Stereofacial Control in Asymmetric Cyanosilylation of Aldehydes Catalyzed by NovelS-Proline-Derived Titanium Complexes

Abstract

Asymmetric cyanosilylation of aryl aldehydes has been achieved utilizing catalytic amounts of novel chiral ligands. Chiral ligands of amino alcohols and aminophosphine gave S-configured cyanosilylated products with up to 84% ee. In contrast, C 2 -symmetric ligands resulted in R-configured products with up to 95% ee.Optically active cyanohydrins are synthetically important intermediates as they may be elaborated to give a number of valuable intermediates, including a-hydroxyacids, 1 ahydroxyketones, 2 primary and secondary b-hydroxy amines, 3,4 a-aminonitriles, 5 a-hydroxyesters, 6 a-sulfonyloxynitriles, 7 a-fluoronitriles, 8 3-amino-2-trimethylsilyloxy-2-alkenoates, 9 2,3-substituted piperidines, 10 and azacycloalkan-3-ols. 11 Thus, the asymmetric cyanosilylation of aldehydes remains an important goal in organic chemistry. Intensive studies on the enantioselective cyanation of aldehydes using chiral ligands have been reported. 12 However, there are few reports about chiral ligands derived from S-proline and S-indoline amino acids. Recently, Corey's group 13 reported that cationic oxazaborolidinium with O=PPh 3 as an additive gave cyanohydrins with high enantiomeric excess. Chiral oxazaborolidinium salt acted as a Lewis acid and O=PPh 3 acted as a Lewis base. Shibasaki's group 14 also reported bifunctional catalysis in cyanosilylation. In order to understand the mechanism of asymmetric cyanosilylation regarding the structural relationships of the chiral ligands and the activity of additives novel chiral ligands have been designed and synthesized from S-proline (Figure 1). Their catalytic activities in enantioselective cyanosilylation have been examined. We wish to report the results on the asymmetric cyanosilylation of aldehydes catalyzed by Ti(IV)-chiral ligand complexes.The synthesis of 1-5 followed the general method -coupling of S-proline with chiral amino alcohols or amino phosphine. In the case of 6 and 7, the synthetic method is described in the literature. 15,16 Firstly, the catalytic activity of different metals was examined with 6 for the catalytic cyanosilylation of benzaldehyde at -20°C with two equivalents of trimethylsilyl cyanide (TMSCN), in the presence of two equivalents of O=PPh 3 . The results are summarized in Table 1. Ti(OiPr) 4 gave more promising enantioselectivity (87% ee) than other Lewis acids (Table 1, entry 1). Therefore, Ti(Oi-Pr) 4 was employed in testing a range of ligands. Figure 1 Chiral ligands used for asymmetric inductionUnder the same reaction conditions, the asymmetric cyanosilylation was studied with ligands possessing different symmetry; 1-4 (amino alcohols), 5 (amino phosphine), and 6-7 (C 2 -symmetric). The results indicated that the enantioselectivity of the reaction and configuration of the cyanohydrins were influenced by the structures and symmetry of the ligands.In order to compare their stereoselectivity, the results are shown in Table 2. The reactions catalyzed by the Ti(IV) complex of 1-3 gave lower enantioselectivities (34-67% ee) than that of complex 4 and 5, prob...

Chiral Tertiary Diamines in Asymmetric Synthesis

“…The reaction conditions were carefully studied, and the adduct was obtained in up to 86% ee. Shortly after, Kim et al reported the use of 461 and 462 . In contrast to Trost's conditions, they obtained the best result with Ti(O i- Pr) 4 as the Lewis acid.…”