Enantioselective Conjugate Additions of Organometallic Species

Chiral amidocuprates have also been demonstrated to function as catalysts in asymmetric conjugate additions for selected substrates [43], A seminal result was disclosed by Lippard, who used amidocuprate 170 (Equation 30) [135]. This complex is generated from the deprotonated aminotropone 

Tomioka documented the use of organolithium reagents in enantioselec-tive conjugate additions to conjugated imines (Equation 31) [136]. The readily available chiral diether 173 served to mediate such additions with high asymmetric induction for example, the addition of PhLi to 172 furnished aldehyde 174 in 94% ee after hydrolysis of the imine adduct. In subsequent developments, Tomioka reported the enantioselective preparation of biaryls in which a naphthyllithium participates in a nucleophilic aromatic substitution catalyzed by only 5mol% of 173 (see insert on the left) and delivers the product in 82% ee [137]. 

Hayashi investigated the asymmetric, rhodium-catalyzed conjugate addition reaction of organoboronic acids to a variety of unsaturated electrophilic acceptors [46, 144-147). The first successful example of such a transformation involved the use of a Rh-BINAP catalyst (187, Equation 34) [144. As shown for cyclohexenone, the rhodium-catalyzed addition of phenylboronic acid takes place to afford 188 in 96% ee and 99% yield. 

Accompanying mechanistic studies by Hayashi have allowed several key intermediates in the catalytic cycle to be observed spectroscopically [146]. These studies also revealed [Rh(OH)(BINAP)2] to be a more active chiral catalyst in the conjugate addition reaction, promoting the formation of 188 in 99% ee. A number of tandem processes using similar conditions have been documented by Hayashi, one prominent example being the formation of the three contiguous stereocenters in 191 in dr 99 1 and 98% ee (Equation 35) [147]. 

Chelating dienes have recently emerged as a promising class of chiral ligands for transition-metal-catalyzed processes as a consequence of independent concurrent studies by Hayashi [148,149] and by Carreira [150-153]. The first example with a chiral rhodium-diene complex for conjugate addition reactions employed chiral C2-symmetric diene ligand 193 (Equation 36) [148, 149]. Addition of boronic acid 192 to cyclohexenone catalyzed by the putative complex formed in situ from 193 and Rh(I) afforded adduct 194 in 90% yield and 99% ee [148]. 

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