Rapid Access to Free Phenols by Photocatalytic Acceptorless Dehydrogenation of Cyclohexanones at Room Temperature

Abstract

Phenols are ubiquitous substructures in natural products and bioactive compounds. However, practical methods for the direct construction of phenols under mild conditions remains challenging. Herein, a photocatalytic acceptorless dehydrogenative aromatization of cyclohexanones or cyclohexenones at room temperature has been developed. The reaction features the visible-light and cobalt co-catalyzed sequential dehydrogenation of in-situ formed enol silyl ethers, which are regarded as a challenging process. This operationally simple method enables a series of phenols with diverse substitution patterns from cyclohexanones or cyclohexenones, providing a general and straightforward method for the synthesis of phenols from simple starting materials under mild conditions.

Rapid Access to Free Phenols by Photocatalytic Acceptorless Dehydrogenation of Cyclohexanones at Room Temperature

“…Using 2,6-lutidine as base delivered 2 in 81% yield, yet the uses of other organic or inorganic bases, such as DABCO, DIPEA and KOAc were totally ineffective (Table 1, entries [11][12][13][14]. Solvent effect evaluation revealed that both 1,2-dichloroethane (DCE) and dichloromethane (DCM) are good solvents for this reaction, allowing the formation of 2 in 77% and 61% yields (Table 1, entries [15][16][17]. Control experiments showed that light, photocatalyst and Co-catalyst are essential to this phenol synthesis (Table 1, entries 18 and 19).…”

“…Next, aryl fused cyclohexanones were tested. Electron-withdrawing and electron-donating groups on aromatic rings can be tolerated, affording corresponding 1-and 2-naphthol products (17)(18)(19)(20)(21)(22)(23)(24)(25) in 50%-92% yields. Moreover, heterocycles including thiophenes (12 and 26), furans (13) and pyrroles ( 27), were also compatible in the reaction.…”

“…[16] The mild conditions allow for the direct hydrogen-evolution aromatization of cyclohexanones or cyclohexenones under the dual catalysis of light and cobalt, affording a wide range of phenols with diverse substitution patterns. [17]…”