Desymmetrization of enone-diones via rhodium-catalyzed diastereo- and enantioselective tandem conjugate addition-aldol cyclization.
Catalytic tandem conjugate addition-enolate trapping represents an effective strategy for the design of catalytic transformations that enable formation of multiple C-C bonds. Recently, using enantioselective rhodium-catalyzed conjugate addition methodology, we developed a catalytic tandem conjugate addition-aldol cyclization of keto-enones. Here, we report related desymmetrizations and parallel kinetic resolutions involving the use of diones as terminal electrophiles. The Rh-enolate generated on enone carbometallation effectively discriminates among four diastereotopic pi-faces of the appendant dione, ultimately providing products that embody four contiguous stereocenters, including two adjacent quaternary centers, with quantitative diastereoselection and high levels of enantiomeric excess. This methodology allows concise entry to optically enriched seco-B ring steroids possessing a 14-hydroxy cis-fused C-D ring junction, as found in naturally occurring cardiotonic steroids derived from digitalis.
Bocknack
Brian M
BM
Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712, USA.
Wang
Long-Cheng
LC
Krische
Michael J
MJ
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D004074:Digitoxin / Q000031:analogs & derivatives; D007659:Ketones / Q000737:chemistry*; D007700:Kinetics; D009942:Organometallic Compounds / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D007659:Ketones; D009942:Organometallic Compounds; D012238:Rhodium; D004074:Digitoxin