Aldehydes sulfinimines

Addition of phosphates to chiral sulfinimines derived from aromatic aldehydes has been used to prepare a-amino phosphonate esters asymmetrically.35 The sulfinimines employed, p- Me Ph S (= O) N=C H A r. have sufficiently bulky substituents to prevent inversion, as shown by 1H-NMR over a wide range of temperatures. 

Diastereoselective Mannich-type reactions between ketene silyl acetals and chiral sulfinimines using simple metal-free Lewis bases such as tetraalkylammonium car-boxylates have been reported. The sulfinimine can even be generated in situ (from aldehyde and a chiral sulfonamide), using cesium carbonate, followed by addition of ketene silyl acetal at -78 °C, and as little as 1 mol% of catalyst.32... 

Sulfinyl sultam 82 was also used in the synthesis of enantiopure sulfinimines 85, useful precursors in the synthesis of enantiomerically pure amine, as well as a- and P-aminoacid derivatives.109 Interestingly, the addition of one equivalent of water to the sulfinylated HMDS 84 prior to the addition of the aldehyde was necessary to convert enolizable aldehyde into enantiomerically pure sulfinimines 85, which cannot be obtained by the Davis procedure. Thus, both enolizable and noneno-lizable aldehydes can afford enantiomerically pure aryl and alkyl sulfinimine 85 in good yield (Scheme 26). 

With LiHMDS sulfinyl chloride 37 gave N,N-bis(trimethylsilyl) sulfinamide 38 in situ. Subsequent addition of an aldehyde and CsF affords sulfinimines 39 in good yield.32 This one-pot procedure is suitable for the preparation of both alkylidene and arylidene sulfinamides. 

A method that makes available aromatic and aliphatic aldehyde derived sulfin-imines 47, for the first time, was recently introduced by Davis and co-workers.23,36 This one-pot procedure entails treatment of the Andersen reagent 40 with LiHMDS to generate 44 which subsequently reacts with the lithium methoxide by-product to produce silyl sulfinamide anion 46. Reaction of 46 with the aldehyde in a Peterson-type olefination reaction affords the sulfinimine 47 in >96% ee. This method was highly effective for the preparation of arylidene sulfmamides 47 (R = aryl) which were usually obtained in 60-76% yield although the alkyl counterparts... 

In a variation of this method, Garcia Ruano and workers prepared 5-alkyl sulfinimines from the diacetone-D-glucose derived sulfinate 50.38 Subsequent treatment with LiHMDS, aldehyde, and CsF afforded S-te/t-butyl sulfinimines 51 in enantiomerically pure form.38... 

In a similar manner, camphorsultam-derived (Rs)-57 reacts with LiHMDS in THF to give (Ss)-44 which reacts with aldehydes in the usual way to give (Ss)-47 in 65-84% yields and 98- > 99.5% ee 43 Interestingly, better yields of enolizable sulfinimines were obtained only if 1 equiv of water was present. 

A particularly effective method for the asymmetric synthesis of both aldehyde-and ketone-derived sulfinimines recently introduced by Davis and co-workers is the condensation of (5)-(+)-p-toluenesulfinamide (63) with aldehydes and ketones using activated 4-A molecular sieves or titanium ethoxide [Ti(OEt)4].46 This procedure avoids the problem of removing the menthol by-product of the one-pot procedure (see Section II.D) which is sometimes problematic.23 Importantly, this methodology affords ketone derived sulfinimines 66 which are difficult to prepare by other means. 

In a similar way, (/ )-fert-butanesulfinamide (67) reacts with aldehydes in methylene chloride in the presence of magnesium sulfate to give sulfinimines (/ s)-68 in 90-96% yields.47 With Ti(OEt)4 the reaction has recently been extended to ketones.47b... 

