Abstract
A radical relay strategy for mono- and di-halogenation (iodination, bromination, and chlorination) of sp3 C-H bonds has been developed. This first example of β C-H di-halogenation is achieved through sequential C-H abstraction by iterative, hydrogen atom transfer (HAT). A double C-H functionalization is enabled by in situ generated imidate radicals, which facilitate selective N˙ to C˙ radical translocation and tunable C-X termination. The versatile, geminal di-iodide products are further elaborated to β ketones and vinyl iodides. Mechanistic experiments explain the unique di-functionalization selectivity of this iterative HAT pathway, wherein the second C-H iodination is twice as fast as the first.
Highlights
The halogenation of an sp3 C–H bond1 enables direct conversion of an inert motif into a versatile synthetic handle that permits broad reactivity via cross-coupling and substitution.2 Generally, C–H halogenation occurs by radical-mediated3 or organometallic4 mechanisms
A radical relay strategy for mono- and di-halogenation of sp3 C–H bonds has been developed. This first example of b C–H di-halogenation is achieved through sequential C–H abstraction by iterative, hydrogen atom transfer (HAT)
To enable access to gem-di-iodides, we proposed an alternate N-selective oxidation may promote a second HAT of the slightly weaker b C–H (103 vs. 105 kcal molÀ1)
Summary
The halogenation of an sp3 C–H bond1 enables direct conversion of an inert motif into a versatile synthetic handle that permits broad reactivity via cross-coupling and substitution.2 Generally, C–H halogenation occurs by radical-mediated3 or organometallic4 mechanisms. A radical relay strategy for mono- and di-halogenation (iodination, bromination, and chlorination) of sp3 C–H bonds has been developed. A second iodination at a distal, primary C–H affords a 1,3-di-iodide.7
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