Reinvestigating FeBr₃-Catalyzed Alcohol Oxidation with H₂O₂: Is a High-Valent Iron Species (HIS) or a Reactive Brominating Species (RBS) Responsible for Alcohol Oxidation?

Abstract

In 2003, Martı ́n et al. reported a green alcohol oxidation with FeBr 3 (cat.)/H 2 O 2 and proposed a high-valent iron species (HIS) responsible for the alcohol oxidation. Reinvestigating this FeBr 3 (cat.)/H 2 O 2 method led us to propose a different mechanism that involves a reactive brominating species (RBS) for the oxidation of alcohols. The evidence to support this RBS-based mechanism includes (1) our recent findings of in situ-generated RBS from the related FeBr 2 /H 2 O 2 or CeBr 3 /H 2 O 2 systems, (2) our results of a series of controlled experiments, and ( 3) some related RBS-based precedents (NBS, NBA, or Br 2 ) showing similar high oxidation selectivity of secondary over primary alcohols. These studies enable us to discover that a RBS from CeBr 3 /H 2 O 2 is much more efficient for the oxidation of secondary and benzylic alcohols, which represents a new green protocol for selective oxidation of alcohols to carbonyls.

Two Green Protocols for Halogenative Semipinacol Rearrangement

“…The product 2aj was derived from the migration of primary carbon in the HSPR (Scheme 3b), while 2ak was derived from the migration of quaternary carbon in the HSPR (Scheme 3c) and might find applications in asymmetric catalysis (2aj) 29 and/or medicinal chemistry (2ak). At last, we studied the HSPR reaction of acyclic allylic alcohols 9,11c,30 Notably, the secondary alcohol was not oxidized by the CeBr 3 −H 2 O 2 system to the corresponding ketone, 27 but the HSPR reaction occurred exclusively to provide the β-bromoaldehyde 30 2aq. Notably, vinyl tertiary alcohols (monosubstituted alkene) could undergo HSPR to provide the expected β-bromo ketone (2ar and 2as) in excellent yields, which could undergo facile HBr elimination in the course of column chromatography on silica gel to afford α,β-conjugate ketones.…”

“…As shown in Scheme 2a, we have exploited the reactive halogenating species (RHS) in situ generated from oxone/ halide and Fenton halide (FeBr 2 −H 2 O 2 or CeBr 3 −H 2 O 2 ) for Achmatowicz rearrangement, 21 oxidative rearrangement of indoles, 22 dihalogenation of alkenes/alkynes, oxidative halocyclization of tryptamines/tryptophols, 23 oxidative halogenation of hydrazones/aldoximes, 24 halogenation of arenes/ alkenes/alkynes, 25 desulfurization of thioacetals/thioketals, 26 and oxidation of alcohols. 27 We envisioned that the in situ generated RHS from both oxone/halide and Fenton halide might be used for HSPR of allyl alcohols (Scheme 2b). The potential challenge lies on the possible competing dihalogena- tion (Scheme 2b, pathway ii) since the halide ion for the planned oxidation into RHS is present in the reaction and as a good nucleophile might compete effectively with semipinacol rearrangement (Scheme 2b, pathway i).…”

“…Our laboratory has a continuous interest in developing green protocols for various halogenation/oxidation reactions. As shown in Scheme a, we have exploited the reactive halogenating species (RHS) in situ generated from oxone/halide and Fenton halide (FeBr 2 –H 2 O 2 or CeBr 3 –H 2 O 2 ) for Achmatowicz rearrangement, oxidative rearrangement of indoles, dihalogenation of alkenes/alkynes, oxidative halocyclization of tryptamines/tryptophols, oxidative halogenation of hydrazones/aldoximes, halogenation of arenes/alkenes/alkynes, desulfurization of thioacetals/thioketals, and oxidation of alcohols . We envisioned that the in situ generated RHS from both oxone/halide and Fenton halide might be used for HSPR of allyl alcohols (Scheme b).…”

Achmatowicz Rearrangement-Inspired Development of Green Chemistry, Organic Methodology, and Total Synthesis of Natural Products

“…has demonstrated superior efficacy in oxidative bromination of arenes, alkenes, and alkynes; 46 oxidative bromocyclization of tryptamines/tryptophols; 46 oxidative rearrangement of indoles and tetrahydro-b-carbolines; 47 alcohols oxidation; 48 and oxidative desulfurization of thioacetals and thioketals 49 (Scheme 5b). Different from oxone, hydrogen peroxide is rather unstable, and its concentration varies significantly over storage at room temperature.…”

“…Although oxone as a terminal oxidant contributes to poor green metrics, it has admirable bench stability and distinct selectivity toward halide oxidation over other electron-rich substrates (arenes, alkenes, indoles, and furans). Our Fenton-halide (FeBr 2 –H 2 O 2 or CeBr 3 –H 2 O 2 ) has demonstrated superior efficacy in oxidative bromination of arenes, alkenes, and alkynes; oxidative bromocyclization of tryptamines/tryptophols; oxidative rearrangement of indoles and tetrahydro-b-carbolines; alcohols oxidation; and oxidative desulfurization of thioacetals and thioketals (Scheme b). Different from oxone, hydrogen peroxide is rather unstable, and its concentration varies significantly over storage at room temperature.…”