Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a Pd II-catalyzed ring-opening strategy

Chemistry : a European Journal
Matthew J FlemingMark Lautens

Abstract

New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a meso-azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2-aryldihydronaphthalenes in high yield and in up to 90 % ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring formation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c]phenanthridine alkaloids, (+)-chelidonine, (+...Continue Reading

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Citations

Jul 9, 2013·Bioscience, Biotechnology, and Biochemistry·Atsuo NakazakiToshio Nishikawa
Sep 30, 2016·Chemical Reviews·Maria ChrzanowskaMaria D Rozwadowska
Mar 13, 2018·Chemical Communications : Chem Comm·Rui-Qi LiTeck-Peng Loh
Mar 2, 2013·Angewandte Chemie·Matthew R Wilson, Richard E Taylor
May 12, 2012·Chemical Communications : Chem Comm·Takahiro SawanoTamio Hayashi
Feb 6, 2021·Chemical Society Reviews·Sundaravel Vivek KumarPatrick J Guiry
Aug 20, 2008·Organic Letters·Takahiro NishimuraTamio Hayashi
Dec 1, 2017·Journal of the American Chemical Society·Mikiko OkumuraDavid Sarlah
Sep 16, 2011·Organic Letters·Deepali WaghrayWim Dehaen
Aug 12, 2014·The Journal of Organic Chemistry·Muthuraj PrakashVenkitasamy Kesavan

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