REGIOSELECTIVEN AND ENANTIOSELECTIVE SUBSTITUTION OF PRIMARY ENDOCYCLIC ALLYLIC SULFOXIMINES WITH ORGANOCOPPER AND ORGANOCUPRATE REAGENTS -THE IMPORTANCE OF IODIDE FOR THE ALLYLIC SUBSTITUTION WITH ORGANOCOPPER COMPOUNDS

The endocyclic N-substituted allylic sulfoximines 17-20 and 26 were sy nthesized from the corresponding cycloalkanones and the various (S)-S- (lithiomethyl)-S-phenylsulfoximine in enantiomerically pure form in yi elds of 60-70% in a process involving the isomerization of the interme diate vinylic sulfoximines. Desilylation of 26 gave the parent N-H sul foximine 27 from which the N-sulfonylsulfoximines 28 and 29 were prepa red. The X-ray crystal structure of 28 was determined. The allylic sul foximines 17-20 and 26-29 did not racemize or rearrange thermally to t he corresponding allylic sulfinamides. Reaction of the allylic sulfoxi mines 18, 28, and 29 with the organocuprate reagents 2/LiI, 35/LiI, an d 47/LiI led with alpha-selectivities of 92:8 to 99:1 to the endocycli c alkenes 39 in good to high yields. Reaction of 17-20, 28, and 29 wit h the organocopper reagents 5/LiI, 30/LiI, 31/LiI, 32/LiI, 33/LiI, 34/ LiI, and 37/LiI in the presence of BF3 resulted in the formation of th e exocyclic alkenes 38, 41, 43, and 45, respectively, in good to high yields with gamma-selectivities of 80:20 to 99:1. The sulfonimidoyl gr oup imparts asymmetric induction to the substitution in the range of 2 7-90% ee. The (S)-sulfonimidoyl group leads to a preferential bond for mation from the si side of the double bond. From the sulfoximines 18 a nd 26-29 the N-methylsulfoximine 18 and the N-tosylsulfoximine 28 show ed the highest and lowest reactivity with the butylcopper reagent 32/L iI in the presence of BF3 respectively, while in the absence of BF3 on ly 29 reacted. The Lewis acid most likely serves to activate the N-met hyl- and N-tosylsulfoximines or intermediates thereof through coordina tion at the sulfonimidoyl and sulfonyl group. Reaction of the sulfoxim ines 18 and 29 with pure Me(3)SiCH(2)Cu (34) revealed a strong rate ac celeration by LiI and an even stronger one by Bu(4)NI. This points to the existence of a heteroleptic cuprate or a related compound as react ive species. In substitutions with the Yamamoto reagents RCu/MX/BF3, t he halide is important and a reaction between RCu and BF3 does not hav e, at least in the case of allylic sulfoximines, to be invoked. In rea ctions of 17-20 besides the alkenes, the sulfinamide ent-4 was formed with an ee value of 97% in high yield with retention of configuration. The absolute configuration of the exocyclic alkenes 38, 41, and 45 wa s determined by ozonolysis to the corresponding cycloalkanones followe d by their conversion to the corresponding lactones and/or CD measurem ent of the former.