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Rhodium/diene-Catalyzed Asymmetric 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Weinreb Amides.
Abstract
Rhodium/chiral diene (S,S)- complex has been found to effectively catalyze the 1,4-addition of arylboronic acids to alpha,beta-unsaturated Weinreb amides, furnishing useful beta-chiral Weinreb amides in high enantioselectivity.
... Such conjugate addition reactions typically involve a metal complex containing a chiral ligand, which, as a Lewis acid, activates the carbonyl group and/or activates and delivers the nucleophile. As highlighted in Scheme 12, this method has been successfully applied to asymmetric conjugate additions of hydroperoxides (to give 44), [19,45] amines (to give 43), [20,46] phosphites (to give 47), [47] phosphane oxides (to give 48), [48] malonates (to give 41, 49), [49,50] dimethylsulfoxonium methylide (to give 46), [51] arylboronic acids [52] and cyanide (to give 45). [53][54][55] Another notable application of α,β-unsaturated N-acylpyrroles is their use in the enantioselective conjugate cyanation/protonation reaction developed by Shibasaki and coworkers (Scheme 13). ...
This microreview highlights the synthetically versatile N-acylpyrrole functional group. The preparation, electronic properties and unique reactivity of these amide systems are highlighted. Capable of functioning as acid, ester, amide, aldehyde and ketone equivalents, of serving as acylating agents, of enhancing the reactivities of α,β-unsaturated systems and of undergoing a wide range of other reactions, this microreview shows N-acylpyrroles to be more than just amides. This microreview highlights the synthesis, properties and reactions of the valuable N-acylpyrrole functional group.
... The 1 H NMR spectroscopic data matched that for an alternative preparation of (R)-19g. 116 Data for 19g: bp 75 °C ABT (0.03 mmHg). ...
The first systematic investigation of unactivated aliphatic sulfur compounds as electrophiles in transition-metal-catalyzed cross-coupling are described. Initial studies focused on discerning the structural and electronic features of the organosulfur substrate that enable the challenging oxidative addition to the C(sp(3))-S bond. Through extensive optimization efforts, an Fe(acac)3-catalyzed cross-coupling of unactivated alkyl aryl thio ethers with aryl Grignard reagents was realized in which a nitrogen "directing group" on the S-aryl moiety of the thio ether served a critical role in facilitating the oxidative addition step. In addition, alkyl phenyl sulfones were found to be effective electrophiles in the Fe(acac)3-catalyzed cross-coupling with aryl Grignard reagents. For the latter class of electrophile, a thorough assessment of the various reaction parameters revealed a dramatic enhancement in reaction efficiency with an excess of TMEDA (8.0 equiv). The optimized reaction protocol was used to evaluate the scope of the method with respect to both the organomagnesium nucleophile and sulfone electrophile.
Chiral dienes are important ligands in asymmetric catalysis but they are less accessible than other commonly used ligands such as chiral bisphosphines. Here, we show that intramolecular [4+2] cycloaddition of a simply attained chiral allenecarboxanilide readily affords pseudoenantiomeric bicyclo[2.2.2]octa‐2,5‐dienes containing an alkenyl bromide, which can be readily functionalized to give diverse chiral diene ligands. The synthesis is straightforward and easily conducted on multigram scales. These ligands exhibit high performance in nine types of enantioselective Rh(I)‐catalyzed 1,4‐addition or 1,2‐addition reactions.
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Asymmetric catalysis has emerged as a general and powerful approach for constructing chiral compounds in an enantioselective manner. Hence, developing novel chiral ligands and catalysts that can effectively induce asymmetry in reactions is crucial in modern chemical synthesis. Among such chiral ligands and catalysts, chiral dienes and their metal complexes have received increased attention, and a great progress has been made over the past two decades. This review provides comprehensive and critical information on the essential aspects of chiral diene ligands and their importance in asymmetric catalysis. The literature covered ranges from August 2003 (when the first effective chiral diene ligand for asymmetric catalysis was reported) to October 2021. This review is divided into two parts. In the first part, the chiral diene ligands are categorized according to their structures, and their preparation methods are summarized. In the second part, their applications in asymmetric transformations are presented according to the reaction types.
Herein, we report a highly efficient versatile synthetic route to Chiraphos derivatives through Rh/Ph-bod catalyzed asymmetric addition of aryl boronic acids to phosphinyl dienes. Various substituted phosphinyl dienes, both on the parent skeleton and the phosphine atoms, were well tolerated with this method and provided chiral phosphine oxides in satisfied yield and up to 95% ee. The corresponding Chiraphos derivative displayed an advantage over Chiraphos in the representative Pd-catalyzed asymmetric 1,4-addition reaction.
The first metal-free catalytic intermolecular enantioselective Michael addition to unactivated α,β-unsaturated amides is described. Consistently high enantiomeric excesses and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane catalyst. Low catalyst loadings (2.0 mol %) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity via analysis of relevant transition structures and provided substantial support for specific noncovalent activation of the carbonyl group of the α,β-unsaturated amide by the catalyst.
