Conjugate addition copper-catalysed

Recently, attempts were made to replace the air- and moisture-sensitive zinc and magnesium reagents in the copper-catalysed asymmetric conjugate addition, with... 

Scheme 2.30 Copper-catalysed asymmetric conjugate addition of organozincs to enones...

Fig. 2.24 Chiral NHC pro-ligands used in copper-catalysed asymmetric conjugate additions...

S)-phenylglycine have been used in the copper-catalysed conjugate addition of MeLi to enones. Trialkylaluminum reagents were also involved in only a few reactions, but these represent an interesting alternative. 

Whereas the mono- and the S/S-dithioether moieties have been used to date, the 1,3-dithianyl motif was used for the first time in 2005 by Ricci et al. as a new hybrid ligand in asymmetric catalysis. Hence, a series of new chiral oxazoline-1,3-dithianes have been successfully applied to the copper-catalysed conjugate addition of ZnEt2 to enones (Scheme 2.16). The expected products were obtained in almost quantitative yields and enantioselectivities of up to 69% ee. 

Another class of new ligands was prepared in quantitative yields by Feringa et al., in 1997, by reaction between a-mercapto acids, aniline and 2-pyridine-carboxaldehyde." These pyridyl-substituted thiazolin-4-one ligands were further involved in the copper-catalysed conjugate addition of ZnEt2 to 2-cyclohexenone,... 

In 2004, excellent enantioselectivities of up to 98% ee were obtained by Morimoto et al. by using a phosphine-sulfonamide-containing 1,1 -binaphthyl-based ligand in the enantioselective copper-catalysed conjugate addition of ZnEt2 to several benzylideneacetones (Scheme 2.27). Similar levels of enan-tioselectivity (up to 97% ee) combined with excellent yields (up to 90%) were obtained by Leighton et al. for the copper-catalysed enantioselective addition of various alkylzincs to cyclic enones performed in the presence of other chiral phosphine-sulfonamide ligands (Scheme 2.27). ... 

In 2000, Gennaii et al. discovered a new family of chiral Schiff-base ligands, with the general structure, Af-alkyl-p-(A -salicylideneamino)alkanesulfonamide, depicted in Scheme 2.28. These ligands were successfully implicated in the copper-catalysed conjugate addition of ZnEt2 to cyclic enones (Scheme 2.28) and, less efficiently, to acyclic enones such as benzalacetone (50% ee) or chalcone... 

On the other hand, S/O ligands have been developed to a lesser extent, but their efficient use as chiral ligands was proven in the enantioselective addition of diethylzinc to aldehydes and also in the copper-catalysed asymmetric conjugate addition. 

The copper-catalysed asymmetric conjugate addition of dialkylzinc leads to homo-chiral zinc enolates.28 These intermediates have been trapped in situ with activated allylic electrophiles, without the need for additional palladium catalysis (Scheme 3). 

The copper-catalysed enantioselective 1,4-conjugate addition of Et2Zn to chalcones was investigated in the presence of a catalytic amount of Af,P-ferrocenyl ligand (179) with central and planar chirality under mild conditions (0 °C to room temper- ature). Chalcones with ortho-substituents (from ortho-substituted benzaldehydes and acetophenones) exhibited a dramatic improvement in the enantioselectivities (<92% ee).229... 

A highly enantioselective synthesis of a-dehydroamino acids (186) with a stereogenic centre at the y -position has been developed, which employs a copper-catalysed asymmetric conjugate addition of diethylzinc to a,j3-unsaturated imines (185) with the TADDOL-derived phosphoramidite (187) as a chiral ligand.234... 

A copper-catalysed, enantioselective, conjugate addition of a terminal alkyne, which undergoes an in situ metallation, has been reported. The addition of phenylacetylene to Meldrum s acid-derived acceptors (196) takes place in aqueous medium, without recourse to an inert atmosphere. The success of the enantioselective reaction was made possible by the use of PINAP (198), a new class of P,IV-ligands (cf. QUINAP), which have the advantage of easier resolution. Furthermore, these modular ligands are responsive to numerous electronic and steric modifications that permit optimization of the reaction. The products (197) were obtained in good yields and with 82-97% ee.235... 

Corey chose a Wittig-style (HWE) reaction to control the aldol process and copper-catalysed addition of vinyl Grignard for the conjugate addition. Oxidation with NaI04 and catalytic OSO4 gave the keto-aldehyde 35 which cyclised cleanly under equilibrating conditions. 

Palladium catalysed cyclic carbozincation of u>-iodoalkenes and copper promoted conjugate addition of alkylzincs to nitroalkenes preparation of 1-butyl-1-(3-nitro-2-phenylpropyl)cyclopentane60... 

Carbene transfer from the silver(I) complex is not only possible to ruthenium(II) to form a catalyst suitable for asymmetric olefin metathesis, but also to copper(I) [17]. This provides a catalyst suitable for copper(I) catalysed conjugate addition of alkyl- and arylzinc reagents to P-substituted cyclic enones. The products, chiral cyclic ketones, are obtained in 88-95% isolated yield and 67-83% ee. 

Copper(I)-catalysed conjugate additions to zirconocene are supposed to have zirconium enolates as intermediates, which can be oxidized with A-halosuccinimides (equation 45)" . 

A synthesis of methyl vinhaticoate and methyl vouacapenate has been described. The key steps involved the conjugate addition of dimethylcopper lithium to (128), prepared from podocarpic acid, the transformation of the product (129) into the methoxymethylene ketone (130), and the formation of the furan ring (131) by the copper-catalysed addition of ethoxycarbonylcarbene. 

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