Enantiomerically pure N-methyl-, N-benzyl-, and N-(methoxyethyl)-S-(phenyl)cinnamylsulfoximines as well as the corresponding crotylsulfoximines have been prepared from N-methyl-, N-benzyl-, and N-(methoxyethyl)-S-(lithiomethyl)sulfoximines and carbonyl compounds by an addition-elimination-isomerization reaction sequence. Under basic conditions, complete isomerization of the vinylic sulfoximines, obtained as intermediates, to the corresponding allylic sulfoximines takes place. Chromatographically separable mixtures of (E) and (Z) allylic sulfoximines were isolated in the case of beta,gamma-disubstituted allylic sulfoximines. The (E/Z) ratio depends on the nature of the substituents in the beta- and gamma-positions, and the equilibrium amount of the (Z) isomer varies from 68% to nil. The allylic N-methylsulfoximines do not racemize thermally, and their rearrangement to the corresponding allylic sulfinamides is negligible. Upon prolonged treatment with boron trifluoride at low temperatures allylic N-methylsulfoximines are recovered unchanged. The crystal structure of S-(3,4-dihydronaphthalen-2-ylmethyl)-N-methyl-S-phenylsulfoximine was determined. Reaction of the allylic sulfoximines with butylcopper in the presence of lithium iodide and boron trifluoride leads with very high gamma-selectivities and moderate to high enantioselectivities to the corresponding chiral alkenes. Their configuration was determined by chemical correlation through ozonolysis to the corresponding carbonyl compounds. The asymmetric induction exerted by the chiral N-methyl-S-phenylsulfoximine group strongly depends on the double bond configuration and the substituents in the beta- and gamma-positions. The (E) allylic sulfoximines are substituted with low to moderate enantioselectivities (2-66%), whereas the (Z) allylic sulfoximines react with much higher enantioselectivities (69-92%). Interestingly, substitution of the beta-methyl-gamma-phenyl-substituted (Z) allylic sulfoximine and its beta-phenyl-gamma-methyl isomer proceeded with almost the same degree of asymmetric induction but with the opposite sense. Replacement of the N-methyl group by a benzyl or a methoxyethyl group has no significant influence on the regio- and enantioselectivity of the substitution.

Enantio-and diastereomerically pure acyclic and cyclic allylic sulfoximines have been obtained by the reaction of (+)-(S)-S-(chloromethyl)-N-methyl-S-phenylsulfoximine with alkenyl cuprates of the type R 2 CuLi . LiCN.Allylic sulfoximines 4 (Scheme 1) are receiving currently much attention. In particular their hydroxyalkylation, 1-4 substitution by cuprates, 5-7 Pd-catalyzed rearrangement 8 and conjugate addition to enones 9 offer interesting possibilities for asymmetric synthesis. Prerequisite to the synthetic application of 4 is their accessibility in an enantio-and diastereomerically pure form. Existing methods 4-7,10 provide only for an access to enantiomerically pure cyclic allylic sulfoximines and acyclic allylic sulfoximines having the (E) configuration. Acyclic allylic sulfoximines having the (Z) configuration were so far accessible only in isolated cases as side products in the synthesis of the (E) isomers from aldehydes (ketones) and S-(lithiomethyl)-N-methyl-S-phenylsulfoximine. 7 It occurred to us that this void could be filled and a general route to 4 could be opened by the substitution 11 of α-halo sulfoximines 2 with 1-alkenyl cuprates 3. The α-chloro sulfoximine 2a is easily accessible in 75% yield by the chlorination of N,S-dimethyl-S-phenylsulfoximine 1 with tert-butyl hypochlorite. 12 The α-iodo sulfoximine 2b was prepared from 1 following the procedure described for the synthesis of the corresponding N-tosyl derivative 13 which gave 2b 14 in 44% yield (cf. Scheme 1). The sulfoximine 1 in turn can be obtained enantiomerically pure on a large scale via a racemate separation. 15 Configurationally stable cuprates of the type 3 16-18 are available from the corresponding (E)-and (Z)-1-alkenyllithium reagents which can be synthesized by various methods in quite a large structural variety. 19 Scheme 1Herein we describe the application of this methodology 11,16,17 to the stereoselective synthesis of acyclic and cyclic allylic sulfoximines.The alkenyl cuprates 3a-d were prepared from (Z)-1-propenyllithium, (E)-1-propenyllithium, (Z)-1-styryllithium and 1-cyclohexenyllithium, 20,21 respectively, by transmetallation with 0.5 equivalents CuCN in THF. 18 The reaction of 3a-d with 1 equivalent of the enantiomerically pure α-chloro sulfoximine 2a 12 at −78°C to −5°C led to the isolation of the allylic sulfoximines 4a, 2,14 4b, 2,14 4c and 4d, 6,14 respectively, in acceptable yields (Table 1, entries 1-4). The diastereomeric purity of 4a-c was shown to be ≥98% by 1 H NMR spectroscopy. We observed, however, that in the case of 4c a delay in the isolation of the sulfoximine from the quenched reaction mixture resulted in its partial isomerization to the (E) isomer. The synthesis of 4d (Table 1, entry 4) shows that cyclic allylic sulfoximines can be obtained by this route, too.The usefulness of the new route to 4 is exemplified by the synthesis of 4c which could not be obtained by the previously existing methods. The (E) isomer of 4c is readily available diastereomerically pure from phenyl acetaldehyde and lithiat...