A catalytic asymmetric conjugate hydrophosphination of α,β-unsaturated amides is accomplished by virtue of the strong nucleophilicity of copper(I)-PPh2 species, which provides an array of chiral phosphines bearing an amide moiety in high to excellent yields with excellent enantioselectivity. Furthermore, the dynamic kinetic resolution of unsymmetrical diarylphosphines (HPAr1Ar2) is successfully carried out through the copper(I)-catalyzed conjugate addition to α,β-unsaturated amides, which affords P-chiral phosphines with good-to-high diastereoselectivity and high enantioselectivity. 1H NMR studies show that the precoordination of HPPh2 to copper(I)-bisphosphine complex is critical for the efficient deprotonation by Barton's Base. Moreover, the relative stability of the copper(I)-(R,R
P
)-TANIAPHOS complex in the presence of excessive HPPh2, confirmed by 31P NMR studies, is pivotal for the high asymmetric induction, as the ligand exchange between bisphosphine and HPPh2 would significantly reduce the enantioselectivity. At last, a double catalytic asymmetric conjugate hydrophosphination furnishes the corresponding product in high yield with high diastereoselectivity and excellent enantioselectivity, which is transformed to a chiral pincer palladium complex in moderate yield. This chiral palladium complex is demonstrated as an excellent catalyst in the asymmetric conjugate hydrophosphination of chalcone.
The rhodium‐catalyzed asymmetric addition reaction of organoboron reagents to α,β‐unsaturated compounds has seen significant growth in the past two decades for their user‐friendly reaction conditions, which generally allow the use of water as a cosolvent. This chapter highlights advancements ranging from 2004 to 2017 in this field and organizes the content in terms of the applicable substrates with respect to the chiral ligands. Bis‐sulfoxide ligands emerged as one of the privileged ligand family in C‐H oxidation reaction by coordinating Pd with sulfur atoms. Ligands with two distinct chelating centers are regarded as hybrid ligands. While dienes generally display greater catalytic activity than phosphorus ligands, the coordinating ability of diene ligands is weaker than that of phosphine‐based ones. α,β‐unsaturated esters are generally good reaction partners in the Rh‐catalyzed conjugate addition reactions for 1,4‐addition products. Nitroolefin compounds are excellent substrates in the rhodium‐catalyzed asymmetric conjugate addition reactions as a result of their highly electrophilic nature.
Copper(I)-catalyzed enantioselective borylation of α,β-unsaturated N- acylindoles as well as N-acylpyrroles was efficiently achieved by means of bis(pinacolato)diboron (B pin ), affording the enantioenriched products in excellent yields with up to 99% ee. The present work provides an alternative class of Michael acceptors, that is, α,β-unsaturated N-acylindoles, for potential asymmetric transformations.
A rhodium–chiral diene complex immobilized on amphiphilic polystyrene–poly(ethylene glycol) (PS–PEG) resin (PS–PEG–diene*–Rh) has been developed. The immobilized rhodium–chiral diene complex (PS–PEG–diene*–Rh) efficiently catalyzed the asymmetric 1,4-addition of various arylboronic acids to cyclic or linear enones in water under batch conditions to give the corresponding β-arylated carbonyl compounds in excellent yields and with excellent enantioselectivity. The catalyst was readily recovered by simple filtration and reused 10 times without loss of its catalytic activity and enantioselectivity. Moreover, a continuous-flow asymmetric 1,4-addition in a flow reactor containing PS–PEG–diene*–Rh proceeded efficiently at 50 °C with retention of high enantioselectivity. Long-term continuous-flow asymmetric 1,4-addition during 12 hours readily gave the desired product on a ten-gram scale with high enantioselectivity.
Here we report that readily available silyl- and boron-based Lewis acids in combination with chiral copper catalysts are able to overcome the reactivity issues of unactivated enamides, known as the least reactive carboxylic acid derivatives, toward alkylation with organomagnesium reagents. Allowing unequaled chemo-reactivity and stereocontrol in catalytic asymmetric conjugate addition to enamides, the method is distinguished by its unprecedented reaction scope, allowing even the most challenging and synthetically important methylations to be accomplished with good yields and excellent enantioselectivities. This catalytic protocol tolerates a broad temperature range (−78 °C to ambient) and scale up (10 g), while the chiral catalyst can be reused without affecting overall efficiency. Mechanistic studies revealed the fate of the Lewis acid in each elementary step of the copper-catalyzed conjugate addition of Grignard reagents to enamides, allowing us to identify the most likely catalytic cycle of the reaction.
