Baylis-Hillman Reaction

This coupling of an activated alkene derivative with an aldehyde is catalyzed by a tertiary amine (for example: DABCO = 1,4-Diazabicyclo[2.2.2]octane). Phosphines can also be used in this reaction, and enantioselective reactions may be carried out if the amine or phosphine catalyst is asymmetric.

---

Mechanism of the Baylis-Hillman Reaction

A key step is the addition of the amine catalyst to the activated alkene to form a stabilized nucleophilic anion. This in situ-generated nucleophile then adds to the aldehyde. Subsequent elimination of the catalyst leads to the observed products.

Other activating nitrogen nucleophiles may be suitable too and DMAP and DBU are superior to DABCO in some cases:

product of the addition of DBU and 

methylacrylate

For aryl aldehydes under polar, nonpolar, and protic conditions, it has been determined that the rate-determining step is second-order in aldehyde and first-order in DABCO and acrylate. On the basis of this reaction rate data, Tyler McQuade recently proposed (J. Org. Chem. 2005, 70, 3980. DOI) the following mechanism involving the formation of a hemiacetal intermediate:

Recent Literature

Octanol-Accelerated Baylis-Hillman Reaction

The First One-Pot Synthesis of Morita-Baylis-Hillman Adducts Starting Directly from Alcohols

Dramatic Rate Acceleration of the Baylis-Hillman Reaction in Homogeneous Medium in the Presence of Water

Synthesis of 1,3-Dialkyl-1,2,3-triazolium Ionic Liquids and Their Applications to the Baylis-Hillman Reaction

Sila-Morita-Baylis-Hillman Reaction of Arylvinyl Ketones: Overcoming the Dimerization Problem

A Highly Active and Selective Catalyst System for the Baylis-Hillman Reaction

Traditional Morita-Baylis-Hillman reaction of aldehydes with methyl vinyl ketone co-catalyzed by triphenylphosphine and nitrophenol

Succesful Baylis Hillman Reaction of Acrylamide with Aromatic Aldehydes

Ionic Liquid-Immobilized Quinuclidine-Catalyzed Morita-Baylis-Hillman Reactions

Morita-Baylis-Hillman Reaction of α,β-Unsaturated Ketones with Allylic Acetates by the Combination of Transition-Metal Catalysis and Organomediation

Guanidine-Catalyzed γ-Selective Morita-Baylis-Hillman Reactions on α,γ-Dialkyl-Allenoates: Access to Densely Substituted Heterocycles

A Practical Preparation of 2-Hydroxymethyl-2-cyclopenten-1-one by Morita-Baylis-Hillman Reaction

Dual Iminium- and Lewis Base Catalyzed Morita-Baylis-Hillman Reaction on Cyclopent-2-enone

Acceleration of the Morita-Baylis-Hillman Reaction by a Simple Mixed Catalyst System

Asymmetric Morita-Baylis-Hillman Reactions Catalyzed by Chiral Brønsted Acids

MgI₂-accelerated enantioselective Morita-Baylis-Hillman reactions of cyclopentenone utilizing a chiral DMAP catalyst

Catalytic Asymmetric Aza-Morita-Baylis-Hillman Reaction of Methyl Acrylate: Role of a Bifunctional La(O-iPr)₃/Linked-BINOL Complex

Chiral Bifunctional Organocatalysts in Asymmetric Aza-Morita-Baylis-Hillman Reactions of Ethyl (Arylimino)acetates with Methyl Vinyl Ketone and Ethyl Vinyl Ketone

A Brønsted Acid and Lewis Base Organocatalyst for the Aza-Morita-Baylis-Hillman Reaction

Organocatalytic Tandem Three-Component Reaction of Imine, Alkyl Vinyl Ketone, and Imide via aza-Baylis-Hillman Reaction

Organocatalysis of the Morita-Baylis-Hillman Alkylation Using Trialkylphosphines