Transannular Michael reaction

SCHEME 20.23. The synthesis of ( )-jasmine ketolactone by the transannular Michael reaction. 

Euphoreppinol class diterpenes show a complex 5-7-6-3 fused ring system, which was proposed to be biosynthesized from lathyrane skeleton by transannular C—C bond formation. Based on this hypothesis, Matsuura and Yama-mura developed a biomimetic synthesis of the euphoreppinol ring system 94 by the transannular Michael reaction of... 

Scheme 20.25). The nucleophUic enolate 93 itself was formed by a diastereoselective intermolecular O-Michael reaction of 92 with a hthium alkoxide through outside attack of the macrocychc enone. The alkoxide also served as a surrogate of the C5-hydroxy group of the natural product. The transannular Michael reaction of 93 led to stereoselective formation of the tetracyclic 94 in 73% yield. The stereoselectivity of the transannular Michael reaction was a result of the favorable conformation of the macrocycle. 

SCHEME 20.25. A transannular Michael reaction approach toward the synthesis of euphoreppinol. 

SCHEME 20.26. The transannular Michael reaction toward the synthesis of waihoensene. 

Norzoanthamine is a heptacychc alkaloid originally isolated from marine zoanthids. In addition to its complex molecular structure, norzoanthamine is well-known for its potent antiosteoporotic activity. In their studies toward the total synthesis of norzoanthamine, Yang and co-workers developed a 12-step enantioselective synthesis of the highly functionalized and stereochemically complex ABC ring system. A transannular Michael reaction cascade was... 

SCHEME 20.27. The transannular Michael reaction cascade in the total synthesis of salvinorin A. 

SCHEME 20.28. The norzoanthamine ABC ring system by a transannular Michael reaction cascade. 

Snider BB, Zhou J. Synthesis of (+)-Sch 642305 by a bio-mimetic transannular Michael reaction. Org. Lett. 

Xue H, Yang J, Gopal P. Toward the synthesis of norzoanth-amine building carbocyclic core by a transannular Michael reaction cascade. Org. Lett. 2011 13 5696-5699. 

For a recent study of a transannular Michael reaction cascade Xue H, Gopal P, Yang J. Stereochemical study of a transannular Michael reaction cascade. J. Org. Chem. 2012 77 8933 945. 

A transannular Michael reaction cascade with both (E,Z)- and ( , )-macrocyclic-1,7-bis-enones (307) has been reported to afford triyclic products (308) with excellent diastereoselectivity. By contrast, (Z,E)- and (Z,Z)-macrocyclic lactones failed to cyclize, apparently due to an unfavourable geometry. 

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