The rhodium‐catalyzed 1,4‐addition of organoboron reagents to electron‐deficient alkenes is a versatile method for the enantioselective construction of carbon–carbon bonds. The scope of these reactions is broad, and alkenes activated by adjacent carbonyls, imines, nitriles, phosphonyl groups, nitro groups, sulfonyl groups, C=N‐containing aromatic heterocycles, electron‐deficient arenes, or boryl groups are effective substrates. Regarding the pronucleophilic component, aryl‐, heteroaryl‐, and alkenylboron reagents have been successfully employed. In addition, numerous chiral ligands have been developed which impart high enantioselectivities onto these reactions. Importantly, these reactions usually proceed under mild, experimentally convenient conditions, with no requirement for precautions to exclude air or moisture.
This chapter presents the scope and limitations of this process, along with a discussion of the current understanding of the mechanistic and stereochemical features. Incorporation of this process into domino reactions is discussed, as is its application in the synthesis of biologically active molecules. The literature is covered up until the end of 2013.
A facile and efficient method for the preparation of allyl amides from the aldehyde of Baylis-Hillman adducts has been developed using hydroxylamine/methanol system under catalyst-free condition. The effect of solvents, temperature effect on the reaction and substituents on the phenyl ring have been examined. This method is best demonstrated by its advantages like operational simplicity, moderate to excellent yields, short reaction time and simple reaction procedure. Most importantly, the reaction proceeds smoothly in the absence of a catalyst and external oxidant.
The Rh-catalyzed asymmetric 1,4-addition of organometallic reagents to an appropriate receptor has been a growing area of research over the last decade. The receptors for such a 1,4-addition reaction are chiefly α,β-unsaturated ketones, esters, amides, enones, nitroalkenes, and occasionally phosphonates etc. This reaction in the presence of chiral rhodium complexes introduce the aryl and alkenyl groups at the β-position of the above electron poor olefins, enantioselectively. Chiral Rh complexes similar to other transition metals can be added to some electron poor olefins, in turn making them viable to attack by various organometallic reagents for highly enantioselective C–C bond formation. The Rh-catalyzed asymmetric 1,4-addition of organometallic reagents to electron poor olefins has been reviewed in 2003. Due to the importance of the asymmetric C–C bond formation via 1,4-conjugate addition reactions and the number of such reactions catalyzed by Rh-complexes, in this review we highlight the recent advances in Rh-complex asymmetric catalyzed 1,4-addition reactions since 2003.
Cooperative catalysts consisting of chiral Rh/Ag nanoparticles and Sc(OTf)3 have been developed that catalyze asymmetric 1,4-addition reactions of arylboronic acids with α,β-unsaturated amides efficiently. The reaction has been considered one of the most challenging reactions because of the low reactivity of the amide substrates. The new catalysts provide the desired products with outstanding enantioselectivities (>98 % ee) in the presence of low loadings (<0.5 mol %) of the catalyst.
Cooperative catalysts consisting of chiral Rh/Ag nanoparticles and Sc(OTf)3 have been developed that catalyze asymmetric 1,4-addition reactions of arylboronic acids with α,β-unsaturated amides efficiently. The reaction has been considered one of the most challenging reactions because of the low reactivity of the amide substrates. The new catalysts provide the desired products with outstanding enantioselectivities (>98 % ee) in the presence of low loadings (<0.5 mol %) of the catalyst.
This chapter focuses on progress achieved for the hydroformylation and related carbonylation reactions of alkenes, alkynes, and allenes. The most recent applications of hydroformylation in organic synthesis as well as selected Tandem reactions are covered. After a general introduction, the review is arranged by the type of selectivity control achievable for different classes of substrates depending on the substitution pattern. Both substrate control including directing groups as well as reaction variants under complete catalyst control are covered.
IntroductionEnantioselective Arylation of AldehydesEnantioselective Arylation of KetonesEnantioselective Arylation of IminesConjugate Asymmetric ArylationTandem ProcessesEnantioselective Friedel–Crafts ArylationConclusions
References
Two characteristics are required for a reagent to be a useful partner in a chiral reaction, it must be able to bind to the catalyst to generate a reacting intermediate with a well-defined enantioface discrimination, and it must have substituents suitable for further modifications of the reaction products. N-Acyliden penta-atomic aza-heterocycles fulfill these conditions, they have the carbonyl group suitable for the coordination to the catalyst, and the leaving character of the heterocycle bound to the carbonyl group allows the conversion of the products into a variety of functionalized chiral building blocks. If the heterocycle has a further point of coordination to the catalyst, the reagent may behave as a bidentate ligand, making the reaction easier and the chiral product more stereoselective, as discussed for many reactions in the previous sections. The products of the enantioselective reactions are often useful intermediates for the syntheses of natural or biologically active compounds.
