Transformations of Less-Activated Phenols and Phenol Derivatives via C–O Cleavage

Abstract

Employing phenols and phenol derivatives as electrophiles for cross-coupling reactions has numerous advantages over commonly used aryl halides in terms of environmental-friendliness and sustainability. In the early stage of discovering such transformations, most efforts have been devoted to utilizing highly activated sulfonate types of phenol derivatives (e.g., OTf, OTs, etc.), which have similar reactivities to the corresponding aryl halides. However, a continuing scientific challenge is how to achieve the direct C–O functionalizations of relatively less-activated phenol derivatives more efficiently. In this review, we will focus on the recent updates on the C–O functionalizations of less-activated phenol derivatives, from aryl carboxylates (e.g., pivalates, acetates, etc.), aryl carbamates and carbonates, to aryl ethers (anisoles, diaryl ethers, aryl pyridyl ethers, aryl silyl ethers), to phenolate salts, and ultimately to simply unprotected phenols, sorted by the types of bond formations. Both transition-metal-catalyzed and transition-metal-free protocols will be covered and discussed in detail. Instead, the C–O functionalizations of aryl sulfonates will not be covered extensively unless they are closely related, due to their high reactivity. Since aryl ethers and phenols represent the main linkages or units in lignin biomass, the successes of such transformations will potentially make major contributions to the direct lignin biomass upgrading and depolymerization.

Synthesis of Polysubstituted Phenols by Rhodium‐Catalyzed C−H/Diazo Coupling and Tandem Annulation

“…For example, each of the analgesic morphine, [2] the selective estrogen receptor modulator (SERM) raloxifene, [3] the conditionally essential amino acid tyrosine, [4] and efficient light absorber tinuvin P [5] to prevent polymers degradation contains phenol skeletons (Figure 1). In addition, phenolic compounds can be employed as ideal synthetic precursors, which can be easily converted into esters, aryl ethers, quinones and cyclohexanones [6] . The currently reported methods for synthesizing phenols typically involve three approaches.…”

“…The conversion of 1 a and 6 mmol of 2 a under standard conditions gave the product 3 aa in 84% yield (1.104 g) (Scheme 1a). Four conversion reactions of 3 aa performed under different conditions could easily convert products of phenols into corresponding ester (4), ethers (5,6) or amide ( 7) (Scheme 1b-1e). The above experiments prove the potential of this protocol in the construction of multi-substituted phenols and further transformation into other types of molecules.…”

“…Then, several additives including HOAc, NaOAc, KAc, and CsOAc were tested, and the highest yield of 3 aa appeared when NaOAc was employed (entries 2-5). Several studies on solvents showed that THF is more suitable for this transformation than DCE, CH 3 OH, CH 3 CN (entries 3, [6][7][8][9] (1 mol%) or NaOAc (0.5 equiv.) significantly decreased the yields of the product 3 aa (entries [14][15].…”

“…In addition, phenolic compounds can be employed as ideal synthetic precursors, which can be easily converted into esters, aryl ethers, quinones and cyclohexanones. [6] The currently reported methods for synthesizing phenols typically involve three approaches. The first path is the functional groups conversion reactions of phenyl substrates such as phenyl halides, phenyl boronic acid, and phenyl diazonium compounds.…”

C–O-Selective Cross-Coupling of Chlorinated Phenol Derivatives

“…Phenols represent an abundant and accessible precursor to electrophilic substrates for cross-coupling reactions. Although cross-couplings typically employ aryl halides as electrophilic coupling partners, phenol derivatives as alternatives to aryl halides have a few notable advantages: (1) because the main source of phenols is fossil fuels, they are widely available and often inexpensive; (2) an emerging source of phenols is lignin biomass, which is considered to be sustainable and renewable; 1 (3) many phenol derivatives are robust enough to be carried through multiple synthetic steps; and (4) some phenol derivatives are able to direct other transformations (such as ortho-metalation, electrophilic aromatic substitution, or C-H functionalization) [2][3][4] prior to being used as electrophiles for cross-coupling reactions. Particularly relevant to this Synpacts, the fifth advantage of phenol derivatives is that their reactivity toward oxidative addition at low-valent metals is sometimes complementary to that of aryl halides.…”