Photoinduced Proton‐Transfer Reactions for Mild O‐H Functionalization of Unreactive Alcohols

Abstract

Hexafluoroisopropanol is typically considered as an unreactive solvent and not as a reagent in organic synthesis. Herein, we report on a mild and efficient photochemical reaction of aryl diazoacetates with hexafluoroisopropanol that enables, under stoichiometric reaction conditions, the synthesis of fluorinated ethers in excellent yield. Mechanistic studies indicate there is a preorganization of hexafluoroisopropanol and the diazoalkane acts as an unreactive hydrogen‐bonding complex. Only after photoexcitation does this complex undergo a protonation‐substitution reaction to the reaction product. Investigations on the applicability of this photochemical transformation show that a broad variety of acidic alcohols can be subjected to this transformation and thus demonstrate the feasibility of this concept for O‐H functionalization reactions (54 examples, up to 98 % yield).

Photochemical O−H Functionalization Reactions of Cyclic Diazoamides

“…[7,8] In all cases, the irradiation with lowenergy visible light enables an operationally simple and straightforward access to conduct carbene or proton transfer reactions of aryldiazoacetates without the need to exclude air or moisture and simple applicability. [6][7][8][9] More recently, our group was able to expand the photochemical reactivity of diazoalkanes towards photoinduced proton transfer reactions, which now open up a new reactivity pattern of diazoalkanes under photochemical conditions (Scheme 1b). [9] Despite this progress, currently available methods for photochemical, metal-free applications of diazoalkanes are mainly limited to the application of aryldiazoacetates, and there is only a limited number of reports on the reaction of other diazoalkanes.…”

“…[6][7][8][9] More recently, our group was able to expand the photochemical reactivity of diazoalkanes towards photoinduced proton transfer reactions, which now open up a new reactivity pattern of diazoalkanes under photochemical conditions (Scheme 1b). [9] Despite this progress, currently available methods for photochemical, metal-free applications of diazoalkanes are mainly limited to the application of aryldiazoacetates, and there is only a limited number of reports on the reaction of other diazoalkanes. Gevorgyan and co-workers recently made a significant progress with regards to the diversity of different carbene precursors.…”

“…Since then, several groups reported on their studies to promote visible light mediated carbene transfer reactions in highly efficient cycloaddition, X−H insertion or olefination reactions [7,8] . In all cases, the irradiation with low‐energy visible light enables an operationally simple and straightforward access to conduct carbene or proton transfer reactions of aryldiazoacetates without the need to exclude air or moisture and simple applicability [6–9] . More recently, our group was able to expand the photochemical reactivity of diazoalkanes towards photoinduced proton transfer reactions, which now open up a new reactivity pattern of diazoalkanes under photochemical conditions (Scheme 1b) [9] …”

Controlling Light‐Induced Proton Transfer from the GFP Chromophore

“…Later, Förster [2] explained that the observation was due to excited state intermolecular‐proton transfer occurring upon light illumination and connected to the fact that photoacids have different proton binding energy in their electronically excited and ground states [3] . Today, excited‐state reactivity, which includes photoinduced proton transfer, is of interest from a basic scientific point of view and in developments of new photoacids for applications in for example protein folding, pH jumps, enzyme regulation, and sensing [4–7] . Photoresponsive molecular devices for single‐molecule optoelectronics may also make use of photoinduced proton‐transfer reactions [8] .…”

“…[3] Today, excited-state reactivity, which includes photoinduced proton transfer, is of interest from a basic scientific point of view and in developments of new photoacids for applications in for example protein folding, pH jumps, enzyme regulation, and sensing. [4][5][6][7] Photoresponsive molecular devices for single-molecule optoelectronics may also make use of photoinduced proton-transfer reactions. [8] Intermolecular excited-state proton (ESPT) transfer is sensitive to the proton affinity of the anionic proton acceptor which may be used in the development of chemosensors for specific anions.…”