Alkyl sulfoximines

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]. 

Later, this reaction sequence was further optimized [42], and also shown to be useful for the synthesis of other N-alkylated sulfoximines, including those (such as 57) prepared from amino acids (Scheme 2.1.1.16). 

An intramolecular redox C-H activation process of alkenyl sulfoximines has been reported. The process is proposed to proceed through a 6-endo-trig hydride transfer to produce a zwitterionic intermediate (Scheme 47). This intermediate can cyclize to novel heterocycles, produce N-H alkyl sulfoximines, or form novel and chiral A-dienyl 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. 

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... 

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>. 

Sulfoxides 8 are resolved by 1 only if they have rather short alkyl chains (8d and 8e), whereas for those with longer alkyl moieties, the binaphthol 7 is the better guest. In general, 7 is very suitable for the resolution of sulfoxides and sulfoximines (10a and 10b). 

V-Methyl-5-phenyl-S -(4-methylphenylsulfinylmethyl)sulfoximine (1), prepared in optically active form from ( (-menthyl (5)-4-methylbenzenesulfinate or ( + )-menthyl (/ )-4-methylben-zenesulfinate and metalated ( -)-(S)-,V,.S -dimethyl-.S-phenylsulfoximine by an Andersen-type reaction84, was alkylated under phase-transfer in a stereoselective manner. 

Furthermore, the sulfoximine is alkylated stereospecifically in all cases, suggesting that in this diastereotner the two sulfur moieties work together to provide double asymmetric induction. 

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]. 

As an extension of these studies on the use of sulfoximines in asymmetric reductions, BlNOL-derived phosphino sulfoximines of the 105 type were tested in both rhodium-catalyzed hydrogenations (yielding optically active diesters 104 or amino acid derivatives Scheme 2.1.1.35) and palladium-catalyzed allylic alkylations (not shown) in collaboration with Reetz and Gais [81, 82]. Here, enantioselectivities of up to >99 and 66% ee, respectively, were achieved. 

TABLE 12. Nucleophilic epoxidation of vinyl sulfoximines with alkali alkyl peroxides [diastereomeric ratios are given in brackets the yields of the two diastereomers are shown]... 

Fu reported the enantioselective addition of diphenylzinc to ketones catalyzed by chiral amino alcohol 6, and observed a slight asymmetric amplification [13]. Bolm also reported asymmetric amplification in enantioselective alkylations using diethylzinc promoted by a chiral 2-pyridyl alkanol 7 and (1-hydroxy sulfoximine 8 (Scheme 9.6) [14,15]. 

T2 resin synthesis of substituted amines, amides(peptides), (thio)urcas, hydrazines, alcohols, esters guanidines alkyl halides, sulfoximines. ... 

Resolution of sulfoximines.1 Alkyl aryl sulfoximines (2) can be resolved by complex formation with ( + )- or (-)-l (equation I). 

An alternative method for preparing sulfoximines is from the imination of sulfoxides with hydrazoic acid15 (prepared in situ from sodium azide and sulfuric acid in chloroform) or O-mesitylsulfonylhydroxylamine (MSH CAUTION potentially explosive)16,17 to afford A-unsubstituted sulfoximines. The former method, however, is not suitable for sulfoximines in which one or more 5-alkyl substituents... 

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