Groups sulfinamide

Catalyst 41 (Fig. 29.29) is based on a sulfmyl imine, with the stereogenic center at the sulfinamide group. The best catalyst in this series, 41a, gave 94% ee in the hydrogenation of substrate 1 [54], The catalyst has low activity, with 5 mol% catalyst being required. 

Chemla and Ferreira effected lithiozincation of TMS propargyl chloride to prepare chloroal-lenylzinc bromide reagents (Table 21)33. Subsequent reaction of these reagents with N-t-butyl-substituted sulfoximines yielded the related traws-sulfoxinyl aziridines, arising from internal displacement of the chloride substituent of the anti sulfinamide adduct. A transition state in which the f-BuSO group is eclipsed with the alkynyl (vs R) substituent accounts for the preferred formation of the major A-sulfinyl diastereomer (equation 41). 

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. 

Introducing the Tau residue into a peptide according to the first approach demands protection of the amino group, usually in the form of a Z-derivative and turning the sulfonic acid into sulfonyl chloride. Synthesis of (j-su Ifonamidopeptides via an iterative process, both in solution and in the solid phase, has been described.11201 Chiral methylene sulfinamide peptides can be synthesized both in solution and in the solid phase using the sulfonyl chlorides derived from enantiomerically pure 2-substituted taurines under mild coupling conditions (DMAP catalysis and excess methyl trimethylsilyl dimethylketene acetal as a proton trap).11261... 

Cationic sulfonamides of the form (29) [obtained from dialkynes (28) upon treatment with acids or halogens] undergo stereoselective reduction of the sulfonamide group to generate a sulfinamide (31) under very mild conditions.279 Indirect 1H NMR evidence suggests that the reaction proceeds via the intermediate (30). Further reactions occur in the presence of I2, including the reduction of the sulfinamide to a sufenamide. 

The ortholithiation of benzenesulfinamides 256 is of use in the regioselective synthesis of m ta-substituted compounds 257 the sulfinamide group is used to set up two ortho... 

Asymmetric reduction of (5s)-sulfmimine 110 with diisobutylaluminum hydride (DIBAL) afforded a diastereomeric mixture of sulfinamides 111 in 92% yield and in a ratio of 96 4.34 Use of sodium boron hydride, lithium aluminum hydride, or lithium alkoxyaluminum hydride resulted in lower optical yields.33,34,75 The sul-finyl group can be removed by treating 111 with trifluoroacetic acid (TFA) and methanol to give a-phenylethyl amine (112). 

Figure 42. Structural comparison of sulfur-containing /3-peptide analogues oligomers in which the peptide bond has been replaced by sulfonamide (i.e., ft sulfonopep tides),306 sulfinamide (i.e., /3-sulfinopeptides), 307 or sulfoximine310 functional groups.

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