(1S,4S)-isomer [862379-81-5] (1R,4R)-isomer [796966-14-8] C22H22 (MW 286.41) InChI = 1S/C22H22/c1-3-7-17(8-4-1)13-21-15-20-12-11-19(21)16-22(20)14-18-9-5-2-6-10-18/h1-10,15-16,19-20H,11-14H2InChIKey = DUTGPXVHLRHXTD-UHFFFAOYSA-NInChI = 1/C22H22/c1-3-7-17(8-4-1)13-21-15-20-12-11-19(21)16-22(20)14-18-9-5-2-6-10-18/h1-10,15-16,19-20H,11-14H2InChIKey = DUTGPXVHLRHXTD-UHFFFAOYAB(chiral ligand for rhodium-catalyzed asymmetric addition of organometallic reagents to unsaturated bonds)Physical Data: mp 69–71 °C. [α]20D +86° (c 0.71, CHCl3; (1R,4R)-isomer).Solubility: soluble in many organic solvents such as THF, toluene, and dichloromethane.Form Supplied in: white solid.Analysis of Reagent Purity: 1H NMR.Preparative Methods: This reagent is prepared in a racemic form in two steps from (±)-bicyclo[2.2.2]octa-2,5-dione: (1) Treatment with lithium diisopropylamide followed by N-(2-pyridyl)trifluoromethanesulfonimide gives (±)-2,5-bis(trifluoromethanesulfonyloxy)bicyclo[2.2.2]octa-2,5-diene; (2) This material is reacted with benzylmagnesium bromide in the presence of PdCl2(dppf) (1 mol %) in diethyl ether at reflux for 24 h to provide the racemic ligand. Optical resolution by preparative chiral HPLC using a Chiralcel OJ column with hexane/2-propanol gives the enantiopure (1S, 4S)- and (1R,4R) enantiomers.1Purification: chromatography on silica gel with hexane/ethyl acetate (10/1) and/or chromatography through GPC with chloroform.Handling, Storage, and Precaution: this reagent is an air-stable solid and can be stored and handled at room temperature in the air.
Octahedral iridium(III) complexes containing two bidentate cyclometalating 5-tert-butyl-2-phenylbenzoxazole (IrO) or 5-tert-butyl-2-phenylbenzothiazole (IrS) ligands in addition to two labile acetonitrile ligands are demonstrated to constitute a highly versatile class of asymmetric Lewis acid catalysts. These complexes feature the metal center as the exclusive source of chirality and serve as effective asymmetric catalysts (0.5-5.0 mol % catalyst loading) for a variety of reactions with α,β-unsaturated carbonyl compounds, namely Friedel-Crafts alkylations (94-99 % ee), Michael additions with CH-acidic compounds (81-97 % ee), and a variety of cycloadditions (92-99 % ee with high d.r.). Mechanistic investigations and crystal structures of an iridium-coordinated substrates and iridium-coordinated products are consistent with a mechanistic picture in which the α,β-unsaturated carbonyl compounds are activated by two-point binding (bidentate coordination) to the chiral Lewis acid.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The conjugate addition reaction has been a useful tool in the formation of carbon-carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams.
7-Azaindoles are versatile building blocks, especially in medicinal chemistry, where they serve as bioisosteres of indoles or purines. Herein, we present an novel rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to 3-benzylidene-1H-pyrrolo[2,3-b]pyridin-2(3H)-ones, as these substrates are exocyclic methylene lactamyl Michael acceptors. Ten new original derivatives of 1H-pyrrolo[2,3-b]pyridin-2(3H)-one have been obtained.
Tropane-derived phosphorus–olefin hybrid ligands bearing various combinations of P-units (chiral BINOL-derived units/achiral PPh2-units) with a tropene skeleton (chiral/achiral) have been synthesized and used in Cu-catalysed conjugate 1,4-additions of diethylzinc to cyclic enones and in Rh-catalysed 1,4-additions of phenylboronic acid (Hayashi–Miyaura reaction) with cyclic and acyclic enones. Whereas in Cu-catalysed reactions only moderate yields and ee values (up to 49 % ee) were obtained, up to 97 % ee was observed in the Hayashi–Miyaura reaction with various substrates. The most promising results in both reactions were achieved with ligands 11 and 15, which contain a chiral alkene/achiral P-unit or an achiral alkene/chiral P moiety, respectively, and where the metal is complexed on the exo side of the tropene skeleton. In contrast, ligands with an endo coordination mode showed only low (13) or no activity (12) in all of the 1,4-additions. NMR and ESI-MS experiments revealed the presence of two cationic [RhI(15)2]+ species in solution.
A novel Pd/Cu-catalyzed chemoselective aerobic oxidative N-dealkylation/carbonylation reaction has been developed. Tertiary amines are utilized as a "reservoir" of "active" secondary amines in this transformation, which inhibits the formation of undesired by-products and the deactivation of the catalysts. This protocol allows for an efficient and straightforward construction of synthetically useful and bioactive (E)-α,β-unsaturated amide derivatives from easily available tertiary amines, olefins and CO.
A modular titanium promoted coupling of unsymmetrical internal alkynes with Weinreb amides is described. The coupling reaction takes place at room temperature affording (E)-trisubstituted enones in moderate to good yields with high levels of regioselectivity. The system showed moderate chemoselectivity.
