Rapid Access to Free Phenols by
Photocatalytic Acceptorless Dehydrogenation of Cyclohexanones at Room
Temperature
Lin Min,[a] Jia-Ni Lin,[a]and Wei Shu*,[a,b]
[a] Dr. L. Min, J.-N. Lin,
Prof. Dr. W. Shu
Shenzhen Grubbs Institute and Department of Chemistry
Southern University of Science and Technology
Shenzhen 518055, Guangdong (P. R. China)
E-mail: shuw@sustech.edu.cn
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 the synthesis of a series of phenols
with diverse substitution patterns from cyclohexanones or
cyclohexenones. Moreover, diverse substituted 1,2-, 1,3-, and
1,4-benzenediols were obtained from cyclohexanediones, providing a
general and straightforward method for the synthesis of phenols from
simple starting materials under mild conditions.
Phenol and its derivatives widely exist in drug
molecules,[1] pesticide
molecules,[2] dyes,[3]flavor components (Fig. 1).[4] Moreover, phenols
serve as important precursors for the synthesis of a range of
value-added targets.[5] Thus, the synthesis of
phenols from diverse precursors has attracted great attention form the
community.[6] Industrial production of simple
phenol is through Hock (cumene oxidation)
process,[7] accounting for annual production of
more than 106 tons. On the other hand, synthesis of
phenols in laboratory heavily rely on nucleophilic substitution of
arenes[8] and transition metal-catalyzed coupling
with oxygen-nucleophile reagent.[9] Despite the
massive progress, these methods typically require the use of strong
bases[10] and high
temperatures.[11] Moreover, phenols can also be
prepared by oxidation the C-H bond of arenes[12]or arylboron compounds.[13] However, these methods
require the use of preformed aromatic compounds as precursors. Thus,
developing the synthesis of phenol from non-aromatic compound precursors
is attractive.
Figure 1 . Selected natural products and drug molecules
containing phenols.
Scheme 1. Dehydrogenative strategies for cyclohexanone.
In 2011, Stahl reported the seminal work on the synthesis of phenols
from cyclohexanones via a palladium-catalyzed oxidative aromatization
strategy under 1 atm O2 in DMSO at 80
°C.[14] Cyclohexanones undergo α-C-H activation to
form Pd(Ⅱ) species, followed by C-H activation and β-H elimination to
form cyclohexenones. Subsequently, cyclohexenone undergoes an iterative
process to give the phenol product. Recently, Leonori reported the
preparation of aniline from cyclohexanone under the dual catalytic
conditions of photocatalyst and cobalt
catalyst.[15] Mechanistic studies reveal that in
situ generated enamine undergoes two SET oxidations, deprotonation, and
release of hydrogen. This method has achieved great success in the
preparation of various substituted aniline compounds. However, the
photocatalytic preparation of phenol from the simple cyclohexanones
remains underdeveloped, partially due to the high oxidation of silyl
enol ethers and their unproductive competing nucleophilicity. Herein, we
reported a photocatalytic acceptorless synthesis of phenols from
cyclohexanones at room temperature.[16] The mild
conditions allow for the direct dehydrogenative aromatization of
cyclohexanones or cyclohexenones under the dual catalysis of light and
cobalt, affording a wide range of phenols with diverse substitution
patterns.
We started to investigate the feasibility of this proposal using
4-methylcyclohexanone (1a ) as the prototype substrate (Table
1). After extensive evaluation, we define the use of 1 mol% of
Ir(dF(CF3)ppy2(4,4’dCF3bpy)(E *red= +1.65 V)[17] and 5 mol% of
Co(dmgH)2(DMAP)Cl as catalyst, TIPSOTF (1.4 eq) as
activating
Table 1 . Condition evaluation for the photocatalytic
dehydrogenative phenol synthesis from
cyclohexanones.[a]