Silver-Mediated Oxidative Decarboxylative Intramolecular Asymmetric Radical Cyclization (C sp3 -C sp2 ) via Memory of Chirality: Access to Circumdatin Alkaloids Pankaj S. Mahajan †,‡ and Santosh B. Mhaske* ,†,‡ † Division of Organic Chemistry and ‡ Academy of Scientific and Innovative Research (AcSIR), CSIR-National Chemical Laboratory, Pune 411008, India * S Supporting Information ABSTRACT: A novel silver-mediated oxidative decarboxyla- tive intramolecular asymmetric radical cyclization has been developed to form a C sp3 -C sp2 bond via memory of chirality. The application of the process has been demonstrated for the synthesis of the circumdatin class of alkaloids in high enantiopurity with retention of the configuration. The developed protocol is mild and works with an inexpensive silver catalyst in the absence of ligand, base, or additives. The involvement of a monoradical in the reaction has been established by trapping the radical intermediate. O xidative decarboxylative coupling (ODC) reactions are the subject of enormous contemporary interest, because of their versatility, leading to a vast array of scaffolds via regioselective formation of a new C-C or C-heteroatom bonds, utilizing carboxylic acid group as a handle. 1 The work in this area, which started in the late 1960s, came to the limelight after the classical Minisci reaction, 2 which has been now largely explored with several different variants (see eqs 1 and 2 in Scheme 1). 1i,3 The discovery of the Heck-type oxidative decarboxylative coupling by Myers truly commenced the research activities in this area (eq 3 in Scheme 1). 4 Lately, the pioneering work by MacMillan in the area of photo- catalyzed decarboxylative radical C-C coupling reactions led to novel transformations and useful scaffolds (eqs 4-6 in Scheme 1), which caught immense attention from organic chemists. 5 The amino acid substrates, upon decarboxylation by a photocatalyst, generate achiral radical intermediates, which provide racemic compounds. However, MacMillan et al. recently demonstrated that intervention of chiral ligands could provide enantioenriched products (eq 6 in Scheme 1). 6 The formation of an enantioenriched product via a conformationally labile stereogenic center of an enantiopure substrate was first reported by Seebach et al. 7 Later, Fuji et al. demonstrated the concept on naphthalenyl substrate and coined the term “memory of chirality (MOC)”. 8 The area of MOC is not fully explored, compared to the other areas of synthetic organic chemistry. 9 Examples of MOC via decarboxylative intermolecular radical coupling are rare, 9 and there are only two examples in the literature, wherein MOC has been reported in the decarbox- ylative intramolecular radical coupling. The first example, reported by Rychnovsky, utilized transannular radical cycliza- tion via photodecarboxylative coupling (eq 1 in Scheme 2), 10 and the second example reported by Griesbeck utilized intramolecular photodecarboxylative 1,7-diradical coupling, which provided a product with complete inversion of the configuration (see eq 2 in Scheme 2). 11 Interestingly, until now, oxidative decarboxylative intramolecular radical coupling with MOC has not been reported in the literature. Received: February 23, 2018 Scheme 1. Intermolecular Decarboxylative Coupling Reactions Letter pubs.acs.org/OrgLett Cite This: Org. Lett. XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/acs.orglett.8b00652 Org. Lett. XXXX, XXX, XXX-XXX