Rhodium-catalyzed asymmetric arylation (RCAA) reactions provide one of the most straightforward and powerful ways to introduce aryl fragments in an enantioselective manner. The discovery of novel chiral ligands and catalytic systems is a major focus in generating optical chiralities for RCAA reactions. In the past decade, the chelating functionalities in ligands have been significantly expanded from traditional phosphorus to interesting diene, bissulfoxide, and their hybrids. Herein we highlight the research on these distinct families of chiral ligands and describe their applications in the RCAA of arylmetals to activated alkenes, aldehydes, ketones and imines, and RCAA-tandem reactions.
Aktiv ohne Aktivierung: In einem preiswerten und atomökonomischen Ansatz der C‐H‐Funktionalisierung wird ein kationischer Cobalt(III)‐Komplex verwendet, um nucleophile metallorganische Spezies in situ ohne Zusatz aktivierender Reagentien herzustellen (siehe Schema). Aryl‐C‐H‐Bindungen addieren effizient an polare Elektrophile, einschließlich α,β‐ungesättigter N‐Acylpyrrole als β‐substituierte Ester‐ und Amid‐Surrogate.
Rh-Catalyzed asymmetric 1,4-selective addition of arylboronic acids to beta,gamma-unsaturated alpha-keto ester was developed using chiral tert-butanesulfinylphosphine as ligand, good yields (up to 87%), good 1,4-regioselectivities (up to 96:4), and high enantioselectivities (up to 94% ee) were achieved.
An asymmetric decarboxylative 1,4-addition of malonic acid half thioesters (MAHTs) to 2-aryl-substituted vinyl sulfones has been developed, yielding adducts with excellent enantioselectivity (up to 97 % ee). In view of tuning pKa values, a quinine-based benzyl-substituted thiourea was designed and demonstrated as the most efficient catalyst. The enantioselective synthesis of 3-monofluorinated analogues of 3-methyl indanone and (+)-turmerone has been accomplished from decarboxylative 1,4-addition adducts with satisfactory results.
A new reagent for the synthesis of the α,β-unsaturated N-methoxy-N-methyl-amide structural unit has been developed. 2-(Benzo[d]thiazol-2-ylsulfonyl)-N-methoxy-N-methylacetamide, a crystalline solid with an indefinite shelf life that can be easily prepared in two convenient steps from 2-chloro-N-methoxy-N-methylacetamide, reacted with a variety of aldehydes under Julia conditions to furnish the α,β-unsaturated N-methoxy-N-methyl-amide functionality. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Palladium-catalyzed arylation of α,β-unsaturated Weinreb amides has been examined to obtain β-aryl-α,β-unsaturated Weinreb amides. The chelation between the palladium center of an alkylpalladium intermediate and Weinreb amide moiety facilitated both coordination and insertion steps.
β-Substituted alkenyl-para-nitroarenes, an unexplored substrate class for catalytic asymmetric addition reactions, undergo highly enantioselective rhodium-catalyzed arylations with arylboronic acids in the presence of a dibenzylamide-containing chiral diene ligand. One example of the asymmetric arylation of an alkenyl-p-cyano-m-(trifluoromethyl)benzene is also presented.
Full details of syn-selective catalytic asymmetric direct Mannich-type reactions of aromatic and heteroaromatic hydroxy ketones promoted by Y[N(SiMe3)2]3/linked-BINOL complexes are described. From a screening of various rare-earth metals and linked-BINOL derivatives, a Y[N(SiMe3)2]3/TMS-linked-BINOL (1.7/1) complex was determined to be the most effective. Mannich-type reactions of aromatic and heteroaromatic hydroxy ketones with aryl and alkenyl N-diphenylphosphinoylimines, catalyzed by 0.1 molar amount of Y[N(SiMe3)2]3 and 0.059 molar amount of TMS-linked-BINOL, afforded syn-β-amino-α-hydroxy ketones in good yields (78–98%), high diastereoselectivity (syn/anti = 81/19–96/4), and high enantioselectivity (86–98% ee).
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.
Design and applications of multimetallic Afunctional asymmetric catalysts based on the proximity-effect-control concept are described. Suitable design of chiral ligands and selection of metals were important to realize cooperative bimetallic catalysis. Homo-multimetallic complexes, using linked-BINOLs (Zn, In, Y, and La), as well as hetero-multi-metallic complexes, using a dinucleating Schiff base, BINOL, and pybox (Cu-Sm, La-Li, and Y-Li), were developed for asymmetric direct aldol reactions, Michael reactions, direct Mannich-type reactions, nitro-Mannich-type reaction,aza-Michael reactions, kinetic resolution of terf-nitroaldols, and cyanation reactions. Synergistic effects of two or more metals played a key role in promoting the reactions in high reactivity and enantioselectivity.
X-ray crystallographic studies on π-allylpalladium complexes coordinated with a chiral phosphine–olefin ligand (−)-1b demonstrate that the phosphine ligand shows a larger trans-influence than the π-bound olefin. The palladium/chiral phosphine–olefin complex efficiently catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with 96% enantioselectivity.
