Photocatalytic deoxygenative Z-selective olefination of aliphatic alcohols

Abstract

Alcohols are one of the most abundant functional groups in commercially available materials and biologically active compounds. Herein, we report a metal-free photocatalytic method for the deoxygenative Z-selective olefination of aliphatic alcohols. Key to this methodology is the radical olefination and isomerization of unstabilized open-shell species generated in situ by a catalytic reductive scission of benzoate esters. These processes are simultaneously orchestrated by a single phenothiazine photocatalyst via singlet and triplet excited states. Our protocol is distinguished by its wide substrate scope and broad applicability, even in the context of pharmaceuticals and saccharides. Given the mild and water-compatible conditions, our chemistry can also be utilized to functionalize DNA headpieces for DELs applications.

Fig. 1. Alcohols in cross-coupling reactions.

A Deoxygenative C(sp²)–C(sp³) cross-coupling reactions of alcohols. B This work: deoxygenative Z-selective olefination of aliphatic alcohols. C Neutral benzoates as precursors for radical functionalization reactions. D Design plan for the deoxygenative Z-selective olefination of alcohols. PC photocatalysis, FG functional group, PHT phenothiazine, SET single electron transfer, EnT energy transfer.

Fig. 2. Optimization studies.

A Screening of phenothiazine derivatives for the photocatalytic activation of neutral benzoates. Reaction conditions: 14 (0.1 mmol), γ-terpinene (0.2 mmol), photocatalyst (10 mol%) in DMSO (0.1 M) at rt for 16 h, 390 nm LED. B Optimization and control experiments for the deoxygenative Z-selective olefination of alcohols. Reaction conditions: 14 (0.1 mmol), styryl boron species (0.3 mmol), catechol (0.1 mmol), photocatalyst 19 (10 mol%) in DMSO (0.33 M) at rt for 16 h, 390 nm LED. ^{a 1}H NMR yields using methyl 3,5-dinitrobenzoate as internal standard. ^b Z:E ratio determined by ¹H NMR. DMSO: dimethyl sulfoxide.

Fig. 3. Aliphatic alcohols scope of the photocatalytic deoxygenative Z-selective olefination.

Reaction conditions as Fig. 2B (entry 6), 0.2 mmol scale. Yield and Z:E ratio determined by ¹H NMR using methyl 3,5-dinitrobenzoate as internal standard. In brackets isolated yields of Z-olefin, unless otherwise noted. All yields refer to the photocatalytic process only. ^‡2 mmol scale. ^†Catechol is used instead of 4-t-Bu catechol, 16 h. *Isolated as mixture of isomers. ^#2 lamps. ^§dr = 1.6:1. ^‖dr > 20:1. DMSO: dimethyl sulfoxide.

Fig. 4. Alkenyl BF₃K scope of the photocatalytic deoxygenative Z-selective olefination.

Reaction conditions as Fig. 2B (entry 6), 0.2 mmol scale. Yield and Z:E ratio determined by ¹H NMR using methyl 3,5-dinitrobenzoate as internal standard. In brackets isolated yields of Z-olefin, unless otherwise noted. All yields refer to the photocatalytic process only. ^†Catechol is used instead of 4-t-Bu catechol, 16 h. *Isolated as mixture of isomers. ^#2 lamps, 6 h. DMSO: dimethyl sulfoxide.

Fig. 5. Preliminary mechanistic studies and on-DNA reactions for DELs applications.

A Stern-Volmer quenching studies. B Radical-clock experiment. C Photoisomerization of the couped product E isomer. D On-DNA reactions for DELs applications. DMSO dimethyl sulfoxide, PHT phenothiazine.