Enantioselectivity cyclic enones

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). ... 

A summary of other chiral ligands with corresponding enantioselectivities in the copper-catalyzed 1,4-addition of dialkylzinc to cyclic enones is shown in Figure 5.55-58... 

A broad substrate scope for the rhodium-catalyzed asymmetric 1,4-addition has been observed.98 Both arylboronic acids with either electron-donating or electron-withdrawing aryl substituents and alkenylboronic acids can be introduced into acyclic or cyclic enones with high enantioselectivities (Scheme 30). 

The enantioselectivity can be increased by changing the methyl group on nitrogen to an isopropyl group. Thus highly diastereoselective additions to cyclic enones are obtained with the phospholidine 3, prepared in several steps from norpseu-doephedrine.1... 

The first example of a chiral carbanionic residual ligand has recently been reported [238]. Chiral mixed cuprates generated from alkyllithium reagents and cyclic a-sulfonimidoyl carbanions transfer alkyl ligands [such as n-Bu, Me, (CH2)30CH(Me)0Etj to cyclic enones with excellent enantioselectivities (77-99% ee). 

Tab. 7.1. Enantioselective 1,4-addition of R2Zn reagents to cyclic enones, catalyzed by Cu(OTf)2/(S,R,R)-18.

In the enantioselective copper(I)-catalyzed conjugate addition of a cyclic enone with a chiral ligand, the observed nonlinear effects indicate that Cu(I) aggregates participate in the reaction [78]. 

When cyclic enones were used as Michael acceptors, both malonates and acetoacetates gave impressive yields and enantioselectivities of the desired Michael addition products (Scheme 5.2Q) NMR spectra and single-crystal X-ray data supported the following ruthenium intermediate (Scheme 5.21) and transition state (Figure 5.8). 

In extending this concept to transformations that formally deliver Diels-Alder products, a one-pot three-component Mannich/Michael reaction pathway was developed in which simple cyclic enones, formaldehyde, and aryl amines were treated with catalytic amounts of proline (2) to provide regio-, diastereo-, and enantioselective bicyclic compounds in high yields (Scheme ll.lOb). Multicomponent domino... 

Yamamoto and coworkers described a highly enantioselective asymmetric domino 0-nitroso aldol-conjugate addition seqnence using cyclic enones 221 and aromatic nitroso compounds 222 as depicted in Scheme 36 [346]. A related reaction with imines was also reported by Cdrdova and coworkers (Scheme 37) [228]. 

The majority of the Michael-type conjugate additions are promoted by amine-based catalysts and proceed via an enamine or iminium intermediate species. Subsequently, Jprgensen et al. [43] explored the aza-Michael addition of hydra-zones to cyclic enones catalyzed by Cinchona alkaloids. Although the reaction proceeds under pyrrolidine catalysis via iminium activation of the enone, and also with NEtj via hydrazone activation, both methods do not confer enantioselectivity to the reaction. Under a Cinchona alkaloid screen, quinine 3 was identified as an effective aza-Michael catalyst to give 92% yield and 1 3.5 er (Scheme 4). 

Tan and co-workers reported the Michael reactions of di-thiomalonates and P-keto-thioesters to a range of acceptors, including maleimides, cyclic enones, furanones and acyclic dioxobutenes [129]. Unlike dimethyl malonate, additions with acidic thioesters proceeded in higher yields, and overall better enantioselectivities (Scheme 74). 

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