Domingo García-Cuadrado’s research while affiliated with University of Valladolid and other places

A group of phosphine/alkene ligands L = Ph2P(2-RC6F4) (R = CH═CHMe, CH═CHPh, CH═CHCOPh) or Ph2P(CH2)2CF═CF2 and their [PdCl2L] complexes have been prepared. These phosphines are easy to prepare and fairly stable toward oxidation. Their palladium complexes feature chelated L structures with the double bond coordinated as the Z isomer, except for Ph2P(CH2)2CF═CF2, where the double bond is not coordinated and the complex is a dimer with Cl bridges. The ligands have been tested for their activity in the Negishi palladium-catalyzed aryl-alkyl coupling, where there is a competition of coupling and reduction products. Only the ligands forming chelated PdII complexes rise the coupling/reduction ratio to values 42/58 or higher. Of these, it is the ligand bearing the more electron-withdrawing substituent (R = CH═CHCOPh) that is the one producing remarkably high selectivity toward coupling: 90/10 under the usual Negishi conditions, and noticeably higher (97/3) if the proportion of ZnEt2 in the reaction is lowered. These results fit well with the hypothesis that chelating phosphines with tethered electron-acceptor olefins improve the selectivity toward coupling products mostly because they reduce the activation barrier for C–C coupling, and not because they protect the complex from β-H elimination.

Mononuclear and dinuclear chiral gold(I) carbene complexes with carbene ligands of the type HBHC (hydrogen bonded heterocyclic carbenes) and NAC (nitrogen acyclic carbenes) have been prepared by reaction of isocyanide gold(I) complexes and chiral amines or diamines. The reaction of [AuCl(CNPy-2)] (1) (Py = pyridyl) with the corresponding chiral primary amines afforded the chiral HBHC complexes (R)-[AuCl{C(NH(CHMePh))(NHPy-2)}] ((R)-2), and (S)-[AuCl{C(NH{CHMe(1-naphthyl)})(NHPy-2)}] ((S)-3), while the reaction of 2 equiv of 1 with diamines produced (S)-2,2'-bis[NH{C(AuCl)(NHPy-2)}](2)-binaphthyl ((S)-4), (1R,2R)-1,2-bis[NH{C(AuCl)(NHPy-2)}]-diphenylethane ((1R,2R)-5), and (1R,2R)-1,2-bis[NH{C(AuCl)(NHPy-2)}]-cyclohexane ((1R,2R)-6). On the other hand the addition of alkyl amines to (S)-2,2'-[NCAuCl](2)-binaphthyl ((S)-8) gave the chiral NAC complexes (S)-2,2'-bis[NH{C(AuCl)(NMe(2))}](2)-binaphthyl ((S)-9) and (S)-2,2'-bis[NH{C(AuCl)(N(i)Pr(2))}](2)-binaphthyl ((S)-10), while the addition to (S)-2,2'-[NCAuCl](2)-3,3'-Ph(2)-binaphthyl ((S)-12) yielded (S)-2,2'-bis[NH{C(AuCl)(NMe(2))}](2)-3,3'-Ph(2)-binaphthyl ((S)-13) and (S)-2,2'-bis[NH{C(AuCl)(NEt(2))}](2)-3,3'-Ph(2)-binaphthyl ((S)-14). All the complexes are active catalysts in the cyclopropanation of vinyl arenes and in the intramolecular hydroalkoxylation of allenes, providing good yields and modest or poor enantioselectivity. The results show that all these ligands are compatible with different functions and reaction conditions and are worth considering as alternative systems to NHCs or phosphines in gold catalyzed reactions.

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.

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.

The regioselectivity observed in the intramolecular palladium-catalyzed arylation of substituted bromobenzyldiarylmethanes as well as theoretical results demonstrate that the Pd-catalyzed arylation proceeds by a mechanism involving a proton abstraction by the carbonate, or a related basic ligand. The reaction is facilitated by electron-withdrawing substituents on the aromatic ring, which is inconsistent with an electrophilic aromatic-substitution mechanism. The more important directing effect is exerted by electron-withdrawing substituents ortho to the reacting site.

[Structure: see text] The 1,1'-, 2,2'-, and 3,3'-biquinolizinium dications are described for the first time and were prepared using palladium-catalyzed homocoupling reactions of the corresponding isomeric bromoquinolizinium bromides. Theoretical calculations show 1,1'- and 4,4'-biquinolizinium dications to be chiral molecules, the latter of which has a high energy of formation, a factor that probably precludes its formation.

An efficient palladium-catalyzed cross-coupling reaction on heteroaromatic cations is described. A comparative study of the Stille and Suzuki reactions shows that only the Stille reaction is able to produce an efficient C-C bond formation between any of the four isomeric bromoquinolizinium bromides and a variety of stannanes. In the presence of the catalysts Pd(PPh3)4 or Pd2(dba)3P(o-Tol)3, vinyl, ethynyl, aryl, and heteroaryl groups are successfully incorporated into the quinolizinium system in satisfactory yields under mild reaction conditions. This procedure represents a marked improvement on the functionalization of this class of heteroaromatic cation.

Under the usual conditions, the Pd-catalyzed arylation does not involve an electrophilic aromatic substitution reaction. On the basis of DFT calculations, we propose a mechanism for the Pd-catalyzed arylation that involves a proton abstraction by a carbonate or related ligand and that provides a satisfactory explanation for the experimental data.

Hexasubstituted truxenes are obtained in one step by alkylation of the potassium anion of truxene. Subsequent derivatization provides truxene derivatives with six carboxy, amino, or hydroxy groups at their peripheries. Alkylation of syn-5,10,15-tribenzyl derivatives with a different benzyl bromide derivative affords mixtures of anti- and syn-hexasubstituted truxenes. Truxenes with phenols or benzoquinone groups have also been synthesized by starting from truxenetrione. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)