The first catalytic enantioselective Fischer indolization of prochiral diketones containing enantiotopic carbonyl groups is developed and shown to proceed through dynamic kinetic resolution (DKR). Catalyzedb yt he combination of as pirocyclic chiral phosphoric acid and ZnCl 2 (Lewis acid assisted Brønsted acid), this direct approach combines 2,2disubstituted cyclopentane-1,3-diones with N-protected phenylhydrazines to furnish cyclopenta[b]indole derivatives containing an all-carbon quaternary stereocenter with good to excellent enantioselectivities. Scheme 1. Catalytic enantioselective Fischer indolizations.

Engineered heme enzymes such as myoglobin and cytochrome P450s metalloproteins are gaining widespread importance due to their efficiency in catalyzing non-natural reactions. In a recent strategy, the naturally occurring Fe...

C−H functionalization of indoles via Fe carbenoids presents an attractive strategy to obtain biologically important structural motifs. However, obtaining good stereoselectivity with Fe has been a significant challenge. It is unclear whether the low selectivity is due to a radical pathway or an ionic mechanism involving metal-free species. We therefore present a density functional theory (DFT) study of indole alkylation with diazoacetates catalyzed by Fe(ClO 4 )TMEDA/spirobisoxazoline and myoglobin. We explore three mechanistic pathways: nucleophilic, radical, and oxocarbenium routes. The nucleophilic pathway is the most feasible with the formation of an enol species that tautomerizes to furnish the alkylated indole. While this mechanism is routinely proposed, the stereochemical model has been conspicuously absent until now. We show that the conventionally invoked enol pathway is not responsible for the low enantiomeric excess. The enol intermediate can stay coordinated to the catalyst via different binding sites placing the enol in proximity to the chiral environment and affecting the stereoselective proton transfer. Both the binding strength and the chiral environment are crucial for obtaining high selectivity. Our study provides the much needed insights for the modest−low selectivities of Fe systems and could help in expediting the discovery of an efficient catalytic system. These mechanistic underpinnings could also be applicable to other metal (Rh, Pd, Cu, etc.)-catalyzed X−H insertion reactions.

The first catalytic enantioselective Fischer indolization of prochiral diketones containing enantiotopic carbonyl groups is developed and shown to proceed through dynamic kinetic resolution (DKR). Catalyzedb yt he combination of as pirocyclic chiral phosphoric acid and ZnCl 2 (Lewis acid assisted Brønsted acid), this direct approach combines 2,2disubstituted cyclopentane-1,3-diones with N-protected phenylhydrazines to furnish cyclopenta[b]indole derivatives containing an all-carbon quaternary stereocenter with good to excellent enantioselectivities. Scheme 1. Catalytic enantioselective Fischer indolizations.

Heterobiaryls serve as relevant structural motifs in many fields of high applicative importance such as drugs, agrochemicals, organic functional materials etc. Cross-dehydrogenative coupling involving direct oxidation of two CÀ H bonds to construct a CÀ C bond is actively being pursued as a more benign and 'greener' alternative for synthesizing heterobiaryls. Herein, we report a Cu(I)-catalyzed crossdehydrogenative coupling of indoles and furans, two of the most important aromatic heterocycles using air as the terminal oxidant. The reaction proceeds with regio-and chemoselectivity to give the cross-coupled products in good to excellent yields generally. A broad substrate scope with respect to both the coupling partners has been demonstrated to prove the generality of this reaction. This represents the hitherto unexplored cross-dehydrogenative coupling methodology to obtain an indole-furan biaryl motif.