Cyclic enones, enantioselective conjugate

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). ... 

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). 

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]. 

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). 

MeOC6H4, respectively. The titanium enolates were converted into silyl enol ethers 54 by treatment with chlorotrimethylsilane and lithium isopropoxide. Additionally, cyclic enones lb and Ic, and linear enones Id and le, are also good substrates for the asymmetric conjugate addition of phenyltitanium triisopropoxide, giving the corresponding arylation products with over 97% enantioselectivity. 

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. 

With cyclic enones, Professor Yamamoto has developed (J. Am. Chem. Soc. 2004,126,5962) an enantioselective double functionalization. The organocatalyst 8 mediates conjugate addition of N and a -oxygenation, to give 9. 

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

For Type II reactions also a variety of useful compounds can be synthesized by changing the combination of the starting materials. In the Michael reaction with cyclic enones, availability of the La-linked-BINOL complex broadened the scope of the Michael acceptor (Scheme 14). It should be noted that less reactive medium-ring-size cyclic enones (7-9membered ring size) underwent conjugate addition highly enantioselectively (up to > 99 % ee) [17]. 

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