[Rh(COD)Cl]2-catalyzed addition reactions of arylboronic acids with aldehydes, with low Rh(I) catalyst loading, are described. We also found that the reaction of arylboronic acids with α,β-unsaturated aldehydes greatly depends on the solvent and the steric hindrance of the reagents/substrates.
A class of optically pure 7,7′-disubstituted BINAPs have been prepared starting with a catalytic asymmetric oxidative coupling reaction. A general, concise, and straightforward synthetic procedure has been established, and is suitable for all optically pure 7,7′-disubstituted BINAPs 1a–h, regardless of the substituents' structure in the 7,7′-positions. The catalytic potential of this class of ligands has been investigated in the highly enantioselective Rh-catalyzed 1,4-addition of aryl boronic acids to enones (up to 99.8% ee), and Ru-catalyzed asymmetric hydrogenation of simple aromatic ketones (up to S/C=100,000, up to 98% ee) and β-ketoesters (up to S/C=10,000, up to 99.8% ee), respectively.
Zwei Ringe auf einen Streich: In der intramolekularen [4+2]-Cycloaddition von 1,3-Dienen mit angebundenen Alkingruppen ist ein Rhodium-Dien-Katalysator aktiver als sein Bisphosphan-Gegenstück (siehe Schema). Mit einem ähnlichen Komplex mit C2-symmetrischem chiralem Dienliganden gelingt eine enantioselektive Variante des Prozesses; außerdem verläuft die intermolekulare Cycloaddition von 1,3-Dienen und Alkinen hoch effizient.
In this paper, we report a one-step convergent synthesis of (E)-β-monosubstituted α,β-unsaturated amides 3 from α-sulfonyl acetamide 1 and benzyl bromide derivatives 2.
Active without activation: In an inexpensive and atom-economical approach to CH bond functionalization, a cationic Co(III) complex was used to generate nucleophilic organometallic species in situ without additional activating reagents. Under these conditions, aryl CH bonds underwent efficient addition to polar electrophiles, including α,β-unsaturated N-acyl pyrroles as β-substituted ester and amide surrogates.
C2-Symmetric bicyclo[2.2.1]hepta-2,5-dienes with various substituents (R=Bn, i-Bu, c-Hex, allyl) are prepared starting from the corresponding enantiomerically pure bis-triflate (R=OTf). These chiral ligands are tested and compared in rhodium(I)-catalyzed 1,4- and 1,2-addition of phenylboronic acid to cyclic enones and aryl aldehydes, respectively. Some interesting reactivity and selectivity effects due to the introduction of sterically demanding or olefinic substituents are reported. Moreover, remarkably high catalytic activity is observed for the rhodium(I)-catalyzed 1,2-addition.Graphical abstract
Addition and substitution reactions with carbon nucleophiles are fundamental processes in organic synthesis, and the development of general catalytic asymmetric variants thereof is still a major challenge today. In contrast to enantioselective alkyl transfer reactions, the corresponding arylations have not yet reached a high level of maturity. The existing protocols are either of no general applicability or are limited in terms of selectivity. This article summarizes established routes for catalytic asymmetric aryl transfer together with the latest developments in this area. The scope and limitations of this reaction are discussed.
The stereoselective addition of lithium (S)-(α-methylbenzyl)benzylamide to αβ-unsaturated Weinreb amides gives the conjugate addition products with high stereoselectivities (99:1) which can be transformed into protected homochiral β-amino aldehydes and ketones.
Readily preparable N-methoxy-N-methylamides couple in good yields with Grignard and organolithium reagents to produce ketones, and are reduced with hydrides to afford aldehydes.
[GRAPHICS] A novel, additive-free, and clean conjugate addition reaction of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a cationic rhodium complex in water-containing solvent has been developed. A plausible reaction mechanism involving the additive-free transmetalation step between the rhodium complex and the silicon reagent is proposed.
The conjugate addition of arylboronic acids to alpha,beta -unsaturated amides was carried out in the presence of a chiral rhodium catalyst and an aqueous base. The catalyst prepared in situ from Rh(acac)(CH2=CH2)(2) and (S)-binap provided (R)-N-benzyl-3-phenylbutanamide with 93% ee in the addition of phenylboronic acid to N-benzyl crotonamide. The reaction suffered from incomplete conversion resulting in moderate yields, but addition of an aqueous base, such as K2CO3 (10-50 mol%) was found to be highly effective to improve the chemical yields. The role of the base giving a RhOH species active for transmetalation with arylboronic acids was discussed.
Catalytic asymmetric synthesis of 4-aryl-2-piperidinones was realized for the first time by asymmetric 1,4-addition of arylboron reagents to 5,6-dihydro-2(1H)-pyridinones in the presence of a chiral bisphosphine−rhodium catalyst. In the reaction introducing 4-fluorophenyl group, the use of 4-fluorophenylboroxine and 1 equiv (to boron) of water at 40 °C gave the highest yield of the arylation product with high enantioselectivity (98% ee). The (R)-4-(4-fluorophenyl)-2-piperidinone obtained here is a key intermediate for the synthesis of (−)-Paroxetine.
