Copper-mediated fluoroalkylation reactions with iododifluoroacetamides: controlling the selectivity among cross-coupling, intramolecular cyclization, and homocoupling reactions.
Cu-mediated fluoroalkylation reactions with iododifluoroacetamides 1 have been systematically investigated. It was found that three types of reactions may coexist in Cu-mediated reactions between iododifluoroacetamides and aryl/alkenyl iodides: cross-coupling, intramolecular cyclization, and homocoupling reactions. The selectivity among these three types of reactions could be controlled by tuning the substituents on the nitrogen atom of iododifluoroacetamides, and/or by removing the cross-coupling reaction partner (aryl/alkenyl halides). The general rule is as follows: (a) in the presence of proper aryl/alkenyl iodides, the cross-coupling products 2 (or 6) are generally formed as the major products; (b) in the absence of aryl/alkenyl iodides, and when R(1) = alkyl and R(2) = aryl groups, or when R(1) = R(2) = aryl groups, the intramolecular cyclization products 3 can be formed predominantly; and (c) in the absence of aryl/alkenyl iodides, and when R(1) = R(2) = alkyl groups, or when R(1) = H and R(2) = alkyl, aryl groups, the homocoupling products 4 can be formed dominantly. Our experimental results also indicate that in many cases when cross-coupling, homocoupling, and intramolecular cyclization reactions coexist in the Cu-mediated reaction system, the reactivity decreases in the following order: cross-coupling > intramolecular cyclization > homocoupling.
Zhu
Jieming
J
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China.
Zhang
Wei
W
Zhang
Laijun
L
Liu
Jun
J
Zheng
Ji
J
Hu
Jinbo
J
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry*; D000478:Alkylation; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D013237:Stereoisomerism
D000081:Acetamides; D003300:Copper