Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Abstract

Although the classical Ritter reaction has been widely applied to prepare sterically hindered amides since 1948, it has intrinsic problems, such as harsh reaction conditions, the multistep preparation of synthetic precursors, and the use of solvent quantities of nitrile. In particular, only a few examples of the total syntheses of natural products using the Ritter reaction as a key step have been reported to date. In this article, an oxidative Ritter-type reaction of α-arylketones was developed to efficiently construct a sterically hindered N-acyl aza-quaternary carbon moiety. The current transformation features the use of 10 equivalents of nitriles, a broad substrate scope (81 examples), a short reaction time, and mild reaction conditions; notably, both of the use of a limited amount of nitriles and the producing carbocation intermediates via the C-H bond oxidation strategy address two intractable problems of the classical Ritter reaction. Furthermore, based on an unprecedented synthetic strategy using this oxidative Ritter reaction to construct a C-5 aza-quaternary carbon center, the collective total syntheses of erythrina alkaloids, including erysotramidine, 11-α-methoxyerysotramidine, 11-β-hydroxyerysotramidine, erytharbine, the proposed 11-βmethoxyerysotramidine and 10,11-dioxoerysotramidine, and the unnatural 11-α-hydroxyerysotramidine, have been completed using a common precursor through a one-step chemical transformation.

Catalyst‐Controlled Divergent Generations and Transformations of α‐Carbonyl Cations from Alkynes**

“…Notably, Zhang and co‐workers managed to obtain α ‐aryl stabilized α ‐carbonyl cations via the direct benzylic oxidation of α ‐arylated carbonyl compounds (Figure 1b). [6a] Maulide, Niggemann, and co‐workers realized an elegant generation of α ‐carbonyl cations from Brønsted acid‐catalyzed oxidative cycloisomerizations of alkynols [6b–c] . Such an approach required alcohol tethered alkyne type precursors to first generate regular carbocations then cyclize to the tethered alkynes for subsequent sulfoxide additions and fragmentations and the intermediacy of α ‐carbonyl cations was evidenced experimentally and theoretically (Figure 1c).…”