Diastereo- and Enantioselective Iridium Catalyzed Coupling of Vinyl Aziridines and Alcohols: Site-Selective Modification of Unprotected Diols and Synthesis of Substituted Piperidines

摘要

The chiral cyclometalated π-allyliridium ortho-C,O-benzoate complex (R)-Ir->VIb derived from [Ir(cod)Cl]2, allyl acetate, 4-cyano-3-nitrobenzoic acid, and (R)-MeO-BIPHEP catalyzes the coupling of N-(p-nitrophenylsulfonyl) protected vinyl aziridine >3a with primary alcohols >1a–>1l to furnish branched products of C-C bond formation >4a–>4l with good levels of anti-diastereo- and enantioselectivity. In the presence of 2-propanol, but under otherwise identical conditions, vinyl aziridine >3a and aldehydes >2a–>2l engage in reductive coupling to furnish an equivalent set of adducts >4a–>4l with roughly equivalent levels of anti-diastereo- and enantioselectivity. Using the enantiomeric iridium catalysts, vinyl aziridine >3a reacts with unprotected chiral 1,3-diols >1m–>1o in a site-selective manner to deliver the diastereomeric products of C-allylation syn->4m, >4n, >4o and anti->4m, >4n, >4o, respectively, with good isolated yields and excellent levels of catalyst-directed diastereoselectivity. These adducts were directly converted to the diastereomeric 2,4,5-trisubstituted piperidines syn->5m, >5n, >5o and anti->5m, >5n, >5o.