Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 15, 2011
Douglass F. Taber
University of Delaware

Organocatalysis of Carbocyclic Construction: The MacMillan Synthesis of (+)-Frondosin B

One of the more powerful applications of organocatalysis has been the enantioselective transformation of preformed prochiral rings. In the five-membered ring series, Nobuyuki Mase of Shizuoka University effected (Synlett 2010, 2340. DOI: 10.1055/s-0030-1258533) enantioselective addition of malonate to cyclopentenone 1, and Eric N. Jacobsen of Harvard University devised (Angew. Chem. Int. Ed. 2010, 49, 9753. DOI: 10.1002/anie.201005183) a guanidinium catalyst for the Claisen rearrangement of 4 to 5.

Jacek Mlynarski of Jagiellonian University accomplished (Tetrahedron Lett. 2010, 51, 4088. DOI: 10.1016/j.tetlet.2010.05.134) the enantioselective hydroxymethylation of 6. This worked equally well for cyclopentanone and cycloheptanone. The dynamic kinetic resolution/reductive amination of 8 described (Angew. Chem. Int. Ed. 2010, 49, 4612. DOI: 10.1002/anie.201001715) by Benjamin List of the Max-Planck-Institut, Mülheim worked best with cyclohexanones such as 8.

Organocatalysts can also be effective for the construction of carbocyclic rings. Teck-Peng Loh of Nanyang Technological University found (Chem. Sci. 2010, 1, 739. DOI: 10.1039/C0SC00123F,) a commercial phosphine catalyst that efficiently mediated the condensation of 10 with 11. David W. C. MacMillan of Princeton University used (J. Am. Chem. Soc. 2010, 132, 10015. DOI: 10.1021/ja104313x) a SOMO catalyst to combine 13 with 14 to make 15. Dawei Ma of the Shanghai Institute of Organic Chemistry employed (Org. Lett. 2010, 12, 3634. DOI: 10.1021/ol101414b) the Hayashi catalyst in the double Michael condensation of 16 with 17. Daniel Romo of Texas A&M University showed (Org. Lett. 2010, 12, 3764. DOI: 10.1021/ol101388h) that the appropriate organocatalyst could direct 19 to either diastereomer of the β-lactone 20. Professor Romo also reported (Angew. Chem. Int. Ed. 2010, 49, 9479. DOI: 10.1002/anie.201004671) the desymmetrization of 2-alkyl cyclohexane-1,3-diones using a similar approach.

In the six-membered ring series, José Alemán and José Luis García Ruano of the Universidad Autónoma de Madrid carried out (Eur. J. Org. Chem. 2010, 4482. DOI: 10.1002/ejoc.201000502) Robinson annulation of 17 with 21. Ying-Chun Chen of Sichuan University, again using the Hayashi catalyst, reported (Angew. Chem. Int. Ed. 2010, 49, 6418. DOI: 10.1002/anie.201002912) the addition of 17 to 23 to give 24.

In another elegant application of visible light-mediated organocatalysis, Professor MacMillan described (Chem. Sci. 2010, 1, 37. DOI: 10.1039/C0SC00204F) the addition of the commercial boronic acid 25 to 17. The addition of the anion 27 to the adduct 26 gave the allylic alcohol 28. Exposure of 28 to BBr3 effected cyclization and demethylation, to complete a very short synthesis of (+)-Frondosin B (29).

D. F. Taber, Org. Chem. Highlights 2011, August 15.