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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. 

Unactivated C(sp3)–H bonds are the most challenging substrate class for transition metal-catalyzed C–H halogenation. Recently, the Yu group [Liu, T.; Myers, M. C.; Yu, J. Q. Angew. Chem., Int. Ed.2017, 56 (1), 306–309] has demonstrated that a CuII/phenanthroline catalyst and BrN3, generated in situ from NBS and TMSN3 precursors, can achieve selective C–H bromination distal to a directing group. The current understanding of the mechanism of this reaction has left numerous questions unanswered. Here, we investigated the mechanism of Cu-catalyzed C(sp3)–H bromination with distal site selectivity using density functional theory calculations. We found that this reaction starts with the Br-atom transfer from BrN3 to the Cu center that occurs via a small energy barrier at the singlet–triplet state seam of crossing. In the course of this reaction, the presence of the N–H bond in the substrate is critically important and acts as a directing group for enhancing the stability of the catalyst–substrate interaction and for the recruitment of the substrate to the catalyst. The required C-centered radical substrate formation occurs via direct C–H dehydrogenation by the Cu-coordinated N3 radical, rather than via the previously proposed N–H bond dehydrogenation and then the 1,5-H transfer from the γ-(C–H) bond to the N-radical center pathway. The C–H bond activation by the azide radical is a regioselectivity-controlling step. The following bromination of the C-centered radical by the Cu-coordinated bromine completes the product formation. This reaction step is the rate-limiting step, occurs at the singlet-to-triplet state seam of the crossing point, and is exergonic. 

Abstract The search for more effective and highly selective C–H bond oxidation of accessible hydrocarbons and biomolecules is a greatly attractive research mission. The elucidating of mechanism and controlling factors will, undoubtedly, help to broaden scope of these synthetic protocols, and enable discovery of more efficient, environmentally benign, and highly practical new C–H oxidation reactions. Here, we reveal the stepwise intramolecular S N 2 nucleophilic substitution mechanism with the rate-limiting C–O bond formation step for the Pd(II)-catalyzed C(sp 3 )–H lactonization in aromatic 2,6-dimethylbenzoic acid. We show that for this reaction, the direct C–O reductive elimination from both Pd(II) and Pd(IV) (oxidized by O 2 oxidant) intermediates is unfavorable. Critical factors controlling the outcome of this reaction are the presence of the η 3 -(π-benzylic)–Pd and K + –O(carboxylic) interactions. The controlling factors of the benzylic vs ortho site-selectivity of this reaction are the: (a) difference in the strains of the generated lactone rings; (b) difference in the strengths of the η 3 -(π-benzylic)–Pd and η 2 -(π-phenyl)–Pd interactions, and (c) more pronounced electrostatic interaction between the nucleophilic oxygen and K + cation in the ortho-C–H activation transition state. The presented data indicate the utmost importance of base, substrate, and ligand in the selective C(sp 3 )–H bond lactonization in the presence of C(sp 2 )–H.