Elsevier

Tetrahedron Letters

Volume 56, Issue 49, 9 December 2015, Pages 6860-6862
Tetrahedron Letters

Ir-catalyzed C–H silylations of phenyldeazapurines

https://doi.org/10.1016/j.tetlet.2015.10.089Get rights and content

Abstract

A study of the Ir-catalyzed C–H silylation of 6-phenyl-7-deazapurines or -9-deazapurines with trialkylsilanes revealed that this reaction preferentially proceeded via ortho-silylation at the aryl group due to the directing effect of the N1 nitrogen of the deazapurine, rather than C–H silylation at the heterocycle which was only a minor side-reaction. A preparative protocol for the ortho-silylation of aryldeazapurines is presented.

Introduction

Aryl-substituted purines,1, 2 deazapurine3, 4 bases, and nucleosides are of great importance due to their cytostatic activities. Apart from classical cross-coupling reactions,5 they are accessible by diverse C–H activation reactions (for recent reviews on the C–H activation of nucleobases, see the literature6). An aryl group can be attached either by direct C–H arylation7 or indirectly by C–H borylation8 or –sulfenylation9 followed by cross-coupling. Some C–H activations have also been used for the functionalization of 6-phenylpurines, which often occurs at the ortho-position of the aryl group due to the directing effect of the N1 atom. In this way, C–H arylations,10 acetoxylations,11 and aminations12 were all reported to proceed at the aryl group. To the best of our knowledge, C–H silylation has not been reported on arylpurines or deazapurines and therefore has become the subject of our current study.

Direct C–H silylation is currently widely studied for the functionalization of arenes13 since the resulting silanes can be further used in Hiyama cross-couplings14 and other functional group transformations. The most widely used protocol utilizes Ir catalysis but there are also reactions catalyzed by other transition metals such as Ru and Rh.13 In substituted benzenes, the Ir-catalyzed C–H silylation typically proceeds with meta-selectivity,15, 16 unless a directing group (coordinating the metal, i.e., 2-pyridyl) is present to facilitate ortho-silylation.17, 18 In indoles and related five-membered heterocycles, C–H silylation has been reported at the 2-position.19 In 6-aryl-substituted purines and deazapurines, the question arose whether the N-1 atom would direct ortho-silylation of the aryl group or whether the C8 atom reactivity would prevail resulting in substitution at the five-membered ring of the nucleobase.

Section snippets

Results and discussion

The study started with testing the reactivity of 9-benzyl-6-phenylpurine (1).20 The reaction with HSiEt3 was examined in the presence of Ir[(COD)OMe]2, dtbpy, and norbornene under different conditions in analogy to the literature15, 16, 17, 18, 19 but no reaction was observed (Scheme 1). This was in accordance with our previous observations regarding the lack of reactivity of purines in Ir-catalyzed C–H borylations8 which is most likely caused by a strong coordination of the metal to the N7

Acknowledgments

This work was supported by the institutional support of the Charles University and Academy of Sciences of the Czech Republic (RVO: 61388963), by the Czech Science Foundation (P207/12/0205 to NS and MH), and by Gilead Sciences, Inc.

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