CONJUGATE REDUCTION VICINAL TO BUTADIENE TRICARBONYL IRON COMPLEXES - APPLICATION TO THE SYNTHESIS OF (+/-)-6,7-DIHYDRO-LTB4 METHYL-ESTER

The conjugate reduction of enones vicinal to butadiene tricarbonyl iron complexes was best performed using Red-Al/CuBr/2-butanol in THF. This reaction was applied to alpha,beta-unsaturated ketone 13 for the synthesis of three possible metabolites of LTB4 (as their methyl esters 4a, 4b, 4c) generated via a 6,7-reductase pathway. Ketone 13 was synthesized in five steps starting from the organometallic complex 5. Conjugate reduction of 13 selectively saturated the 6,7 double bond to give ketone 14. Potassium borohydride reduction of 16 yielded a mixture of diols 17 which upon decomplexation using CAN afforded (+/-)-6,7-dihydro-LTB4 methyl ester 4a along with its 5-epimer 4b. The 5-keto derivative 4c was also prepared by direct decomplexation of 16.