Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 10, 2023
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Louie Synthesis of Septicine

Malte Brasholz of the University of Rostock developed a protocol for the photochemically-driven in situ oxidation of the quinoxalinone 1 followed by [2+2] cycloaddition with methacrylonitrile 2 to give the azetidine 3 with high diastereocontrol (Org. Lett. 2022, 24, 8041. DOI: 10.1021/acs.orglett.2c03291). Varinder K. Aggarwal of the University of Bristol assembled the azetidine 5 by a telescoped series of transformations from the dibromo amine 4 (Angew. Chem. Int. Ed. 2022, 61, e202114049. DOI: 10.1002/anie.202214049).

Marina Rubini of University College Dublin achieved high diastereoselectivity in the conversion of the pyroglutamic acid derivative 6 to the protected 4-methyl proline 8, via initial condensation with Bredereck's reagent (7) (Org. Biomol. Chem. 2022, 20, 6324. DOI: 10.1039/D2OB01011A). Todd K. Hyster of Princeton University effected the enantioselective enzymatic cyclization of the chloroacetamide 9 to the γ-lactam 10 (ACS Catal. 2022, 12, 9801. DOI: 10.1021/acscatal.2c02294). Takahiro Nishimura of Osaka Metropolitan University added styrene (12) and t-butyl acrylate (13) sequentially to the benzimidazolyl pyrrolidine 11 to give the pyrrolidine 14 in high ee (Org. Lett. 2022, 24, 6828. DOI: 10.1021/acs.orglett.2c02733). Brian M. Stoltz of Caltech developed conditions for carbonyl extrusion to convert the N-hydroxylactam 15, prepared in high ee, to the pyrrolidine 16 (Tetrahedron 2022, 123, 132940. DOI: 10.1016/j.tet.2022.132940).

James M. Mayer and Jonathan A. Ellman of Yale University and Shuming Chen of Oberlin College developed conditions for equilibrating the cis dialkyl δ-lactam 17 to the more stable trans dialkyl δ-lactam 17 (ACS Catal. 2022, 12, 7798. DOI: 10.1021/acscatal.2c02232). Bang-Guo Wei and Chang-Mei Si of Fudan University established a reductive protocol for assembling the alkynyl piperidine 21 by coupling the methoxy piperidine 19 with the sulfonyl alkyne 20 (Chem. Commun. 2022, 58, 10841. DOI: 10.1039/D2CC03984B). Zhiming Li and Junliang Zhang, also of Fudan University, prepared the piperidine 24 by combining the alkenyl iodide 22 with the aryl diazomethane generated in situ from the tosylhydrazone 23 (Chem. Sci. 2022, 13, 11150. DOI: 10.1039/D2SC03999K). Jun-An Ma of Tianjin University, Manfred T. Reetz of the Max-Planck-Institut für Kohlenforschung and Zhoutong Sun of the Tianjin Institute of Industrial Biotechnology designed an enzyme that cyclized the prochiral oxetane 25 to the piperidine 26 in high ee (Nature Commun. 2022, 13, 7813. DOI: 10.1038/s41467-022-35468-y).

Stefano Nicolai and Jérôme Waser of the Ecole Polytechnique Fédérale de Lausanne used a Cu catalyst to mediate the assembly of the lactam 29 by coupling the racemic cyclopropane 27 with the imine 28 (Angew. Chem. Int. Ed. 2022, 61, e202209006. DOI: 10.1002/anie.202209006). Lara R. Malins of Australian National University established reductive conditions for bridging the two free amines of an oligopeptide with the dialdehyde 30 to give the cyclic peptide 31 (Org. Biomol. Chem. 2022, 20, 6250. DOI: 10.1039/D2OB00782G).

Septicine (35) was isolated from the Borneo fig Ficus septica. Janis Louie of the University of Utah cyclized the pyroglutamic acid-derived diazo ketone 32 to the α-lactam 33, and combined that with the alkyne 34, leading to 35 (J. Org. Chem. 2022, 87, 8871. DOI: 10.1021/acs.joc.2c00365).

D. F. Taber, Org. Chem. Highlights 2023, April 10.