Application of sulfonimidoyl substituted allyltitanium (IV) complexes to the asymmetric synthesis of alkenyloxiranes, 2,3-dihydrofurans, tetrahydrofurans, unsaturated proline analogues and allylic alcohols

Abstract

An asymmetric synthesis of 3-substituted unsaturated proline derivatives starting from the g,d-unsaturated a-amino acids is described in chapter 3. Amino acid derivatives were obtained through aminoalkylation of the sulfoximine substituted allyl (trisdiethylamino) titanium (IV) complexes with the N-tert-butylsulfonyl imino ester. Activation of sulfoximines through methylation, of the sulfoximine group follwed by Cl substitution, and subsequent DBU-mediated, intramolecular, nucleophilic substitution afforded the optically-pure proline derivatives in medium to high yields. An asymmetric synthesis of allylic alcohols from allylic sulfoximines and aldehydes is described in chapter 4. Lithiation and titanation of cyclic and acyclic allylic sulfoximines with ClTi(NEt2)3 and subsequent treatment with aldehydes gave, as described previously, enantio- and diastereomerically-pure, syn-configured, sulfoximine-substituted homoallylic alcohols. Treatment of these alcohols with n-BuCu resulted in a SN2¢ reaction, and delivered a enantio- and diastereomerically-pure allylic alcohols. An asymmetric synthesis of cycloalkenyl and alkenyloxiranes from allylic sulfoximines and aldehydes is described in chapter 1. Lithiation and titanation of cyclic and acyclic allylic sulfoximines with ClTi(NEt2)3 and subsequent treatment with aldehydes gave, as described previously, enantio- and diastereomerically pure, syn-configured, sulfoximine-substituted homoallylic alcohols with ClCO2CH(Cl)Me resulted in a facile substitution of the sulfoximine group by a Cl atom, with formation of the corresponding alkenyl chlorohydrins. In the case of the cycloalkenyl derivatives the substitution proceeded with high diastereoselectivities and retention of configuration, while in the case of the alkenyl derivatives, medium diastereoselectivities with invertion of configuration were observed. An asymmetric synthesis of 2,3-dihydrofurans and of unsaturated bicyclic tetrahydrofurans from allylic sulfoximines and aldehydes is described in chapter 2