活性烯烴和醛在三級(jí)胺（如 DABCO = 1,4-Diazabicyclo[2.2.2]octane）的催化下發(fā)生的偶聯(lián)反應(yīng)被稱為Baylis-Hillman 反應(yīng)。膦也可以用于此反應(yīng)，如果胺或膦是手性的，則發(fā)生非對(duì)映選擇性的Baylis-Hillman 反應(yīng)。
堿催化下吸電子基團(tuán)活化的烯烴和一些親電子化合物（如醛）偶聯(lián)得到非常有用的有機(jī)合成中間體。當(dāng)以三級(jí)胺作為堿時(shí)，特別是以1,4-二氮雜二環(huán)[2.2.2]辛烷（ DABCO = 1,4-Diazabicyclo[2.2.2]octane）此反應(yīng)被稱為Baylis-Hillman反應(yīng)。1972年Baylis和Hillman首先報(bào)道了α，β-不飽和酯，腈，酰胺和酮與各種醛類化合物進(jìn)行反應(yīng)。現(xiàn)在用此反應(yīng)可以合成各種化合物（吸電子基團(tuán)可以是磺?；?，膦?；?，親電子化合物也不僅僅是醛）。此反應(yīng)的一個(gè)缺點(diǎn)就是反應(yīng)速率比較慢，經(jīng)常需要延長(zhǎng)反應(yīng)時(shí)間?，F(xiàn)在也發(fā)展了好多加快反應(yīng)速率的方法，如加入膦鹽，加入 Lewis酸，加壓，超聲和微波等方法。
反應(yīng)機(jī)理：
此反應(yīng)的關(guān)鍵步驟是胺催化劑加成到活性烯烴上形成穩(wěn)定的親核陰離子。此親核陰離子加成到醛上，隨后胺催化劑消除得到產(chǎn)物。
其他的氮親核陰離子也可以參與此反應(yīng)，如在一些反應(yīng)中DMAP和DBU比DABCO的效果還好：
對(duì)于芳香醛在極性，非極性和質(zhì)子性溶劑條件下，都確定了反應(yīng)的速度決定步驟首先是DABCO和丙烯酸酯的加成，而后是和醛的反應(yīng)。基于反應(yīng)速率數(shù)據(jù)，Tyler McQuade 最近提出 (J. Org. Chem. 2005, 70, 3980.DOI)，以下有半縮醛參與反應(yīng)的機(jī)理。
反應(yīng)實(shí)例：
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.
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.
Guanidine-Catalyzed γ-Selective Morita-Baylis-Hillman Reactions on α,γ-Dialkyl-Allenoates: Access to Densely Substituted Heterocycles
P. Selig, A. Turo?kin, 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.
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 Br?nsted 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 Br?nsted 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.
General procedure[Johnson C. L. et al. Tetrahedron Lett. 2004,45 7359]
Benzaldehyde (5 mmol) and methyl acrylate (5.5 mmol)were added to a round-bottomed flask containing the phosphonium salt (0.5 mmol)and DBACO (2.5 mmol). The flask was stoppered and the mixture was stirred atroom temperature for 24 h. the mixture was diluted with DCM (10mL) and washedsuccessively with aq. HCl (2M) and water. The organic phase was dried andconcentrated. The residue was purified by flash chromatography (ethyl acetate/hexane, 1:3) to give methyl 3-hydroxy-2-methylidene-3-phenylpropionate.
