Regio- and Stereoselective Cyclopentannulation with Ketones and Propargyl Alcohol Derivatives. Synthesis of dl-Nootkatone and dl-Muscopyridine

Article abstract of DOI:10.1246/bcsj.54.2747

A highly regio- and stereoselective five-membered ring annulation involving the acid-treatment of propargyl alcohol dianion adducts of ketones is described.The propargyl alcohol adduct of 2-octanone was converted into 2-methyl-3-pentyl-2-cyclopentenone by treatment with sulfuric acid-methanol (1:1) at 0 deg C.As the major product, 1-methylbicyclo<5.3.0>dec-6-en-8-one was produced from 2-methylcycloheptanone.Remarkable regioselective cyclopentannulation was observed in 2-methylcyclohexanone and 2,3-dimethylcyclohexanone wherein 1-methyl- and trans-1,2-dimethyl-substituted bicyclo<4.3.0>non-5-en-7-one (BNO) are produced, respectively.With 3-butyn-2-ol, 2-methylcyclohexanone was converted into the cis-1,9-dimethyl-substituted BNO. 4-Isopropyl-2-methylcyclohexanone was transformed into an 83-85:17-15 mixture of c-3-isopropyl-r-1,c-9-dimethyl-BNO and its 3-epimer.These results are explained in terms of the conrotatory ring-closure of thermodynamically most favorable hydroxypentadienyl cation intermediates. 3-Methoxycarbonyl-cis-1,9-dimethyl-BNO produced from 4-methoxycarbonyl-2-methylcyclohexanone and 3-butyn-2-ol was successfully transformed into dl-nootkatone by converting the methoxycarbonyl group into isopropenyl of correct stereochemistry followed by ring enlargement.Cyclopentannulation using propargyl alcohol dianion adducts of 2-cycloalkenones is discussed.Annulation takes place regioselectively to give conjugated dienones, e.g., (E)-bicyclo<10.3.0>pentadeca-1(12),2-dien-13-one from 2-cyclododecenone.This product is led to dl-muscopyridine by conjugate 1,6-addition of methyl group followed by ring expansion and finally by aromatization with hydroxylamine hydrochloride.