Substituted 2-oxazolidones 165 are useful chiral auxiliaries for diastereoselective functionalization at the a-carbon of their amide carbonyl group. The a-fluoroaldehydes 166 were prepared by a series of reactions electrophilic fluorination of the corresponding oxazolidinone sodium enolates with AMluorobenzenesulfonimine reductive removal of the auxiliary with LiBH4 and Dess-Martin oxidation. The aldehydes are so unstable for isolation that they are converted with (R)-/ -toluenesulfinamide to /7-toluenesul(inimines 167, which are isol-able and satisfactorily enantio-enriched. Chiral sulfinimine-mediated diastereoselective Strecker cyanation with aluminum cyanide provided cyanides 168 in excellent diastereose-lectivity, which were finally derived to 3-fluoroamino acids 169 (see Scheme 9.37) [63]. 

One of the most effective ways of preparing enantiomerically pure secondary amines is the addition of organometallic reagents to chiral sulfinimines, which are prepared by the condensation of an aldehyde (or ketone) with a sulfinamide. The preparation of 1-butyl sulfinamide had been problematic, but the synthesis (and supplies) now seems to be more reliable. 

The aza Diels-Alder reactions of a, ff-unsaturated sulfinimines (140) represent a very efficient approach to enantiopure dihydro- and tetrahydropyridines (141) (Scheme 8.34, Table 8.11) for a reasonable reaction rate the 1-aza-l,3-butadiene moiety 140 must carry an electron-withdrawing group at the 3-position [65]. The compounds are accessible in only three steps starting from commercially available substrates. Thus, the enantiopure 1-aza-l,3-butadiene can be prepared from the enantiopure menthyl sulfinate with lithium hexamethyldisilazide followed by addition of acetic acid and an a, -unsaturated aldehyde. The cycloadditions of sulfinimines such as 140 run under mild conditions with high yields and excellent endo-selectivity in most cases when high pressure is applied. In these reactions two endo and two exo transition structures namely syn and anti to the sulfoxide moiety should be discussed. The cycloaddition of 140 and t-butyl vinyl ether was performed under various pressures ranging from 0.2 to 1.2 GPa. 

Cyclomarin A 98 exhibits cytotoxicity towards cancer cells and has antiinflammatory activity. It is a cyclopeptide isolated from an actinomycete and has attracted the attention of synthetic chemists due to the number of non-natural amino acids present in this structure. The (2S,4R)-D-hydroxyleucine 103 contained within the target has been prepared by using the Davis chiral auxiliary vide supra) Condensation of an enantiopure /7-toluenesulfinamide 100 with aldehyde 99 afforded sulfinimine 101. 

Bromohydrins from epoxy sulfoximines. Chiral epoxides available from the unsaturated sulfoximines may be used as precursors of bromohydrins. Ring opening via the magnesium chelates affords a-bromoaldehydes, as a result of sulfinimine elimination. In the presence of BU4NBH4 the aldehydes are immediately reduced without much racemization. 

Addition of diethyl lithiodifluoromethylphosphonate to enantiomerically pure aromatic, heteroaromatic and aliphatic aldehyde-derived sulfinimines afforded diastereomerically pure N-sulfinyl oc,a-difluoro-P-aminophosphonates (200) which were used to prepare a,a-difluoro-P-aminophosphonic adds (201) and the sodium salt of difluorophosphonamidic acid (7 )-(202) (Scheme 73). ... 

Cyclic (hetero- and carbocyclic) vinyl sulfoxides have been prepared by a tandem Michael addition/Homer olefination reaction of a-phosphorylvinyl sulfoxides and carbonyl compounds bearing a nucleophilic center. Using optically active a-phosphorylvinyl sulfoxides a series of enantiomeric cyclic vinyl sulfoxides in which the chiral sulfinyl group is bonded to a chromene, pyrrazolyne, quinoline or cyclopen-tene ring, has been obtained. The H-W-E reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates (228) represents a new method for the asymmetric synthesis of ring-functionalized cw-2,5-disubstituted 3-oxo pyrrolidines (229) (Scheme 90). ... 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

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