Recent advances in Michael addition of H-phosphonates

Abstract

The review discusses recent achievements in the development of more environmentally friendly and economically competitive processes for the synthesis of biologically and synthetically important phosphorus-bearing compounds by conjugate addition of hydrogen-phosphonates to different Michael acceptors.

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives

“…Carboxylic acids can be also used as an acylating agents for α-hydroxy phosphonates supported by coupling reagents e.g., N , N ′-dicyclohexylcarbodiimide and 4-dimethylaminopyridineas as the base [ 31 ]. Apart from Michaelis–Arbuzov and Michaelis–Becker reactions, the phosphorus–carbon bond is formed using phospha-Michael addition under basic conditions [ 32 , 33 , 34 , 35 , 36 , 37 ]. Therefore, the possibility of using this approach in the synthesis of bioactive α-acyloxy phosphonates should be considered.…”

Recoverable Phospha-Michael Additions Catalyzed by a 4-N,N-Dimethylaminopyridinium Saccharinate Salt or a Fluorous Long-Chained Pyridine: Two Types of Reusable Base Catalysts

“…Hosseini-Sarvari and Etemad reported a nanosized zinc oxide catalyzed similar reaction by using [P(O)(OEt)2] phosphite substrate showing a similar trend of shorter reaction time for the unsubstituted malononitrile substrate (2.5 h) than the methyl substituent (5 h) [23,25]. For the base A-catalyzed reactions of diorganophosphite compounds (1a or 1b) with 2-benzylidenemalononitrile-type substrates (3 or 4), the reactions followed the cited reaction mechanism [39,40], demonestrating the base assisted P-H bond cleavage and adding the H and P-containing moiety into the two sides of the double bond (see Figure S1 The phospha-Michael addition of diisopropyl phosphite (1a) with benzylidenemalononitrile (3) was also studied kinetically at 80 °C (see Figure 1). The reaction showed a drastic increase in product concentration within the initial 10 min to 54 %, and the reaction reached 100 % yield after 1 h. The integrated rate law derived from the concentration of reactant 3 vs. time showed the ln[reactant 3] = −kt + ln[reactant 3]o plot with a rate constant coworkers reported that the reaction of diethyl phosphite with the electron withdrawing group substituted 2-[(4-chlorophenyl) methylene]malononitrile in the absence of the catalyst gave no product after 24 h [23].…”

“…For the base A -catalyzed reactions of diorganophosphite compounds ( 1a or 1b ) with 2-benzylidenemalononitrile-type substrates ( 3 or 4 ), the reactions followed the cited reaction mechanism [ 39 , 40 ], demonestrating the base assisted P-H bond cleavage and adding the H and P-containing moiety into the two sides of the double bond (see Figure S1 in SM ). However, the A -catalyzed similar reaction of tris(organo)phosphite ( 2 ) with 2-benzylidenemalononitrile ( 3 ) followed a different mechanism through the O-C bond cleavage of one -OC 2 H 5 group to add the phosphonate group [P(O)(O C 2 H 5 ) 2 ] and the ethyl groups into the two sides of the double bond ( Scheme 4 ).…”

“…For the base A-catalyzed reactions of diorganophosphite compounds (1a or 1b) with 2-benzylidenemalononitrile-type substrates (3 or 4), the reactions followed the cited reaction mechanism [39,40], demonestrating the base assisted P-H bond cleavage and adding the H and P-containing moiety into the two sides of the double bond (see Figure S1 in SM). However, the A-catalyzed similar reaction of tris(organo)phosphite ( 2 The phospha-Michael addition of diisopropyl phosphite (1a) with benzylidenemalononitrile (3) was also studied kinetically at 80 • C (see Figure 1).…”

Regioselectivity of the Conjugate Addition of Amines to Dissymmetrical Pull‐Pull Alkenes

“…Doubly activated olefins bearing two different electron‐withdrawing groups in vicinal position (so‐called pull–pull olefins) [1b,8] could a priori be regarded as highly reactive compounds because of their global electron depletion. However, a few articles published during the last decades on the reaction of nucleophiles on such derivatives (Scheme 2) bars generalization [9–23] .…”