinyl ether afforded the bicyclo[2.2.2]octane derivative involving two molecules of cyclic vinyl ethers. These products contain interesting substructures that have been found in many biologically active molecules and natural products. In addition, a gold-catalyzed homo-dimerization of 2-phenylethynyl benzaldehyde 1 a was observed when the reaction was carried out in the absence of vinyl ether, affording a set of separable diastereomeric products. Plausible mechanisms for these transformations are discussed; a gold-containing benzopyrylium was regarded as the crucial intermediate by which a number of these new transformations took place.
The reaction between metal-bound isonitriles in cis-[PdCl2(CNRt)(2)] [R-1 = cyclohexyl (Cy) 1, Bu-t 2, C6H4(2,6-Me-2) (Xyl) 3, CMe2CH2CMe3 4] and 1,3-diiminoisoindoline (9) in CHCl3 under reflux for 4 h provides the carbene species [Pd{C(N=C-a(C6H4CNHNb))=N(H)R-1}(2)](a-b) (R-1 = Cy 10, 82% isolated yield) or cis-[PdCl{C(N=C-a(C6H4CNHNb))=N(H)R-1}(CNRt)](a-b) (R-1 = Bu-t 11, 78%; Xyl 12, 84%; CMe2CH2CMe3 13, 79%), derived from the addition of two or one equivs of 9 to the starting 1-4, respectively. The corresponding integration of cis-[PdCl2(CNRt)(PPh3)] (R-1 = Cy 5, Bu-t 6, CMe2CH2CMe3 8) with 1 equiv of 9 in CHCl3 under reflux for 4 h affords the carbene species cis-[PdCl{C(N=C-a(C6H4CNHNb))=N(H)R-1}(PPh3)](a-b) (R-1 = Cy 14, 84%; Bu-t 15, 76%; CMe2CH2CMe3 16, 75%). Complexes 10-16 were characterized by elemental analyses (C, H, N), ESI+-MS, IR, and 1D (H-1, C-13{H-1}) and 2D (H-1,H-1-COSY, H-1,C-13-HMQC/H-t,C-13-HSQC, H-1,C-13-HMBC) NMR spectroscopies. In addition, the structures of aminocarbene complexes 10 and 12 were elucidated by X-ray diffraction. The catalytic properties of 10-16 in the Suzuki-Miyaura cross-coupling of aryl halides, viz., 4-(RC6H4X)-C-2 (X = I, R-2 = OMe; X = Br, R-2 = Me, OMe, and NO2), with phenylboronic acid (in EtOH as solvent, K2CO3 or Cs2CO3 as base, 80 degrees C) yielding biaryl species 4-(RC6H4Ph)-C-2, were evaluated. Complexes 14-16 exhibit a high catalytic activity (yields up to 98%, TONs up to 9.8 x 10(4), TOFs up to 3.9 x 10(4)).
Gold(I) complexes of 1-[1-(2,6-dimethylphenylimino)alkyl]-3-(mesityl)imidazol-2-ylidene (C^Imine(R) ), 1,3-dimesitylimidazol-2-ylidene (IMes) and of the corresponding thione derivatives (S^Imine(R) and IMesS) were prepared and structurally characterised. The solid-state structure of the C^Imine(R) and S^Imine(R) gold(I) complexes showed monodentate coordination of the ligand and a dangling imine group that could bind reversibly to the metal centre to stabilise otherwise unstable catalytic intermediates. Interestingly, reaction of C^Imine(tBu) with [AuCl(SMe(2) )] led to the formation of [(C^Imine(tBu) )AuCl], which rearranges upon crystallisation into the unusual complex cation [(C^Imine(tBu) )(2) Au](+) , with AuCl(2) (-) as the counterion. The activity of the gold complexes in the hydroamination of phenylacetylene with substituted anilines was tested and compared to control catalyst systems. The best catalytic performance was obtained with [(C^Imine(tBu) )AuCl], with the exclusive formation of the Markovnikov addition product in excellent yield (>95 %) regardless of the substituents on aniline.
