The asymmetric synthesis of chiral cyclic α-hydroxy phosphonates and quaternary cyclic α-hydroxy phosphonates

Abstract

A highly practical, catalytic enantioselective cyclic phosphite addition to aldehydes and ketones was developed. The reaction rate of the asymmetric hydrophosphonylation was significantly enhanced by the addition of silver carbonate. Particularly, significant improvement has been achieved on the asymmetric hydrophosphonylation of unactivated ketones, giving quaternary α-hydroxy phosphonates with excellent enantioselectivity (up to 99% ee).

Synthesis and Biological Activity of O‐Methyl Methyl 1‐(Substituted Phenoxyacetoxy)‐1‐(thien‐2‐yl)methylphosphinates

“…The reaction of O,O-dialkyl phosphonates with aldehydes is a convenient method used to synthesize 1-hydroxyphosphonates, which have been reported in many literatures [14][15][16]. However, there are few reports on the reaction of O-methyl methylphosphinate 1 with thiophene-2-carbaldehyde.…”

Recent Advances in the Catalytic Asymmetric Construction of Phosphorus-Substituted Quaternary Carbon Stereocenters

“…The reactions using simple aryl alkyl ketones as electrophiles have not gained good results in terms of yield and enantioselectivity. 4,24,41 As for the asymmetric electrophilic phosphination, only one example using α-substituted cyanoacetates as the nucleophile has been reported. Therefore, the development of new catalytic system to enlarge the substrate scope would be an exciting direction.…”

“…In 2012, He, Tan, and co-workers developed an asymmetric phospha-aldol reaction of acetophenone derivatives 5 with cyclic phosphonate 6b (Scheme 4). 24 The use of 10 mol% tridentate Schiff base 7b-Al(III) complex and 4 mol% Ag 2 CO 3 as base proved to be powerful for this reaction, giving α-hydroxyphosphonates 12 in good yields with high ee. According to the crystal structure of the 7b-Et 2 AlBr complex, two possible pathways can be considered for the reaction: monometallic catalysis and bimetallic catalysis.…”

Synthesis of α‐Hydroxyphosphonates Containing Functionalized 1,2,3‐Triazoles

“…Considering the formation of a new asymmetric center and the number of methods to obtain enantiopure α ‐ and β ‐hydroxyphosphonate compounds, [62–74] there is a great interest in the development of facile protocols for their chiral discrimination. These features encouraged us to explore the 1 H and 31 P‐{1H} NMR chiral discrimination employing a chiral solvating agent (CSA) to provide a simple and convenient procedure.…”