Complexity-building annulations of strained cycloalkanes and C═O π bonds.
This Perspective details a developing research program that emerged from simple plans for achieving the synthesis of tetrahydrofurans from cyclopropanes and C═O π bonds. Lewis acid catalyzed annulations of malonate-derived donor-acceptor cyclopropanes with aldehydes are unusually broad in scope and lead to the synthesis of structurally diverse tetrahydrofurans. The reactions are stereospecific, with inversion observed at the cyclopropane donor site. Substituent effects on the aldehyde suggest that it acts as a nucleophile in the reaction. An unusual mechanism emerges in which the aldehyde traps a configurationally stable intimate ion pair to stereospecifically construct the C-O bond. In addition to the stereospecific conversion of enantiomerically enriched cyclopropanes into nonracemic heterocycles, we have also demonstrated that racemic cyclopropane 1,1-diesters can undergo dynamic kinetic asymmetric annulations catalyzed by (pybox)MgI(2) complexes. Asymmetric syntheses of (+)-polyanthellin A and (+)-virgatusin have been achieved; both rely upon cyclopropane/aldehyde annulation for construction of the core tetrahydrofurans.
Campbell
Matthew J
MJ
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
Johnson
Jeffrey S
JS
Parsons
Andrew T
AT
Pohlhaus
Patrick D
PD
Sanders
Shanina D
SD
D000447:Aldehydes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003516:Cycloparaffins / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
D000447:Aldehydes; D003516:Cycloparaffins; D005663:Furans