Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

Abstract

Synthesis of complex organic molecules from simple, cheap, and readily available starting materials is one of the most challenging and desirable factors in organic synthesis. In the last two decades, various methods have been developed for the de-aromatization reaction of planar aromatics compounds which lead to reactive intermediates like 2,5-cyclohexadienone ketal and para-quinol having a non-planar framework. Recently, there is an upsurge of interest in the development of the chemistry of these intermediates due to their inherent dual electrophilic and nucleophilic character. The presence of diverse functionality makes them important scaffolds and thus these are intensively utilized for the development of methodologies towards the synthesis of the highly functionalized and diverse chemical framework. These synthons have also been used in the total synthesis of many natural products. Interestingly, these are also adaptable for asymmetric synthesis. This review is a summary of the recent development of methods for 2,5-cyclohexadienone ketal and para-quinol synthesis and their application in natural product synthesis.

Antiproliferative Phenanthrenes from Juncus tenuis: Isolation and Diversity-Oriented Semisynthetic Modification

“…While quinones, in general, are considered as unfavorable to be included in screening libraries due to their tendency to behave as pan-assay interference compounds (PAINS) [ 15 ], many approved anticancer drugs have such a structure. Furthermore, the quinone and quinol moieties are not only versatile synthons to increase chemical diversity [ 16 ], but these may also serve as warheads for potential covalent inhibitors of well-defined biochemical targets [ 17 , 18 ]. Concerning further structure–activity relationships of phenanthrene derivatives, the combined presence of methyl, hydroxy, and vinyl substituents on ring C, a methyl and a hydroxy group on ring A, and a single bond between C-9 and C-10 increase the antiproliferative effect of phenanthrenes [ 19 ].…”

Visible-light-promoted generation of p-(N,N-dimethyl)benzyl equivalents and their reactions with quinols: easy access to diarylalkanes

“…Firstly, trifluoromethyl-containing naphthaquinol 1a was selected as the acceptor of the benzyl equivalents (Table 1) as trifluoromethylcontaining quinols showed excellent reactivity toward the synthesis of trifluoromethylated arenes (Scheme 1b). [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] Visiblelight promoted the construction of 1,1-diarylmethanes, which was initially investigated by the reaction of 1a with N,Ndimethyl aniline 2a in the presence of a photosensitizer, Ir( ppy) 3 (1 mol%), in acetonitrile (CH 3 CN, 2 mL) without any other additives under 15 W blue LED irradiation at room temperature (Table 1, entry 1); this reaction produced diarylalkane 3a in 42% isolated yield. The yield of 3a was improved to 47% when [Ir(dtbbpy)( ppy) 2 ][PF 6 ] was used as the photosensitizer (Table 1, entry 2).…”

Efficient Oxidative Dearomatisations of Substituted Phenols Using Hypervalent Iodine (III) Reagents and Antiprotozoal Evaluation of the Resulting Cyclohexadienones against T. b. rhodesiense and P. falciparum Strain NF54

“…p -Benzoquinones and p -quinols can both be prepared from phenols by oxidative dearomatization [ 25 , 27 ]; however, a p -substituted phenol and water as a nucleophile is necessary for the synthesis of the 4-hydroxy quinol framework ( Scheme 1 ). Among all environmentally friendly and non-metallic organic oxidants, hypervalent iodine reagents represent one of the most promising tools for the oxidative dearomatization of phenolic compounds [ 26 , 32 , 33 ].…”

“…For our purpose, hypervalent iodine (III) reagents like diacetoxy iodobenzene (PhI(OAc) 2 , PIDA), bis(trifluoroacetoxy) iodo benzene (PhI(OCOCF 3 ) 2 , PIFA) and the μ -oxo-bridged phenyl iodine trifluoroacetate 1 ( Figure 1 ) evolved as reagents of choice. These reagents have been extensively used in organic synthesis [ 25 , 26 , 27 ]. The continued interest in hypervalent iodine species has led to the development of several chiral hypervalent iodine reagents and catalysts [ 28 , 29 , 30 , 31 ].…”