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

Selective addition of the chiral, sulfonimidoyl substituted bis(allyl)titanium complexes <b>5a</b>−<b>d</b>, which are configurationally labile in regard to the Cα-atoms, to <i>N</i>-toluenesulfonyl (Ts)-, <i>N</i>-2-trimethylsilylethanesulfonyl (SES)-, and <i>N</i>-<i>tert</i>-butylsulfonyl (Bus) α-imino ester (<b>9a</b>−<b>c</b>) in the presence of Ti(O<i>i</i>Pr)<sub>4</sub> and ClTi(O<i>i</i>Pr)<sub>3</sub> afforded with high regio- and diastereoselectivities in good yields the (<i>syn</i>, <i>E</i>)-configured β-alkyl-γ,δ-unsaturated α-amino acid derivatives <b>2a</b>−<b>g</b>, 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 <b>14</b> to <i>N</i>-Bus α-imino ester <b>9c</b> afforded with similar high regio- and diastereoselectivities the (<i>E</i>)- and (<i>Z</i>)-configured amino acid derivatives (<i>E</i>)-<b>8</b> and (<i>Z</i>)-<b>8</b>. Reaction of complexes <b>5a</b>−<b>d</b> with α-imino esters <b>9a</b>−<b>c</b> in the presence of Ti(O<i>i</i>Pr)<sub>4</sub> occurs stepwise to give first the mono(allyl)titanium complexes containing <b>2a</b>−<b>g</b> as ligands, which react in the presence of ClTi(O<i>i</i>Pr)<sub>3</sub> with a second molecule of <b>9a</b>−<b>c</b> with formation of two molecules of <b>2a</b>−<b>g</b>. Formation of (<i>S</i>,<i>R</i>,<i>E</i>)-configured homoallylic amines <b>2a</b>−<b>g</b> entails <i>Si</i>,<i>Re</i>,<i>E</i> processes of α-imino esters <b>9a</b>−<b>c</b> with the (<i>R</i>,<i>R</i>)-configured bis(allyl)titanium complexes (<i>R</i>,<i>R</i>)-<b>5a</b>−<b>d</b> and (<i>R</i>)-configured mono(allyl)titanium complexes (<i>R</i>)-<b>17a</b>-<b>d</b>, both of which are most likely in rapid equilibrium with their (<i>S</i>,<i>S</i>)-diastereomers and (<i>S</i>)-diastereomers, respectively. Interestingly, in the reaction of <b>5a</b>−<b>d</b> with aldehydes, the (<i>S</i>,<i>S</i>)-configured complexes (<i>S</i>,<i>S</i>)-<b>5a</b>−<b>d</b> are the ones which react faster. Reaction of the N-titanated amino acid derivatives Ti-<b>2a</b> and Ti-<b>2b</b> with <i>N</i>-Ts α-imino ester <b>9a</b> led to the highly diastereoselective formation of imidazolidinones <b>15a</b> and <b>15b</b>, respectively. Cleavage of the sulfonamide group of the <i>N</i>-Bus amino acid derivative <b>2d</b> with CF<sub>3</sub>SO<sub>3</sub>H gave quantitatively the sulfonimidoyl functionalized amino acid H-<b>2d</b>. A Ni-catalyzed cross-coupling reaction of the amino acid derivative <b>2e</b> with ZnPh<sub>2</sub> led to a substitution of the sulfonimidoyl group by a phenyl group and furnished the enantiomerically pure protected α-amino acid Bus-<b>1</b>. Two new <i>N</i>-sulfonyl α-imino esters, the SES and the Bus α-imino esters <b>9b</b> and <b>9c</b>, respectively, have been synthesized from the corresponding sulfonamides by the Kresze method in medium to good yields. The <i>N</i>-SES α-imino ester <b>9b </b>and the <i>N</i>-Bus α-imino ester <b>9c</b> should find many synthetic applications, in particular, in cases where the <i>N</i>-Ts α-imino ester <b>9a</b> had been used before.