Abstract
Di(hetero)arylmethane is a unique structural motif for natural and synthetic functional molecules. To date, it remains challenging to functionalize the diaryl methyl sp3 carbon-hydrogen bond directly in an enantioselective manner. This is likely due to the relatively inert nature of the carbon-hydrogen bond and the difficult enantiofacial discrimination of two sterically similar aryl substituents. Here we disclose an N-heterocyclic carbene-catalyzed direct oxidative coupling of enals and di(hetero)arylmethanes. Our method allows for highly enantioselective transformation of diaryl methanes and quick access to benzimidazole fused lactams.
Highlights
Diarylmethyl units are widely present in functional molecules and natural products
The most wellstudied approach for the incorporation of diaryl methane unit relies on reactions between diarylmethyl carbocations and nucleophilic substrates[5] (Fig. 1b)
As a potentially more straightforward approach, direct modi cation of diarylmethanes is much less studied (Fig. 1c). This is in part due to the weak acidity of the methyl C–H and the difficult enantiofacial discrimination of two sterically similar aryl substituents
Summary
Diarylmethyl units are widely present in functional molecules and natural products. Examples of such molecules include the antidepressant drug Sertraline,[1] Bz–IB conjugates with antiin ammatory activities[2] and the natural product voacamine[3] with cannabinoid CB1 receptor antagonistic activity (Fig. 1a). Diarylmethyl carbocation intermediates are typically generated in situ from their precursors such as diarylmethanols.[6] In contrast, as a potentially more straightforward approach, direct modi cation of diarylmethanes is much less studied (Fig. 1c) This is in part due to the weak acidity of the methyl C–H and the difficult enantiofacial discrimination of two sterically similar aryl substituents. Deprotonation of such a benzylic C–H bond typically requires the use of a strong base such as nBuLi or Na.[7] As an alternative choice, oxidative transformations of diarylmethanes via benzylic organometallic species[8] or benzylic radicals[9] can be realized under milder conditions In all these approaches, direct enantioselective modi cation of diarylmethane remains challenging. Mechanistic studies suggest that some of our carbenecatalyzed reactions likely go through single-electron-transfer (SET) processes and radical intermediates in the key steps, an electron pair pathway cannot be completely ruled out
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