Sulfinimine-mediated

Davis and Fanelli applied the sulfinimine mediated asymmetric Strecker synthesis to the enantioselective synthesis of the racemization-prone (/ )-(4-methoxy-3,5-dihydroxyphenyl)glycine (134) from 133.81 This amino acid is the central amino acid of the clinically important glycopeptide antibiotic vancomycin as well as related antibiotics. 

The sulfinimine-mediated asymmetric Strecker reaction was developed by F.A. Davis et al. This method involves the addition of ethylaluminumcyanoisopropoxide to functionalized sulfinimines and the resulting diastereomeric a-amino nitriles are easily separated. Subsequent hydrolysis directly affords the enantiopure a-amino acids. This protocol was applied for the synthesis of polyoxamic acid lactone. ... 

Davis, F. A., Prasad, K. R., Carroll, P. J. Asymmetric Synthesis of Polyhydroxy a-Amino Acids with the Sulfinimine-Mediated Asymmetric Strecker Reaction 2-Amino 2-Deoxy L-Xylono-1,5-lactone (Polyoxamic Acid Lactone). J. Org. Chem. 2002, 67, 7802-7806. 

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]. 

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... 

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. 

Finally, in 2006, Ellman reported a single example of a sulfinimine-alkene coupling mediated by Sml2 in their work on the total synthesis of the anticancer agent, tubulysin D. It was found that the coupling of enantiomerically pure sulfinimine 67 with methyl methacrylate was effectively promoted by the... 

Examples of the oxaziridine mediated amination of thiols are rare (Scheme 12). 4-Nitro-benzenethiol, for example reacts with spirooxaziridine (51) to give sulfinimine (57) <79JA667i>, while benzenethiol on treatment with m-2-methyl-3-phenyloxaziridine (56) gives sulfenamide (58) <81JOC610>. 

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