A Catalytic Carbon–Phosphorus Ylide Reaction: Phosphane‐Catalyzed Annulation of Allylic Compounds with Electron‐Deficient Alkenes

Abstract

To ensure high efficiency, turning a stoichiometric reaction into a catalytic one, and developing new catalytic reactions have been long-standing goals in modern synthesis. Ylide reactions are among the most powerful tools for constructing olefins [1] and small rings, [2] but few are catalytic, in particular those involving phosphorus ylides.[3] The first example of a catalytic Wittig-type reaction of arsenic ylides, in which a stoichiometric amount of reducing agent was used to regenerate the arsane, was described by Huang's group in 1989. [4] Afterwards, catalytic olefinations, epoxidations, aziridinations, and cyclopropanations of tellurium or sulfur ylides were accomplished. [2,5] Aggarwal's group developed catalytic, asymmetric ylide reactions that afforded three-membered rings by a carbene approach, in which the ylide was formed directly from aryl diazomethane in the presence of a catalytic amount of a chiral sulfide and a transition-metal complex. [6] To our knowledge, there are no phosphane-catalyzed versions of the carbon-phosphorus ylide reaction. [7] This might be due to the fact that, compared to other elemento-organic compounds of Groups 15 and 16, phosphanes exhibit higher oxyphilicity and the phosphorus-oxygen bond in phosphine oxides have a higher bond energy. To develop a catalytic reaction with carbon-phosphorus ylides, it was thus necessary to explore a new type of reaction.Two types of reactions of allylic phosphorus ylides A with electron-deficient alkenes have been reported (Scheme 1). The initial nucleophilic addition of the ylide to the olefin is followed by an intramolecular Wittig reaction to afford 1,3-cycloalkadienes [8a-f] or by intramolecular nucleophilic substitution to give cyclopropanes.[8f,g] However, both reactions are stoichiometric with regard to the phosphane and the products are obtained in low yields.The success of the phosphane-catalyzed isomerizations, aand g-additions, and [3þ2] cycloadditions of electron-deficient allenes or alkynes was ascribed to the presence of electron-withdrawing groups, which facilitated the nucleophilic additions and the elimination of phosphanes to complete the catalytic cycles. [9] With this in mind, we thought that phosphane-catalyzed reactions might be realized with a modified allylic phosphorus ylide B (see Scheme 1). Here we report a novel phosphane-catalyzed annulation reaction of modified allylic compounds with electron-deficient alkenes.To initiate our study, phosphonium salt 1, compound 2, and potassium carbonate were stirred in toluene at 90 8C to afford the adduct 3 a and triphenylphosphane [Eq. (1); E = CO 2 Et]. Since 1 was prepared from ethyl 2-bromomethyl-2-propenoate (4 a) and PPh 3 , it was expected that this reaction might take place starting from 4 a by utilizing a catalytic amount of PPh 3 . Indeed, the phosphane-catalyzed annulation Scheme 1. Two types of reactions of allylic phosphorus ylides.

Advances in Annulation Reactions Initiated by Phosphorus Ylides Generated in situ

“…[3] In the presence of 10 mol-% PPh 3 and 1.5 equiv. of K 2 CO 3 additive, in toluene as solvent at 90°C, [3 + 2] annulation of modified MBH adducts 1, including bromides and acetates, with electron-deficient alkenes such as maleimides 3 or α, -unsaturated ketones 4 readily occurred, affording multifunctionalized cyclopentenes 5 or 6 in moderate to good yields with high diastereoselectivity (Scheme 2).…”

“…[51] Through the joint forces of computation and isotopic labeling experiments, the authors demonstrated that the reaction required the cocatalysis of triphenylphosphane and water. Mechanistically, the catalytic cycle starts with the formation of a zwitterionic intermediate 114, generated from α-methyl allenoate 113 and PPh 3 . Then a water-assisted [1,4] As demonstrated by Kwon [41] and Ye, [52] α-alkyl allenoates could serve as a versatile set of C 4 synthons in phosphanecatalyzed [4 + 2] annulations with imines, ketones, and electron-deficient alkenes, affording efficient syntheses of tetrahydropyridines, dihydropyrans, and cyclohexenes.…”

Nucleophilic Phosphine Organocatalysis

“…[64] Presumably, the phosphine triggers the reaction through salt formation with the allylic bromide. The inorganic base then generates the allylic anion setting up for the cycloaddition reaction.…”

Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs

“…60 These new phosphonium species grant access to new reaction pathways with nucleophiles, electrophiles, and electrophile–nucleophiles.…”

“…60 By installing a β'-acetate or β'- tert -butylcarbonate group, novel phosphonium species are obtained through new annulation pathways. The mechanism proceeds with conjugate addition into the MBHAD 109 with the ejection of the β'-leaving group, forming the phosphonium species 110 (Scheme 70).…”