Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

Abstract

SummaryA variety of chiral N-phosphinyl α-imino esters have been synthesized for the first time from ketoesters and phosphinylamide, which were then reduced by L-selectride to give the corresponding N-phosphinyl-protected α-amino esters. The reduction proceeded very well with excellent chemical yields (88–98%) as well as high diastereoselectivities (96:4 to 99:1). Some of these products could be obtained without column chromatography and recrystallization. The chiral phosphinyl auxiliary could be easily cleaved under acidic conditions.

Enantioselective Catalytic Synthesis of α‐Stereogenic Chromen‐4‐one Amino Derivatives

“…To determine absolute configuration, product 3 aa was subjected to oxidative fragmentation under the action of Ru(III)/NaIO 4 . Specific optical rotation of the product was similar to the data reported for (S)enantiomer of phenylglycine methyl ester [10] (Scheme 3). The same (S)-configuration was assigned to other chromen-4-one amino derivatives 3 by analogy.…”

N-Phosphonyl/phosphinyl imines and group-assisted purification (GAP) chemistry/technology

“…The new phosphinyl auxiliary can be readily cleaved by treating the product with aqueous HBr solution to give phosphinoic acid 38, which can be recycled for The asymmetric synthesis of α-amino esters has been performed via reduction of the chiral N-phosphinyl α-imino esters 40 (Scheme 23). 27 Among the several reduction agents, such as Hantzsch esters, silanes, DIBAL, and NaBH 4 , L-selectride was found to be the most efficient in regard to yield and diastereocontrol when the reaction was performed in polar solvents. A series of α-amino esters 41 were obtained in excellent yields (up to 98%) and diastereoselectivities (up to 99 : 1 dr).…”

α-Imino Esters in Organic Synthesis: Recent Advances

“…Treatment of N -PMP protected α-imino esters with 1.6 equiv of catecholborane in the presence of chiral BINOL-derived phosphoric acid L34 (10 mol %) in toluene at −22 °C for 24 h, resulted in the formation of α-amino esters 534 in 81–99%, with 57–96% ee. Lithium tri- sec -butyl­(hydrido)­borate (L-Selectride) was reported for the reduction of chiral N -phosphinyl α-imino esters 544 , by Han et al Reactions were conducted using 2 equiv of L-Selectride in THF at −78 °C under argon atmosphere for 8 h, to afford corresponding α-amino esters 545 in 88–98% yields, with 96/4–99/1 dr. Used α-imino esters 544 were prepared in 26–59% yields, by subjecting phosphinyl amide 543 with α-ketoester (2 equiv) in the presence of TiCl 4 (100 mol %) and Et 3 N (400 mol %) in DCM at room temperature for 12 h (Scheme ).…”