Sulfinimines preparation

More recently, Davis and co-workers developed a new method for the asymmetric syntheses of aziridine-2-carboxylates through the use of an aza-Darzens-type reaction between sulfinimines (N-sulfinyl imines) and a-haloenolates [62-66]. The reaction is highly efficient, affording cis- N-sulfmylaziridine-2-carboxylic esters in high yield and diastereoselectivity. This method has been used to prepare a variety of aziridines with diverse ring and nitrogen substituents. As an example, treatment of sulfinimine (Ss)-55 (Scheme 3.18) with the lithium enolate of tert-butyl bromoacetate gave aziridine 56 in 82% isolated yield [66],... 

Within the biooxidation of disulfides, chiral thiosulfinates become available. Tert-Butyl tert-butanethiosulfinate represents a particularly valuable chiral auxiliary for the preparation of several chiral sulfoxides and sulfinimines, which can be subsequently transformed into branched amine compounds, P-aminoacids, and chiral aziridines. This product is accessible readily by mediated biooxidation of tert-butyl... 

The preparation of chiral isoquinoline derivatives continued to be investigated. Sulfanamide 59 was prepared by addition of a lateral lithiated o-toluonitrile with the corresponding sulfinimine. Treatment of 59 with MeLi followed by acidification afforded cyclic imine 60. Reduction of imine 60 with liAlHi/MejAl afforded the trans-1,3 derivative, and... 

Chiral sulfinimines 236 are very useful intermediates for the preparation of enantiomer-ically pure primary amines 237 (equation 158) . This reaction has been applied to the synthesis of a-amino acids . For sulfinimines obtained from simple ketones, lithium reagents are preferable for the addition , while for cyclic ketones organomagnesium compounds gave the best results. Addition of alkyl and aryl Grignard compounds to sulfinimines, derived from 3- and 4-substituted cyclohexanones, proceeds with excellent diastereoselectivity, depending on the stereochemistry of the ring substituents rather than the sulfinyl group . 

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. 

Unusual -branched Baylis-Hillman adducts have been prepared by Li and coworkers by a novel Et2AlCl promoted domino Michael-aldol reaction of propynoates 50 with organo-cuprates and chiral p-toluenesulfinimines 52 (Scheme 10) [42], These condensations proceeded with very good diastereoselectivity to give allylic amines 53. The selectivity can be explained through the chairlike transition state 54. The anion intermediate approaches the sulfinimine from the sterically less hindered side of the lone pair of electrons. The nucleo-... 

The presence of a coordinating group in the sulfinimine may strongly influence the selectivity of the reaction with Grignard derivatives. In the case of 2-pyridyl ftrt-butylsulfinimines, the diastereoselectivity of the addition is reversed due to the coordination with the pyridine nitrogen. " Attempts have been made to prepare sulfinyl chiral... 

Chemoselective oxidation of sulfenimines 2 is a useful method for the preparation of sulfinimines 3.10-12 The oxidation was usually carried out with m-CPBA (3-chlo-roperbenzoic acid) in a biphasic mixture of chloroform and aqueous sodium bicarbonate and a variety of sulfinimines have been prepared in this way. Sulfinimines 3 were usually obtained as a single -isomer despite the fact that their precursors 2 may exist as mixtures of E- and Z-isomers.10 Other oxidants which have been demonstrated to be effective for oxidation include MMPP (magnesium monoperoxyphthalate)13 and chlorine.14,15... 

Optically active sulfinimines were prepared by Yang and co-workers by oxidation of nonracemic sulfenimines.20 Thus, treatment of 11 with m-CPBA or MMPP afforded sulfinimines 12 in 83-99% yield. The diastereoselectivity, however, was highly dependent on the R group in the chiral auxiliary. When R = H, diastereopure sulfinimine (/ s)-12 was obtained. 

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. 

Enantiopure sulfinimines 43 were prepared for the first time by Cinquini and co-workers from the commercially available Andersen reagent, (lR,2S,5R)-(-)-menthyl (S)-p-toluenesulfinate (40) or (lS,2/ ,5S)-(+)-menthyl (R)-p-toluenesulfi-... 

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... 

R = alkyl) were obtained in more moderate yields (60-65%). Bis-sulfinimines 49 can be prepared in a similar way from isophthalaldehyde (48).37... 

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... 

Bravo et al. treated (Ss)-(+)-p-toluenesulfinamide (63), prepared by hydrolysis of 44,23 with triphenylphosphine in the presence of DEAD to give the N-sulfinyl iminophosphorane 64 in 92% yield.45 The Staudinger, aza-Wittig reaction of 64 with methyl or ethyl trifluoropyruvate afforded the unstable sulfinimine 65. Attempts to purify the imino sulfinimines by flash chromatography resulted in hydrolysis. 

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. 

A variety of heterocyclic sulfinimines 85 have been prepared by a [4+2] cycloaddition of alkenes 83 with N-sulfinylurethanes (84, R = Me, Et).53-59 The reaction was found to proceed with the retention of the configuration of the alkene. Alkynes 86 react with 84 in a similar manner.60,61... 

Etiolates. Asymmetric addition of enolates to enantiopure sulfinimines is an important method for the preparation of P-amino esters.21,84,85 For example, treatment of (Ss)-sulfinimine 47 with the sodium enolate of methyl acetate in ether afforded P-amino ester 149 in 84-85% yield and in >98% de.86,87 After removal of the N-sulfinyl group, P-amino esters 150 were obtained in >90% yield.84 The P-amino esters were further elaborated into the Taxol C-13 side chain 151a,21 its fluoro analogue 151b,85 (+)-2-phenylpiperidine (152a), and (+)-dihydropinidine (152b).87... 

Enantiopure bis-P-amino acids can be prepared from chiral bis-sulfinimines.37 Bis-sulfinimine (Ss,Ss)-160 and the sodium enolate of methyl acetate react to give 161 as a diastereomeric mixture. The major isomer (5s,/ ,Ss,/ )-161 can be isolated by preparative reverse-phase HPLC in 46% yield. Hydrolysis of (Ss,/ ,Ss,/ )-161 gave bis-P-amino ester (/ ,/ )-162 in >97% ee and 86% yield.37... 

The availability of f j-di-r-butyl disulfide monoxide from selective oxidation catalyzed by vanadyl-88 enables the preparation of chiral r-butyl sulfinamides, sulfoxides, and sulfinimines. Very similar reaction conditions bring about the transformation of various 1,3-dithianes to chiral monoxides. (/ ,Rl-2,2,5,5-Tetramethyl-3,4-hexanediol is a chiral ligand for the Ti(IV)-catalyzed oxidation of sulfides with cumene hydroperoxide. ... 

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]. 

An efficient asymmetric synthesis of P-aminoalkylphosphonates 212 via addition of phosphonate carbanions to enantiopure sulfinimines has been reported (Scheme 25). A range of novel 3-phosphonocyclobutyl amino acids have been prepared via the versatile intermediate 3-oxocyclobutylphosphonate (213) (Scheme 26). Sphingosine-1-phosphonate (215) has been synthesised from the 2-A,3-0-protected 1-0-mesyl derivative 214 of sphingosine via conversion to the bromide and an Arbuzov reaction with trimethyl phosphite.Chain extension of 215 provided a route to homo-sphingosine-1-phosphonate (216). 

---