Allylmetalation of terminal alkynes is predominantly governed by substrate electronic properties, leaving no effective strategy for anti-Markovnikov addition (allyl addition to the terminal carbon) of general terminal alkynes. Herein, we report a 2-(imino)quinoline iron-catalyzed anti-Markovnikov allylzincation of aryl- and alkyl-substituted terminal alkynes. This protocol affords anti-Markovnikov addition products, 1,4-dienylzinc reagents, in high yields (up to 99%) with excellent regio- and stereoselectivities (mostly >95:5), featuring broad substrate scope and good functional group tolerance. It provides a direct, efficient route to 1,4-dienylzinc reagents which are inaccessible via reported methods, and has been applied to the concise synthesis of polysubstituted 1,4-dienes, as well as key intermediates for several natural products. Mechanistic studies reveal that alkyne activation by Fe(0) catalyst and the semiopen steric effect of 2-(imino)quinoline ligands are critical to overcoming electronic biases and achieving the desired selectivity. This work highlights the unique advantages of low-valent iron catalysts in regulating classical organic reaction selectivity and offers an effective method for accessing novel 1,4-dienes.
Li et al. (Wed,) studied this question.