Morita-Baylis-Hillman reaction general scheme

Azocanes with nitrogen at a bridgehead such as fused azocane 289 were prepared starting from /V-protected amino aldehydes 286. Those amino aldehydes were converted into allylic alcohols by the classical Morita-Baylis-Hillman reaction or by condensation with selenium-stabilized carbanions, followed by oxidation <2007JOC5608>. Fused azocane 289 was prepared in good yield as described in Scheme 120. Formation of [ z, ,0]-bicyclic structures via these reactions is general and the stereochemistry of the starting amino-aldehyde is preserved. 

The Morita-Baylis-Hillman reaction is, in general, a carbon-carbon bondforming reaction of an a,(3-unsaturated compound with an aldehyde mediated by an organic nucleophilic base resulting in the formation of an allylic alcohol. Morita reported the use of a phosphine as catalyst and Baylis and Hillman used a tertiary amine. Variation of the electrophile to electron-deficient alkenes in a Michael-Michael elimination sequence leads to homo- and heterodimerisation and is known as the Rauhut-Currier reaction. The electrophilic aldehyde could be substituted by an imine or derivative in the aza-Morita-Baylis-Hillman reaction. Recently, there has been an increase in the use of this reaction for the construction of many different targets using many different amine derived catalysts. Scheme 2.2 shows a general view of this reaction and the accepted mechanism. ... 

In addition, Liu and Gamier have designed novel chiral trifunctional organocatalysts which were successfully applied as promoters to the aza-Morita-Baylis-Hillman reaction of methyl vinyl ketone with various aromatic A -tosyl imines in the presence of benzoic acid. In these conditions, the reaction yielded the products in moderate to high yields (31-95%) and general high enantioselectivities (88-94% ee), as shown in Scheme 3.32. 

Nucleophilic amines or alkyl phosphines can mediate the addition of electron-deficient alkenes to reactive carbonyls such as aldehydes or ketones. This transformation, which affords functionalized allylic alcohols, is generally termed the Morita-Baylis-Hillman (MBH) reaction (Scheme 5.1) [1, 2]. 

Scheme 5.1 The general reaction scheme of the Morita-Baylis-Hillman (MBH) reaction.

The Morita-Baylis-Hillman (MBH) reaction is an important 100% atom economic transformation that allows the formation in one step of a flexible allylic alcohol motif. Efforts in this field have been directed recently to the solution of two problems to enhance the generally sluggish reaction rate and to achieve asymmetric catalytic versions. Scheme 1.15 gives the catalytic cycle of the MBH reaction. The catalyst is a highly nucleophilic tertiary amine, generally DABCO, or a tertiary phosphine, which adds to the oc,P-unsaturated electrophile in a 1,4 fashion to deliver an enolate that, in turn, adds to the aldehyde. A critical step is the proton transfer from the enolizable position to the oxygen atom this process is catalysed by an alcohol that plays the role of a proton shuttle between the two positions. Water has also been reported to strongly speed up the reaction at a well-defined concentration. Moreover, the... 

The Baylis-Hillman (also called Morita-Baylis-Hillman) (MBH) reaction (see Sect. 10.2.4 and Scheme 10.17) is the base-catalyzed addition of keto compounds to acrylic derivatives. The catalyst is a cyclic tertiary amine such as 1,4-diazabicyclo[2.2.2]octane (DABCO). Due to the generally poor yields observed, the reaction has not received sufficient attention despite the great synthetic value of the polyfunctional adducts. Among the various methods proposed to activate the reaction, pressure 107] and hydrophobic effects [70] have been used. Table 10.31 presents the results obtained in some Baylis-Hillman reactions carried out under pressure in aqueous solution [108]. 

A general, one-pot synthesis of substituted tetraethyl 2-aminoethylidene-1,1-bisphosphonates (133) has been developed by Gajda. The direct and efficient conversion of the latter into aza-Moritae-Baylis-Hillman-type adducts (134), via the Horner-Wittig reaction with paraformaldehyde, has been also elaborated (Scheme 44). 

Schaus and coworkers have developed a general route to the Clerodane diter-pene core by the use of previously developed B rousted acid catalyzed asymmetric Morita-Baylis-Hillman (MBH) reaction/Lewis acid mediated ring-annulation process (Scheme 1.33) [31]. Excellent diastereoselectivity was achieved in the key MBH reaction in the presence of 10mol% of the chiral BINOL derivative (29), affording the key intermediate for the synthesis of Clerodane decalin core. 

---