Michael addition chiral metal complexes

Other reviews deal with aldol additions of group 1 and 2 enolates,103 direct catalytic asymmetric aldol reactions catalysed by chiral metal complexes,104 the exploitation of multi-point recognition in catalytic asymmetric aldols,105 and recent progress in asymmetric organocatalysis of aldol, Mannich, Michael, and other reactions.106... 

The catalytic enantioselective addition of aromatic C - H bonds to alkenes would provide a simple and attractive method for the formation of optically active aryl substituted compounds from easily available starting materials. The first catalytic, highly enantioselective Michael addition of indoles was reported by Jorgensen and coworkers. The reactions used a,fl-unsaturated a-ketoesters and alkylidene malonates as Michael acceptors catalyzed by the chiral bisoxazoline (BOX)-metal(II) complexes as described in Scheme 27 [98,99]. 

Trimethylsilyloxyfuran reacted stereoselectively with chiral tungsten carbene complexes in a Mukaiyama-Michael addition fashion to provide -products, as shown in Equation (18) <2005AGE6583>. The metal carbene in the butenolide product serves as a useful functional group for further transformations. 

With regard to the catalytic asymmetric reaction , only a few successful examples, except those reactions using chiral transition metal complexes, have been reported. For example, the cinchona-alkaloid-catalyzed asymmetric 1,4-addition of thiols or 6-keto esters to Michael acceptors quinidine catalyzed the asymmetric addition of ketene to chloral and the highly enantioselective 1,4-addition of ) -keto esters in the presence of chiral crown ethers to Michael acceptors have been most earnestly studied. 

Based on the finding that ruthenium complexes catalyzed the Michael addition of cyanoesters, Ito developed a system of RhH(CO)(PPh3)3 and chiral bi-dentated phosphine, (S,S)-(P,P)-TRAP. The catalyst promoted the asymmetric addition of 66 to 7 giving R)-67 [64, 65, 66]. In the case of a reactive acceptor, acrolein, even 0.1 mol % of the complex effectively catalyzed the reaction. An enantiomeric excess of up to 93% was attained with the diisopropylmethyl ester. Since BINAP, DIOP, CHIRAPHOS, etc., did not induce such high stereoselectivities, the frans-coordinated structure constructed by the TRAP was considered to be critical. The structure of the ruthenium complex obtained by X-ray analysis indicated the interaction of the metal with the nitrile nitrogen atom. The frans-coordinated ligand might be required to affect the remote reaction site. 

The products are versatile auxiliaries not only for enantioselective deprotonation and elimination (Section C.), but are also valuable chiral ligands for complex hydrides in the enantioselective reduction of ketones (Section D.1.4.5.)- They are also applied in enolate reactions (Section D.l.5.2.1., D.1.5.2.4.). transition-metal-catalyzed Michael additions (Section D.l.5.8.), 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), and additions ofGrignard reagents (Section D.l.3.1.4.2.5.). (5 )-2-(Phenylaminomethyl)pyrrolidine has found most application and is also commercially available. Several methods exist for the preparation of such compounds. Two typical procedures for the synthesis of (.S)-2-(l-pyrrolidinylmcthyl)pyrrolidine are presented here. The methodology can be readily extended to other amides and alkylamino derivatives of proline. 

Abstract Progress in the field of metal-catalyzed redox-neutral additions of oxygen nucleophiles (water, alcohols, carboxylic acids, and others) to alkenes, alkynes, and allenes between 2001 and 2009 is critically reviewed. Major advances in reaction chemistry include development of chiral Lewis acid catalyzed asymmetric oxa-Michael additions and Lewis-acid catalyzed hydro-alkoxylations of nonacti-vated olefins, as well as further development of Markovnikov-selective cationic gold complex-catalyzed additions of alcohols or water to alkynes and allenes. 

The asymmetric 1,4-addition (Michael addition) of a cyanide ion to nitroalkenes is a potentially useful route for preparing p-amino acids via transformation of 3-nitropropanonitriles. ° In 2013, North reported the first vanadium-catalysed, enantioselective Michael addition of trimethylsilyl cyanide to aliphatic p-nitroalkenes, which provided (S)-19, as shown in Scheme 9.9. The reaction was promoted by a 3 mol% catalyst loading of chiral vanadium(v) salen complex 18 ° providing (S)-19 in 74-88% conversions with up to 89% enantiomeric excess. North proposed that the nitro group acts as a bridge for the two vanadium metals in the possible transition... 

Beyond secondary amines, various chiral Brpnsted acid and hydrogen-bonding donor catalysts, supported primary amines were also demonstrated to be suitable catalysts to implement metal/organic binary catalytic systems. In 2006, McQuade et al. reported a cascade three-component reaction by combining encapsulated amine and nickel catalysts with high reactivity and chemoselectivity [81]. The reaction proceeded through an encapsulated amine-promoted nitroalkene formation via iminium ion intermediate followed by a nickel complex-promoted chemoselective Michael addition of dimethyl malonate to the newly generated nitroalkene (Scheme 9.76). 

The successful achievement of the (/ )-LSB catalyst in asymmetric Michael addition suggested that the metal centers other than rare earths might lead to a novel heterobime-talhc asymmetric catalyst with unique properties. With this foundation, the same group further developed a new heterobimetallic chiral catalyst (/ )-ALB consisting of aluminum, lithium, and (/ )-BINOL in 1996 (Table 9.3). They reported that this type of catalyst could be more efficiently prepared from LiAlH with two equivalents of (/ )-BINOL. When this AlLibis(binaphthoxide) complex (/ )-ALB was employed as catalyst, up to 99% ee and 88% yield of products could be obtained in the reaction of dibenzyl malonate to 2-cyclohexen-l-one. Notably, both dimethyl and diethyl malonates furnished the 1,4-adducts with more than 90% of enantioselectivities. In particular, the catalytic asymmetric tandem Michael-aldol reactions were also achieved in the presence of (/ )-ALB. This protocol provides a usefid method for the catalytic asymmetric synthesis of complex molecules. 

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