Yet another indole miracle: The sequential combination of organocatalysis and gold catalysis on C2,C3‐unsubstituted indoles provides an efficient one‐pot access to tetracyclic indole derivatives in very good yields and excellent enantioselectivities (see scheme). The double Friedel–Crafts type reaction, including a rare 7‐endo‐dig cyclisation, opens a new entry to highly enantioenriched anticancer drugs, such as DNA intercalators.

Halogen bonding (XB) has recently emerged as a promising noncovalent activation mode that can be employed in catalysis. However, methodologies utilizing XB remain rare, and the hydrogen-bonding (HB) catalysis congeners are more widespread in comparison. Herein, we demonstrate a remarkable case whereby employment of XB catalysis in strain-release glycosylation generates O,N-glycosides in excellent anomeric selectivity exceeding HB activation. Deeper investigation unraveled XB catalyst dependencies on multiple stages of the mechanism and a hitherto unknown XB-glycosyl acceptor activation. We present a proof of concept to interrogate sp 3 -rich glycosidic chemical space for novel biological activity, by integrating XB-catalyzed construction of a glycosidic compound collection, and evaluating these analogues via cell-based phenotypic screens. We show that XB-catalyzed strain-release glycosylation defines a new class of glycosides that inhibit the hedgehog signaling pathway through a nonsmoothened mode of action, opening new opportunities to combat acquired cancer resistance.

While both organocatalysis and gold catalysis have their roots deeply entrenched in the landscape of modern organic chemistry, an exciting trend in the complementary merging of organocatalysis and especially Au(I) catalysis has emerged in the last four years. This niche area has been developing rapidly and this minireview serves to pin-point the fundamental concepts guiding reaction design in these binary catalytic systems. Moreover, the proven synthetic utility of organo/Au(I) multicatalytic systems in accessing molecular frameworks, previously a challenge to single catalytic systems, has resulted in this new concept permeating numerous areas of organocatalysis, such as primary/secondary amine, Brønsted acid, hydrogen-bonding as well as N-heterocyclic carbene (NHC) catalysis. The first detailed account of these recent developments is systematically presented.

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