Abstract
A transition metal-free dehydrogenative method for the direct mono-arylation of a wide range of activated C(sp3)-H bonds has been developed. This operationally simple and environmentally friendly aerobic arylation uses tert-BuOK as the base and nitroarenes as electrophiles to prepare up to gram quantities of structurally diverse sets (>60 examples) of α-arylated esters, amides, nitriles, sulfones and triaryl methanes. DFT calculations provided a predictive model, which states that substrates containing a C(sp3)-H bond with a sufficiently low pK a value should readily undergo arylation. The DFT prediction was confirmed through experimental testing of nearly a dozen substrates containing activated C(sp3)-H bonds. This arylation method was also used in a one-pot protocol to synthesize over twenty compounds containing all-carbon quaternary centers.
Highlights
Introduction aArylated carbonyl derivatives and triaryl methanes are versatile structural motifs present in a large number of natural products and active pharmaceutical ingredients.[1]
We describe extensive synthetic efforts and a density functional theory (DFT)-based reactivity model for this transition metal-free direct arylation of activated C(sp3)–H bonds
It was found that nitroarenes containing an electronwithdrawing group in the ortho position successfully reacted with methyl phenylacetate (1) to give the desired arylated products 3a–3e in moderate to good yields (Scheme 3, entries 1–6)
Summary
Introduction aArylated carbonyl derivatives and triaryl methanes are versatile structural motifs present in a large number of natural products and active pharmaceutical ingredients.[1]. One prominent example is the palladium-catalyzed a-arylation of esters and nitriles rst reported by Hartwig and Buchwald (Scheme 1A).[4,5] Hartwig improved these a-arylation
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