S-chiral sulfinamides

Subtilisin E was found to efficiently catalyse enantioselective hydrolysis of certain A-acyl arenesulfinamides 34 to arenesulfinamides 35. Noteworthy, among 

However, when subtilisin E was replaced by subtilisin Carlsberg, the hydrolysis of the S-N bond in some A(-acyl arenesulfinamides 34 unexpectedly became the main hydrolytic process giving under the kinetic resolution conditions, in addition to the unreacted substrates, the corresponding sulfinic acids and 

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Synthesis of Sulfinamides. The nucleophilic substitution of chiral enantiopure sulfinate esters with NaHMDS led to S-O bond breakage with inversion of configuration at the S atom, giving quantitative conversion to chiral sulfinamides (eq 10). Lithium amide in liquid ammonia at —78°C could be also used, although in some cases such as in the synthesis of (/ )-(+)-p-toluenesulfinamide higher ee s were observed when using NaHMDS. ... 

Two formal syntheses of unnatural 5-ep/-cermizine C (1160) are included for completeness (Scheme 149). Following Snider s procedure for the transformation of racemic pelletierine into ( )-5- -cermizine, ° Bosque et al. converted their chiral sulfinamide (- -)-1183 (cf Scheme 148) into (—)-pelletierine (1184), condensation of which with Meldrum s acid yielded the unconjugated bicyclic lactam (—)-1185. DiastereofaciaUy selective hydrogenation then afforded the saturated quinoHzidinone (—)-1186 (dr 13 1), which was converted in by-now famihar steps into the trifluoroacetate salt of (- -)-5- i-cermizine C. The approach of Chou et al. also converged with Snider s route when their racemic vinyl sulfide intermediate ( )-1107, previously used in the synthesis of (ih)-epimyrtine (rac-1098) (c Scheme 139 Section 4.7) was converted into (ib)-1187 upon treatment with excess methyUithium. ... 

Double asymmetric induction operates when the azomethine compound is derived from a chiral a-amino aldehyde and a chiral amine, e.g., the sulfin-imine 144 [70]. In this case, the R configuration at the sulfur of the chiral auxihary, N-tert-butanesulfinamide, matched with the S configuration of the starting a-amino aldehyde, allowing complete stereocontrol to be achieved in the preparation of the diamine derivatives 145 by the addition of trifluo-romethyl anion, which was formed from trifluoromethyltrimethylsilane in the presence of tetramethylammonium fluoride (Scheme 23). The substituents at both nitrogen atoms were easily removed by routine procedures see, for example, the preparation of the free diamine 146. On the other hand, a lower diastereoselectivity (dr 80 20) was observed in one reaction carried out on the imine derived from (it)-aldehyde and (it)-sulfinamide. 

By modification of the elegant method of preparation of optically active sulfinates previously reported by Mikolajczyk and coworkers , an efficient stereospecific method for the conversion of readily available optically active sulfinamides to optically active sulfinates of inverted configuration at the sulfinyl function, has been recently reported by Hiroi and coworkers . The same authors subsequently reported the thermal rearrangement of several optically active cis- and trans-y-substituted allylic p-toluenesulfinates to optically active chiral sulfones with high stereoselectivity. For example, trans and cis (S)-( — )-crotyl p-toluenesulfinates rearranged to optically active (S)-(-l-)- and (R)-( — )-a-methylallyl p-tolyl sulfone, respectively (equation 19). 

In the Sepracor synthesis of chiral cetirizine di hydrochloride (4), the linear side-chain as bromide 51 was assembled via rhodium octanoate-mediated ether formation from 2-bromoethanol and ethyl diazoacetate (Scheme 8). Condensation of 4-chlorobenzaldehyde with chiral auxiliary (/f)-f-butyl sulfinamide (52) in the presence of Lewis acid, tetraethoxytitanium led to (/f)-sulfinimine 53. Addition of phenyl magnesium bromide to 53 gave nse to a 91 9 mixture of two diastereomers where the major diasteromer 54 was isolated in greater than 65% yield. Mild hydrolysis conditions were applied to remove the chiral auxiliary by exposing 54 to 2 N HCl in methanol to provide (S)-amine 55. Bisalkylation of (S)-amine 55 with dichlonde 56 was followed by subsequent hydrolysis to remove the tosyl amine protecting group to afford (S)-43. Alkylation of (5)-piperizine 43 with bromide 51 produced (S)-cetirizine ethyl ester, which was then hydrolyzed to deliver (S)-cetirizine dihydrochloride, (5)-4. 

In the case of the oxidation of methyl alkyl sulfides, enantioselectivity remains in the range of 50-60% ee (Table 6C.2). Disufides R-S-S-R, sulfenamides R-S-NR 2, and sulfenates R-S-O-R were oxidized to the corresponding chiral thiosulfinates, sulfinamides, and sulfinates, respectively (<52% ee, Table 6C.3) [21]. 

Chiral N-benzylidene-p-toluenesulfinamides p- and y-amino acids.1 Reaction of benzonitrile with CH3Li and then with (S)-l at 0° provides sulfinamide 2,... 

Around the time of Solladie s initial work on 3-ketosulfoxide reduction, Cinquini reported an enantioselective route to chiral amines by reduction of non-racemic N-alkylidene sulfinamides [36]. The A-alkylidene sulfinamide substrates were readily prepared in one pot by addition of alkyl or aryl Grignard reagents to a nonenolizable aromatic nitrile to yield an imino-Grignard intermediate which was allowed to react with (5 )-(-)-menthyl p-toluene sulfinate (Scheme 4.25). The resulting A-alkylidene sulfinamides were found to be enantiomerically pure and of (S) configuration. 

In 2014, Guan and co-workers reported the direct synthesis of a-chiral tert-butanesulfinylamines from the reaction of racemic alcohols and Ellman s sulfinamide catalyzed by ruthenium (II) pincer catalyst 23 (Eq. 54) [176], providing an effective method for the synthesis of chiral amine derivatives. 

Synthesis of Sulfinamides. The nucleophilic substitution of (l/ ,25, 5/J)-(—)-menthyl (5)-p-toluenesulfinate with LHMDS leads to the synthesis of (S)-(+)-p-toluenesulfinamidem72% yield with complete stereochemical inversion (eq 18). S)- +)-p-Toluenesulfinamide is a versatile intermediate for the preparation of various chiral sulfinimines that are used for the synthesis of chiral amine derivatives via diastereoselective addition of nucleophiles. ... 

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