Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 8, 2021
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Breuning Synthesis of Leontidine

Jonathan T. Reeves of Boehringer Ingelheim constructed the aziridine 3 by adding the formyl anion derived from the formamide 1 to the azirine 2 (Org. Lett. 2021, 23, 4396. DOI: 10.1021/acs.orglett.1c01334). Using a chiral bicyclic lactam photocatalyst, Thorsten Bach of the Technisches Universität München achieved high selectivity in the [2+2] cycloaddition of the quinoxalinone 4 with the styrene 5, leading to the azetidine 6 (Angew. Chem. Int. Ed. 2021, 60, 2684. DOI: 10.1002/anie.202013276).

Paul A. Clarke of the University of York used a Binol-derived phosphoric acid to direct the absolute sense of the cyclization of the unsaturated thioester 7 to the pyrrolidine 8 Org. Lett. 2020, 22, 8116, DOI: 10.1021/acs.orglett.0c03090; Tetrahedron 2021, 78, 131789, DOI: 10.1016/j.tet.2020.131789). Emma K. Edelstein of Merck Process achieved high ee in the construction of the pyrrolidine 11 by the conjugate addition of phenylboronic acid 10 to the dehydroproline 9 (ACS Catal. 2021, 11, 743. DOI: 10.1021/acscatal.0c04648). Yoshiharu Iwabuchi of Tohoku University observed high regioselectivity in the cyclization of the γ-epoxy amine 12 to the hydroxypyrrolidine 13 (Chem. Eur. J. 2021, 27, 1961. DOI: 10.1002/chem.202004455). Steven L. Castle of BYU followed up the radical cyclization of the O-phenyl oxime 14 in the presence of TEMPO (15) with the direct addition of allyl magnesium chloride, leading to the pyrrolidine 16 with high diastereoselectivity (Org. Lett. 2021, 23, 3970. DOI: 10.1021/acs.orglett.1c01148).

Daniel Seidel of the University of Florida used BF3.OEt2 to promote the diastereoselective addition of lithioacetonitrile (18) to the 1-piperideine 17, to give the piperidine 19 (Org. Lett. 2021, 23, 797, DOI: 10.1021/acs.orglett.0c04024; Angew. Chem. Int. Ed. 2021, 60, 1625, DOI: 10.1002/anie.202011641). Gurunath Suryavanshi of CSIR-National Chemical Laboratory assembled the allylic alcohol 22 by combining the 4-piperidinone 20 with nitrosobenzene 21 in the presence of L-proline catalyst (Tetrahedron Lett. 2021, 67, 152838. DOI: 10.1016/j.tetlet.2021.152838). Frank Glorius of the Westfälische Wilhelms-Universität Münster described the partial hydrogenation of the oxazolidinone-linked pyridine 23, leading, after hydrolysis, to the piperidinone 24 in high ee (Angew. Chem. Int. Ed. 2021, 60, 6425. DOI: 10.1002/anie.202016771). Kun Liu of Tianjin Normal University and Xiaofeng Tong of Changzhou University achieved high enantioselectivity in the Pd-catalyzed cyclization of the alkenyl iodide 25 to the α-quaternary iodide 26 (J. Am. Chem. Soc. 2021, 143, 1924. DOI: 10.1021/jacs.0c10797).

Brian M. Stoltz of Caltech devised the cyclization and ring expansion of 27 to the eight-membered cyclic amine 28 (Org. Lett. 2021, 23, 3300. DOI: 10.1021/acs.orglett.1c00763). Hendrik Zipse of LMU München and Philippe Renaud of the University of Bern showed that the rearrangement of the azide 29 to the bicyclic amine 30 proceeded with high diastereoselectivity (Angew. Chem. Int. Ed. 2021, 60, 10179. DOI: 10.1002/anie.202016892).

The tetracyclic alkaloid leontidine (33) was isolated in 1932 from the perennial herb Leontice ewersmanni of central Asia. Matthias Breuning of the University of Bayreuth assembled 33 by the cyclization of the acetal 31 to the pyrrole 32, followed by diastereoselective hydrogenation (Eur. J. Org. Chem. 2021, 2498. DOI: 10.1002/ejoc.202100270).

D. F. Taber, Org. Chem. Highlights 2021, November 8.