Aryltriethoxysilanes add to aldehydes and α,β-unsaturated carbonyl compounds in high yield in the presence of a rhodium(I) catalyst and aqueous sodium hydroxide.
The rhodium-catalyzed conjugate addition of tolylboronic acid to α,β-unsaturated ketones, esters or amides was carried out in water. [RhCl(cod)]2 and 2β-cyclodextrin-[Rh(OH)(cod)]2 complexes were found to catalyze the reaction efficiently in a single aqueous medium.
The first total synthesis of a spongipyran macrolide, altohyrtin C, is described. The convergent synthesis strategy relies on a regioselective macrolactonization, a stereoselective Wittig coupling of the two major synthetic fragments, a complex anti aldol reaction to join the C1–C15 and C16–C28 spiroketal regions, and an anomeric sulfone acylation to join the C29–C37 and C38–C43 pyran regions. The incorporation of the C44–C51 sidechain in the final stages of the synthesis establishes a viable route for the construction of variants in this pharmacologically important region. Methodological developments en route to the total synthesis include a 1,5 anti-selective methyl ketone aldol reaction and a diastereoselective approach to Lewis acid mediated β-C-glycosidation. Completion of the synthesis has confirmed the stereochemical assignments proposed in the altohyrtin series and has established the identity of the altohyrtin and spongistatin marine macrolides.
Diastereoselective conjugate addition of lithium (S)-N-allyl-N-α-methylbenzylamide to a range of α,β-unsaturated esters followed by ring closing metathesis is used to afford efficiently a range of substituted cyclic β-amino esters in high d.e. Alternatively, conjugate addition to α,β-unsaturated Weinreb amides, functional group conversion and ring closing metathesis affords cyclic amines in high d.e. The further application of this methodology to the synthesis of a range of carbocyclic β-amino esters via conjugate addition, enolate alkylation and ring closing metathesis is also described. Application of this methodology affords, after deprotection, (S)-homoproline, (S)-homopipecolic acid, (S)-coniine and (1S,2S)-trans-pentacin.
Catalytic asymmetric synthesis of 4-aryl-2-piperidinones was realized for the first time by asymmetric 1,4-addition of arylboron reagents to 5,6-dihydro-2(1H)-pyridinones in the presence of a chiral bisphosphine-rhodium catalyst. In the reaction introducing 4-fluorophenyl group, the use of 4-fluorophenylboroxine and 1 equiv (to boron) of water at 40 degrees C gave the highest yield of the arylation product with high enantioselectivity (98% ee). The (R)-4-(4-fluorophenyl)-2-piperidinone obtained here is a key intermediate for the synthesis of (-)-Paroxetine.
The conjugate addition of arylboronic acids to alpha,beta-unsaturated amides was carried out in the presence of a chiral rhodium catalyst and an aqueous base. The catalyst prepared in situ from Rh(acac)(CH(2)=CH(2))(2) and (S)-binap provided (R)-N-benzyl-3-phenylbutanamide with 93% ee in the addition of phenylboronic acid to N-benzyl crotonamide. The reaction suffered from incomplete conversion resulting in moderate yields, but addition of an aqueous base, such as K(2)CO(3) (10-50 mol%) was found to be highly effective to improve the chemical yields. The role of the base giving a RhOH species active for transmetalation with arylboronic acids was discussed.
[reaction: see text] A novel, additive-free, and clean conjugate addition reaction of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a cationic rhodium complex in water-containing solvent has been developed. A plausible reaction mechanism involving the additive-free transmetalation step between the rhodium complex and the silicon reagent is proposed.
Highly enantioselective 1,4-addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds was found to be catalyzed by a chiral rhodium complex generated from [Rh(cod)(MeCN)(2)]BF(4) and (S)-BINAP. Both (E)- and (Z)-1-alkenyl groups as well as aryl groups can be introduced enantioselectively into the beta-position of a variety of ketones, esters, and amides. [reaction--see text]
For Abstract see ChemInform Abstract in Full Text.
The effects of ligands and bases in the rhodium(I)-catalyzed 1,4-addition of arylboronic acids to alpha,beta-unsaturated carbonyl compounds were reinvestigated to carry out the reaction under mild conditions. Rhodium(I) complexes possessing a 1,5-cyclooctadiene (cod) and a hydroxo ligand such as [RhOH(cod)](2) exhibited excellent catalyst activities compared to those of the corresponding rhodium-acac or -chloro complexes and their phosphine derivatives. The reaction was further accelerated in the presence of KOH, thus allowing the 1,4-addition even at 0 degrees C. A cationic rhodium(I)-(R)-binap complex, [Rh(R-binap)(nbd)]BF(4), catalyzed the reaction at 25-50 degrees C in the presence of Et(3)N with high enantioselectivities of up to 99% ee for alpha,beta-unsaturated ketones, 92% for aldehydes, 94% for esters, and 92% for amides.
