Aldehydes Nazarov reagents

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). 

Divinyl ketones.1 These butadienes react with aromatic aldehydes in the presence of MgBr2-0(C2H3)2 or ZnCl2 to furnish divinyl ketones (Nazarov reagents). 

Scheme 7.29 Enantioselective formal [3 + 3] cycloaddition between Nazarov reagents and a,3-unsaturated aldehydes.

Similar conditions were applied by Gong et al. to the asymmetric formal [3 + 3] cycloaddition of a,p-unsaturated aldehydes with Nazarov reagents bearing an aryl group at C5, which, after oxidation, afforded the corresponding 3,4-dihydropyranones in good yields combined with excellent enantioselectivities of up to 97% ee. The best results are collected in Scheme 6.23. 

Scheme 6.23 Formal [3 + 3] cycloadditions of a,P-unsaturated aldehydes with Nazarov reagents.

The equilibrium between 1,3-diones and the corresponding enol form renders it a suitable reactant for [3+3] reactions of a,p-unsaturated aldehydes [128]. The Michael-Morita-Baylis-HiUman reaction between a,P-unsaturated aldehydes and 5-substituted Nazarov reagent (Scheme 1.81) was inhibited because of the steric effect. However, oxo-[3+3] cyclization proceeded in good yields and high enantiose-lectivies in this system [129]. 

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