Sulfoximines substituted

Gais and co-workers recently reported the preparation and use of chiral sulfoximine-substituted allyltitanium(iv) complexes of type 78 for the asymmetric synthesis of 3-substituted unsaturated proline derivatives 79 (Scheme 31).108... 

The sulfoximine-substituted spiroacetals 147 were obtained in good yield using this approach. Reductive removal of the sulfoximine over Al/Hg amalgam afforded the simple 5,5-spiroacetals 149 in moderate to high yield, as approximately 1 1 mixtures of diastereomers. 

Illustrating the importance of the sulfoximine, Waldmann and Basu found that related conjugated dienes lacking sulfoximine substitution gave the smaller of the two possible rings when exposed to [Ru]-I, [Ru]-II, or [Ru]-III catalyst (Scheme 3.8) [19]. For example, when triene 73 was subjected to any of these catalysts, only oxepine 74 was isolated. 

Chiral (-E)-vinyl-substituted sulfoximines, in which the iV-substituent was derived from (+)-norephedrine or ( —)-(S)-l-phenylethylamine2, underwent addition reactions with organolithi-um and organocopper reagents1,2. The diastereoselection ranged from moderate to good. 

Sulfoximines bearing a chiral sulfur atom have recently emerged as valuable ligands for metal-catalysed asymmetric synthesis.In particular, C2-symmetric bis(sulfoximines), such as those depicted in Scheme 1.51, were applied to the test reaction, achieving enantioselectivities of up to 93% ee. The most selective ligand (R = c-Pent, R = Ph) of the series was also applied to the nucleophilic substitution reaction of l,3-diphenyl-2-propenyl acetate with substituted malonates, such as acetamido-derived diethylmalonate, which provided the corresponding product in 89% yield and 98% ee. 

Reggelin et al. reported the application of methylated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines 203 for the synthesis of highly substituted aza(poly)cyclic ring systems 204 under complete stereocontrol <06JA4023 06S2224>. 

Condensation of sulfoximine 717 with an aldehyde and benzotriazole produces Ar-[ -(bcnzotnazol-l -yl)alkyl]sul-foximine 718. Treatment with allyl silanes in the presence of BF3 etherate or with organozinc reagents allows substitution of the benzotriazolyl moiety in compound 718 to produce variety of substituted sulfoximines 719... 

The first attempts to develop reactions offering control over the absolute stereochemistry of a chiral center, created by y-selective substitution of an achiral allylic alcohol-derived substrate, involved the use of chiral auxiliaries incorporated in the nucleofuge. The types of stereodirecting groups utilized vary, and have included sulfoximines [15], carbamates [16], and chiral heterocyclic sulfides [17-19]. 

A reaction of sulfoximine 268 with ort o-substituted halobenzaldehydes 269 takes place in the presence of a catalytic amount of Pd(ii), 2,2 -bis(diphenylphosphanyl)-l,l -binaphthyl (BINAP), and caesium carbonate at 110°C to afford fully conjugated 2-phenyl-2,l-benzothiazine 2-oxides 270 with a S(vi) oxidation state (Scheme 38) <1999AGE2419>. Bis-benzothiazine 75 has been prepared from dibromo-dialdehyde 271 in a similar manner and investigated as a ligand for Pd-catalyzed allylic alkylation reactions (see Section 8.07.12.3) <20010L3321>. 

We have developed asymmetric syntheses of isocarbacyclin [3] (Scheme 1.3.2) and cicaprost [4] (Scheme 1.3.3) featuring a Cu-mediated allylic alkylation of an allyl sulfoximine [5-7] and a Ni-catalyzed cross-coupling reaction of a vinyl sulf-oximine [8-10], respectively, transformations that were both developed in our laboratories. The facile synthesis of an allyl sulfoximine by the addition-elimination-isomerization route aroused interest in the synthesis of sulfonimidoyl-sub-stituted aiiyititanium complexes of types 1 and 2 (Fig. 1.3.2) and their application as chiral heteroatom-substituted allyl transfer reagents [11]. 