For Abstract see ChemInform Abstract in Full Text.
The total synthesis of the antifungal macrolide antibiotic roxaticin has been accomplished. The synthesis relies principally on aldol and directed reduction steps to construct the extended 1,3-polyol array present in the natural product. Three principal nonpolyene containing fragments were assembled and then coupled using Julia olefination and methyl ketone aldol addition reactions. A series of functionalization reactions incorporated the sensitive polyene and provided the protected roxaticin seco-acid, which was lactonized in good yield. Acidic deprotection completed this convergent synthesis of roxaticin.
[reaction: see text] We document a series of investigations that led to new substituted [2.2.2]-diene ligands which display high selectivity in Rh(I)-catalyzed conjugate addition reactions to substrates not previously examined with diene ligands. Moreover, we disclose an unexpected, interesting effect that results from the introduction of a third C=C onto the ligand scaffold (cf. 1).
Asymmetric synthesis of diarylmethylamines with high enantioselectivity (95-99% ee) was realized by use of a new C2-symmetric diene ligand, (1R,4R)-2,5-diphenylbicyclo[2.2.2]octa-2,5-diene (Ph-bod*), for the rhodium-catalyzed asymmetric arylation of N-tosylarylimines with arylboroxines.
Catalytic arylative cyclization of alkynals has been developed by the use of phosphine-free rhodium/diene complexes as catalysts. An asymmetric variant of this process has been successfully realized by employing a C2-symmetric chiral bicyclo[2.2.2]octadiene ligand. The rhodium/diene catalyst system is also effective for arylative cyclization of other substrates such as alkynones and enynes, achieving multiple carbon-carbon bond formations in a single step.
[reaction: see text] C2-symmetric bicyclo[2.2.2]octa-2,5-dienes containing benzyl, phenyl, and substituted phenyl groups at 2 and 5 positions were prepared enantiomerically pure by way of bicyclo[2.2.2]octane-2,5-dione as a key intermediate. These chiral diene ligands were successfully applied to rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to alpha,beta-unsaturated ketones. High enantioselectivity (up to 99% ee) as well as high catalytic activity was observed in the addition to both cyclic and linear substrates.
7 Carreira recently reported a single example of the rhodium/chiral diene-catalyzed 1,4-addition of phenylboronic acid to an a,b-unsaturated amide, achieving 93% ee
- R Shintani
- K Okamoto
- Y Otomaru
- K Ueyama
- T Hayashi
R. Shintani, K. Okamoto, Y. Otomaru, K. Ueyama and T. Hayashi, J. Am. Chem. Soc., 2005, 127, 54. 7 Carreira recently reported a single example of the rhodium/chiral diene-catalyzed 1,4-addition of phenylboronic acid to an a,b-unsaturated amide, achieving 93% ee: C. Defieber, J.-F. Paquin, S. Serna and E. M. Carreira, Org. Lett., 2004, 6, 3873. Table 1 Rh/(S,S)-3b-catalyzed asymmetric 1,4-addition of arylboro-nic acids to a,b-unsaturated Weinreb amides: scope
3 For examples of rhodium-catalyzed (nonasymmetric) 1,4-additions to a,b-unsaturated amides
- M Chippindale
- S G Davies
- K Iwamoto
- R M Parkin
- C A P Smethurst
- A D Smith
- H Rodriguez-Solla
- D A Evans
- B W Trotter
- P J Coleman
- B Côté
- L C Dias
- H A Rajapakse
- A N D A Tyler
- B T Evans
- S Connell
- Y Oi
- Y Honma
- Inoue
Tel: +81-75-753-3983 Notes and references Synlett, 1995, 700; A. M. Chippindale, S. G. Davies, K. Iwamoto, R. M. Parkin, C. A. P. Smethurst, A. D. Smith and H. Rodriguez-Solla, Tetrahedron, 2003, 59, 3253; D. A. Evans, B. W. Trotter, P. J. Coleman, B. Côté, L. C. Dias, H. A. Rajapakse and A. N. Tyler, Tetrahedron, 1999, 55, 8671; D. A. Evans and B. T. Connell, J. Am. Chem. Soc., 2003, 125, 10899. 3 For examples of rhodium-catalyzed (nonasymmetric) 1,4-additions to a,b-unsaturated amides, see: R. Itooka, Y. Iguchi and N. Miyaura, Chem. Lett., 2001, 722; A. Mori, Y. Danda, T. Fujii, K. Hirabayashi and K. Osakada, J. Am. Chem. Soc., 2001, 123, 10774; S. Oi, Y. Honma and Y. Inoue, Org. Lett., 2002, 4, 667; M. Murata, R. Shimazaki, M. Ishikura, S. Watanabe and Y. Masuda, Synthesis, 2002, 717. 4 For reviews on the rhodium-catalyzed asymmetric 1,4-addition reactions, see: T. Hayashi and K. Yamasaki, Chem. Rev., 2003, 103, 2829;
- Bolm
- Pucheault