The gold-catalyzed endo-cycloisomerization of allenes bearing nucleophilic sub- stituents in the α- or β-position opens up a versatile access to various five- and six-membered heterocycles. Key features of these transformations are the high reactivity of the allene in the presence of Lewis-acidic, carbophilic gold(I) or gold(III) catalysts, and the chirality transfer from the allenic axis of chirality to the new stereogenic center in the cyclization product. Recent contributions of our group include the optimization of chirality transfer by using σ-donor ligands to gold, and applications in the total synthesis of natural products, e.g., of the β-carboline alkaloids (−)-isocyclocapitelline and (−)-isochrysotricine.
Addition of a sterically demanding cyclic (alkyl)(amino)carbene (CAAC) to AuCl(SMe2) followed by treatment with [Et3Si(Tol)]⁺[B(C6F5)4]⁻ in toluene affords the isolable [(CAAC)Au(η²-toluene)]⁺[B(C6F5)4]⁻ complex. This cationic Au(I) complex efficiently mediates the catalytic coupling of enamines and terminal alkynes to yield allenes and not propargyl amines as observed with other catalysts. Mono-, di-, and tri-substituted enamines can be used, as well as aryl-, alkyl-, and trimethylsilyl-substituted terminal alkynes. The reaction tolerates sterically hindered substrates and is diastereoselective. This general catalytic protocol directly couples two unsaturated carbon centers to form the three-carbon allenic core. The reaction most probably proceeds through an unprecedented “carbene/vinylidene cross-coupling.”
• catalysis
• enamines
• alkynes
• transition metal
Primary amines, RNH2 react with (p-tolyl isocyanide)chlorogold(I), to give two-coordinate [(ArNH)(RNH)C]AuCl or four-coordinate [(ArNH)(RNH)C]2(RNH2)2Au2Cl2 carbene complexes. Geometrical isomers are identified in solutions of the former type, by NMR spectroscopy. Both types of product react with bases to give insoluble [(ArN)(RNH)CAu]x, species, related to the known trimers, [(ArN)(RO)CAu]3.
The reaction of isocyanides and amines with AuCl−4 produces bis(carbene) complexes of the type Au{C(NR2)NR′H}+2. Treatment of (C6H5)3PAuCl with methyl isocyanide in basic methanol produces cyclic [AuC(OCH3)NCH3]3 which is cleaved by hydrogen chloride to give HNCH3(CH3O)CAuCl. In the solid state these AuI complexes luminesce under ultraviolet irradiation. Treatment of Au{C(NHCH3)2}+2, Au{C(NHCH3)N(CH3)2}2+2 and HNCH3(CH3O)CAuCl with cyanide ion in dimethyl sulfoxide solution produces HC(NCH3)NHCH3, HC(NCH3)N(CH3)2 and HC(OCH3)NCH3, respectively. Other ligand displacement reactions are described. Methyl isocyanide reacts with Au{C(NHCH3)2}+2 to yield the diamidide CH3NCHN(CH3)CHNCH3 which is also formed upon prolonged heating of N,N′-dimethylformamidine. These ligand displacement reactions establish the role of carbene complexes as intermediates in the α-addition reaction of protic nucleophiles with isocyanides.
Hong C. Shen was born in Chengdu, China in 1974. In 1997, he received his B.S. degree in Chemistry from Peking University under the guidance of Professor Yunhua Ye. Hong Shen subsequently moved to University of Minnesota, where he developed a formal [3+3] cycloaddition under the direction of Professor Richard Hsung, and obtained his M.S. degree in 1998. Hong Shen then joined the research group of Professor Barry Trost at Stanford University. His work spanned from Ru- and Pd-catalyzed reactions to their applications in total syntheses of natural products. After having his Ph.D. degree in 2003, Hong Shen became a medicinal chemist at Merck Research Laboratories, Rahway, New Jersey. He is currently a research fellow working on the discovery of novel drugs for the treatment of cardiovascular and metabolic diseases. He has authored over 24 papers and 8 patents.
