New Synthetic Technologies for the Construction of Heterocycles and Tryptamines
- 25 February 2009
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 131 (10) , 3690-3699
Abstract
New synthetic methods for the construction of novel heterocycles and tryptamines are described. Thus, N-Boc anilines (I) are sequentially converted to heterocycles II ((3-(2-aminophenyl)pyrrolidin-3-ol) derivatives), III (substituted 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3′-pyrrolidines), and VI (2-(4,5-dihydro-1H-pyrrol-3-yl)aniline) derivatives through a route involving t-BuLi induced ortho-metalation/LaCl3·2LiCl metal exchange, reaction with N-Boc pyrrolidin-3-one (5), and subsequent decarboxylative fragmentation. Labile intermediates VI are effectively converted to tryptamines Xa and Xb under controlled protic acid conditions. In addition to providing expedient access to the 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3′-pyrrolidines (III), the method is applicable to the synthesis of the corresponding 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3′-piperidine series of spirocycles (e.g., 42) and their precursors (3-(2-aminophenyl)piperidin-3-ol derivatives, e.g., 43) by using N-Boc-protected piperidin-3-one (40). Applications of the developed synthetic technologies to the synthesis of regioisomeric spirocycles 87 and 90, tryptamines 88 and 91, Corey’s aspidophytine tryptamine (97), and efavirenz (1) are also described.Keywords
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