New synthetic technologies for the construction of heterocycles and tryptamines.
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/LaCl(3).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.
Nicolaou
K C
KC
Department of Chemistry and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Krasovskiy
Arkady
A
Majumder
Utpal
U
Trépanier
Vincent E
VE
Chen
David Y-K
DY
D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D014363:Tryptamines / Q000138:chemical synthesis* / Q000737:chemistry
D006571:Heterocyclic Compounds; D014363:Tryptamines