Michael-Baylis-Hillman tandem reaction

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. 

Scheme 2.30 Tandem Michael-Morita-Baylis-Hillman -Knoevenagel reaction catalysed by a chiral diarylprolinol trimethylsilyl ether and L-proline.

An interesting alternative intramolecular cyclisation was discovered by Jprgensen and co-workers [187]. Although not strictly exploiting an enamine intermediate, the transformation represents a secondary amine catalysed Morita-Baylis-Hillman reaction leading to a series of highly functionalised cyclohexene products. Reaction of the Nazarov reagent 137 with a,P-unsaturated aldehydes in the presence of the diarylprolinol ether 30 led to the cyclohexene products 138 (49-68% yield 86-96% ee) via a tandem Michael/Morita-Baylis-Hillman reaction (Scheme 54). 

A new tandem Michael-aldol reaction of a,ft-unsaturated compounds bearing a chalcogenide or thioamide group with electrophiles has been reviewed.163 The product o -(o -hydroxyalkyl)enones - Morita-Baylis-Hillman (MBH) adducts - can be formed with significant stereocontrol when an optically active thione is used. 

Polyhaloalkyl-substituted chromones and 7-pyrones react with salicylaldehydes in the presence of piperidine to give a variety of fused 277-chromenes in good yields (Scheme 58) <2006JOC4538>. Although it is conceivable that this reaction could proceed through a Baylis-Hillman reaction pathway, studies of this reaction point to the mechanism being a tandem intramolecular oxa-Michael addition and subsequent Mannich condensation. 

A similar reaction was also reported by Jprgensen s group regarding the addition of Nazarov reagents (75) to enals (15). The reaction furnishes highly substituted cyclohexanones in high yields and stereoselectivities via an organocatalytic tandem Michael/Morita-Baylis-Hillman reaction catalyzed by the diphenylprolinol derivative VII [50]. 

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