Transition metal-free intramolecular regioselective couplings of aliphatic and aromatic C-H bonds.

Hua Tian,Hua Fu,Haijun Yang,Changjin Zhu

doi:10.1038/srep19931

Hua Tian, Hua Fu + Show 2 more

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https://doi.org/10.1038/srep19931

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Abstract

Cross-dehydrogenative couplings of two different C-H bonds have emerged as an attractive goal in organic synthesis. However, achieving regioselective C-H activation is a great challenge because C-H bonds are ubiquitous in organic compounds. Actually, the regioselective couplings promoted by enzymes are a common occurrence in nature. Herein, we have developed simple, efficient and general transition metal-free intramolecular couplings of alphatic and aromatic C-H bonds. The protocol uses readily available aryl triazene as the radical initiator, cheap K2S2O8 as the oxidant, and the couplings were performed well with excellent tolerance of functional groups. Interestingly, α-carbon configuration of some amino acid residues in the substrates was kept after the reactions, and the couplings for substrates with substituted phenylalanine residues exhibited complete β-carbon diastereoselectivity for induction of the chiral α-carbon. Therefore, the present study should provide a novel strategy for regioselective cross-dehydrogenative couplings of two different C-H bonds.

Highlights

Since aryl radicals were confirmed to be highly reactive, very short-lived intermediates[46,47]
In order to confirm whether trace amount of transition metals in the system mediate this reaction, the solvent in the resulting solution of entry 4 was removed by a rotary evaporator, and the residue was determined by ICP mass spectrometry
Three common transition-metal catalysts, Pd(OAc)[2], CuBr2 and AgNO3 (Table 1, entries 21–23), were added to the reaction system, respectively, and the results showed that addition of transition-metal catalysts did not improve efficiency of the reaction, which exhibits that the present reaction is a transition metal-free process

Summary

Introduction

Since aryl radicals were confirmed to be highly reactive, very short-lived intermediates[46,47]. 2-N-Tzo-amino-N,3-dimethyl-N-phenylbutanamide (1a) was chosen as the model substrate to optimize the reaction conditions including catalysts, oxidants, additives, solvents and temperature under nitrogen atmosphere.

Results

Conclusion