New tartrate based cyclic phosphoric acids as organocatalysts in Mannich reactions

Abstract

Cyclic phosphoric acids have attracted much attention as chiral organocatalysts. While binaphthol based ligands have been extensively used in various transformations, the analogous TADDOL-type ligands are less explored. A library of seventeen cyclic phosphoric acids with structural variation of the TADDOL backbone were synthesized and an optimization study of the Mannich reaction of aromatic N-(2-hydroxyphenyl)imines with 2,2-dimethyl-1-methoxy-silylenolate was performed. Enantioselectivities between 96% (S) and 70% (R) were observed and a rationalisation, based on crystal structure analysis and DFT calculations, is provided.

Green Chemistry Meets Asymmetric Organocatalysis: A Critical Overview on Catalysts Synthesis

“…It was necessary to wait until 2016 to see the following application of TPAs in organocatalysis, this time by Widhalm and co‐workers, who designed a small library of 17 new TPAs to catalyse Mannich reactions with fluctuating results, although yielding the desired product in up to 96 % yield and 96 % ee . [156b] …”

“…The authors probably did not take into consideration the possibility of avoiding the use of VOCs, but since THF can be often replaced by green 2‐methyl THF or cyclopentyl methyl ether (CPME), the greenness of this route could be potentially improved. It was necessary to wait until 2016 to see the following application of TPAs in organocatalysis, this time by Widhalm and co‐workers, who designed a small library of 17 new TPAs to catalyse Mannich reactions with fluctuating results, although yielding the desired product in up to 96 % yield and 96 % ee [156b] …”

An overview of the applications of chiral phosphoric acid organocatalysts in enantioselective additions to CO and CN bonds

“…In the same year, Widhalm's group reported the same transformation using ( R )- TPA1 as the catalysts. 76 In this case, the reaction was carried out at slightly higher temperatures, obtaining excellent yields and enantioselectivities up to 96% ee. Unfortunately, the scope of the reaction is limited to α-dimethyl silyl enol ethers, and only the formation of a single chiral carbon is reported.…”