283594-71-8Relevant articles and documents
Asymmetric synthesis of protected β-substituted and β,β-disubstituted β-amino acids bearing branched hydroxyalkyl side chains and of protected 1,3-amino alcohols with three contiguous stereogenic centers from allylic sulfoximines and aldehydes
Gais, Hans-Joachim,Loo, Ralf,Roder, Daniel,Das, Parthasarathi,Raabe, Gerhard
, p. 1500 - 1526 (2007/10/03)
We describe a new method for the asymmetric synthesis, from allylic sulfoximines and aldehydes, of N,O-protected, cyclic and acyclic, β-substituted and β,β-disubstituted δ-hydroxy-β-amino acids and of N,O-protected 1,3-amino alcohols, both possessing three contiguous stereogenic centers. Treatment of enantiomerically pure, acyclic allylic sulfoximines with aldehydes after successive lithiation and titanation afforded sulfonimidoyl-substituted homoallylic alcohols with high regio- and diastereoselectivities. Diastereomerically pure, cyclic, sulfonimidoyl-substituted homoallylic alcohols were synthesized in a similar manner from the corresponding enantiomerically pure, cyclic allylic sulfoximines and isobutyraldehyde. A highly diastereoselective amination of the sulfonimidoyl-substituted homoallylic alcohols with the generation of secondary and tertiary C atoms and formation of the sulfonimidoyl-substituted, protected 1,3-amino alcohols (oxazinones) was achieved by the carbamate method, through cyclization of the corresponding carbamates after their lithiation with nBuLi. The sulfonimidoyl-substituted, monocyclic and bicyclic oxazinones were converted into protected, acyclic and cyclic, β-substituted and β,β-disubstituted β-amino acids and protected 1,3-amino alcohols by two different routes: the carbanion route and the substitution route. The carbanion route involves: (1) a double lithiation of the protected β-amino sulfoximines, (2) treatment of the dilithiated sulfoximines with electrophiles, and (3) reductive removal of the sulfonimidoyl group. By the carbanion route, double lithiation of the sulfonimidoyl-substituted oxazinones with nBuLi gave the corresponding dilithium salts, which reacted readily with a number of electrophiles to give the corresponding α-substituted sulfoximines in good yields. Reduction of the sulfoximines with Raney nickel afforded the corresponding protected monocyclic and bicyclic 1,3-amino alcohols and the protected acyclic and cyclic β-amino acids in good yields. The substitution route involves: (1) a facile substitution of the sulfonimidoyl group by a Cl atom, and (2) a substitution of the Cl atom of the protected β-amino chlorides by a cyano group. Treatment of the sulfoximines with ClCO2Me readily afforded the corresponding β-amino chlorides in good yields, and so treatment of alkyl sulfoximines with chloroformates seems to be a general method for the replacement of an N-methylsulfonimidoyl group by a Cl atom. Introduction of a cyano group was achieved through treatment of chlorides with NaCN, which gave the corresponding β-amino nitriles in good yields. Finally, hydrolysis of the nitriles afforded the protected acyclic and cyclic, β-substituted and β,β-disubstituted β-amino acids. Treatment of the protected β-amino sulfoximines with ClCO2Me gave - besides the corresponding chlorides - methyl (S)-N-phenyl-sulfinylcarbamate with ≥ 99% ee in good yield. Treatment of the sulfinamide with MeMgCl afforded (S)-methyl phenyl sulfoxide with 97% ee, and this could be converted with complete retention of configuration into (S)-N,S-dimethyl-S-phenylsulfoximine, the starting material for the synthesis of the allylic sulfoximines used in this work. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
