Chem
Volume 6, Issue 8, 6 August 2020, Pages 2110-2124
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Article
Site-Selective C–H Benzylation of Alkanes with N-Triftosylhydrazones Leading to Alkyl Aromatics

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Highlights

  • Silver-catalyzed site-selective C–H benzylation of unactivated alkanes

  • First intermolecular C(sp3)–H insertions with donor carbene

  • Reductive alkylation of aryl aldehydes by alkanes

The Bigger Picture

The direct and selective conversion of simple alkanes into value-added specialty chemicals is a dream reaction because alkanes are low cost and readily obtained by reforming petroleum feedstocks. Metal carbenoid-induced alkylation of C(sp3)–H bond is one of the most versatile strategies toward this goal. Here, we report the first site-selective insertion reaction of donor carbene into C–H bonds of simple alkanes leading to alkyl aromatics, which are among the most important building blocks in the chemical industry. The reaction extends the carbene-induced C–H insertion to low-reactive donor-only carbene for the first time, which may provide a new way for the resource and high value utilization of feedstock alkanes.

Summary

Alkanes are an abundant and valuable resource for transformation into value-added fine chemicals. However, selective functionalization of specific C(sp3)–H bonds in alkanes for alkyl-alkyl bond formation is a significant challenge because of their intrinsic inertness and the small differences in reactivity among various C(sp3)–H bonds. Here, we report a silver-catalyzed site-selective C(sp3)–H benzylation of simple alkanes using N-triftosylhydrazones as a convenient carbene precursor, which enables the synthesis of high value-added alkylated aromatics. A one-pot two-step protocol starting from aldehydes was also realized, thereby constituting a formal reductive alkylation of aryl aldehydes by alkanes. Experimental investigations and DFT calculations reveal that the role of the [TpBr3Ag]2 catalyst is 3-fold: it modulates the carbene reactivity, inhibits carbene dimerization, and avoids over insertion of the product. All three aspects are crucial for the success of this first site-selective intermolecular insertion of donor carbenes into C(sp3)–H bonds of simple alkanes.

Keywords

alkane
N-triftosylhydrazone
C–H alkylation
silver carbenoid
alkyl aromatics
C(sp3)–C(sp3) bond formation

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SDG12: Responsible consumption and production

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These authors contributed equally

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