Stereoselective Synthesis of 2,4,6-Trimethylcyclohex-4-Ene-1,3-Diol Derivatives and of Polypropionate Fragments with 4 Contiguous Stereogenic Centers

The Diets-Alder adduct (+/-)-3 of 2,4-dimethylfuran and 1-cyanovinyl acetate was converted stereoselectively into benzyl 6-(4-chlorophenylsulfonyl)-1,3-exo,5-trimethyl-7-oxabicyclo[2.2.1]hept-5 -en-2-exo-yl (26) and -2-endo-yl ether (36). Addition of LiAlH4 to the latter led to the 3-O-benzyl derivatives 28 and 37 of (1RS,2SR,3SR,6SR)- and (1RS,2SR,3RS,6SR)-5-(4-chlorophenylsulfonyl)-2,4,6-trimethylcyclohex-4-e ne-1,3-diol, respectively. Methylenation of 6-exo-(4-chlorophenylthio)-1-methyl-5-methylidene-7-oxabicyclo[2.2.1]hep tan-2-one (16), obtained by reaction of (+/-)-3 with 4-Cl-C6H4SCl and saponification gave, 6-exo-(4-chloro-phenylthio)-1-methyl-3, 5-dimethylidene-7-oxabicyclo[2.2.1]heptan-2-one (43), the reduction of which with K-Selectride afforded 6-exo-(4-chlorophenylthio)-1,3-endo-dimethyl-5-methylidene-7-oxabicyclo[ 2.2.1]heptan-2-endo-ol (44). The 3-O-benzyl derivative 48 of (1RS,2RS,3RS,6SR)-5-(4-chlorophenylsulfonyl)2,4,6-trimethylcyclohes-4-en e-1,3-diol was derived from 44 via based-induced oca-ring opening of benzyl 6-endo-(4-chlorophenylsulfonyl)-1,3-endo,5-endo-trimethyl-7-oxabicyclo[2 .2.1]hept-2-endo-yl ether (49). Benzylation of 28, followed by reductive desulfonylation and oxidative cleavage of the cyclohexene moiety afforded (2RS,3SR,4RS,5RS)-3,5-bis(benzyl-oxy)-2,4-dimethyl-6-oxoheptanal (32).