Complexes [AuCl{C(NHR)(NHR′)}] and [AuCl{C(NHR)(NEt2)}] (R = tBu, p-Tol, Xylyl, p-C6H4COOH, p-C6H4COOEt, R′ = Me, nBu, iPr, nheptyl, p-Tol) have been prepared by reaction of the corresponding isocyanogold complexes [AuCl(CNR)] with either primary amines or diethylamine. All the prepared carbenes are reactive and highly selective catalysts for skeletal rearrangement, methoxycyclization of 1,6-enynes, and other mechanistically related gold-catalyzed transformations. Overall, these easily accessible nitrogen acyclic carbene (NAC) gold complexes were not second to NHC complexes and were advantageous to obtain different products.
A study concerning the synthesis of new N-heterocyclic carbene gold(I) complexes using the bis(trifluoromethanesulfonyl)imidate moiety (Tf2N-) as a weakly coordinating counteranion is described. These new air-stable (NCH)AuNTf2 complexes are convenient to prepare, stoe, and handle and proved to be active in a range of gold(I)-catalyzed transformations.
The title compounds are stable, not cluster-type molecules, having an enneaatomic and probably planar cycle. They are prepared by action of potassium hydroxide in an alcohol on a mixture of an isocyanide and a gold(I) complex, such as Me2SAuCl or Ph3PAuCl; alternatively they are obtained by deprotonation of a carbene complex, [(RO)(R′NH)C]AuCl, which is re-formed when the trimer is treated with hydrochloric acid.
Lithium bis((trifluoromethyl)sulfonyl)amide (1) reacts with S2O6F2 to form FSO2ON(SO2CF3)2 (2). Reaction of 2 with KF results in the cleavage of the S-N bond with the concomitant formation of CF3SO2F. The ease of electrophilic addition reactions of HN(SO2CF3)2 (3) with CH2=CHF, CH2=CF2, and CHF=CF2 depends upon the hydrogen content of the olefin. Addition occurs in a unidirectional fashion according to Markovnikov's rule to form CH3CHFN(SO2CF3)2(4), CH3CF2N(SO2CF3)2(5), and CH2FCF2N(SO2CF3)2 (6), respectively. Cleavage of the CF2-N bond in 5 by reaction with CsF leads to the formation of CH3CF3 in about 12% yield. The major product formed is CF3SO2F. The reactivity of fluorine atoms of the difluoromethylene group of 5 is shown by its reaction with (CH3)3SiN(CH3)2 in the presence of CsF under mild conditions where CF3SO2F, (CH3)3SiF, and CH3C[N(CH3)2]=NSO2CF3 (7) are formed. AgN(SO2CF3)2 is formed by the reaction of Ag2CO3 with anaqueous solution of 3 and undergoes metathetical reactions readily with compounds containing active halogen atoms to introduce the N(SO2CF3)2 group. Strong Lewis acids such as ZN(SO2CF3)2 [Z = R3Sn, R = CH3 (8), n-C4H9 (9), and C6H5 (10); Z = (CH3)3Si (11)] can thus be conveniently prepared. The vinyltin(IV) compound (CH3)3-SnCF=CF2 (12) is synthesized by the reaction between (CH3)3SnCl and CF2=CFBr in hexaethylphosphorus triamide and benzonitrile. Multinuclear NMR studies of the trialkylstannyl/silyl derivatives suggest a quasitetrahedral structure around the central silicon or tin atom as reflected by their very low Si-29 (55.9 ppm) and Sn-119 (approximately 250 ppm) NMR chemical shifts and 1J(Sn-119-C-13) and 2J(Sn-119-H-1) coupling constants. Compounds 8, 9, and 11 can also be isolated by reaction of ClN(SO2CF3)2(13) with the respective alkylmetal chlorides in a noncoordinating solvent. However, 13 fails to add a cross the perfluorovinyl group in CF2=CFSn(CH3)3 (12) and forms CF2=CFCl and 8 instead. Reactions of 13 with a variety of per/polyfluoroolefins, such as CF2=CFX [X = H, F, CF2CF2CF2CF2N- and CF2CF2OCF2CF2N-], CH2=CXY [X = H; Y = F, CF3; X = Y = F] result in uni- or bidirectional addition to give 14-23. Insertion of ClCN into the N-Cl bond of 13 results in the formation of an azaalkene, CCl2=NN(SO2CF3)2(24). Reaction of CFCl2S(O)Cl with 13 forms CFCl2S(O)N(SO2CF3)2 (25) with concomitant evolution of chlorine.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Five different alkenylgold(I) phosphane complexes were prepared and then investigated in [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-catalyzed cross-coupling reactions with different aryl halides, heterocyclic halides, an alkenyl halide, an alkynyl halide, allylic substrates, benzyl bromide and an acid chloride. With regard to the halides, the iodides were highly reactive, bromides or chlorides gave significantly reduced yields or failed, allylic acetates failed, too. The cross-coupling partners contained a number of different functional groups, while free carboxylic acids did not deliver cross-coupling products and o,o-disubstituted arenes failed as well, a broad range of other functional groups like nitro groups, nitrile groups, ester groups, α,β-unsaturated ester groups and lactones, aldehydes, alkoxy groups, pyridyl groups, thienyl groups, unprotected phenols and anilines, even aryl azides were tolerated. The structures of one alkenylgold(I) species and of four of the cross-coupling products were proved by crystal structure analyses.
