Indolizidine 167B, synthesis

A novel approach to azabicyclic ring systems, based on an epoxide-initiated electrophilic cyclization of an alkyl azide, has been developed by Baskaran. A new stereo- and enantioselective synthesis of the 5-hydroxymethyl azabicyclic framework 91a, present in (+)- and (-)-indolizidines 167B and 209D, for example, was... 

Reddy, P. G., Baskaran, S. (2004) Epoxide-initiated cationic cyclization of azides a novel method for the stereoselective construction of 5-hydroxymethyl azabicyclic compounds and application in the stereo- and enan-tioselective total synthesis of (+)- and ( —) -indolizidine 167B and 209D. J Org Chem 69, 3093-3101. 

As with the synthesis of (-)-halosaline, the proposed retrosynthetic strategy of (-)-indolizidine 167B includes use of the dimethylallylsilyl protecting group in the RCM-ROM-RCM sequence (Scheme 22).51... 

In the short synthesis of (-)-524 by Back and Nakajima, an efficient cyclization between the proline-derived chloroamine 556 and the alkynylsulfone 557 yielded the unsaturated indolizidine 558 (94%) (Scheme 71) (451). Stereoselective reduction of the conjugated double bond with sodium cyanoborohydride followed by cleavage of the sulfone with sodium in ammonia yielded a mixture of (-)-524 and the unsaturated analog 559. Catalytic hydrogenation ensured complete conversion of 559 into (- )-indolizidine 167B (524). 

A sequence of tandem-Mannich-Michael reactions and conjugate additions of organocuprates has been used for the synthesis of enantiomerically pure alkaloids such as (—)-dihydro-pinidine 193, the indolizidine alkaloid (5/, 8a/ )-gephyrotoxin 167B 194 and the decahydroquinoline alkaloid 4a- p/-pumiliotoxin C 195 (Figure 10.18) [150]. 

Kiewel, K., Tallant, M. and Sulikowski, G.A. (2001) Asymmetric Heck cyclization route to indolizidine and azaazulene alkaloids synthesis of (+)-5-epiindolizidine 167B and indolizidine 223AB. Tetrahedron Lett., 42, 6621-3. 

Yoda, H., Katoh, H., Ujihara, Y. and Takabe, K. (2001) SmI2-mediated hetero-coupUng reaction of lactams with aldehydes synthesis of indolizidine alkaloids, (—)-D-coniceine, (-l-)-5-epiindolizidine 167B and (-l-)-lentiginosine. Tetrahedron Lett., 42, 2509-12. 

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