Scalable Total Synthesis of (−)-Triptonide: Serendipitous Discovery of a Visible-Light-Promoted Olefin Coupling Initiated by Metal-Catalyzed Hydrogen Atom Transfer (MHAT)

Abstract

An efficient and scalable total synthesis of (−)-triptonide is accomplished based on a metal-catalyzed hydrogen atom transfer (MHAT)-initiated radical cyclization. During the optimization of the key step, we discovered that blue LEDs significantly promoted the efficiency of reaction initiated by Co­(TPP)-catalyzed MHAT. Further exploration and optimization of this catalytic system led to development of a dehydrogenative MHAT-initiated Giese reaction.

Aldehydes as O-Nucleophiles in Cobalt Hydride Hydrogen Atom Transfer Catalysis: Overriding the Innate Somophilicity

“…1 The versatility of this radical intermediate in participating in a colorful spectrum of subsequent transformations has rendered MHAT a powerful synthetic tool. 2 Pioneered by Mukaiyama and Carreira, a variety of somophiles has been used to intercept the alkyl radicals in MHAT catalysis, for instance, dioxygen, atom/ group transfer reagents, and electron-deficient π-bonds. 3 Recent works by Shigehisa and, later, by Pronin, Zhu, Ohmiya, Zhang, and others involve an alternative pathway, namely, metal-mediated oxidative trapping of the alkyl radical.…”

Light-Driven Cobalt Hydride Catalyzed Hydroarylation of Styrenes

“…The metal hydride could then add a hydrogen atom to the styrene, generating the benzylic radical, which would selectively couple with the radical anion of the cyanoarene, produced via single-electron reduction. This combination of two distinctive modes of catalysis would diversify recent reports of dual MHAT/photoredox catalysis, which had been limited to hydrogenation, isomerization, Giese, or radical polar crossover reactions …”

Electrochemically Driven Hydrogen Atom Transfer Catalysis: A Tool for C(sp3)/Si–H Functionalization and Hydrofunctionalization of Alkenes

“…In the catalytic cycle, the hydrogen atom donation process serves as a radical termination step in the hydrofunctionalization of alkene, and the HAT donor was regenerated through photoreduction and protonation. In contrast, the metal-hydride mechanism generates Co­(III)–H (or Ir­(II)–H) as the reactive HAT donor via photoreduction or photooxidation, and the HAT donor initiates the hydrofunctionalization of alkenes by generating a carbon-centered radical (Figure g). − …”