Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 11, 2014
Douglass F. Taber
University of Delaware

Organocatalyzed C-C Ring Construction: The Carreira Synthesis of (+)-Crotogoudin

Kazuaki Kudo of the University of Tokyo developed (Org. Lett. 2013, 15, 4964. DOI: 10.1021/ol402227y) a peptide catalyst for the enantioselective construction of 3 by the addition of 2 to 1. Thorsten Bach of the Technische Universität München devised (Science 2013, 342, 840, DOI: 10.1126/science.1244809; J. Am. Chem. Soc. 2013, 135, 14948, DOI: 10.1021/ja408167r) a Lewis acid organocatalyst for the photocyclization of 4 to 5.

Albert Moyano of the Universitat de Barcelona effected (Eur. J. Org. Chem. 2013, 3103. DOI: 10.1002/ejoc.201300197) enantioselective conjugate addition of 7 to 6 to give the cyclopentane 8. Daniel Romo of Texas A&M optimized (Nature Chem. 2013, 5, 1049. DOI: 10.1038/nchem.1788) the addition of 9 to 10 to give the β-lactone 11. Kamal Kumar and Herbert Waldmann of the Technische Universität Dortmund found (Angew. Chem. Int. Ed. 2013, 52, 9576. DOI: 10.1002/anie.201302045) that the addition of 12 to 13 followed by Baeyer-Villiger oxidation and deacylation delivered 14 in high ee. David W. Lupton of Monash University opened (Angew. Chem. Int. Ed. 2013, 52, 9149. DOI: 10.1002/anie.201304081) the cyclopropane of 15 in situ, leading to an ester enolate that added to 16 to give 17.

Jeffrey S. Johnson of the University of North Carolina used (Chem. Sci. 2013, 4, 2828. DOI: 10.1039/C3SC51022K) an organocatalyst to mediate the addition of the prochiral 18 to 19, leading to 20. M. Belén Cid of the Universidad Autónoma de Madrid added (J. Org. Chem. 2013, 78, 10737. DOI: 10.1021/jo401686u) the nitroalkane 22 to the unsaturated aldehyde 21, leading, after intramolecular Julia-Kocienski addition, to the cyclohexene 23. Additions that proceed in high ee with cyclopentenone and cyclohexenone are often not as selective with cycloheptenone 24. Wei Wang of the University of New Mexico and Wenhu Duan of the Shanghai Institute of Materia Medica observed (Tetrahedron Lett. 2013, 54, 3791. DOI: 10.1016/j.tetlet.2013.05.019) that addition of nitromethane and of nitroethane to 24 were both highly effective.

Strategies have been developed for applying organocatalysis to the assembly of polycarbocyclic ring systems. Sanzhong Luo of the Beijing National Laboratory for Molecule Sciences uncovered (Synthesis 2013, 45, 1939. DOI: 10.1055/s-0033-1338891) a simple amine that efficiently catalyzed the Robinson annulation of 26 with 27 to give 28. We (J. Org. Chem. 2013, 78, 8437. DOI: 10.1021/jo401158d) allylated 29 to give, after methyl coupling and oxy-Cope rearrangement, a ketone that condensed with methyl vinyl ketone 27 to give 31. Bor-Cherng Hong of the National Chung Cheng University effected (Org. Lett. 2013, 15, 6258. DOI: 10.1021/ol403113c) coupling of 32, 19, and 33 to give 34.

En route to (+)-Crotogoudin (37), Erick M. Carreira of ETH Zürich reduced (Angew. Chem. Int. Ed. 2013, 52, 11168. DOI: 10.1002/anie.201305822) the prochiral diketone with baker's yeast to give 36 in high ee. Following the precedent of Frejd (Tetrahedron: Asymm. 2010, 21, 1374. DOI: 10.1016/j.tetasy.2010.06.003) sugar was added for the reduction. Smallridge showed (Tetrahedron: Asymm. 1997, 8, 1049. DOI: 10.1016/S0957-4166(97)00050-5) some years ago that such reductions often proceed well in a heterogeneous mixture of solid yeast, petroleum ether and water, without added sugar.

D. F. Taber, Org. Chem. Highlights 2014, August 11.