Nickel‐Catalyzed Barton Decarboxylation and Giese Reactions: A Practical Take on Classic Transforms

Abstract

Two named reactions of fundamental importance and paramount utility in organic synthesis have been reinvestigated, the Barton decarboxylation and Giese radical conjugate addition. N-hydroxyphthalimide (NHPI) based redox-active esters were found to be convenient starting materials for simple, thermal, Ni-catalyzed radical formation and subsequent trapping with either a hydrogen atom source (PhSiH3) or an electron-deficient olefin. These reactions feature operational simplicity, inexpensive reagents, and enhanced scope as evidenced by examples in the realm of peptide chemistry.

Catalyst‐free Decarboxylation and Decarboxylative Giese Additions of Alkyl Carboxylates through Photoactivation of Electron Donor‐Acceptor Complex

“…The reactions present a green method to decarboxylatively construct carbon-carbon bond and to perform hydrodecarboxylation with broad substrate scope and functional group tolerance under mild blue light irradiation condition without recourse of popularly used photoredox catalysts.Decarboxylative carbon-carbon bond construction [1] and efficient decarboxylation [2] are transformations still receiving intensive developments in synthetic community, because of the easy accessibility, abundance, and environmentally benign properties of aliphatic carboxylic acids for green organic synthesis. The reactions present a green method to decarboxylatively construct carbon-carbon bond and to perform hydrodecarboxylation with broad substrate scope and functional group tolerance under mild blue light irradiation condition without recourse of popularly used photoredox catalysts.…”

Nickel‐Catalyzed Barton Decarboxylation and Giese Reactions: A Practical Take on Classic Transforms

“…It is also of note that the addition is unencumbered by a or b substitutions on the Michael acceptor (26)(27)(28)(29). It is also of note that the addition is unencumbered by a or b substitutions on the Michael acceptor (26)(27)(28)(29).…”

“…Scope of the Ni-catalyzed decarboxylation and conjugatea dditions of NHPI redox-active esters [27]. Reaction conditionsf ordecarboxylation:R AE (1.0 equiv), NiCl 2 ·6 H 2 O(10 mol %), L1 (20 mol %), PhSiH 3 (1.5 equiv), Zn (0.5 equiv), THF/DMF/iPrOH (10:2:1), 0.15 m, 40 8 8C, 1h.Reaction conditionsfor Giese conjugatea ddition: RAE (1.0 equiv), Ni(ClO 4 ) 2 ·6 H 2 O( 20 mol %), Michael acceptor (2.0 equiv), LiCl (3.0 equiv), Zn (2.0 equiv), MeCN,1 2h,RT.…”

Decarboxylative couplings as versatile tools for late‐stage peptide modifications

“…Given the overlap between redox‐active esters (RAEs) and the intermediates formed using standard peptide coupling reagents, it is perhaps unsurprising that RAEs have gradually emerged as powerful tools for the coupling of peptide‐based alkyl carboxylic acids. In addition to a variety of nickel‐catalyzed transformations, concurrent work has exploited Okada's photoinduced fragmentation of phthalimide esters for the decarboxylative arylation, thiolation, and selenation of peptide substrates ( vide infra ). Despite a conceptual similarity to prior work on decarboxylative functionalizations, the renewed impetus for the contemporary advancement of RAE‐mediated decarboxylative couplings stems largely from a growing demand for modified peptides from both academia and industry.…”

“…Drawing from the early successes of Barton and Okada on decarboxylative Giese reactions, Baran and coworkers extended their suite of on‐resin, nickel‐catalyzed RAE modifications to include reactions with electron‐deficient alkenes (Scheme A) . Following activation as the corresponding NHPI‐ester, resin‐bound acid 39 could be coupled with phenylvinylsulfone or acrylonitrile in the presence of Ni(acac) 2 , LiCl, and Zn powder to afford modified peptides 40 and 41 , respectively.…”