Biphenyl-Based Bis(thiourea) Organocatalyst for Asymmetric and syn-Selective Henry Reaction

Abstract

A scalable, efficient and chromatography-free synthesis of a new enantiopure C 2-symmetric bis(thiourea) catalyst was accomplished from a readily available starting material. The developed strategy could be conducted on a multi-gram scale. Both the prepared enantiomers of the bis(thiourea) organocatalyst have been tested in the asymmetric Henry reaction under thoroughly optimized conditions during which an unusual solvent effect on enantioselectivity was found. The corresponding adducts were obtained in excellent yields with good to excellent enantioselectivities. The achieved high reactivity and enantioselectivity in the nitroaldol reaction of nitroalkanes with aromatic aldehydes suggests promising potential for this catalyst. Moreover, a significant syn-diastereoselectivity was observed.

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

“…A series of binaphthyl-derived thiourea catalysts were applied by Kim and co-workers in asymmetric Mannich-type reactions of fluorinated ketoesters [324]. For the asymmetric Henry reaction, bis-thioureas were prepared connected with 4,4 -bisindanyl [325], and substituted biphenyl-and bianthryl-based linkers (Figure 26) [326][327][328]. High yields and stereoselectivities were observed for certain derivatives.…”

“…Figure26. Examples of thioureas and bis-thioureas with axial chirality[28,29,[323][324][325][326][327][328].…”