MORITA-BAYLIS-HILLMAN Vinyl Ketone

MORITA-BAYLIS-HILLMAN Vinyl Ketone Alkylation Amine catalyzed conversion of acrylates to a-(hydroxyalkyl) acrylates or of vinyl ketones to a-(hydroxyalkyl) vinyl ketones, also with chiral induction (see 1st edition). 

Also known as Morita-Baylis-Hillman reaction, and occasionally known as Rauhut-Currier reaction. It is a carbon—carbon bond-forming transformation of an electron-poor alkene with a carbon electrophile. Electron-poor alkenes include acrylic esters, acrylonitriles, vinyl ketones, vinyl sulfones, and acroleins. On the other hand, carbon electrophiles may be aldehydes, a-alkoxycarbonyl ketones, aldimines, and Michael acceptors. 

The most efficient catalyst system for the Morita-Baylis-Hillman reaction of methyl vinyl ketone has been reported by Miller [183, 184], Use of L-proline (58) (10 mol%) in conjunction with the A-methyl imidazole containing hexapeptide 131 (10 mol%) provided an efficient platform for the reaction of 125 with a series of aromatic aldehydes 127 (52-95% yield 45-81% ee) (Scheme 52). Importantly, it was shown that the absolute configuration of the proline catalyst was the major factor in directing the stereochemical outcome of the reaction and not the complex peptide backbone. 

M. Shi and Y.-L. Shi reported the synthesis and application of new bifunctional axially chiral (thio) urea-phosphine organocatalysts in the asymmetric aza-Morita-Baylis-Hillman (MBH) reaction [176, 177] of N-sulfonated imines with methyl vinyl ketone (MVK), phenyl vinyl ketone (PVK), ethyl vinyl ketone (EVK) or acrolein [316]. The design of the catalyst structure is based on axially chiral BINOL-derived phosphines [317, 318] that have already been successfully utilized as bifunctional catalysts in asymmetric aza-MBH reactions. The formal replacement of the hydrogen-bonding phenol group with a (thio)urea functionality led to catalysts 166-168 (Figure 6.51). 

The Morita-Baylis-Hillman (MBH) reaction is the formation of a-methylene-/ -hydroxycarbonyl compounds X by addition of aldehydes IX to a,/ -unsaturated carbonyl compounds VIII, for example vinyl ketones, acrylonitriles or acrylic esters (Scheme 6.58) [143-148]. For the reaction to occur the presence of catalytically active nucleophiles ( Nu , Scheme 6.58) is required. It is now commonly accepted that the MBH reaction is initiated by addition of the catalytically active nucleophile to the enone/enoate VIII. The resulting enolate adds to the aldehyde IX, establishing the new stereogenic center at the aldehydic carbonyl carbon atom. Formation of the product X is completed by proton transfer from the a-position of the carbonyl moiety to the alcoholate oxygen atom with concomitant elimination of the nucleophile. Thus Nu is available for the next catalytic cycle. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Peptide-based imidazole catalyst 63 in the presence of L-proline as a cocatalyst promoted asymmetric Morita-Baylis-Hillman reactions between methyl vinyl ketone and aromatic aldehydes (Scheme 22.14). The combination... 

The Morita-Baylis-Hillman reaction is a powerful transformation in organic synthesis, consisting of the formation of a-methylene-p-hydroxy-carbonyl compounds by the addition of aldehydes to a,p-unsaturated carbonyl compounds, such as vinyl ketones, acrylonitriles or acrylic esters. For the... 

As an extension of this work, the same authors have used polystyrene-supported proline as a recyclable catalyst in the Morita-Baylis-Hillman reaction of a range of aryl aldehydes with methyl or ethyl vinyl ketone. These reactions were performed in the presence of imidazole and provided a series of Morita-Baylis-Hillman adducts in moderate to high yields (17 88%) combined with high enantioselectivities of up to 95% ee (Scheme 2.55). This study represented the first example of supported proline as heterogeneous catalyst for the Morita-Baylis-Hillman reaction. In addition, Zhou et al. reported that these reactions could be eatalysed by combinations of L-proline with chiral tertiary amines derived from various readily available chiral sources, such as L-proline or (5)-a-phenylethylamine. In these conditions, the Morita-Baylis-Hillman adducts were obtained in reasonable chemical yields (34-97%) and low to good enantioselectivities (12 83% ee). In this study, it was demonstrated that the proline stereochemistry was the sole factor to determine the eonfiguration of the newly formed chiral centre. 

Good to excellent yields combined with excellent enantioselectivities of up to 94% ee were obtained for the Morita Baylis Hillman reaction of methyl vinyl ketone with various aromatic aldehydes by using a new class of chiral phosphino-... 

On the other hand, an axially chiral phosphine alcohol organocatalyst was successfully employed by Shi and Liu to promote the aza-Morita-Baylis-Hillman reaction between A -(arylmethylidene)arylsulfonamide and methyl vinyl ketone, providing the corresponding adducts in moderate to good yields (26-85%) and high enantioselectivities of up to 94% ee, when used at 10 mol % of catalyst loading in Furthermore, these authors have shown that the... 

In the same area, these authors have also investigated the efficiency of various chiral sterically congested phosphane-amide bifunctional organocatalysts with a binaphthyl scaffold in asymmetric aza-Morita-Baylis-Hillman reactions of A -sulfonated imines with activated olefins such as methyl and ethyl vinyl ketones." The corresponding aza-Morita-Baylis-Hillman adducts could be obtained in moderate to excellent yields (37-98%) and moderate to good... 

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