Heterocycles as Key Substrates in MCRs

SCHEME 6.10 Synthesis of cannabinol 83 in a multicomponent domino reaction. 

SCHEME 6.11 Organocatalytic oxa-Michael-Michael-Michael-aldol as the key step in the synthesis of (+)-conicol 89. 

Hong and coworkers have demonstrated the three-component organocatalytic oxa-Michael-Michael-Michael-aldol condensation of a,p-unsaturated aldehyde 84 with 2-(( )-2-nitrovinyl)benzene-l,4-diol (83), as the key step in the total synthesis of (+)-conicol 89 (Schane 6.11) [31], 

The reaction started with the tandem oxa-Michael-Michael reaction of 83 and 84 to give 87 in 76% yield and greater than 99% ee. The following Michael-aldol condensation with 4,4-dimethoxy-but-2-enal 85 works nicely in 69% yield and also excellent enantioselectivity. The obtained hexahydro-6//-benzo[c]chromene 88 is a highly functionalized intermediate in the total synthesis of (+)-conicol 89. The two-step reaction could be achieved in one pot from 83 and 84, without isolation of the intermediate 87, with a 55% overall isolated yield of 88. 

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