Diastereoselective construction of syn-α-oxyamines via three-component α-oxyaldehyde-dibenzylamine-alkyne coupling reaction: application in the synthesis of (+)-β-conhydrine and its analogues.
A Cu(I)-catalyzed α-oxyaldehyde-dibenzylamine-alkyne coupling reaction was delineated for the construction of α-oxyamines with excellent yields and diastereoselectivity. Crystal structure analysis and theoretical calculations were also supportive of the formation of syn-α-oxyamines as the major products. Application of the methodology addresses the synthesis of (+)-β-conhydrine along with analogs having two different diversity features. A ring size variation allows construction of piperidine and pyrrolidine rings while a variation of side arm functionality is achieved by complete regioselective opening of epoxide by different organocopper ylides (Gilman reagents). A lactam-Cu(I) complexation motif is proposed which allows an intramolecular attack of ylides at the terminal epoxy carbon via the six-membered cyclic transition state. The present work features the synthesis of (+)-β-conhydrine over eight steps in 26% yield and its seven analogs in 21-28% yields.
Department of Chemistry, Dmitri Mendeleev Block, Indian Institute of Science Education and Research, Pune, India.
Sharad Chandrakant
SC
Deshmukh
Arundhati
A
Roy
Pinaki
P
Talukdar
D000447:Aldehydes / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D001596:Benzylamines / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D000480:Alkynes; D000588:Amines; D001596:Benzylamines; D010880:Piperidines; C520251:alpha-conhydrine; C005051:dibenzylamine; D003300:Copper