Enantioselective Synthesis of Alkylated Centers: The Fukuyama Synthesis of (-)-Histrionicotoxin

Vinod K. Singh of the Indian Institute of Technology, Kanpur optimized (Org. Lett. 2011, 13, 6520. DOI: 10.1021/ol202808n) an organocatalyst for the enantioselective addition of thiophenol to an imide 1 to give 2 in high ee. Amir H. Hoveyda of Boston College developed (Angew. Chem. Int. Ed. 2011, 50, 7079. DOI: 10.1002/anie.201102398) a Cu catalyst for the preparation of 4 by the enantioselective hydroboration of a 1,1-disubstituted alkene 3.

Yong-Qiang Tu of Lanzhou University effected (Chem. Sci. 2011, 2, 1839. DOI: 10.1039/C1SC00295C) enantioselective bromination of the prochiral 5 to give the bromoketone 6. Song Ye of the Institute of Chemistry, Beijing established (Chem. Commun. 2011, 47, 8388. DOI: 10.1039/C1CC12316E) the alkylated quaternary center of the dimer 8, by condensing a ketene 7 with CS₂.

Li Deng of Brandeis University added (Angew. Chem. Int. Ed. 2011, 50, 10565. DOI: 10.1002/anie.201105536) cyanide in a conjugate sense to an acyl imidazole 9, to give 11. Pier Giorgio Cozzi of the Università di Bologna prepared (Angew. Chem. Int. Ed. 2011, 50, 7842. DOI: 10.1002/anie.201102562) the thioacetal 14 by condensing 13 with an aldehyde 12, followed by reduction.

Takahiro Nishimura and Tamio Hayashi of Kyoto University devised (Chem. Commun. 2011, 47, 10142. DOI: 10.1039/C1CC14098A) a Co catalyst for the enantioselective addition of a silyl alkyne 16 to an enone 15, to give the alkynyl ketone 17. Ping Tian and Guo-Qiang Lin of the Shanghai Institute of Organic Chemistry described (Tetrahedron 2011, 67, 10186. DOI: 10.1016/j.tet.2011.08.070) improved catalysts for the enantioselective conjugate addition of dimethyl malonate 19 to the nitroalkene 18, to give 20.

Keiji Maruoka, also of Kyoto University, established (Chem. Sci. 2011, 2, 2311. DOI: 10.1039/C1SC00453K) conditions for the enantioselective addition of an aldehyde 21 to the acceptor 22, to give, after reduction, an alcohol 23 that could readily be cyclized to the lactone. Jianrong (Steve) Zhou of Nanyang Technological University prepared (J. Am. Chem. Soc. 2011, 133, 15882. DOI: 10.1021/ja2066829) the ester 26 by arylation, under Pd catalysis, of a ketene silyl acetal 24 with the aryl triflate 25. Benjamin List of the Max-Planck-Institut, Mülheim employed (Angew. Chem. Int. Ed. 2011, 50, 9471. DOI: 10.1002/anie.201103263) a system of three catalysts to effect the enantioselective alkylation of an aldehyde 27 with the allyic alcohol 28, to give 29. Valery V. Fokin of Scripps, La Jolla used (J. Am. Chem. Soc. 2011, 133, 10352. DOI: 10.1021/ja202969z) a chiral Rh catalyst to mediate insertion of the carbene derived from 31 selectively into just one of the 14 H’s of 30.

Tohru Fukuyama of the University of Tokyo established (Org. Lett. 2011, 13, 4446. DOI: 10.1021/ol2018032) the central stereogenic center of (-)-Histrionicotoxin 35 by an ene reaction of paraformaldehyde with the readily-prepared allene 33. It is a measure of the challenge of constructing enantiomerically-pure α-quaternary amines that the authors chose to first prepare the all-carbon center, then invert one of the substituents.