Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 13, 2023
Douglass F. Taber
University of Delaware

Enantioselective Synthesis of Alcohols and Amines: The Huang/Chen Synthesis of α-Tocopherol

Pinhong Chen and Guosheng Liu of the Shanghai Institute of Organic Chemistry developed a protocol for the enantioselective conversion of a terminal alkene 1 to the secondary benzoate 2 (J. Am. Chem. Soc. 2022, 144, 7972. DOI: 10.1021/jacs.2c02753). Osamu Onomura of Nagasaki University devised a procedure for the enantioselective oxidation of the prochiral triol 3 to the ester 4 (J. Org. Chem. 2022, 87, 6479. DOI: 10.1021/acs.joc.2c00398).

Andrea Gualandi, Paola Ceroni and Pier Giorgio Cozzi of the Università di Bologna and Luigi Cavallo of KAUST combined the aldehyde 5 with allyl acetate 6 to assemble the secondary alcohol 7 (Angew. Chem. Int. Ed. 2022, 61, e202114981. DOI: 10.1002/anie.202114981). Phil S. Baran of Scripps/La Jolla coupled the racemic phthalimido ester 8 with the organozinc 9 to give the secondary benzoate 10 in high ee (J. Am. Chem. Soc. 2022, 144, 10992. DOI: 10.1021/jacs.2c04358). Qinglei Chong and Fanke Meng, also of the Shanghai Institute of Organic Chemistry, used a Co catalyst to mediate the coupling of the benzoate 12 with the aldehyde 11, leading to the α-quaternary secondary alcohol 13 (J. Am. Chem. Soc. 2021, 143, 12755. DOI: 10.1021/jacs.1c05690). Gui-Juan Cheng of The Chinese University of Hong Kong and Benjamin List of the Max-Planck-Insitut für Kohlenforschung used a BINOL-derived imidodiphosphorimidate catalyst to direct the enantioselective conversion of the ketone 14 to the protected cyanohydrin 15 (Nature 2022, 605, 84. DOI: 10.1038/s41586-022-04531-5).

Xumu Zhang of the Southern University of Science and Technology and Qin Yin of the Shenzhen Institute of Advance Technology used a Ru catalyst to convert the ketone 16 to the secondary amine 17 (Chem. Commun. 2022, 58, 513. DOI: 10.1039/D1CC06601C). Shuming Chen of Oberlin College and Eric Meggers of Philipps-Universität Marburg used an iron catalyst to rearrange the hydroxylamine derivative 18 to the α-amino acid 19 (Nature Chem. 2022, 14, 566. DOI: 10.1038/s41557-022-00895-3). Marc Garcia-Borràs of the Universitat de Girona, K. N. Houk of UCLA and Frances H. Arnold of Caltech prepared the amine 21 by the enantioselective enzymatic amination of the alkyne 20 (J. Am. Chem. Soc. 2022, 144, 80. DOI: 10.1021/jacs.1c11340). Shaolin Zhu of Nanjing University assembled the benzamide 24 via Ni-catalyzed multicomponent coupling of the alkene 22 with the phthalimido ester 23 and chloroformate (J. Am. Chem. Soc. 2021, 143, 14089. DOI: 10.1021/jacs.1c07851).

Jialin Wang, also of the Southern University of Science and Technology, and Professor Zhang prepared the versatile α-quaternary amine chiron 26 by the hydroformylation of the enamide 25 (Chem. Sci. 2022, 13, 7215. DOI: 10.1039/D2SC02139K). Jonas C. Peters and Gregory C. Fu, also of Caltech, assembled the α-quaternary amine 28 by coupling an aniline with the racemic chloride 27 (J. Am. Chem. Soc. 2022, 144, 4550. DOI: 10.1021/jacs.1c12749).

α-Tocopherol 31, specifically the (2R, 4R', 8R') isomer depicted, is the biologically most active of the vitamin E family. Zedu Huang and Fener Chen of Fudan University established the absolute configuration of the precursor 30 by enantioselective lipase-mediated hydrolysis of the prochiral diester 29 (Org. Biomol. Chem. 2022, 20, 2909. DOI: 10.1039/D2OB00384H).

D. F. Taber, Org. Chem. Highlights 2023, February 13.