Stereoselective syntheses of 5-arylsulfanyl-2(3H)-dihydrofuranones: Synthetic intermediates towards germacranolides. (1993)

(4R,5R)-4-(Alkyl malonyl)-5-arylsulfanyl-2(3H)-dihydrofuranones were synthesized and examined as potential intermediates towards the preparation of germacranolides. The key step in their preparation was a stereospecific reaction between chiral vinyl sulfoxides and dichloroketene, resulting in the formation of chiral 4-(alkyl malonyl)-5-arylsulfanyl-2,2-dichloro-2(3H)-dihydrofuranones. The chlorines were readily removed with aluminum amalgam to afford the furanones of interest. Two routes were examined towards the preparation of the furanones. Route I involved the preparation of (E)-(2-((R)-p-tolylsulfinyl)ethenyl)-p-tolylsulfonate (71). This sulfoxide could be coupled to substituted malonates, including the (E) and (Z) isomers of diethyl (3,7-dimethyl-2,6-octadienyl)malonate (88E) and (88Z), diethyl (2R,3S)-1,1-dicarboethoxy-4,8-dimethyl-3,4-epoxy-7-nonene (118), and diethyl ((Z)-2,6-dimethyl-7-dimethylphenylsilyl-3-oxo-6-heptenyl)malonate (169). The substituted malonates, (88E) and (88Z), gave the (E) and (Z) isomers of (4R,5R)-4-(1,1-dicarboethoxy-4,8-dimethyl-3,7-nonadienyl)-5-p-tolylsulfanyl-2(3H)-dihydrofuranone, (90E) and (90Z), respectively. Route II involved the preparation of (4R,5R)-4-(dicarboethoxy)methyl-5-p-tolylsulfanyl-2(3H)-dihydrofuranone (132) from (E)-3,3-dicarboethoxy-3-chloro-1-(R)-p-tolylsulfinyl-1-propene (127a). This furanone could be selectively deprotonated at the active methine position and coupled with primary halides, including (Z)-7-bromo-3-tert-butyldimethylsiloxy-1-dimethylphenylsilyl-2-methyl-1-heptene (159), (E)-8-bromo-2-dimethylphenylsilyl-3-methyl-3-octene (161), and 7-bromo-2-methyl-3-triethylsiloxy-1-heptene (168). Two methods were investigated for the cyclization of the furanones. The first method used a homolytic cleavage of the carbon-sulfur bond. The resulting $\alpha$-acyloxy radical should react in an intramolecular fashion with a double bond to afford bicyclic lactone products. The 3,7-nonadienylfuranones, (90E) and (90Z), were of interest because they contained two double bonds in the side chain and therefore could afford either a 5- or 9-membered cyclization product. When either of the 3,7-nonadienylfuranones, (90E) or (90Z), were treated with tributyltin hydride in refluxing toluene, a 5-membered cyclization product, cis-(3aR,6R,6aR)-4,4-dicarboethoxy-6-((1RS)-1,5-dimethyl-4-heptenyl)-hexahydro-2(3H)-cyclopenta (b) furan-2-one (115a/b), was isolated as a mixture of diastereomers. The ratio of diastereomers was dependent on the geometry of the double bond in the starting material. The second method involved a heterolytic cleavage of the carbon-sulfur bond to afford an oxygen stabilized carbocation intermediate. This carbocation should react in an intramolecular fashion with a double bond to afford bicyclic lactone products. When either of the 3,7-nonadienylfuranones, (90E) or (90Z), were treated with copper(I) triflate, a 5-membered cyclization product, cis-(3aR,6aR)-4,4-dicarboethoxy-6(6-methyl-$2 $-hept-5-enylidine)-2(3H)-hexahydrocyclopenta (b) furan-2-one, was isolated (112). When (4R,5R)-4-((Z)-6-(tert-butyldimethylsiloxy)-1,$1 $-dicarboethoxy-8-(dimethylphenylsilyl)-7-methyl-7-octenyl)-5-p-tolylsulfanyl-2(3H)-furanone (176) and (4R,5R)-4-((E)-1,1,-dicarboethoxy-8-dimethylphenylsilyl-7-methyl-6-nonenyl)-5-p-tolylsulfanyl-2(3H)-furanone (177) were treated, (4RS,4aR,6aS)-4-((E)-5-(tert-Butyldimethylsiloxy)-7-(dimethylphenylsilyl)-$6 $-methyl-6-heptenyl)-4-(carboethoxy)dihydrofuro (2,3-b) furan-2,5-dione (182a/b) and (4RS,4aR,6aS)-4-(carboethoxy)-4-((EZ)-6-methyl-6-heptenyl)dihydrofuro (2,3-b) furan-2,5-dione (194a/b) were isolated respectively.