Compared to an acetyl acyl group, the 3- (3-pyridine)propionyl group increases substrate bind- ing to many proteases and substrate solubility in water, thereby increasing the rates of protease-cata- lyzed reactions. For example, proteases reacted up to six hundred-fold faster with the 3-(3-pyridine)pro- pionyl ester of 1-phenylethanol than with the corre- sponding acetate ester. In addition, the 3-(3-pyridi- ne)propionyl group enables a simple, mild acid ex- traction to separate the remaining starting material and product. To demonstrate the synthetic usefulness of this strategy, we resolved multi-gram quantities of (R)- and (S)-p-toluenesulfinamide with a-chymotryp- sin and gram quantities of (R)- and (S)-2,2-dimethyl- cyclopentanol with subtilisin Carlsberg. The 3-(3-pyr- idyl)propionyl group was better for these resolutions than the corresponding acetate or dihydrocinnamate because it decreased the reaction time due to in- creased reactivity, decreased the reaction volume due to increased substrate solubility and enabled pu- rification without chromatography. Molecular model- ing suggests the enantioselectivity of a-chymotrypsin toward (R)-p-toluenesulfinamide is high (E = 52) be- cause of a favorable hydrophobic interaction be- tween the p-tolyl group of the fast-reacting (R)-enan- tiomer and leaving group pocket. The enantioselec- tivity of subtilisin Carlsberg toward (S)-2,2-dimethyl- cyclopentanol is high (E = 43) because the large sub- stituent (the 2,2-dimethyl quaternary carbon) of the slow-reacting (R)-enantiomer cannot fit in the S1' leaving group pocket.
Isocyanides ligating medium to high-valent electron-poor metal centers can undergo activation toward α-nucleophilic addition to afford a variety of aminocarbene complexes with either heterocyclic or acyclic aminocarbene ligands. These reactions as well as the structural and electronic properties of such products are reviewed.
The solutions with the problems regarding the ligand effects in homogeneous catalysis through December 2007 has been given. Specifically, the problems with the obvious differences in reactivity and selectivity that comes from changing neutral or anionic ligands will be addressed with a focus on ligands and complexes that enables enantioselective catalysis. There are at times when catalyst choice gives off better improvement within the reaction yields or efficiencies. Meanwhile, an emphasis will be given on the privileged ligands and catalysts for a given class of reactions. Finally, the Hayashi/Ito asymmetric aldol reaction will be dealt with.
A review has been given on the alternative gold-catalyzed synthetic methods in both homogeneous and heterogeneous catalysis that has been published until November 2007. A description is given regarding the gold-catalyzed cycloisomerization of enynes. Specific topics that has been covered include: the gold-catalyzed additions to C-C multiple bonds; activation of carbonyl/imine groups and alcohols; gold-catalyzed C-H bond functionalization; gold-catalyzed selective reductions; and finally the oxidation reactions. It has been found out that gold catalysts has the ability to do certain processes that other catalyst cannot. Gold is also found to be of alternative for platinum and palladium. Meanwhile, gold salts can activate either or both C-C multiple bonds or make σ-complexes with heteroatoms. In addition, gold salts have great potential with its ability to catalyze direct C-H bonds functionalization. Overall, gold is found to be of as a means of developing new "green" technologies.
