| The first total synthesis of (+/-)-acanthodoral has been achieved in 2.5% overall yield and 19 steps from 3-methylcyclohex-2-en-1-one. The key intermediate, (2,7,7-trimethyl-3,4,5,6,7,7a-hexahydro-3aH -inden-3a-yl)acetic acid was prepared efficiently through a Pd-catalyzed metallo-ene reaction of (2,2-dimethyl-6-methylenecyclohexyl)-2-methylprop-2-enyl methyl carbonate. Electrocyclic ring-opening of its 1,1-dibromocyclopropane derivative in (CF3)2CHOH with p-methoxybenzenethiol as a nucleophile provided methyl [(4aS*,8R*,8a S*)-7-bromo-1,1,6-trimethyl-8-(4-methoxy-phenylsulfanyl)-1,3,4,5,8,8a-hexahydronaphthalen-4a(2 H)-yl]acetate with high regio- and stereoselectivity in excellent yields. Acyl radical 5-exo cyclization in an SH2 ' process afforded 8-phenylthio-5,5,9-trimethyltricyclo[7.2.1.0 1,6]dodec-7-en-10-one, which was then converted into acanthodoral in 5 steps including a highly diastereoselective Wolff rearrangement. An enantioselective synthesis of (+)-acanthodoral has been achieved by starting from enantiomerically pure (+)-[(1S)-2,2-dimethyl-6-methylenecyclohexyl] methanol and following the procedures established for the synthesis of racemic acanthodoral.; A general approach toward highly-substituted bicyclo[3.2.0]heptanes has been developed by utilizing homo-Favorskii rearrangement, acid-catalyzed skeleton rearrangement, and deoxygenation. This method was successfully applied to the total synthesis of kelsoene (starting from 1-methoxycyclohexa-1,4-diene in 16 steps and 12.5% overall yield). An enantioselective synthesis of (+)-kelsoene has been accomplished by using enantiomerically pure (+)-(S)-1,4-dioxaspiro[4.5]dec-8-en-7-yl pivaloate, which was efficiently accessed by Pd-catalyzed deracemization of the corresponding racemic methyl carbonate.; In connection with an effort to develop a new, efficient method for the generation of radicals from alcohols and acids, a novel conversion of alcohols into iodides has been devised. Alkyl 2'-iodo-1,1 '-biphenyl-2-yl(phenyl)phosphinites derived from alcohols were converted into iodides efficiently under neutral conditions (toluene, reflux). Moreover, the iodides thus obtained could be directly reduced under standard radical conditions (Bu3SnH, cat. AIBN, 80°C) in the same reaction vessel without purification of the iodides, achieving an efficient two-pot deoxygenation of alcohols. |
