Stereoselective synthesis of cyclic ethers using vinylogous sulfonates as radical acceptors: effect of E/Z geometry and temperature on diastereoselectivity.
Treatment of the E-vinylogous sulfonates 1a-g with tris(trimethylsilyl)silane and triethylborane, in the presence of air, furnished the cyclic ethers 2/3a-g with good to excellent diastereoselectivity favoring the cis-isomer 2. This study demonstrated the level of stereocontrol in a 6-exo radical cyclization and may be attributed to the type of radical intermediate. Hence, the modest selectivity obtained for the cyclization of 1e may be a function of the acyl radical geometry (sp2) and high inversion barrier (29 kcal/mol) as compared to the alkyl (1 kcal/mol) and vinyl (2.9 kcal/mol) radicals. This is consistent with the acyl radical cyclization having an earlier transition state than the corresponding alkyl and vinyl radicals. The modest diastereoselectivity can be improved dramatically using the Z-vinylogous sulfonate (> or =34:1; R = Ph) to promote kinetic trapping of the s-trans rotamer I and III, respectively (Figure 1). The 5-exo alkyl radical cyclization reaction under nonreductive Keck-allylation conditions was also examined, in which 8 was formed in 91% overall yield. This transformation provides a convenient method for in situ homologation and should be applicable to target directed synthesis.
Evans
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PA
Department of Chemistry and Biochemistry, University of Delaware, Newark, 19716, USA. paevans@udel.edu
Manangan
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D003500:Cyclization; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D013237:Stereoisomerism; D013451:Sulfonic Acids / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D014753:Vinyl Compounds / Q000737:chemistry* / Q000378:metabolism
D004988:Ethers, Cyclic; D013451:Sulfonic Acids; D014753:Vinyl Compounds