Visible Light‐Enabled sp³‐C−H Functionalization with Chloro‐ and Bromoalkynes: Chemoselective Route to Vinylchlorides or Alkynes

Abstract

An unprecedented direct atom‐economic chemo‐ and regioselective hydroalkylation of chloroalkynes and an sp3‐C−H alkynylation of bromoalkynes was achieved. The reaction partners are unfunctionalized ethers, alcohols, amides, and even non‐activated hydrocarbons. We found that a household fluorescent bulb was able to excite a diaryl ketone, which then selectively abstracts a H‐atom from an sp3‐C−H bond. The product of a formal alkyne insertion into the sp3‐C−H bond was obtained with chloroalkynes, providing valuable vinyl chlorides. The photo‐organocatalytic hydrogen atom transfer strategy gives rise to a broad range of diversely functionalized olefins. When bromoalkynes are applied in the presence of a base, a chemoselectivity switch to an alkynylation is observed. This reaction can even be performed for the alkynylation of unactivated sp3‐C−H bonds, in this case with a preference of the more substituted carbon. Accompanying quantum chemical calculations indicate a vinyl radical intermediate with pronounced linear coordination of the carbon radical center, thus enabling the formation of both diastereoisomers after H‐atom abstraction, suggesting that the (Z)‐diastereoisomer is preferred, which supports the experimentally observed (E/Z)‐distribution.

Decatungstate as Direct Hydrogen Atom Transfer Photocatalyst for SOMOphilic Alkynylation

“…At the time of writing, Hashmi and co-workers reported the visible light-photocatalyzed hydroalkylation of chloroalkynes. 19 Thus, we started wondering about the role of the radicofugal group in the present methodology and reacted compounds 2m – r (see Chart S1 ) with 1a under optimized conditions. We found that only sulfonyl alkynes gave product 3 in good yields ( Scheme 4 a; reactivity order: 2a > 2n > 2m ), while the well-known benziodoxolone-based alkynylating reagent ( 2o , see Chart S1 ) proved to be photochemically unstable under our conditions and 3 was formed only in a poor yield (17%, data not shown).…”

“…Turning to halogenated derivatives, while (iodoethynyl)benzene ( 2p ) and (bromoethynyl)benzene ( 2q ) were recovered unreacted, chloroalkyne 2r led to the formation of product 31 only (41% isolated yield, Z isomer; Scheme 4 b), in accordance with the report by Hashmi. 19 Intrigued by this marked difference in reactivity, we undertook a computational analysis based on density functional theory (DFT; UωB97xD/def2tzvp level of theory in the gas phase) and compared the aptitude of the different RSO 2 • moieties vs Cl • in the role of radicofugal groups ( Table S2 ). In particular, the equation reported in Scheme 4 c compares the tendency of MeSO 2 and Cl to stabilize the vinyl radical adduct with respect to their intrinsic stability as free radicals.…”

“…At the time of writing, Hashmi and co-workers reported the visible light-photocatalyzed hydroalkylation of chloroalkynes . Thus, we started wondering about the role of the radicofugal group in the present methodology and reacted compounds 2m – r (see Chart S1) with 1a under optimized conditions.…”

“…We found that only sulfonyl alkynes gave product 3 in good yields (Scheme a; reactivity order: 2a > 2n > 2m ), while the well-known benziodoxolone-based alkynylating reagent ( 2o , see Chart S1) proved to be photochemically unstable under our conditions and 3 was formed only in a poor yield (17%, data not shown). Turning to halogenated derivatives, while (iodoethynyl)­benzene ( 2p ) and (bromoethynyl)­benzene ( 2q ) were recovered unreacted, chloroalkyne 2r led to the formation of product 31 only (41% isolated yield, Z isomer; Scheme b), in accordance with the report by Hashmi . Intrigued by this marked difference in reactivity, we undertook a computational analysis based on density functional theory (DFT; UωB97xD/def2tzvp level of theory in the gas phase) and compared the aptitude of the different RSO 2 • moieties vs Cl • in the role of radicofugal groups (Table S2).…”

“…On the other hand, when 2r is used as alkynylating reagent, the elimination of the chlorine atom is disfavored (Scheme c) and the hydroalkylation product 31 is formed via back-HAT or sequential electron transfer/proton transfer (see Schemes S3). This scenario is corroborated by deuterium labeling experiments reported in Scheme S3.…”