An efficient one-pot process to functionalize the alpha-and omega-positions of RAFT-derived poly(N-isopropylacrylamide) (PNIPAM) by two inherently different mechanistic pathways is reported. The method relies on the RAFT polymerization of NIPAM using a new alkyne-based RAFT agent, namely 2-cyano- 5-oxo-5-(prop-2-yn-1-ylamino) pentan-2-yl dodecyltrithiocarbonate (COPYDC) and the combination of thiol-yne click chemistry and thiocarbonylthio chain-end removal reactions. COPYDC was prepared in good yield and used as an efficient chain transfer agent during the RAFT polymerization of NIPAM. Well-defined polymers with controlled molar masses ((M-n,(SEC)) over bar = 7500-14,700 g.mol(-1)) and narrow dispersities (D = 1.18-1.26) are thus obtained. Cascade thiol-yne click reaction at the alkyne alpha-chain end and trithiocarbonate removal at the omega-chain end are successfully achieved using benzyl mercaptan and excess AIBN. The reported method provides a facile and mild route to heterofunctional telechelic RAFT polymers with predictable molar masses and low dispersities. (C) 2017 Wiley Periodicals, Inc.