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Monday, August 26, 2013
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Defucogilvocarcin V (Bodwell), (+)-Carrisone (Danishefsky), (+)-Fusarisetin A (Theodorakis), 9β-Presilphiperfolan-1α-ol (Stoltz), 7-Isocyano-11(20), 14-epiamphilectadiene (Shenvi)

Graham J. Bodwell of Memorial University constructed (J. Org. Chem. 2012, 77, 8028. DOI: 10.1021/jo3012682) the third aromatic ring of Defucogilvocarcin V (4) by the inverse electron demand addition of 1 to 2. The methyl ester 3 provided a useful departure point for the preparation of analogues of 4.

Samuel J. Danishefsky of Columbia University and Sloan-Kettering found (Chem. Sci. 2012, 3, 3076. DOI: 10.1039/C2SC20868G) that the kinetic product from the addition of 5 to 6 could be equilibrated with a trace of acid to the more stable regioisomer 7. Oxidation to the enone followed by deoxygenation led to (+)-Carissone (8). Michael E. Jung of UCLA developed (Org. Lett. 2012, 14, 5169. DOI: 10.1021/ol302172y) Me3Al-triflimide catalyts (not illlustrated) for promoting difficult additions, such as 5 to 6.

Professor Danishefsky had demonstrated the efficacy of cyclobutenones as Diels-Alder dienophiles. More recently, he showed (J. Am. Chem. Soc. 2012, 134, 16080. DOI: 10.1021/ja307708q) that intramolecular cyclization of the cyclobutenone 9 led to the trans-fused, angularly-substituted product 11.

To prepare (+)-Fusarisetin A (14), Emmanuel A. Theodorakis of UC San Diego needed (Chem. Sci. 2012, 3, 3378. DOI: 10.1039/C2SC21308G) the all-E geometric isomer of 12. He showed that equilibration of a 3:2 mixture with I2 led to a single dominant isomer, that could be taken directly into the cycloaddition.

Brian M. Stoltz of CalTech prepared (Angew. Chem. Int. Ed. 2012, 51, 9674. DOI: 10.1002/anie.201205276) the triene 15 in enantiomerically-enriched form by enantioselective allylation of a cycloheptenone derivative. Intramolecular cycloaddition of 15 established the tricyclic skeleton of 9β-Presilphiperfolan-1α-ol (17).

Ryan A. Shenvi of Scripps/La Jolla devised (J. Am. Chem. Soc. 2012, 134, 19604. DOI: 10.1021/ja310129b) the triene 19. Addition of 18 to 19 gave an intermediate that was unraveled with catalytic Yb(OTf)3 to give a trienone, which on heating engaged with the distal alkene to cyclize to 20. This set the stage for diastereoselective conjugate addition leading to 7-Isocyano-11(20), 14-epiamphilectadiene (21).

D. F. Taber, Org. Chem. Highlights 2013, August 26.