Iron‐Catalyzed C−O Bond Activation: Opportunity for Sustainable Catalysis

Abstract

Oxygen-based electrophiles have emerged as some of the most valuable cross-coupling partners in organic synthesis due to several major strategic and environmental benefits, such as abundance and potential to avoid toxic halide waste. In this context, iron-catalyzed C-O activation/cross-coupling holds particular promise to achieve sustainable catalytic protocols due to its natural abundance, inherent low toxicity, and excellent economic and ecological profile. Recently, tremendous progress has been achieved in the development of new methods for functional-group-tolerant iron-catalyzed cross-coupling reactions by selective C-O cleavage. These methods establish highly attractive alternatives to traditional cross-coupling reactions by using halides as electrophilic partners. In particular, new easily accessible oxygen-based electrophiles have emerged as substrates in iron-catalyzed cross-coupling reactions, which significantly broaden the scope of this catalysis platform. New mechanistic manifolds involving iron catalysis have been established; thus opening up vistas for the development of a wide range of unprecedented reactions. The synthetic potential of this sustainable mode of reactivity has been highlighted by the development of new strategies in the construction of complex motifs, including in target synthesis. The most recent advances in sustainable iron-catalyzed cross-coupling of C-O-based electrophiles are reviewed, with a focus on both mechanistic aspects and synthetic utility. It should be noted that this catalytic manifold provides access to motifs that are often not easily available by other methods, such as the assembly of stereodefined dienes or C(sp )-C(sp ) cross-couplings, thus emphasizing the synthetic importance of this mode of reactivity.

2‐Methyltetrahydrofuran: A Green Solvent for Iron‐Catalyzed Cross‐Coupling Reactions

“…Comparison of the results (Tables 2and 3) clearly indicates that 2-MeTHF serves as av ery effective solvent for the cross-coupling, even in the absence of trace quantities of THF.S ince many Grignard reagents are commerciallya vailable as solutionsi n2 -MeTHF as part of ag reen chemistry initia-tive, [6][7][8] the incorporation of 2-MeTHFa sagreen solvent for iron-catalyzed cross-couplingsr epresents as ignificant benefit from ap ractical green chemistry standpoint. [17,18] We were delighted to find that challenging secondary Grignardr eagentsa re competents ubstrates in this alkylation, furnishing the sterically hinderedp roducts with high efficiency (2m, n,S cheme 2). The use of phenole lectrophiles further demonstrates the practicality of this protocol.…”

“…The use of phenole lectrophiles further demonstrates the practicality of this protocol. [17,18] We were delighted to find that challenging secondary Grignardr eagentsa re competents ubstrates in this alkylation, furnishing the sterically hinderedp roducts with high efficiency (2m, n,S cheme 2). The reaction of iPrMgBri ss elective for the branched product (2n,B /L > 20:1).…”

N‐Methylcaprolactam as a Dipolar Aprotic Solvent for Iron‐Catalyzed Cross‐Coupling Reactions: Matching Efficiency with Safer Reaction Media

“…Pleasingly, the reaction of a tosyl electrophile afforded the cross‐coupling product with high C−O coupling selectivity (Scheme ), demonstrating that after suitable O‐activation phenols can be used as alternative electrophile sources to aryl chlorides in this cross‐coupling …”

Palladium‐catalyzed decarboxylative coupling of α,β‐unsaturated carboxylic acids with aryl tosylates

“…Goossen et al [40] accomplished similar PdBr 2 /CuBr-catalyzed decarboxylative reaction under ligand-free conditions at 170°C in a 79% yield (Scheme 1, equation (2)). [44][45][46][47][48] The use of phenol derivatives instead of halides reduces the production of halide waste, thus lowering the environmental impact of the cross-coupling process. A yield of 82% of (E)-1-methyl-4-styrylbenzene was obtained under catalysis of PdBr 2 /CuF 2 with (o-biphenyl)PtBu 2 at 170°C (Scheme 1, equation (3)).…”