A detail description on gold-catalyzed cycloisomerization reactions of 1,n-enynes has been given as well as its mechanisms. In addition, a discussion will also be given regarding the cyclizations with concomitant addition of nucleophiles to 1,n-enynes. Two bonds with C-C/ C-X or two C-C are formed as these reactions are domino-type transformations. Other topics that have been discussed include: the reactions of arenes and heteroarenes with alkynes that are mechanistically related to enynes; the cycloisomerizations of enynes bearing propargylic carboxylates or ethers; and finally, the addition of nucleophiles to 1,n-Enynes.
(Chemical equation presented) The gold rush: A cationic gold (I) complex, supported by a CAAC ligand, promotes the intramolecular addition of N-H or N-Me bonds (from ammonium salts or tertiary amines, respectively) to carbon-carbon triple bonds; the same complex allows for the isolation of vinylgold intermediates. X= (C6F5)4B. CAAC = cyclic (alkyl) (amino)carbene.
A cationic (CAAC)gold(I) complex promotes the addition of all types of nontertiary amines to a variety of allenes, affording allylic amines in good to excellent yields; the amino fragment always adds to the less substituted terminus of the CCC skeleton.
N-heterocyclic carbenes (NHC) are cyclic carbenes bearing at least one α-amino substituent that have marked the field of late transition metal catalysis. Their ability to stabilize otherwise highly reactive intermediates and yet promote and enhance constructive chemical steps at the metal center has been important in their extremely rapid development. Presently, in terms of catalytic applications with NHCs, late transition metals can be divided into four categories, including the heavyweights (Ru, Rh, Ni, and Pd), the well-established (Ir, Pt, Cu, and Au), the underdeveloped (Fe, Os, Co, and Ag), and the nonexistents (Mn, Tc, and Re). Great achievements have already been made in the fields of cycloisomerization and hydrofunctionalization. The ability of NHCs to stabilize important catalytic intermediates and yet to promote subsequent reaction in the coordination sphere of gold will surely lead to exciting discoveries.
A 95/5 mixture of cis and trans 2,4-dimethyl-3-cyclohexenecarboxaldehyde (trivertal), a common fragrance and flavor material produced in bulk quantities, serves as the precursor for the synthesis of a stable spirocyclic (alkyl)(amino)carbene, in which the 2-methyl-substituted cyclohexenyl group provides steric protection to an ensuing metal. The efficiency of this carbene as ligand for transition metal based catalysts is first illustrated by the gold(I) catalyzed hydroamination of internal alkynes with secondary dialkyl amines, a process with little precedent. The feasibility of this reaction allows for significantly enlarging the scope of the one-pot three-component synthesis of 1,2-dihydroquinoline derivatives, and related nitrogen-containing heterocycles. Indeed, two different alkynes were used, which include an internal alkyne for the first step.
The special issue of Chemical Reviews focused on the most significant achievements of researchers in the development of persistent noncyclic singlet carbenes. It was informed that these carbenes differed from their cyclic analogues in the absence of geometric constraint, resulting in a broader variation of the carbene bond angle and in free orientation of the substituents susceptible to interact with the carbene center. The variety of noncyclic carbenes was more than that of cyclic carbenes due to better synthetic accessibility. The known stable noncyclic carbenes were classified as phosphino- or amino carbenes depending on the predominant stabilizing substitient. The special issue also discussed the synthesis and electronic structure of the various noncyclic singlet carbenes. It presented their reactivity, including carbene and unusual reactivity and coordination to transition metals.
A cationic gold (I) complex was reported to catalyze the addition of various types of non-tertiary amines to terminal and internal alkynes. The one-pot preparation of allenes by coupling two alkynes using a sacrificial secondary amine was also investigated. The results show that a mixture of Markovnikov and anti-Markovnikov products are obtained when methylphenylacetylene and tert-butyl-acetylene are used. It is also found that hydroamination with ammonia is a very general pre-catalyst for the addition of amines to alkynes. The coupling of two alkynes to form allenes, using an amine as a two hydrogen donor is a process that combines two distinct chemical reactions and relies on single catalyst. Gold complex is found to feature oxophilic character and display excellent functional group tolerance and low air moisture sensitivity.