Chiral alkenyl and cycloalkenyl oxiranes are valuable intermediates in organic synthesis [38]. Their asymmetric synthesis has been accomplished by several methods, including the epoxidation of allyl alcohols in combination with an oxidation and olefination [39a], the epoxidation of dienes [39b,c], the chloroallylation of aldehydes in combination with a 1,2-elimination [39f-h], and the reaction of S-ylides with aldehydes [39i]. Although these methods are efficient for the synthesis of alkenyl oxiranes, they are not well suited for cycloalkenyl oxiranes of the 56 type (Scheme 1.3.21). Therefore we had developed an interest in the asymmetric synthesis of the cycloalkenyl oxiranes 56 from the sulfonimidoyl-substituted homoallyl alcohols 7. It was speculated that the allylic sulfoximine group of 7 could be stereoselectively replaced by a Cl atom with formation of corresponding chlorohydrins 55 which upon base treatment should give the cycloalkenyl oxiranes 56. The feasibility of a Cl substitution of the sulfoximine group had been shown previously in the case of S-alkyl sulfoximines [40]. 

Scheme 1.3.21 Asymmetric synthesis of cycloalkenyl oxiranes via substitution of allyl sulfoximines.

The acyclic sulfonimidoyl-substituted amino acids 24 were selected as starting material for the synthesis of the unsaturated prolines of type 63. Because of the facile synthesis of the unsaturated bicyclic tetrahydrofurans 53 from the vinyl aminosulfoxonium salts 46 (cf. Scheme 1.3.20), it was speculated that upon treatment with a base the vinyl aminosulfoxonium salts 67 would experience a similar isomerization with formation of the allyl aminosulfoxonium salts 69, which in turn could suffer an intramolecular substitution of the allylic aminosulfoxonium group (Scheme 1.3.24). The methylation of sulfoximines 24 with Me30Bp4 gave... 

During the investigation of the synthesis and use of sulfilimines (such as 22 and 23) [21, 23, 24] and sulfondiimides (of the 25 type) [27], it became apparent that appropriately substituted nonsymmetric derivatives of these compounds were much more difficult to prepare in enantiopure form than their sulfoximine counterparts. It was therefore decided to retain the sulfur/oxygen moiety and to concentrate further efforts exclusively on the synthesis and application of sulfoximines. 

Hartwig-Buchwald, Suzuki, and Stille type cross-coupling reactions with key intermediate 46 led to a wide range of substituted sulfoximines such as 47-49 [37]. In order to demonstrate the synthetic utility of the resulting products, pseudo tripeptide 50 was prepared from a related intermediate. 

Chemla and Ferreira effected lithiozincation of TMS propargyl chloride to prepare chloroal-lenylzinc bromide reagents (Table 21)33. Subsequent reaction of these reagents with N-t-butyl-substituted sulfoximines yielded the related traws-sulfoxinyl aziridines, arising from internal displacement of the chloride substituent of the anti sulfinamide adduct. A transition state in which the f-BuSO group is eclipsed with the alkynyl (vs R) substituent accounts for the preferred formation of the major A-sulfinyl diastereomer (equation 41). 

Data with substitution labile Co(II)-nucleotides were also obtained. Titrations with both Co(II)-ADP and Co(II)-ATP in the presence of the inhibitor methionine sulfoximine produced a diminution of the EPR spectrum of enzyme-bound Mn(II). The Co-to-Mn distances were 6.5 and 5.2 A for the Co-ADP and Co-ATP complexes, respectively. 

Stabilized lithiated sulfoximines (112) undergo highly diastereoselective Michael additions to cyclic enones at —78 °C under kmetically controlled conditions. At room temperature, the initially formed adducts (113) undergo intramolecular substitution of the sulfonimidoyl group, with inversion of configuration to afford the corresponding cyclopropanes (114).92... 

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