Asymmetric synthesis of 2-alkyl-perhydroazepines from [5,3,0]-bicyclic lactams.
The synthesis and utility of a novel class of [5,3,0]-bicyclic lactams are described. Produced by the cyclodehydration of (R)-phenylglycinol with omega-keto acids, lactams 4-6 were obtained as separable diastereomeric mixtures ( approximately 2:1) in low yields ( approximately 40%). Higher chemical yield (up to 61%) was realized via an alternate route involving ring closure metathesis of 2-allyl-N-acroyl oxazolidines, 8. Stereoselective reductions of the syn-bicyclic lactams, 4a and 5a, occurred with the use of alane or lithiumaluminum hydride, affording azepine alcohols, 11a and 15a, of the R configuration at the 2-position, in good to moderate yields (50-88%). High selectivity was also observed in the diisobutylaluminum hydride reduction of the epimeric anti lactams, 4b and 5b, affording azepine alcohols, 11b and 15b, of the S configuration at C-2. Hydrogenolytic cleavage of the N-benzyl moiety afforded chiral 2-substituted perhydroazepines, (R)- and (S)-12, in good yields and good enantiomeric excesses (84-94%).
Meyers
A I
AI
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA. aimeyers@lamar.colostate.edu
Downing
S V
SV
Weiser
M J
MJ
D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013237:Stereoisomerism
D001381:Azepines; D007769:Lactams