Sulfoximine derivative

A wide variety of sulfonyl or carboxyl amides can be applied as nitrogen sources and nontoxic iodobenzene diacetate serves as a mild oxidant. Furthermore, the reaction conditions (e.g., room temperature) are mild, and the imina-tion proceeds with retention of configuration at the stereogenic sulfur (as shown in Scheme 2.1.1.3 for the conversion of (R)-14 into (i )-15). Most importantly, sulfoximine derivatives with easy-to-cleave protective groups at the sulfoximine nitrogen are obtainable, which allow access to the synthetically important free NH-sulfoximines (vide infra). 

Resolved P-hydroxy sulfoximines derived from cyclic enones undergo dias-tereoselective Simmons-Smith cyclopropanation reactions to give, after thermolysis, cyclopropylketones in high enantiomeric purity (94-98%). Cyclopropanation occurs syn to the hydroxyl group of the P-hydroxy sulfoximine. This method is less diastereoselective for acyclic enones.73... 

Osmylation of diastereomerically pure P-hydroxy sulfoximines, derived from 2a and cyclic enones, with a catalytic amount of osmium tetroxide (5 mol%) and trimethylamine V-oxide (1.5 equiv) gives diastereomerically pure triols which on thermolysis yield 2,3-dihydroxy cyclic ketones in high enantiomeric purity ( 100% ee). Osmylation occurs syn to the sulfoximine group.74... 

Treatment of thietanes with chloramine T gives N-tosylsulfilimines, for example, 126. Acyclic and five-, six-, and seven-membered cyclic sulfides all react more rapidly than thietane. The mechanism has been investigated. The IR stretching vibrations of the S-N-SO2 system are at 948 and 759 cm", and the nmr spectrum of 3,3-dimethylthietane 1-tosylsulfilimine in benzene and chloroform suggests an equatorial conformation for the sulfilimine. Oxidation of this sulfilimine gives the sulfoximine derivative, 127. The two diastereomeric tosyl-sulfilimines of 3-methyl-3-phenylthietane complex at nitrogen with silver ion. ... 

The most commonly used reagents to effect the addition of a methylene group to an aldehyde or ketone are sulfur ylides such as dimethylsulfonium methylide (1) or dimethyloxosulfonium methylide (2) (Corey-Chaykovsky reaction). This reaction is well reviewed in standard treatises of organic synthesis - and several useful monographs. - This update will concentrate on progress attained from 1975. The reader is also encouraged to consult reviews on the chemistry of the related sulfoximine-derived ylides such as (3). -"... 

Bolm prepared a wide range of N-vinyl sulfoximine derivatives by means of copper-promoted coupling of A//-sulfoximines and vinyl bromides (Scheme 38) [126]. The major drawback of such protocol, which relied on the use of stoichiometric amounts of both copper and diamine ligands, was balanced by the fact that the present method exhibited broader scope than the one involving palladium-catalyst [73] being found compatible with the conversion of di-, tri-, and even tetra-substituted vinyl bromides. 

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. 

Associated to copper(II) pre-catalysts, bis(oxazolines) also allowed the asymmetric Diels-Alder and hetero Diels-Alder transformations to be achieved in nearly quantitative yield and high diastereo- and enantioselectivities. Optically active sulfoximines, with their nitrogen-coordinating site located at close proximity to the stereogenic sulfur atom, have also proven their efficiency as copper ligands for these asymmetric cycloadditions. Other precursors for this Lewis acid-catalyzed transformation have been described (e.g., zinc salts, ruthenium derivatives, or rare earth complexes) which, when associated to bis(oxazolines), pyridine-oxazolines or pyridine-bis(oxazolines), led to efficient catalysts. 

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. 

Scheme 1.53 Test reaction with BINOL-derived A -phosphino sulfoximines.

A series of chiral p-hydroxysulfoximine ligands have been synthesised by Bolm et al. and further investigated for the enantioselective conjugate addition of ZnEt2 to various chalcone derivatives. The most eiScient sulfoximine, depicted in Scheme 2.33, has allowed an enantioselectivity of up to 72% ee to be obtained. These authors assumed a nonmonomeric nature of the active species in solution, as suggested by the asymmetric amplification in the catalysis with a sulfoximine of a low optical purity. 

On the other hand, Bolm et al. have reported, more recently, the use of BINOL-derived A -phosphino sulfoximines as ligands in the rhodium-catalysed hydrogenation of dimethyl itaconate and a-acetamidoacrylates, achieving excellent enantioselectivities of up to 99% ee (Scheme 8.12). In the main... 

In 1994, the scope of this p-hydroxy sulfoximine ligand was extended to the borane reduction of ketimine derivatives by these workers. The corresponding chiral amines were formed with enantioselectivities of up to 72% ee, as shown in Scheme 10.57. It was found that the A -substituent of the ketimine had a major influence on the asymmetric induction, with a ketoxime thioether (SPh) being the most successful substrate. 

Scheme 10.57 Borane reductions of ketimine derivatives with P-hydroxy sulfoximine ligand.

Aside from the methylide and cyclopropylide reagents, the sulfonium ylides are not very stable. A related group of reagents derived from sulfoximines offers greater versatility in alkylidene transfer reactions.286 The preparation and use of this class of ylides is illustrated below. 

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 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]. 

Ketones. The lithio derivative of ( +)-(.S )-. Y,.S -dimethyl-S-phenylsulfoxiinine (16), or its enantiomer, may be used both to resolve racemic ketones164 and to determine absolute configurations of ketones. For example, rac-19 on addition of 16 formed the diastereomeric /j-hydroxy-sulfoximines 17 and 18 which were separated. The configuration of 17 was established by an X-ray analysis. The ketones can be regenerated from the /1-hydroxysulfoximines by thermolysis. Thus, heating of 17 and 18 to 80 °C (for 12 h) furnished 19 [a precursor of (+ )-modhephen] and ent-l9165. 

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