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
Other activating nitrogen nucleophiles may be suitable too and DMAP and DBU
are superior to DABCO in some cases:
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.
following mechanism involving the formation of a hemiacetal intermediate:
Octanol-Accelerated Baylis-Hillman Reaction
K.-S. Park, J. Kim, H. Choo, Y. Chong, Synlett, 2007,
The First One-Pot Synthesis of Morita-Baylis-Hillman Adducts Starting
Directly from Alcohols
L. D. S. Yadav, V. P. Srivasta, R. Patel, Synlett, 2010,
Dramatic Rate Acceleration of the Baylis-Hillman Reaction in Homogeneous
Medium in the Presence of Water
J. Cai, Z. Zhou, G. Zhao, C. Tang, Org. Lett., 2002, 4, 4723-4725.
Synthesis of 1,3-Dialkyl-1,2,3-triazolium Ionic Liquids and Their
Applications to the Baylis-Hillman Reaction
Y. Jeong, J.-S. Ryu, J. Org. Chem., 2010,
Sila-Morita-Baylis-Hillman Reaction of Arylvinyl Ketones: Overcoming the
A. Trofimov, V. Gevorgyan, Org. Lett., 2009,
A Practical Preparation of 2-Hydroxymethyl-2-cyclopenten-1-one by
H. Ito, Y. Takenaka, S. Fukunishi, K. Iguchi,
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Acceleration of the Morita-Baylis-Hillman Reaction by a Simple Mixed
A. Bugarin, B. T. Connell, J. Org. Chem., 2009,
A Highly Active and Selective Catalyst System for the Baylis-Hillman
J. You, J. Xu, J. G. Verkade, Angew. Chem. Int. Ed., 2003,
Traditional Morita-Baylis-Hillman reaction of aldehydes with methyl vinyl
ketone co-catalyzed by triphenylphosphine and nitrophenol
M. Shi, Y.-H. Liu, Org. Biomol. Chem., 2006, 4, 1468-1470.
Succesful Baylis Hillman Reaction of Acrylamide with Aromatic Aldehydes
C. Yu, L. Hu, J. Org. Chem., 2002, 67, 219-223.
Ionic Liquid-Immobilized Quinuclidine-Catalyzed Morita-Baylis-Hillman
X. Mi, S. Luo, J.-P. Cheng, J. Org. Chem., 2005, 70, 2338-2341.
Asymmetric Morita-Baylis-Hillman Reactions Catalyzed by Chiral Brønsted Acids
N. T. McDougal, S. E. Schaus, J. Am. Chem. Soc., 2003, 125, 12094-12095.
MgI2-accelerated enantioselective Morita-Baylis-Hillman reactions of
cyclopentenone utilizing a chiral DMAP catalyst
A. Bugarin, B. T. Connell, Chem. Commun., 2010,
Catalytic Asymmetric Aza-Morita-Baylis-Hillman Reaction of Methyl Acrylate:
Role of a Bifunctional La(O-iPr)3/Linked-BINOL Complex
T. Yukawa, B. Seelig, Y. Xu, H. Morimoto, Y. Xu, H. Morimoto, S. Matsunaga,
A. Berkessel, M. Shibasaki, J. Am. Chem. Soc., 2010,
Chiral Bifunctional Organocatalysts in Asymmetric Aza-Morita-Baylis-Hillman
Reactions of Ethyl (Arylimino)acetates with Methyl Vinyl Ketone and Ethyl Vinyl
M. Shi, G.-N. Ma, J. Gao, J. Org. Chem., 2007,
A Brønsted Acid and Lewis Base Organocatalyst for the
K. Matsui, S. Takizawa, H. Sasai, Synlett,
Organocatalytic Tandem Three-Component Reaction of Imine, Alkyl Vinyl
Ketone, and Imide via aza-Baylis-Hillman Reaction
S.-e. Syu, Y.-T. Lee, Y.-J. Jang, W. Lin, J. Org. Chem., 2011,
Organocatalysis of the Morita-Baylis-Hillman Alkylation Using
M. E. Krafft, K. A. Seibert, Synlett, 2006,