Organocatalytic enantioselective hydrophosphonylation of aldehydes

Abstract

We report our results concerning the first squaramide-catalysed hydrophosphonylation of aldehydes. In all cases, the reactions proceeded smoothly and cleanly under mild reaction conditions rendering final α-hydroxy phosphonates in very good yields and high enantioselectivities. It is one of the few organocatalytic examples of this reaction using aldehydes. It is the first time that diphenylphosphite (1e) has been successfully employed in a chiral Pudovik reaction with aldehydes, in contrast to the dialkylphosphites used in previously published procedures, extending the generality of this asymmetric methodology.

Phosphorylation of bio-based compounds: the state of the art

“…(Scheme 2) A catalytic, enantioselective variant of the Pudovik reaction has recently been developed. 24 The same reaction was used for the preparation of dialkyl 2-(alkoxycarbonyl)ethyl phosphonates which involves the conjugate addition of a dialkyl phosphite to a C=C double bond of α,β-unsaturated carboxylates in the presence of base. 25 Derivative of the Pudovik reaction, the radical addition of H-phosphonate to unsaturated hydrocarbons, especially on C=C represents another useful synthetic route for the phosphorylation of compounds, and can produce following different methodologies.…”

Squaramides with cytotoxic activity against human gastric carcinoma cells HGC-27: synthesis and mechanism of action

“…Substituents with different stereoelectronic properties and Substantial inhibition can be seen for compounds 15-20 all of them sharing a cinchona-based substituent. Interestingly, the presence of a 3,5-bisIJtrifluoromethyl)phenyl moiety confers almost in all the cases inhibition of cell viability (15,16,21,27,(34)(35)(36)(37)(38), irrespective of the other substituent present at the second amide. Similarly, 3,5-bisIJtrifluoromethyl)benzyl substituted squaramides 22 and 26 also show good activities in HGC-27 cells, whereas they are less active in HeLa cells.…”

Organocatalytic Hydrophosphonylation Reaction of Carbonyl Groups

“…[29] In our work, the first asymmetric squaramide-organocatalyzed Pudovik reaction using aldehydes was disclosed (Scheme 7). [30] Our methodology covers a broader range of compounds compared with the pioneering protocol described by Wynberg and co-workers. [15] It tolerates the use of aromatic aldehydes with different functional groups such as halides, nitro, cyano, and also aliphatic aldehydes through a simple and general approach, with very good results in terms of enantioselectivity and reactivity.…”