Palladium-Catalyzed Regioselective 2-Carbethoxyethylation of 1H–Indoles By C-H Activation: One-Step Synthesis of Ethyl 2-(1H-Indol-2-Yl) Acetates

An efficient and convenient method was developed for the one-step synthesis of various substituted ethyl 2-(1H-indol-2-yl) acetates via a palladium-catalyzed regioselective cascade C-H activation reaction. Importantly, this practical approach can be carried out with readily accessible starting materials and exhibits excellent functional group compatibility. chemistry, methods for regioselective direct C2/C3-alkenylation [2733], alkynylation [34-41], cyano [42,43] and arylation [44-52] of indole nucleus have been well developed to date. However, regioselective C2alkylation of indole is more challenging. The Catellani reaction, a palladium-catalyzed norbornenemediated cascade reaction, has been modified to achieve the direct functionalization of indoles [53-55]. Recently, Bressy et al. reported an intramolecular direct arylation of indoles based on modified Catellani conditions [56]. More recently, Jiao et al. reported a direct 2-alkylation reaction of indoles relying on a Pd(II)-catalyzed norbornene-mediated direct alkylation method for indoles, which regioselectively installs an alkyl group to the C2-position of free N-H indoles [57,58]. However, the original publication did not report the use of 2-bromoacetate as an alkylating reagent. To the best of our knowledge, a straight-forward approach for direct C2alkoxycarbonylalkylation of indoles has not yet been well established. Given its high C2-regioselectivity and excellent Figure 1: Examples of 2-(1H-indol-2-yl) acetic acids-related natural products and natural product analogues. HN N