Complexes [AuCl{C(NHR)(NHPy-2)}] (Py-2 ) 2-pyridyl; R ) Me, tBu, nBu, iPr, nheptyl) have been prepared in amodular way from [AuCl(CNPy-2)]. The carbene moiety has a hydrogen-bond supported heterocyclic structure similar to the nitrogen heterocyclic carbenes in the solid state, and in CH2Cl2 or acetone solution, which is open in the presence of MeOH. The compounds are good catalysts for the skeletal rearrangement of enynes, and for the methoxycyclization of enynes. In contrast, the complexes [AuCl{C(NHR)(NHPy-4)}] are scarcely active due to the blocking effect of the coordination position required for the catalysis by the nitrogen of the NHPy-4 group.
The complete basis set method CBS-QB3 was used in conjunction with the CPCM solvation model to predict both the absolute and relative pKa's of 12 nucleophilic carbenes in dimethyl sulfoxide (DMSO), acetonitrile (MeCN), and water. Average absolute pKa values in DMSO ranged from 14.4 +/- 0.16 for 3-methylthiazol-2-ylidene (12) to 27.9 +/- 0.23 in the case of bis(dimethylamino)carbene (11), while values in MeCN were determined to be between 25.7 +/- 0.16 (12) and 39.1 +/- 0.25 (11). Relative pKa calculations yielded similar results. Calculations in aqueous solution gave pKa's between 21.2 +/- 0.2 (12) and 34.0 +/- 0.3 (11). Excellent agreement between calculated and experimental pKa's was obtained for the few cases where experimental numbers are available, confirming that this theoretical approach may be used to calculate highly accurate pKa values.
Reaction of benzyl (2,2-diphenyl-4,5-hexadienyl)carbamate (4) with a catalytic 1:1 mixture of Au[P(t-Bu)2(o-biphenyl)]Cl (2) and AgOTf (5 mol %) in dioxane at 25 degrees C for 45 min led to isolation of benzyl 4,4-diphenyl-2-vinylpyrrolidine-1-carboxylate (5) in 95% yield. The Au(I)-catalyzed intramolecular hydroamination of N-allenyl carbamates tolerated substitution at the alkyl and allenyl carbon atoms and was effective for the formation of piperidine derivatives. gamma-Hydroxy and delta-hydroxy allenes also underwent Au-catalyzed intramolecular hydroalkoxylation within minutes at room temperature to form the corresponding oxygen heterocycles in good yield with high exo-selectivity. 2-Allenyl indoles underwent Au-catalyzed intramolecular hydroarylation within minutes at room temperature to form 4-vinyl tetrahydrocarbazoles in good yield. Au-catalyzed cyclization of N-allenyl carbamates, allenyl alcohols, and 2-allenyl indoles that possessed an axially chiral allenyl moiety occurred with transfer of chirality from the allenyl moiety to the newly formed stereogenic tetrahedral carbon atom.
Catalysis by gold has rapidly become a hot topic in chemistry, with a new discovery being made almost every week. Gold is equally effective as a heterogeneous or a homogeneous catalyst and in this Review we attempt to marry these two facets to demonstrate this new found and general efficacy of gold. The latest discoveries are placed within a historical context, but the main thrust is to highlight the new catalytic possibilities that gold-catalyzed reactions currently offer the synthetic chemist, in particular in redox reactions and nucleophilic additions to pi systems. Indeed gold has proved to be an effective catalyst for many reactions for which a catalyst had not been previously identified, and many new discoveries are still expected.
