Stereo- and Enantiospecific Syntheses of (-)-Reiswigins A and B. Assignment of Absolute and Relative Configuration

Article abstract of DOI:10.1021/jo00301a034

The first synthesis of reiswigin A (20) was accomplished in only eight steps providing optically pure material in 7percent overall yield with control of the relative and absolute stereochemistry at carbons 1, 7, and 8.The synthesis was designed to provide a mixture of isomers at carbon 13 since the stereochemistry at this center was not assigned in the structure determination.Sakurai reaction of allylic silane 12 with enone 13 affords ketone 5 as a mixture of diastereomers.Protection of the ketone, cleavage of the double bond, and intramolecular aldol reaction gives cyclopentenecarboxaldehyde 4.Addition of 3-methyl-3-butenylmagnesium bromide to imine 17 by Koga's procedure followed by alkylation of the enamide with methyl iodide gives 3.This crucial step not only controls the relative stereochemistry at carbons 1, 7, and 8 but also effects a kinetic resolution, permitting assignment of absolute stereochemistry to reiswigin A as shown in 20.Me2AlCl-catalyzed ene reaction of 3 gives alcohol 19.Oxidation of the alcohol and acid-catalyzed conjugation of the double bond and hydrolysis of the ketal gives a mixture of reiswigin A (20) and 21.The stereochemistry at carbon 13 is assigned based on NMR shifts.Addition of cyclohexenylpotassium to crotonaldehyde gives dienol 26b.Anionic oxy-Cope rearrangement gives aldehyde 28, which was used for stereo- and enantiospecific syntheses of both reiswigins A (20) (11 steps, 12percent) and B (36) (11 steps, 6percent).