Anti-selective direct catalytic asymmetric aldol reaction of thiolactams.

An anti-selective direct catalytic asymmetric aldol reaction of thiolactam is described. A soft Lewis acid/hard Brønsted base cooperative catalyst comprised of mesitylcopper/(R,R)-Ph-BPE exhibited high catalytic performance to produce an anti-aldol product with high stereoselectivity. The highly chemoselective nature of the present catalysis allows for the use of enolizable aldehydes as aldol acceptors.

Concise enantioselective synthesis of duloxetine via direct catalytic asymmetric aldol reaction of thioamide.

Direct catalytic asymmetric aldol reaction of thioamide offers a new entry to the concise enantioselective synthesis of duloxetine. The direct aldol protocol was scalable (>20 g) to afford the aldol product in 92% ee after LiAlH(4) reduction, and 84% of the chiral ligand was recovered after recrystallization. The following four steps of transformation delivered duloxetine.

Direct catalytic enantio- and diastereoselective aldol reaction of thioamides.

A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH(3)CN)(4)]PF(6)/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Brønsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides.

Direct catalytic asymmetric aldol reactions of thioamides: toward a stereocontrolled synthesis of 1,3-polyols.

A direct catalytic asymmetric aldol reaction of thioamides with a soft Lewis acid/hard Brønsted base cooperative catalytic system comprising (R,R)-Ph-BPE/[Cu(CH(3)CN)(4)]PF(6)/LiOAr is described. Highly chemoselective deprotonative activation of thioamides allows for a direct aldol reaction of alpha-nonbranched aliphatic aldehydes, which are susceptible to self-condensation. Facile reduction of the thioamide functionality and a catalyst-controlled second aldol reaction provides 1,3-diols in a highly stereoselective manner.