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Highly Selective Addition of Chiral, Sulfonimidoyl Substituted Bis(allyl)titanium Complexes to N-Sulfonyl α-Imino Esters:  Asymmetric Synthesis of γ,δ-Unsaturated α-Amino Acids Bearing a Chiral, Electron-Withdrawing Nucleofuge at the δ-Position

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journal contribution
posted on 07.06.2002, 00:00 by Marcel Schleusner, Hans-Joachim Gais, Stefan Koep, Gerhard Raabe
Selective addition of the chiral, sulfonimidoyl substituted bis(allyl)titanium complexes 5ad, which are configurationally labile in regard to the Cα-atoms, to N-toluenesulfonyl (Ts)-, N-2-trimethylsilylethanesulfonyl (SES)-, and N-tert-butylsulfonyl (Bus) α-imino ester (9ac) in the presence of Ti(OiPr)4 and ClTi(OiPr)3 afforded with high regio- and diastereoselectivities in good yields the (syn, E)-configured β-alkyl-γ,δ-unsaturated α-amino acid derivatives 2ag, which carry a chiral, electron-withdrawing nucleofuge at the δ-position and a cyclohexyl, an isopropyl, a phenyl, and a methyl group at the β-position. Addition of the cyclic bis(allyl)titanium complex 14 to N-Bus α-imino ester 9c afforded with similar high regio- and diastereoselectivities the (E)- and (Z)-configured amino acid derivatives (E)-8 and (Z)-8. Reaction of complexes 5ad with α-imino esters 9ac in the presence of Ti(OiPr)4 occurs stepwise to give first the mono(allyl)titanium complexes containing 2ag as ligands, which react in the presence of ClTi(OiPr)3 with a second molecule of 9ac with formation of two molecules of 2ag. Formation of (S,R,E)-configured homoallylic amines 2ag entails Si,Re,E processes of α-imino esters 9ac with the (R,R)-configured bis(allyl)titanium complexes (R,R)-5ad and (R)-configured mono(allyl)titanium complexes (R)-17a-d, both of which are most likely in rapid equilibrium with their (S,S)-diastereomers and (S)-diastereomers, respectively. Interestingly, in the reaction of 5ad with aldehydes, the (S,S)-configured complexes (S,S)-5ad are the ones which react faster. Reaction of the N-titanated amino acid derivatives Ti-2a and Ti-2b with N-Ts α-imino ester 9a led to the highly diastereoselective formation of imidazolidinones 15a and 15b, respectively. Cleavage of the sulfonamide group of the N-Bus amino acid derivative 2d with CF3SO3H gave quantitatively the sulfonimidoyl functionalized amino acid H-2d. A Ni-catalyzed cross-coupling reaction of the amino acid derivative 2e with ZnPh2 led to a substitution of the sulfonimidoyl group by a phenyl group and furnished the enantiomerically pure protected α-amino acid Bus-1. Two new N-sulfonyl α-imino esters, the SES and the Bus α-imino esters 9b and 9c, respectively, have been synthesized from the corresponding sulfonamides by the Kresze method in medium to good yields. The N-SES α-imino ester 9b and the N-Bus α-imino ester 9c should find many synthetic applications, in particular, in cases where the N-Ts α-imino ester 9a had been used before.