Double intramolecular hetero-Michael addition

Forsyth, C.J. Hao, J. Aiguade, J. (2001) Synthesis of the (-i-)-C26-C40 domain of the azaspiric acids by a novel double intramolecular hetero-Michael addition strategy. Angew. Che. Int. Ed. Engl., 40, 3663-7. 

Scheme 16.6. Construction of the FGHI rings of azaspiracid-1 using a double intramolecular hetero-Michael addition (Forsyth 2001).

Double Intramolecular Hetero-Michael Addition (DIHMA)... 

Alternatively, a double intramolecular hetero-Michael addition (DIHMA) can be used to assemble a spiroacetal from an a,p-ynone (Scheme 61). NMR smdies have shown that, in accordance with Baldwin s rules, initial 6-endo-dig cyclization rather than 6-exo-dig is favored. Subsequent 5-exo-trig cyclization furnishes the 5,6-spiroacetal [132]. The corresponding 6,6-spiroacetals are obtained in an analogous manner. 

Scheme 61 Double intramolecular hetero-Michael addition in the synthesis of spiroacetals...

The synthesis of a series of 6,6-bisbenzannulated spiroketals has been achieved by a novel microwave-assisted double intramolecular hetero-Michael addition approach, with good yield (Choi et al, 2009). In this synthesis, coupling of an aryl acetylene and an aryl aldehyde led to an alky mol via acetylide anion addition, which was followed by oxidation to give the desired ynone. Spirocyclization afforded bis-benzannulated spiroketals. 

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