In this feature article we cover most recent efforts in gold-catalysed transformations, highlighting the wide molecular diversity that can be achieved, in particular with regard to the formation of C-C bonds. Mechanistic interpretations of some cyclisations are based on our own work on the skeletal rearrangement of 1,6-enynes.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Transition-metal catalysts containing gold present new opportunities for chemical synthesis, and it is therefore not surprising that these complexes are beginning to capture the attention of the chemical community. Cationic phosphine-gold(i) complexes are especially versatile and selective catalysts for a growing number of synthetic transformations. The reactivity of these species can be understood in the context of theoretical studies on gold; relativistic effects are especially helpful in rationalizing the reaction manifolds available to gold catalysts. This Review draws on experimental and computational data to present our current understanding of homogeneous gold catalysis, focusing on previously unexplored reactivity and its application to the development of new methodology.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Although homogeneous gold catalysis was known previously, an exponential growth was only induced 12 years ago. The key findings which induce that rise of the field are discussed. This includes early reactions of allenes and furanynes and intermediates of these conversions as well as hydroarylation reactions. Other substrate types addressed are alkynyl epoxides and N-propargyl carboxamides. Important vinylgold intermediates, the transmetalation from gold to other transition metals, the development of new ligands for gold catalysis, and significant contributions from computational chemistry are other crucial points for the field highlighted here.
Isocyanide [AuX(CNPy-2)] (X = Cl, C6F5, fluoromesityl, 1/2 octafluorobiphenyl) and carbene [AuX{C(NR1R2)(NHPy-2)}] (R1R2NH = primary or secondary amines or 1/2 primary diamine) gold(I) complexes have been synthesized and characterized. For X = Cl, the carbene complexes show aurophilic interactions. The fragment NHPy-2, formed in the carbenes, can give rise to intra- (for primary amines) or intermolecular (for secondary amines) hydrogen bonds, depending on the amine used. These bonds and contacts have been studied in the solid state and in solution. The intermolecular hydrogen bonds are split in an acetone solution, but the intramolecular ones, which close a six-membered ring, survive in solution. Except for the fluoromesityl derivatives, the carbene complexes display luminescent properties.
The use of gold(I) complexes as catalysts for organic transformations has become increasingly common over the past decade, leading to the development of a number of useful carbon-carbon and carbon-heteroatom bond-forming processes. In contrast, enantioselective catalysis employing gold(I) complexes was, until recently, exceedingly rare, due in large part to the pronounced tendency of gold(I) to form linear, two-coordinate complexes. However, new approaches and strategies have emerged over the past two years, leading to the development of a number of effective gold(I)-catalyzed enantioselective transformations, most notably the enantioselective hydrofunctionalization of allenes. Outlined herein is an overview of enantioselective gold(I) catalysis since 2005.
(Chemical Equation Presented) A golden ticket to the synthesis of reactive nitrogen-containing compounds, such as imines, enamines, and allyl amines, through the addition of NH3 to unsaturated bonds is the cationic cyclic (alkyl)-(amino)carbene-gold(I) catalyst shown in blue (Dipp=diisopropylphenyl). An ideal initial step for the preparation of simple bulk chemicals, this reaction is also useful for the synthesis of more complex molecules (see examples).
A review on the coinage metals as with Cu, Ag, and Au is given regarding its uses in the synthesis of heterocycles. In addition, a discussion with the mechanism of the C-C and C-X bond formation reactions will be provided so as to show the activation of substrates and possible reaction pathways. Then, a description on the use of coinage metals as a sole catalyst for the synthesis of heterocycles is also offered. However, only the reactions where a heterocyclic ring that is essentially generated will only be discussed. Specific topics to be discussed include: the cyclization of unsaturated C-C bonds with tethered nucleophiles; cycloaddition reactions; the cycloisomerization of enynes/diynes; the intramolecular friedel-crafts-type reactions; reactions of α-Diazocarbonyl compounds; aziridination of olefins; N/O-vinylation/arylation; and finally, the radical cyclization of haloalkenes and haloalkynes.
A review on organic reactions which involves gold that are from literatures published from the beginning of 2004 to the end of 2007 has been given. Similar reaction types or reaction mechanisms will be used for the discussion. The reactions include: gold-catalyzed nucleophilic additions; gold-catalyzed friedel, which includes crafts reactions and C-H activations; and finally the gold-catalyzed hydrogenations and oxidations. More specifically, the reactions involves: gold-catalyzed cyclizations with olefins as nucleophiles; gold-catalyzed tandem nucleophilic additions; and the gold-catalyzed nucleophilic additions that uses nitrogen nucleophiles, oxygen, sulfur nucleophiles, HX, and the carbon nucleophiles.
- Reetz M. T.