Elsevier

Tetrahedron Letters

Volume 59, Issue 52, 26 December 2018, Pages 4551-4556
Tetrahedron Letters

Visible-light-induced 1,2-alkylarylation of alkenes with a-C(sp3)–H bonds of acetonitriles involving neophyl rearrangement under transition-metal-free conditions

https://doi.org/10.1016/j.tetlet.2018.11.025Get rights and content

Highlights

  • The 1,2-alkylarylation occurs under transition-metal-free and oxidant-free conditions.

  • A variety of important 5-oxo-pentanenitriles were obtained.

  • The results proved that the cleavage of C(sp3)–H bond of acetonitrile is a rate-limiting step.

Abstract

An efficient visible-light-induced difunctionalization of alkenes with a-C(sp3)–H bonds of nitriles is described for the constructing of diverse 5-oxo-pentanenitriles under transition-metal-free conditions. This protocol proceeds via the functionalization of C(sp3)–H bond and radical addition/intramolecular 1,2-aryl migration processes, which features a wide scope of substituted α,α-diaryl allylic alcohols. The results of kinetic isotope experiments show that the cleavage of C(sp3)–H bond of acetonitriles is a rate-limiting step.

Introduction

Recently, the direct C–H functionalization for the constructing of carbon-carbon bonds or heteroatom bonds has been even more attractive strategy for its playing an important role in building complex molecules [1]. As a result, many chemists pay their attention to the development of new strategies for radical C(sp3)–H functionalization [2], [3]. Especially, significant advances have been made in selective activation of C(sp3)–H bond in alcohols, ethers, alkanes, amines and other activated compounds [4]. However, it is a more taxing target for functionalization of C(sp3)–H in simple nitriles under mild conditions.

Nitriles, commonly exist in bioactive molecules and natural products, are important synthetic intermediates in organic synthesis, agricultural and pharmaceutical chemistry, as well as polymers and materials science [5]. Thus, the preparation and utilization of organonitriles have become one of the most popular and interesting topics in organic and biological chemistry [6].

The difunctionalization of alkenes has become a class of powerful and efficient chemical transformation in organic synthesis, by that two functional groups can be simultaneously introduced into a double bond [7]. In recent years, aryl allylic alcohols were proved to be practicable substrates for difuctionalization of alkenes [8], [8](a), [8](b), [8](c), [9], [9](a), [9](b), [9](c), [9](d), [9](e), [9](f), [9](g), [9](h), [9](i), [9](j), [9](k), [10], [10](a), [10](b), [11], [11](a), [11](b), [11](c), [11](d), [11](e), [11](f), [12], [13], [14], [14](a), [14](b), [15], [16], which deliver a series of α-aryl-β-substituted ketones via 1,2-migration. Through this method, a series of radicals such as alkyl [9], acyl [10], CF3 [11], N3 [12], S [13], P,[14] Si [15], Se-contained [16] radicals, were introduced to the radical-mediated difunctionalization of aryl allylic alcohols (Scheme 1, a). The alkyl radicals mainly generated from cleavage of C–X, C–C or C(sp3)–H bonds. However, 1,2-alkylarylation of α,α-diaryl allylic alcohol with C(sp3)–H bonds in alcohols, ethers, alkanes, nitriles, amines have made great progress. In 2016, Cheng’s group developed the peroxide facilitated [3 + 2] cyclization of α,α-diaryl allylic alcohols with sec-alcohols via neophyl rearrangements under transition-metal-free conditions [9c]. Ji’s group presented the no*vel and straightforward strategy for the synthesis of α-aryl-β-alkylated ketones by peroxide initiated difunctionalization of aryl allylic alcohols with ethers (open-chain and cyclic ethers) without any metal catalyst, which formed two new carbon–carbon bonds in one step [9d]. In 2014, Tu and co-workers described the Ni-mediated difunctionalization of inactive alkenes with the α-C(sp3)–H bonds of N, N-substituted amides for the building of α-aryl-γ-amine ketones [9g]. Li and Ji groups reported the oxidative difunctionalization of allylic alcohols with the C(sp3)–H bonds of acetonitriles [9](a), [9](b), ketones [9e] or alkanes [9f]. Unfortunately, most of these conversions exist the defects of harsh reaction conditions, such as expensive catalysts, high temperatures, strong oxidants or limitation to the start materials. Hence, a simple and economic, environmentally benign method for difunctionalization of α,α-diaryl allylic alcohols with C(sp3)–H bonds is lacking.

Recently, organic chemists have paid close attention to the visible-light photoredox catalysis for the view of economy and environment-friendliness [17]. Particularly, organic photosensitizers, usually organic small molecular dyes, which have been widely used as photocatalysts in pharmaceutical and organic synthesis [18]. Eosin Y, a common photocatalyst, can avoid metal remain in the final products. Additionally, eosin Y is greener than the transition-metal based photocatalysts [18](d), [18](e), [18](f), [18](g), [18](h), [18](i), [18](j), [18](k). According to the previous researches on α,α-diaryl allylic alcohols and our works on the development of visible-light phororedox catalysis [19], we also present the first visible-light-induced difunctionalization of α,α-diaryl allylic alcohols with α-C(sp3)–H bonds of nitriles for the building of 5-oxo-pentanenitriles under transition-metal-free and oxidant-free conditions with high efficiency and selectivity.

Section snippets

Results and discussion

Based on the visible-light photoredox catalysis strategy, we initially chose 1,1-diphenylprop-2-en-1-ol (1a) and acetonitrile (2a) as the model substrates to optimize the reaction conditions (Table 1). Firstly, the α,α-diaryl allylic alcohol 1a (0.2 mmol) reacted with acetonitrile 2a (2 mL) in presence of cyclobutanone O-(4-(trifluoromethyl)-benzoyl) oxime (additive I, 1.5 equiv) as additive and Eosin Y (5 mol%) as photocatalyst, under an argon atmosphere at 100 °C by irradiation with a 5 W

Conclusion

In conclusion, we have described the first visible-light-mediated difunctionalization of α,α-aryl allylic alcohols with the α-C(sp3)–H bonds of nitriles under transition-metal-free and oxidant-free conditions, during which two new carbon–carbon bonds were formed in this transformation via a C(sp3)–H bond functionalization and 1,2-aryl migration process. This difunctionalization of alkenes avoids limitations commonly associated with transition-metal and strong oxidant mediated C(sp3)–H bond

General information and materials

All reactions were carried out with magnetic stirring and in dried glassware. Standard syringe techniques were applied for transfer of dry solvents. All reagents and solvents were commercially available and used without any further purification unless specified. Proton (1H NMR) and carbon (13C NMR) nuclear magnetic resonance spectra were recorded at 400 MHz and 100 MHz, respectively. The chemical shifts are given in parts per million (ppm) on the delta (δ) scale. High-resolution mass spectra

Acknowledgments

We thank the Scientific Research Fund of Education Department of Hunan Provincial (No. 16A087), Natural Science Foundation of Hunan Province (No. 2018JJ3208) and National Natural Science Foundation of China (No. 21602056) for financial support.

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