skip to main content

Attention:

The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 5:00 PM ET until 11:00 PM ET on Friday, June 21 due to maintenance. We apologize for the inconvenience.


Title: Expanding Reaction Profile of Allyl Carboxylates via 1,2-Radical Migration (RaM): Visible-Light-Induced Phosphine-Catalyzed 1,3-Carbobromination of Allyl Carboxylates
Allyl carboxylates are useful synthetic intermediates in a variety of organic transformations, including catalytic nucleophilic/electrophilic allylic substitution reactions and 1,2-difunctionalization reactions. However, the catalytic 1,3-difunctionalization of allyl carboxylates remains elusive. Herein, we report the first photoinduced, phosphine-catalyzed 1,3-carbobromination of allyl carboxylates, affording a range of valuable substituted isopropyl carboxylates (sIPC). The transformation has broad functional group tolerance, is amenable to the late-stage modification of complex molecules and gram-scale synthesis, and expands the reaction profiles of allyl carboxylates and phosphine catalysis. Preliminary experimental and computational studies suggest a non-chain-radical mechanism involving the formation of an electron donor–acceptor complex, 1,2-radical migration (RaM), and Br-atom transfer processes. We anticipate that the 1,2-RaM reactivity of allyl carboxylates and the phosphine-catalyzed radical reaction will both serve as a platform for the development of new transformations in organic synthesis.  more » « less
Award ID(s):
1700982 1848463
NSF-PAR ID:
10440147
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Journal of the American Chemical Society
ISSN:
0002-7863
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Paired redox‐neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non‐toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C−C cross‐coupling reactions. Here, we report the electro/Ni dual‐catalyzed redox‐neutral decarboxylative C(sp3)−C(sp2) cross‐coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar−Br bond by a NiI‐bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2‐phenoxy propionic acid, undergo oxidative decarboxylation to form carbon‐based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)−C(sp2) cross‐coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual‐catalyzed cross‐coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)−C(sp2) cross‐coupling and represent a promising method for the construction of the C(sp3)−C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow‐synthesis technology.

     
    more » « less
  2. Abstract

    Paired redox‐neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non‐toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C−C cross‐coupling reactions. Here, we report the electro/Ni dual‐catalyzed redox‐neutral decarboxylative C(sp3)−C(sp2) cross‐coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar−Br bond by a NiI‐bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2‐phenoxy propionic acid, undergo oxidative decarboxylation to form carbon‐based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)−C(sp2) cross‐coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual‐catalyzed cross‐coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)−C(sp2) cross‐coupling and represent a promising method for the construction of the C(sp3)−C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow‐synthesis technology.

     
    more » « less
  3. Catalytic site-selective hydroallylation of vinyl arenes and 1,3-dienes is reported. Transformations are promoted by a readily accessible bidentate carbodicarbene-rhodium complex and involve commercially available allyltrifluoroborates and an alco-hol. The reaction is applicable to vinyl arenes, and aryl or alkyl-substituted 1,3-dienes (30 examples). Allyl addition products are generated in 40–78% yield and in up to >98:2 site-selectivity. Reaction outcomes are consistent with the intermedi-acy of a Rh(III)-hydride generated by protonation of Rh(I) by an acid. A number of key mechanistic details of the reaction are presented: (1) Deuterium scrambling into the product and starting alkene indicates reversible Rh(III)–H migratory insertion. (2) A large primary kinetic isotope effect is observed. (3) With substituted allyltrifluoroborates (e.g., crotyl-BF3K) mixtures of site isomers are generated as a result of transmetalation followed by Rh-(allyl) complex equilibration; consequently, disproving outer-sphere addition of the allyl nucleophile to Rh(III)-(η3-allyl). (4) The stereochemical analysis of a cyclohexadiene allyl addition product supports a syn Rh(III)–hydride addition. (5) A Hammett plot shows a negative slope suggesting reductive elimination as the rate-determining step. Finally, utility is highlighted by a iodocyclization and cross metathesis. 
    more » « less
  4. Abstract

    Catalytic enantioselective 1,2-dicarbofunctionalization (1,2-DCF) of alkenes is a powerful transformation of growing importance in organic synthesis for constructing chiral building blocks, bioactive molecules, and agrochemicals. Both in a two- and three-component context, this family of reactions generates densely functionalized, structurally complex products in a single step. Across several distinct mechanistic pathways at play in these transformations with nickel or palladium catalysts, stereocontrol can be obtained through tailored chiral ligands. In this Review we discuss the various strategies, mechanisms, and catalysts that have been applied to achieve enantioinduction in alkene 1,2-DCF.

    1 Introduction

    2 Two-Component Enantioselective 1,2-DCF via Migratory Insertion

    3 Two-Component Enantioselective 1,2-DCF via Radical Capture

    4 Three-Component Enantioselective 1,2-DCF via Radical Capture

    5 Three-Component Enantioselective 1,2-DCF via Migratory Insertion

    6 Miscellaneous Mechanisms

    7 Conclusion

     
    more » « less
  5. null (Ed.)
    Excited-state catalysis, a process that involves one or more excited catalytic species, has emerged as a powerful tool in organic synthesis because it allows access to the excited-state reaction landscape for the discovery of novel chemical reactivity. Herein, we report the first excited-state palladium-catalyzed 1,2-spin-center shift reaction that enables site-selective functionalization of carbohydrates. The strategy features mild reaction conditions with high levels of regio- and stereoselectivity that tolerate a wide range of functional groups and complex molecular architectures. Mechanistic studies suggest a radical mechanism involving the formation of hybrid palladium species that undergoes a 1,2-spin-center shift followed by the reduction, deuteration, and iodination to afford functionalized 2-deoxy sugars. The new reactivity will provide a general approach for the rapid generation of natural and unnatural carbohydrates. 
    more » « less