DOI: 10.1002/adsc.201300048 Palladium(II)-Catalyzed Efficient C-3 Functionalization of Indoles with Benzylic and Allylic Alcohols under Co-Catalyst, Acid, Base, Additive and External Ligand-Free Conditions Debjit Das a and Sujit Roy b, * a Organometallics & Catalysis Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur – 721302, India b Organometallics & Catalysis Laboratory, School of Basic Sciences, Indian Institute of Technology, Bhubaneswar – 751013, India Fax: (+ 91)-674-230-6303; phone: (+ 91)-674-257-6021; e-mail: sujitroy.chem@gmail.com or sroy@iitbbs.ac.in Received: January 19, 2013; Revised: March 26, 2013; Published online: April 30, 2013 Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300048. Abstract: The bis(acetonitrile)palladium(II) chlo- ride complex, PdCl 2 ACHTUNGTRENNUNG(MeCN) 2 , efficiently catalyzes the regioselective alkylation of indoles with various benzylic and allylic alcohols under moisture and air insensitive conditions. Notably the reaction does not require any other co-catalyst, acid, base, addi- tive, or external ligand. Keywords: alkylation; allylic alcohols; benzylic al- cohols; homogeneous catalysis; indoles; palladi- ACHTUNGTRENNUNGum(II) complex The functionalization of indoles via low cost, selec- tive, and eco-friendly strategies has attracted wide at- tention since structural motifs bearing the indole core are frequently found in natural products, phar- maceuticals, and other functional synthetics. [1] Con- ventionally 3-alkylated indoles are synthesized from alkyl halides and surrogates by carbon-carbon bond forming reactions such as (i) acid- or base-promoted alkylation [1c,2] or (ii) transition metal-catalyzed alkyla- tion. [1c,3] Among the transition metals, the palladium- catalyzed reactions of indoles with reactive electro- philes (halides, acetates, etc.) have become powerful tools to synthesize functionalized indoles. [1c,4] In con- trast, examples of palladium-catalyzed C-alkylation of indole using an alcohol are few. Indeed the direct cou- pling of indole with an alcohol is considered to be synthetically attractive, mechanistically challenging and environmentally benign due to ready availability and significantly lower toxicity of alcohols (compared to alkylating agents like halides, acetates, etc.), and the fact that only stoichiometric amounts of water are generated as the side product in the alkylation reac- tion. [1c,5] One may also appreciate that a major diffi- culty in the direct alkylation reaction from an alcohol using a transition metal catalyst is the inertness of the OH group towards such activation. [1c,6] In light of the above, the available reports on the palladium-cata- lyzed syntheses of allylindoles from the corresponding alcohols are noteworthy. [7] In 1980 Billups et al. first reported that the reaction of indole and allyl alcohol in refluxing benzene under the catalytic influence of palladium acetylacetonate/PPh 3 gave rise to 3-allylin- dole in 45% yield along with 1-allylindole (7%) and 1,3-bisallylindole (9%). [7a] More recently Tamaru et al. achieved the desired transformation using PdACHTUNGTRENNUNG(PPh 3 ) 4 as the catalyst (5 mol%) and Et 3 B (30– 240 mol%) as the promoter. [7b] A closely related enantioselective variant of this approach was later proposed by Trost et al. using Pd 2 dba 3 ·CHCl 3 as the catalyst and 9-BBN-C 6 H 13 (105 mol%) as an addit- ACHTUNGTRENNUNGive. [7c] Pullarkat et al. employed a palladacycle cata- lyst (10 mol%) for the C-3 allylation of 2-substituted indoles. [7d] Breit et al. accomplished the allylation of indoles using the unique concept of self-assembling palladium phosphane catalysts. [7e] Recent reports on the development of multimetallic catalysts based on palladium for alcohol activation are also notewor- thy. [7f,g] In light of the above literature reports, we were pleasantly surprised with the serendipitous result when a simple monometallic palladium(II) complex, namely PdCl 2 ACHTUNGTRENNUNG(MeCN) 2 , catalyzed the alkylation of indole with benzylic and allylic alcohols with high ef- ficiency and exclusive C-3 regioselectivity. We also noted that the reaction neither requires the assistance of external acid/base, additive and ligand, nor is it sensitive towards moisture and air. The details of our findings are presented below. 1308  2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Synth. Catal. 2013, 355, 1308 – 1314 COMMUNICATIONS