Further Information
Literature
Related Reactions
Synthesis of Baylis-Hillman Adducts
(enones),
Synthesis of Baylis-Hillman Adducts (α,β-unsaturated compounds)
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
K.-S. Park, J. Kim, H. Choo, Y. Chong, Synlett, 2007,
395-398.
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,
1047-1050.
Efficient Baylis-Hillman Reaction Using Stoichiometric Base Catalyst and an
Aqueous Medium
C. Yu, B. Liu, L. Hu, J. Org. Chem., 2001,
66, 5413-5418.
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,
75, 4183-4191.
Sila-Morita-Baylis-Hillman Reaction of Arylvinyl Ketones: Overcoming the
Dimerization Problem
A. Trofimov, V. Gevorgyan, Org. Lett., 2009,
11, 253-255.
A Highly Active and Selective Catalyst System for the Baylis-Hillman
Reaction
J. You, J. Xu, J. G. Verkade, Angew. Chem. Int. Ed., 2003,
41,
5054-5066.
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
Reactions
X. Mi, S. Luo, J.-P. Cheng, J. Org. Chem., 2005, 70, 2338-2341.
Morita-Baylis-Hillman Reaction of α,β-Unsaturated Ketones with Allylic
Acetates by the Combination of Transition-Metal Catalysis and Organomediation
Y.-Q. Li, H.-J. Wang, Z.-Z. Huang, J. Org. Chem.,
2016,
81, 4429-4433.
Guanidine-Catalyzed γ-Selective Morita-Baylis-Hillman Reactions on
α,γ-Dialkyl-Allenoates: Access to Densely Substituted Heterocycles
P. Selig, A. Turočkin, W. Raven, Synlett, 2013, 24,
2535-2539.
A Practical Preparation of 2-Hydroxymethyl-2-cyclopenten-1-one by
Morita-Baylis-Hillman Reaction
H. Ito, Y. Takenaka, S. Fukunishi, K. Iguchi,
Synthesis, 2005, 3035-3038.
Dual Iminium- and Lewis Base Catalyzed Morita-Baylis-Hillman Reaction on
Cyclopent-2-enone
R. Innocenti, G. Menchi, A. Trabocchi,
Synlett, 2018, 29, 820-824.
Acceleration of the Morita-Baylis-Hillman Reaction by a Simple Mixed
Catalyst System
A. Bugarin, B. T. Connell, J. Org. Chem., 2009,
74, 4638-4641.
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,
46, 2644-2646.
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,
132, 11988-11992.
Chiral Bifunctional Organocatalysts in Asymmetric Aza-Morita-Baylis-Hillman
Reactions of Ethyl (Arylimino)acetates with Methyl Vinyl Ketone and Ethyl Vinyl
Ketone
M. Shi, G.-N. Ma, J. Gao, J. Org. Chem., 2007,
72, 9779-9781.
A Brønsted Acid and Lewis Base Organocatalyst for the
Aza-Morita-Baylis-Hillman Reaction
K. Matsui, S. Takizawa, H. Sasai, Synlett,
2006, 761-765.
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,
76, 2888-2891.
Organocatalysis of the Morita-Baylis-Hillman Alkylation Using
Trialkylphosphines
M. E. Krafft, K. A. Seibert, Synlett, 2006,
3334-3336.
4-Dimethylaminopyridine (DMAP), A Superior Mediator for Morita-Baylis-Hillman Reaction-Triggered Annulative Condensation of Salicylaldehydes and Acrylonitrile to Form 3-Cyano-2H-chromenes
B. Kang, K. Ikeda, Chem. Pharm. Bull., 2023, 71, 318-325.
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