First Base-Free Catalytic Wittig Reaction

Abstract

The first base-free catalytic Wittig reaction utilizing readily available Bu3P (5 mol %) as an organocatalyst is reported. The initial Michael addition of the phosphine to a suitable acceptor substituted alkene ultimately results in the formation of an ylide which is subsequently converted with an aldehyde. The presented (1)H NMR studies actually reveal evidence for the Michael addition and proposed ylide formation. Under the optimized reaction conditions various maleates and fumarates were converted with aromatic, heteroaromatic, and aliphatic aldehydes to evaluate the scope and limitations of this unprecedented reaction. Notably, maleates and fumarates react in a stereoconvergent fashion. The corresponding products were obtained in up to 95% isolated yield and E/Z-selectivities up to 99:1.

Novel Base‐Free Catalytic Wittig Reaction for the Synthesis of Highly Functionalized Alkenes

“…Subsequently the ylide is formed by a proton shift, which might also be catalyzed by the proton source in the reaction system ( III ) . This ultimately leads to the in situ formation of the ylide, as previously reported for the stoichiometric and catalytic reaction –. Notably, this allows the generation of the usual waste products to be bypassed and also avoids the commonly required preparation of a phosphonium salt intermediate as a precursor for ylide formation.…”

“…Me 3 P gave the desired product in 13 % yield (entry 2). In the presence of Bu 3 P, which has previously been reported as a stoichiometric reagent and catalyst, this reaction gave 3 aa in 32 % yield. In contrast, t Bu 3 P and air stable Ph 3 P showed no conversion into 3 aa (entries 4 and 5).…”

“…The key step is the reduction of precatalyst 4 to the corresponding phosphine 5 ( I ). This is probably facilitated by the Brønsted acidic additive . In some cases we observed the formation of hexamethoxydisiloxane as a byproduct of the reduction process, which was detected by GC‐MS analysis .…”

“…Recently, we reported the first catalytic version of this reaction utilizing tri‐ n ‐butylphosphine as the catalyst . We envisioned developing a novel base‐free catalytic Wittig reaction that operates under much milder conditions.…”

Catalytic Wittig and aza-Wittig reactions

“…Additionally, the same authors have reported base-free Wittig reactions using diethyl maleate ( 31 ) as the starting material to form products 32 catalyzed by tributylphosphine ( 33 , 0.05 equivalents) (Scheme 9) [26]. In these transformations the initial reaction between 31 and 33 generated zwitterion 34 , that underwent internal proton transfer to generate ylide 35 .…”