Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 28, 2015
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Sarcandralactone A (Snyder), Pseudopterosin (-)-G-J aglycone (Paddon-Row/Sherburn), IBIR-22 (Westwood), Muironolide A (Zakarian), Platencin (Banwell), Chatancin (Maimone)

En route to Sarcandralactone A (3), Scott A. Snyder of Scripps Florida effected (Angew. Chem. Int. Ed. 2015, 54, 7842. DOI: 10.1002/anie.201500925) Diels-Alder cycloaddition of the activated enone 1 to the Danishefsky diene. On exposure to trifluoroacetic acid, the adduct was unraveled to the ene dione 2.

Michael N. Paddon-Row of the University of New South Wales and Michael S. Sherburn of the Australian National University prepared (Nature Chemistry 2015, 7, 82. DOI: 10.1038/nchem.2112) the allene 4 in enantiomerically-pure form. Sequential cycloaddition with 5 followed by 6 gave an adduct that was decarbonylated to 7. Further cycloaddition with nitroethylene 8 led to the Pseudopterosin (-)-G-J aglycone (9).

The protein-protein interaction inhibitor IBIR-22 (12) contains a quaternary α-amino acid pendant to a bicyclic core. Nicholas J. Westwood of the University of St. Andrews set (Angew. Chem. Int. Ed. 2015, 54, 4046. DOI: 10.1002/anie.201411141) the absolute configuration of the core 11 by using an organocatalyst to activate the cyclization of 10.

Metal catalysts can also be used to set the absolute configuration of a Diels-Alder cycloaddition. In the course of establishing the structure of the marine natural product Muironolide A (15), Armen Zakarian of the University of California, Santa Barbara cyclized (J. Am. Chem. Soc. 2015, 137, 5907. DOI: 10.1021/jacs.5b03531) the enol form of 13 preferentially to the diastereomer 14.

Unactivated intramolecular Diels-Alder cycloadditions have been carried out with more and more challenging substrates. A key step in the synthesis (Chem. Asian. J. 2015, 10, 427. DOI: 10.1002/asia.201403069) of (-)-Platencin (18) by Martin G. Banwell, also of the Australian National University, was the cyclization of 16 to 17.

In another illustration of the power of the unactivated intramolecular Diels-Alder reaction, Thomas J. Maimone of the University of California, Berkeley, cyclized (Angew. Chem. Int. Ed. 2015, 54, 1223. DOI: 10.1002/anie.201410443) the tetraene 19 to the tricycle 20. Allylic chlorination followed by reductive cyclization converted 20 to Chatancin (21).

D. F. Taber, Org. Chem. Highlights 2015, December 28.