Highly efficient synthesis of azabicyclo[x.y.0]alkane amino acids and congeners by means of Rh-catalyzed cyclohydrocarbonylation.
A highly efficient method for the synthesis of 1-azabicyclo[x.y.0]alkane amino acid derivatives and their congeners by means of extremely regioselective cyclohydrocarbonylation (CHC) is described. The CHC reactions are catalyzed by Rh-BIPHEPHOS complex under mild conditions. These CHC reaction processes involve (i) an extremely linear-selective hydroformylation of the terminal alkene moiety of a dehydrodipeptide substrate, (ii) intramolecular condensation to form cyclic N-acyliminium key intermediate, and (iii) the second cyclization through intramolecular nucleophilic addition of a heteoatom nucleophile to the cyclic N-acyliminium moiety to afford the corresponding 1-azabicyclo[x.y.0] system. This consecutive double cyclization process proceeds with extremely high diastereoselectivity in most cases. This method has been successfully applied to the syntheses of 1-azabicyclo[4.4.0], -[5.4.0], and -[4.3.0] systems. The mechanisms of the reactions and the rationale for the observed extremely high diastereoselectivity are presented. This Rh-catalyzed CHC process would serve as a highly efficient and versatile method for the syntheses of a variety of conformationally restrained dipeptides, peptidomimetics, alkaloids, and other biologically active natural or unnatural products.
Chiou
Wen-Hua
WH
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA.
Mizutani
Nobihiro
N
Ojima
Iwao
I
D000473:Alkanes; D000596:Amino Acids / Q000138:chemical synthesis*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D002384:Catalysis; D006844:Hydrocarbons, Cyclic; D012238:Rhodium
D000473:Alkanes; D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006844:Hydrocarbons, Cyclic; D012238:Rhodium