Reevaluation of the Mechanism of the Baylis–Hillman Reaction: Implications for Asymmetric Catalysis

Abstract

One step beyond: Proton transfer (step 3, see scheme), not CC bond formation (step 2) as previously thought, is the rate‐limiting step (RLS) in the initial stage of the Baylis–Hillman reaction, which involves the amine‐catalyzed addition of an aldehyde to an activated alkene to generate an allylic alcohol. This finding has considerable implications for asymmetric catalysis of the reaction.

Microwave-promoted morita-baylis-hillman reactions: efficient synthesis of new monoacylglycerols (MAGs) as potential anti-parasitic compounds

“…We can point out that depending on the aldehydes used in the MBH reaction can be obtained good yields in both protic 4,6 or aprotic 5,6 media, confirming that slight changes in reaction conditions can change the RDS of these reactions and then, there are not, up to now, a clear general relationship between substrates-solvents-yields-rate, which corroborates the unified mechanism proposed by Cantilo and Kappe for this exquisite reaction. 7 Completing the pathway 2 (step vi, Scheme 3), the synthesis of adducts 8-13 from intermediates 22-27 was first performed using the same methodology used on MAG 21 preparation (step iii, Scheme 3).…”

“…The first catalytic cycle suggested by Hill and Isaacs 3 is still accepted, but being the rate-determining step (RDS) it remains at the center of the scientific debate. For example, the nonprotic 4 and protic 5 currently accepted mechanisms suggested by McQuade and Aggarwal respectively and corroborated by Coelho 6 have been very recently revisited by Cantillo and Kappe. 7 In our continuing search for bioactive substances 8 and in connection with our efforts towards reactivity of MBH reaction study, 9 our research group described in 2006 the molluscicidal activities of simple aromatic MBHA against Biomphalaria glabrata (Say) snails, intermediate schistosomiasis host.…”

The aza-Morita–Baylis–Hillman reaction of electronically and sterically deactivated substrates

“…Subsequent intramolecular proton transfer within zwitterionic intermediate II and elimination of the nucleophilic catalyst close the catalytic cycle. Previous kinetic studies by Lloyd-Jones et al 11 indicate that reaction rates are most likely limited by the imine addition and/ or the subsequent proton transfer step. The step most strongly affected by deactivated Michael acceptors is the initial nucleophilic addition step, and sluggish reaction rates for this class of substrates may simply derive from the reduced preequilibrium formation of zwitterionic enolate I.…”

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

“…A reasonably low transition state barrier would require the H δ+ to reach the electron lone pair of N of the imine arm. Proton-transfer (H-transfer) shuttles were recently identified in facilitating various H-transfer processes in related reactions [58,[97][98][99][100][101][102][103][104][105][106][107][108]. The mediating agents for the H-transfer process can be protonic solvent molecules (alcohols and water), substrates, or products.…”