Hydrogen Atom Transfer (HAT): A Versatile Strategy for Substrate Activation in Photocatalyzed Organic Synthesis

Abstract

The adoption of hydrogen atom transfer (HAT) in a photocatalytic approach, in which an excited catalyst is responsible for substrate activation, offers unique opportunities in organic synthesis, enabling the straightforward activation of R–H (R = C, Si, S) bonds in desired reagents. Either a direct strategy, based on the intrinsic reactivity of a limited number of photocatalysts in the excited state, or an indirect one, in which a photocatalytic cycle is used for the generation of a thermal hydrogen abstractor, can be exploited. This microreview summarizes the most recent advances (mainly from the last two years) in this rapidly developing area of research, collecting the selected examples according to the nature of the species promoting the HAT process. From the synthetic point of view, this area has led to the development of a plethora of strategies for C–C, C–Si, C–N, C–S, and C–halogen (particularly, fluorine) bond formation, as well as for oxidation reactions.

Microtubing‐Reactor‐Assisted Aliphatic C−H Functionalization with HCl as a Hydrogen‐Atom‐Transfer Catalyst Precursor in Conjunction with an Organic Photoredox Catalyst

“…

Chlorine radical, which is classically generated by the homolysis of Cl 2 under UV irradiation, can abstract ah ydrogen atom from an unactivated C(sp 3 )ÀHb ond. [2] In general, upon irradiation with light, the activated photocatalyst can oxidize the HATc atalyst through singleelectron transfer (SET) to form ahydrogen abstractor,either in the presence or absence of abase;the hydrogen abstractor will abstract ah ydrogen atom to deliver ac arbon radical to enable C À Hactivation (Scheme 1a). The key to success relied on the utilization of microtubing reactors to maintain the volatile HCl catalyst.

…”

Selective C(sp3)−H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow

“…Another approach to enable C À Hb ond oxidation is through hydrogen-atom transfer (HAT), which can be promoted either thermally, [11] photochemically, [12] or electrochemically (Scheme 1b). [3d,13] Following this strategy,h ydrogen atoms can be abstracted to produce highly reactive radical species,w hich are subsequently trapped in aw ide variety of synthetically useful transformations.T his synthetic pathway can be considered appealing, since the transformation is promoted by the use of photons or electrons as traceless reagents,t hus simplifying the catalytic systems involved and reducing the environmental impact of the transformation itself.…”

Regioselective Vinylation of Remote Unactivated C(sp3)−H Bonds: Access to Complex Fluoroalkylated Alkenes

“…[1] Generally,transitionmetal catalysis takes advantage of installing an extra directing group to gain the reactivity and/or regiocontrol in C(sp 3 ) À H activation. [1] Generally,transitionmetal catalysis takes advantage of installing an extra directing group to gain the reactivity and/or regiocontrol in C(sp 3 ) À H activation.…”

“…[1] Generally,transitionmetal catalysis takes advantage of installing an extra directing group to gain the reactivity and/or regiocontrol in C(sp 3 ) À H activation. [3] Nevertheless,t his process is largely dependent upon the inherent characters of C À H bonds,t hat is,t he abstraction of tertiary C(sp 3 ) À Hb onds is more feasible than secondary and primary ones.The reaction with multiple reactive sites usually proceeds without regiocontrol to afford amixture of regioisomers. [3] Nevertheless,t his process is largely dependent upon the inherent characters of C À H bonds,t hat is,t he abstraction of tertiary C(sp 3 ) À Hb onds is more feasible than secondary and primary ones.The reaction with multiple reactive sites usually proceeds without regiocontrol to afford amixture of regioisomers.…”

“…[13] With this idea in mind, we firstly investigated the addition of the CF 3 radical to propargyl alcohols (1), aiming to selectively convert d-C(sp 3 )ÀHb onds into trifluoromethyl alkene. [14] After an extensive survey of reaction parameters,i tw as found that the CF 3 radical was readily delivered in the presence of fac-Ir(ppy) 3 and Tognis reagent II when irradiated by visible light, [15] and thus triggered the following 1,5-HATa nd intramolecular olefin migration to lead to the desired C À Hvinylation. Theaddition of K 2 HPO 4 slightly improved the reaction yields.T hen the generality of protocol was evaluated with the optimized reaction conditions (Scheme 2).…”