The Chemistry of β‐Hydroxy Hydroperoxides

Abstract

β-Hydroxy hydroperoxides (β-hydroperoxy alcohols) are interesting chemical platforms, notably for the preparation of 1,2,4trioxanes, that are key features of numerous bioactive products such as artemisinin. In this review, the main synthetic methods to prepare β-hydroxy hydroperoxides are presented, such as the photooxidation of allylic alcohols with singlet oxygen and the ring-opening of epoxides with H 2 O 2 . The main applications of β-hydroxy hydroperoxides are also detailed, including their peracetalization to 1,2,4-trioxanes, their use as epoxidating agents and their fragmentation to carbonyl compounds. A final section is dedicated to the general characteristics and practical aspects of β-hydroxy hydroperoxides, including their stability, safety and characterization through spectroscopic means.

Regioselective Hydroperoxylation of Aziridines and Epoxides Only with Aqueous Hydrogen Peroxide

“…In a similar condition, PTSA catalyzed rearrangement reaction of β-hydroperoxy alcohol 7 f furnished synthetically useful keto-alcohol 10 f but with lower yield (35%; Scheme 7b). Along with this, the formation of acid-catalyzed cleavage byproduct, benzaldehyde (detected by MS-analysis and 13 C NMR of the crude reaction mixture) and other uncharacterized compounds were also noticed. It seemed, hydroperoxides 7 underwent acid-catalyzed Kornblum-DeLaMare type rearrangement (Scheme 7c), [19c] which was mostly known for dialkyl peroxides mediated by amine base.…”

“…Analytical TLC was performed on aluminium-backed plates coated with silica gel 60 with F 254 indicator and compounds were visualized by irradiation of UV light. The 1 H NMR and 13 C NMR spectra were recorded with Bruker 400 MHz, 100 MHz, using CDCl…”

“…Gummy liquid (0.040 g; 74% yield); 1 H NMR (400 MHz, CDCl 3 ) δ 9.70 (s, 1H), 7.27 (d, J = 4.4 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H), 4.84 (t, J = 6.2 Hz, 1H), 4.09 (dd, J = 14.4, 6.8 Hz, 1H), 3.65 (dd, J = 14.0, 5.2 Hz, 1H), 3.60 (s, 3H), 1.35 (s, 9H); 13…”

“…[12] Duguet group also reported the ring-opening of epoxy methyl oleate using a 50% aqueous H 2 O 2 in presence of phosphotungstic acid (H 3 PO 4 .12WO 3 ) in tert-amyl alcohol solvent and the detailed chemistry of βhydroxy hydroperoxides has been described in their recent review. [13] However, the utilization of hazardous ethereal solution of anhydrous H 2 O 2 on a large scale, retards practical scalability and synthesis. We chose to explore a general strategy that will tone down these issues by using an aqueous solution of H 2 O 2 for the construction of hydroperoxide-containing organic compounds.…”

“…hydroperoxy-3-(hydroxymethyl)indolin-2-one (4 e). Yellow gummy liquid (0.051 g; 84% yield); 1 H NMR (400 MHz, Methanol-d 4 ) δ 7.49 (d, J = 7.4 Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 3.91 (d, J = 11.2 Hz, 1H), 3.78 (d, J = 11.2 Hz, 1H); 13 C{ 1 H} NMR (100 MHz, Methanol-d 4 ) δ 176.5, 142.8, 129.6, 126.9, 125.1, 122.0, 109.6, 87.8, 62.5; FT-IR(ν cm À 1 ) 3407, 2921, 2851, 1733, 1468, 1215, 1049, 760; HRMS (ESI-TOF) m/z: [M + Na] + calcd for C 9 H 9 NNaO 4 ; 218.0429; found 218.0426.3-hydroperoxy-3-(hydroxymethyl)-5-methoxy-1-methylindolin-2-one (4 f).White solid (0.050 g; 86% yield); mp 120-122 °C; 1 H NMR (400 MHz, Methanol-d 4 ) δ 7.05 (d, J = 2.4 Hz, 1H), 6.87-6.77 (m, 2H), 4.54 (s, 1H), 3.78 (d, J = 11.6 Hz, 1H), 3.71 (s, 3H), 3.62 (d, J = 11.4 Hz, 1H), 3.07 (s, 3H);13 C{ 1 H} NMR (100 MHz, Methanol-d 4 ) δ 174.4, 156.4, 137.9, 127.6, 114.0, 112.1, 108.7, 87.8, 62.5, 54.9, 25.1; FT-IR(ν cm À 1 ) 3368, 2917, 1737, 1604, 1681, 1467, 1288, 1035, 769; HRMS (ESI-TOF) m/z: [M + Na] + calcd for C 11 H 13 NNaO 5 ; 262.0691; found 262.0685. 3-hydroperoxy-3-(hydroxymethyl)-1,5,7-trimethylindolin-2one (4 g).…”