Asymmetric formal synthesis of (-)-pancracine via catalytic enantioselective C-H amination process

The reaction of silyl cool ethers derived from cyclohexanone with 1(4-nitropheylsulfonyl)imino|phenyliodinane (pNsN=IPh) catalyzed by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate] Rh-2(S-TCPTTL)(4), provides, after desilylation, N-pNs-protected (S)-beta-aminocyclohexanone in Lip to 72% ee. This represents the first example of the insertion of nitrene species into ail allylic C-H bond of silyl enol ethers. Using this process, a new catalytic asymmetric route to an advanced intermediate in Overman's synthesis of the montanine-type Amaryllidaceae alkaloid (-)-pancracine has been developed. The key steps involve (a) a one-pot Rh-2(R-TCPTTI_)(4)-catalyzed sequential 1,4-hhydrosilylation/enantio-selective C-H amination of 2-cyclohexen-1-one, (b) N-alkylation and subsequent intramolecular Mukaiyama aldol reaction/dehydration, and (c) a regio- and steieocontrolled reductive deoxygenation of bicyclic enone 27 with migration of the double bond to create the C1/C11a double bond and the stereogenic center at Cl I of 3-arylhexahydroindole 31. (C) 2008 Elsevier Ltd. All right,. reserved.