The use of directing groups has proven to be a successful strategy to enhance reactivity and control selectivity in C-H functionalization reactions. In the past decade, a multitude of new transformations and new directing groups have been explored, and several recent reviews have discussed directing group approaches for C-H functionalization. This review focuses specifically on the use of monodentate nitrogen-based directing groups published during the past two years, with the aim of covering a body of literature that is complementary to existing reviews.

The first copper-catalyzed direct β-functionalization of saturated ketones is reported. This protocol enables diverse ketones to couple with a wide range of nitrogen, oxygen and carbon nucleophiles in generally good yields under operationally simple conditions. The detailed mechanistic studies including kinetic studies, KIE measurements, identification of reaction intermediates, EPR and UV-visible experiments were conducted, which reveal that this reaction proceeds via a novel radical-based dehydrogenation to enone and subsequent conjugate addition sequence.

Scheme 1. Three examples of useful alkynylated thiophenes: a) 5-(2-Phenylethynyl)-2-b-glucosylmethyl-thiophene, a natural product; [10a] b) S-3304, a matrix metalloproteinase inhibitor; [10b] c) R = n-C 4 H 9 , a liquid-crystalline semiconductor. [10c]