Sulfoximines

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

The cyclic sulfoximine 93a,b, a key intermediate in the synthesis of sulfoximine 94 designed as inhibitors of Escherichia Coli y-glutamyl synthetase, was synthesized stereoselectively (96BMC(6)1437, 98BMC(6)1935). X-ray analysis (99AX(C55)1598) of 93b was performed, elucidating the configuration. 

Racemic 5-methyl-5 -(sodiomethyl)-A-(4-methylphenylsulfonyl)sulfoximine reacts with ketones to give an initial methylene transfer which produces an intermediate epoxide that is ring expanded to the oxctanc56. Application to 4-rerf-butylcyclohexanonc affords a single oxetane in 69% yield. While only achiral alkylidcne transfer reagents were utilized, in principle this reaction is amenable to the asymmetric synthesis of oxetanes. 

Addition of Metalated Allylic Phosphine Oxides, Phosphonates, Sulfones, and Sulfoxides and Sulfoximines to a,/i-l nsaturated Carbonyl Compounds... 

In contrast to allylic phosphine oxides, phosphonates, sulfones and sulfoxides, the chemistry of lithiated allylic sulfoximines has been less extensively developed25 27. The reaction of lithiated racemic A-phenyl-A -(4-rnethylphenyl)-S -(2-propenyl)sulfoximine with either 2-cy-clopentenone or 2-cyclohexenone gave a complicated mixture with 1,4-oc-ad ducts being slightly favored over the 1,4-7-adducts. The yields of these adducts were poor25. In contrast, lithiated racemic Ar-tert-butyldiphenylsilyl-5-phenyl-5,-(2-propenyl)sulfoximine gives mainly 1,4-y-ad-ducts on reaction with the same enones26. 

Addition of lithiated Ar-(4-methylphenylsulfonyl)-S-phenyl-S -(2-propenyl)sulfoximine to acyclic enones gives exclusively 1,4-a-adducts in high diastereomeric purity. The configuration of the adduct (R2 = R3 = C6H5) has been determined by a single crystal X-ray structure determination27. 

Formation of C-C Bonds by Addition to Olefinic Double Bonds Enimines, Nitroalkenes, 4,5-Dihydrooxazoles, a,/MJnsaturated Sulfones, Sulfoxides and Sulfoximines... 

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. 

Optically active sulfoximines (133) and sulfilimines (134) may be converted to optically active sulfoxides12,142. 

Addition of nitrogen to the lone pair of sulfoxides or of oxygen to the lone pair of sulfilimines is quite common and leads to sulfoximines (see also Section II.G). Such reactions have been reviewed12,13. 

Recently, enantiomerically pure vinylic sulfoximines have been shown to undergo effective and highly stereocontrolled conjugate addition of hydrocarbon groups using organocopper reagents108. 

Besides sulfonamides, chiral sulfoximines have also been used in C - N bond formation under microwave irradiation [103]. The only heteroaryl chloride used in the study—namely, 2-chloropyridine—gave the desired M-(pyridin-2-yl)sulfoximine at a yield of 43% (Scheme 101). Interestingly,... 

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. 

Bolm et al. [106] have carefully studied the synthesis and the hganding ability of salen-like bis(sulfoximines). The chirahty which is indeed generally introduced via the use of chiral diamines in the salen series, is in sulfoximines present via the sulfur atom. They investigated the Diels-Alder cycloaddition between cyclopentadiene and acryloyl-2-oxazolidinones with various bis(sulfoximines) (see Scheme 42) and Cu(OTf)2 as the copper source [107]. 

The authors observed that the reaction could be run using a 1/1 mixture of bis(sulfoximine) and Cu(OTf)2, at a 10 mol % ratio to give the expected product in excellent yield and high enantioselectivity (ratio endojexo 94/6 and 83% ee for 77 and up to 93% ee for 78). The authors studied next exhaustively how the other reaction parameters do influence the selectivity. They... 

Bolm et al. [108] prepared a C2-symmetric bis (sulfoximine) as ligand for the copper-catalyzed hetero-Diels-Alder reaction. The stereogenic sulfur atom being located near the AT-coordinating atom, these structures were assumed to be promising for asymmetric catalysis. Their Hgand (79 in Scheme 43) was synthesized by palladium-catalyzed N-aryl imination from 1,2-dibromobenzene and (S)-S-methyl-S-phenylsulfoximine with Pd2dba3 in 70% yield. 

From all these results, optically active sulfoximines, with their nitrogencoordinating site located at the close proximity to the stereogenic sulfur atom, have thus proven their efficiency as copper-ligands for asymmetric Diels-Alder and hetero Diels-Alder reactions. 

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