Treatment of various phenylsulfoximines with nBuLi (1 equiv.) at -78°C in THF resulted in single ortho-lithiations and gave the corresponding o-lithiosulfoximines. According to NMR spectroscopy, the o-lithiosulfoximines are generally stable at 0°C. The o-lithiosulfoximines were efficiently trapped through deuteration, alkylation, silylation, and phosphanylation. Treatment of cyclic phenylsulfoximines also containing H atoms at their α-positions with nBuLi (1 equiv.) at -78°C furnished the o-lithiosulfoximines with high selectivity, whereas similar treatment at -50°C to room temperature yielded the corresponding α-lithiosulfoximines. At elevated temperatures, o-lithiosulfoximines also possessing α-H atoms underwent quantitative o,α-transmetalation to afford the corresponding α-lithiosulfoximines. Treatment of α,α-disubstituted cyclic and α,α,α-trisubstituted acyclic phenylsulf-

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The cyclic sulfoximines 4a and 4b have been prepared from (+)-(S)-S-methyl-S-phenylsulfoximine (1). Deprotonation of 4a and 4b and alkylation of lithiosulfoximines Li-4a and Li-4b gave a-alkyl substituted sulfoximines 5a (89% de), 5b (90% de), 6a (≥98% de), 6b (≥98% de), 7b (≥98% de) and 8b (≥98% de). The configuration of 6b was determined by X-ray structure analysis. Consecutive treatment of 5b, 6b and 8b with BuLi and CF 3 CO 2 H gave epimers epi-5b (64% de), epi-6b (89% de) and epi-8b (81% de). a,a-Dialkyl substituted sulfoximines 9 (≥98% de) and epi-9 (≥98% de) were obtained by alkylation of Li-5b and Li-6b. Conjugate addition of cuprates 11-14, containing the acyclic sulfonimidoyl carbanions Ia-c, to cyclohex-2-en-1-one gave ketones 15 and 16 in good yields but with low asymmetric induction (8-49% ee). However, conjugate addition of cuprates 19b, 20b, 21b and 22b, derived from the cyclic lithiosulfoximines Li-7b and Li-8b, to cyclopent-2-en-1-one, cyclohex-2-en-1-one and cyclohept-2-en-1-one gave ketones 15a-c, 23b and 24b with good to high asymmetric inductions (77-99% ee) in good yields. The bicyclic ketone 27 (79% ee) was prepared from cyclohex-2-en-1one via 24b in three steps.