Bidentate ligand 8-aminoquinoline-aided Pd-catalyzed diastereoselective b-arylation of the prochiral secondary sp 3 CeH bonds of 2-phenylbutanamides and related aliphatic carboxamides Bojan Gopalakrishnan, Srinivasarao Arulananda Babu * , Rayavarapu Padmavathi Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, Mohali, Manauli P.O., Punjab, 140306, India article info Article history: Received 2 June 2015 Received in revised form 17 August 2015 Accepted 20 August 2015 Available online 22 August 2015 Keywords: Aliphatic carboxamides CeH activation/arylation Diastereoselectivity Palladium sp 3 CeH functionalization abstract Investigations on the Pd-catalyzed 8-aminoquinoline-aided diastereoselective b-arylation of the pro- chiral 2  sp 3 CeH bonds of various aliphatic carboxamides having substituents at the a- or g-positions are reported. The Pd-catalyzed b-arylation of the 2  sp 3 CeH bonds of racemic 2-phenylbutanamides with aryl iodides gave the arylated products ()-3ael (anti isomers) with moderate to good diaster- eoselectivities (dr up to 86:14). Next, the Pd-catalyzed b-arylation of various g-substituted aliphatic carboxamides with aryl iodides furnished the corresponding CeH arylated products with poor diaster- eoselectivities. Then, the arylation of the C(b)-H bonds of 2-ethyl-N-(quinolin-8-yl)butanamide pos- sessing two prochiral centers with aryl iodides successfully furnished the bis arylated products meso- 8eAehA and ()-8eBehB (diastereomers). The arylation of (S)-2-phenylbutanamide also gave the cor- responding enantiomerically enriched compounds 10aec (anti isomers). The stereochemistry of the products ()-3ael (major isomers), meso-8eAehA (major isomers), ()-8eBehB (minor isomers) and enantiomerically enriched compounds 10aec (major isomers) were assigned based on the X-ray struc- tures of the major isomers 3b,c,e,l, 8eA, 10c and minor isomers 8eB and 8fB. The limitations and outcome of the stereocontrol in the Pd-catalyzed CeH arylation reactions involving aliphatic carboxamides are illustrated. Ó 2015 Elsevier Ltd. All rights reserved. 1. Introduction Transition metal-catalyzed CeH activation/functionalization reactions have emerged as a powerful carbon-carbon bond forming tactics. 1e3 Especially, the directing group based CeH activation/ functionalization strategy has emerged as a robust method to functionalize organic compounds. 1e3 In the past two decades, by exercising the directing group-aided CeH activation tactics, nu- merous reactions comprising the functionalization of the sp 2 CeH bonds of organic molecules have been reported. 1e8 Apart from the well-known CeH functionalization protocols encompassing, (a) the benzylic CeH bonds, 5f and (b) the sp 3 CeH bonds of the a-position next to a heteroatom or diazocarbonyl compound-based CeH in- sertion reactions; 2a,g,5gej in general, the functionalization of non- acidic/unactivated sp 3 CeH bonds is considered as a challenging task. Consequently, the direct functionalization of the sp 3 CeH bonds of organic compounds has been considered as one of the important research areas. 1e14 In 2005, Daugulis reported a seminal work on the use of the bidentate directing group for the Pd- catalyzed arylation of non-acidic sp 3 CeH bonds of various car- boxamide substrates. 1a,b,11a Concomitantly, Yu’s group reported the pioneering works and demonstrated the Pd-catalyzed arylation of non-acidic sp 3 CeH bonds directed by pyridyl, carboxyl, and acidic N-arylamide groups. 3a,b,10 Later, Chen’s group revealed the Pd- catalyzed arylation of the non-acidic sp 3 CeH bonds directed by a picolyl group. 14a Based on the inspiring works of the Daugulis, 1b,11a Yu, 3a,b Shi, 11q Chen 14a and other research groups; 4e14 the direct and selective arylation of the sp 3 b-CeH bonds or remote sp 3 CeH bonds of carboxamide substrates can be achieved by using an appropriate directing group (e.g., 8-aminoquinoline, 2-(methylthio)aniline, 2,3,5,6-tetrafluoro-4-(trifluoromethyl)-aniline and 2-picolyl de- rivative). Correspondingly, the directing group-aided Pd-catalyzed functionalization strategy has been successfully demonstrated by * Corresponding author. Tel.: þ91 172 2293165; fax: þ91 172 2240266; e-mail address: sababu@iisermohali.ac.in (S.A. Babu). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet Tetrahedron 71 (2015) 8333e8349 http://dx.doi.org/10.1016/j.tet.2015.08.049 0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.