Cyclic enones, enantioselective conjugate addition

The use of vinyl epoxides as substrates in enantioselective copper-catalyzed reactions, on the other hand, has met with more success. An interesting chiral ligand effect on Cu(OTf)2-catalyzed reactions between cyclic vinyloxiranes and dialkylzinc reagents was noted by Feringa et al. [51]. The 2,2 -binaphthyl phosphorus amidite ligands 32 and 43 (Fig. 8.5), which have been successfully used in copper-catalyzed enantioselective conjugate additions to enones [37], allowed kinetic resolution of racemic cyclic vinyloxiranes (Scheme 8.26). 

Enantioselective conjugate addition can also be carried out with cyclic enones. Shuichi Oi and Yoshio Inoue of Tohoku University in Sendai report (Tetrahedron Lett. 2004, 45, 5051) that a BINAP complex of Rh catalyzes the enantioselective conjugate addition of alkenyl Zr species such as 5, to give 7 in high enantiomeric excess. Alkenyl Zr species such as 5 are readily prepared by hydridozirconation of alkynes. It is particularly important that addition of TMS-C1 to the reaction mixture at the end of the conjugate addition leads cleanly to the enol ether 6. 

Highly enantioselective conjugate addition of Et2Zn to acyclic and cyclic enones has been performed in the presence of copper/phosphorus containing catalysts.117-119... 

The preparation of silyl enol ethers from carbonyl compounds represents one of the major uses of TMSOTf. Recently, the stereochemistry and regiospeciflcity of such transformation has been addressed for aldehydes and Q -(lV-alkoxycarbonylamino) ketones, respectively. On the other hand, enantiopure silyl enol ethers can be formed by addition of TMSOTf to zinc enolates, which are obtained from the copper-catalyzed enantioselective conjugate addition of dialkyIzinc reagents to cyclic (eq 36) and acyclic enones. ... 

Sebesta also studied the enantioselective conjugate additions of various Grignard reagents 21 to cyclic enones catalyzed by the Cu(l) complex of TADDOL-based... 

A nickel-catalyzed carbozincation in which an allylzinc adds across the double bond of an unsaturated acetal has also been reported (Scheme 79). ] This procedme effectively provides a reverse-polarity approach to the functionalization of unsaturated carbonyl derivatives. Non-allylic Grignard reagents, however, add to cychc unsaturated acetals with the opposite regiochemistry. This latter procedure provides the basis for an enantioselective conjugate addition to cyclic enones (in 53% ee for the cyclopentenyl substrate and 85% ee for the cyclohexenyl homologue). ... 

In 2009, Lee and Hoveyda developed a Cu-catalyzed method for enantioselective conjugate additions of aryl and alkenyl groups to cyclic enones (Scheme 3.52) [79]. Reactions were promoted by chiral monodentate, non-C2-symmetric NHC-Cu complexes generated in situ from carbene salts such as 91. The desired p-aryl- or p-vinylcycloalkanones were obtained in up to 97 and 92% ee, respectively. Remarkably, the easily accessible aryl- or alkenylsilane reagents were used as nucleophiles and thus did not require the use of air- and moisture-sensitive organometallics. 

Scheme 3.52 Enantioselective conjugate addition to cyclic enones.

Kikushima, K. Holder, J. C. Gatti, M. Stoltz, B. M. Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Five-, Six-, and Seven-Membered 3-Substituted Cyclic Enones Enantioselective Construction of All-Carbon Quaternary Stereocenters. /. Am. Chem. Soc. 2011,133,6902-6905. 

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). ... 

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