An Efficient Conjugate Addition of Dialkyl Phosphite to Electron-Deficient Olefins: The Use of a Nucleophilic Organocatalyst to Form a Strong Base

Abstract

The formation of a zwitterionic species between electrondeficient olefins and tertiary amine or phosphine is a pivotal and the starting point for the Morita-Baylis-Hillman (MBH) reaction 1 and Rauhut-Currier (RC) reaction. 2 A subsequent 1,2-addition of the zwitterion I, which was generated from methyl acrylate as an example, to aldehyde and a proton movement furnished the Morita-Baylis-Hillman adduct, whereas a conjugate addition to electron-deficient olefins is the Rauhut-Currier reaction, as shown in Scheme 1. Basically, the zwitterion is an ester enolate and could act as a base. 3,4In this respect, White and Baizer reported a phosphinecatalyzed conjugate addition of 2-nitropropane to various electron-deficient olefins, as also shown in Scheme 1.3a Toste and co-workers reported a phosphine-catalyzed conjugate addition of alcohol or water to electron-deficient olefins. Later, Pedduri and Williamson have applied the concept to make tetrahydrofurans.3c Vallribera and co-workers also reported the conjugate addition of β-dicarbonyl compounds to electron-deficient olefins.3d The mechanism of the conjugate additions likely involves the zwitterion I behaving as a base to deprotonate the nitroalkane, alcohol, water and β-dicarbonyl; the nitronate, alkoxide, hydroxide or the enolate of β-dicarbonyl then undergoes the following conjugate additions to electron-deficient olefins. Recently, Tian and co-workers have developed an efficient alternative way to Henry reaction involving a deprotonation of a nitroalkane with the zwitterionic ester enolate to form a nitronate and a subsequent reaction with aldehyde. 4The conjugate addition of a dialkylphosphonate anion to electron-deficient olefins provided an efficient way to alkylsubstituted phosphonates;5,6 however, the method required usually a strong base 6a,b,d-h or somewhat drastic conditions. Thus, an alternative way has been used more widely involving the use of trialkyl phosphite. 7 The reaction between electron-deficient olefins such as methyl acrylate and trialkyl phosphite generated a zwitterionic species at elevated temperature. A subsequent Michaelis-Arbuzov type rearrangement in the presence of phenol afforded the desired alkyl phosphonate, as shown in Scheme 2. In these respects, we presumed that the conjugate addition reactions catalyzed by a nucleophilic organocatalyst such as tributylphosphine could be applied for the synthesis of alkyl phosphonate, as also shown in Scheme 2.At the outset of our experiment we examined the reaction of methyl acrylate and diethyl phosphite in the presence of various nucleophilic catalyst including DABCO, n-Bu 3 P and PPh 3 in CH 3 CN. The use of DABCO (10 mol %, rt, 6 days) did not produce 2a in any trace amount.3b The use of n-Bu 3 P (20 mol %, rt, 2 h) produced 2a in good yield (72%), whereas the reaction in the presence of PPh 3 (20 mol %, reflux, 24 h) produced 2a in a trace amount (< 5%).3b Further studies revealed that the use of 5-10 mol % of n-Bu 3 P showed cleaner reaction and increased the yield of 2a.The reaction mecha...

Phosphine Organocatalysis

“…With the great results disclosed by Bergman and Toste, the phosphine-catalyzed Michael addition was quickly adopted by many research groups. The range of pronucleophiles increased to include allyl alcohols, 61 ethanol, 62 oximes, 63 malonates, 64 pyrimidine-2,4-diones, 65 aminoindolizines (Scheme 10), 66 α -fluorinated and α -trifluoromethylated nucleophiles (Scheme 11), 67,68 hydrogen phosphoryl compounds (Scheme 12), 69–71 and various phosphorus-centered nucleophiles (Scheme 12), 72,73 producing an array of functionalized aliphatic cyanides, sulfones, ketones, and esters.…”

“One-Pot” Aminolysis/Thiol–Maleimide End-Group Functionalization of RAFT Polymers: Identifying and Preventing Michael Addition Side Reactions

“…While DBU is optional during “one-pot” aminolysis/thiol–maleimide modification of RAFT polymers, mild reducing agents such as TBP are generally required to prevent disulfide formation from occurring between polymeric thiols during the RAFT agent aminolysis step. , Recently, Ho et al reported the use of trialkyl phosphites as cheaper and less toxic alternatives to trialkylphosphines as reducing agents during “one-pot” RAFT polymer aminolysis/thiol–ene reactions . While trialkyl phosphites can undergo conjugate addition to electron-deficient olefins, they are less nucleophilic than phosphines and typically require elevated temperatures (100 °C) for such reactions to occur. , As shown in Figure d, the reaction of trimethyl phosphite (TMP) with NMM results in no measurable change in [Mal]/[Mal] 0 in MeCN, EtOH, and CH 2 Cl 2 . Only after prolonged reaction times (12 h) in DMSO is a 65% decrease in [Mal]/[Mal] 0 observed.…”

“…45 While trialkyl phosphites can undergo conjugate addition to electron-deficient olefins, they are less nucleophilic than phosphines and typically require elevated temperatures (100 °C) for such reactions to occur. 46,47 As shown in Figure 1d, the reaction of trimethyl phosphite (TMP) with NMM results in no measurable change in [Mal]/[Mal] 0 in MeCN, EtOH, and CH 2 Cl 2 . Only after prolonged reaction times (12 h) in DMSO is a 65% decrease in [Mal]/[Mal] 0 observed.…”

Investigation of Hydrophosphorylation Reaction of Pentacoordinate Hydrospirophosphorane and Electron‐Deficient Alkenes Catalyzed by Organic Phosphine

“…Unfortunately, preliminary experiments proved that the hydrophosphorylation reaction could not take place for AA‐HSP and alkene without catalyst. In recent years, with the development of organic catalysis, phosphine catalysts have been found to be effective in P−C bond formation involving activated electron‐deficient alkenes [33–38] . Among them, tertiary phosphines have emerged as versatile catalysts for many synthetically useful transformations of electron‐deficient alkenes [38] .…”

“…In recent years, with the development of organic catalysis, phosphine catalysts have been found to be effective in PÀ C bond formation involving activated electron-deficient alkenes. [33][34][35][36][37][38] Among them, tertiary phosphines have emerged as versatile catalysts for many synthetically useful transformations of electron-deficient alkenes. [38] Inspired by the PMe 3catalyzed addition reaction of electron-deficient alkenes and alkyl H-phosphonates or secondary phosphine oxides reported by Han group (Scheme 3a), [34] we herein present a novel and simple method for the formation of pentacoordinate PÀ C bond by the hydrophosphorylation reaction of alkene and AA-HSP under PMe 3 catalysis (Scheme 3b).…”