Baylis-Hillman reaction functional group

Hydroxyazetidin-2-ones can be oxidised efficiently to azetidine-2,3-diones by P205 in DMSO <00JPR585>, and then the 3-carbonyl group can be alkylated stereoselectively by application of the Baylis-Hillman reaction <99TL7537> or by use of substituted propargyl bromides to provide densely functionalized 3-hydroxy-P-lactams . 

P-Amino carbonyl compounds containing an a-atkyUdene group are densely functionalized materials, which are widely applied in the synthesis of medicinal reagents and natural products [265]. These products are usually prepared through the classic aza-Morita-Baylis-Hillman reaction [176, 177] of activated imines and electron-deficient alkenes catalyzed by tertiary amines or phosphines. Chen and co-workers, in 2008, identified bis-thiourea 106 as a suitable catalyst for the... 

Sasai et al developed a bifunctional BINOL-derived organocatalyst (37) and reported an aza Morita-Baylis-Hillman reaction (Scheme 2.80) [148]. While the 3-pyridyl moiety functioned as a Lewis basic site, the diol moiety worked as a Bronsted acidic site. It is noted that introduction of N-isopropyl-N-3-pyridinylaminomethyl moiety at the 3-position is essential for attaining excellent enantioselectivity. They subsequently introduced 2-diphenylphosphinophenyl group onto the third position and successfully utilized it in the aza Morita-Baylis-Hillman reaction [149]. 

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). 

More significant results are the multi-component condensation by way of Michael-aldol and Michael-Michael-aldol reaction sequences and the Michael-Baylis-Hillman tandem, each leading to cyclohexenes bearing multiple functional groups and stereogenic centers. 

The Wang group also realized enantioselective oxidative cross-coupling reactions between tertiary amines and the activated olefins by merging Cu(OTf)2 with quinine as the best cooperative catalysts/ A Morita-Baylis-Hillman-type mechanism is in operation. It was notable that molecular oxygen was employed as the sole oxidant. As shown in Scheme 2.12, the reactions between Ai-aryl THIQs and the a,p-unsaturated aldehydes or ketones 30 proceeded smoothly to afford the a-functionalized products 31 in up to 81% yield and 99% ee. 

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