Alkene Dioxygenation with Malonoyl Peroxides: Synthesis of γ-Lactones, Isobenzofuranones, and Tetrahydrofurans

Abstract

Treatment of homoallylic alcohols or carboxylic acids with malonoyl peroxide 1 provides a stereoselective method for the preparation of tetrahydrofurans, γ-lactones, and isobenzofuranones in 44-82% yield and up to 27:1 trans selectivity. Application of this simple and effective heterocyclization in the synthesis of the antidepressant citalopram is also described.

Alkene Oxyamination Using Malonoyl Peroxides: Preparation of Pyrrolidines and Isoxazolidines

“…Synthesis of malonoyl peroxide (1). 15 Methane sulfonic acid (30 mL) was placed in a round bottomed flask equipped with a large magnetic stirrer bar and immersed in a bath of water at 22 °C. Urea hydrogen peroxide (9.8 g, 104.0 mmol) was added in a single portion and stirred for 30 seconds.…”

“…3462, 3447, 2950, 2921; 1 H NMR (400 MHz, CDCl3) δ 7.73 (d,J = 8.3 Hz,2H),7.29 (d,J = 8.3 Hz,2H),7.21 (at,J = 7.5 Hz,1H),2H),7.06 (d,J = 7.4 Hz,1H),4.63 (bs,1H),4.14 (bs,1H),3.71 (ddd,J = 9.4,8.5,2.4 Hz,1H), 3.53 (td, J = 9.9, 6.9 Hz, 1H), 2.42 (s, 3H), 2.32 (s, 3H), 2.07-1.98 (m, 1H), 1.76-1.70 (m, 1H), 1.55 (bd, J = 2.6 Hz, 1H); 13 C NMR (101 MHz, CDCl3) δ 143. 6, 139.9, 138.3, 134.8, 129.7, 128.6, 128.4, 127.8, 127.0, 123.4, 79.0, 72.0, 46.9, 31.5, 21.7, 21.6 (15). Reaction of (E)-4-methyl-N-(4-(o-tolyl)but-3-en-1-yl)benzenesulfonamide (100 mg, 0.32 mmol) and malonoyl peroxide 1 (61 mg, 0.48 mmol) in HFIP (0.6 mL) according to General Procedure 3 followed by hydrolysis in 1 M NaOH:THF (3.2 mL, 1:1) gave the crude alcohol (1:4.6 cis:trans 6, 138.2, 134.8, 134.4, 130.5, 129.7, 127.8, 127.5, 126.4, 126.2, 77.6, 69.7, 46.9, 31.5, 21.7, 19.6; LRMS (ES + APCI) m/z: 332.0 [M+H] + ; HRMS (ESI-TOF) m/z:…”

Fluorinated Alcohols: Magic Reaction Medium and Promoters for Organic Synthesis

“…In 2016, Tomkinson and co‐workers developed a dioxygenation reaction of homoallylic alcohols 98 or β,γ‐unsaturated carboxylic acids 100 in HFIP (Scheme ) . In this reaction, malonoyl peroxide 99 served as oxygenation reagent.…”

“…In 2016, Tomkinson and co-workers developed a dioxygenation reaction of homoallylic alcohols 98 or β,γ-unsaturated carboxylic acids 100 in HFIP (Scheme 31). [54] In this reaction, malonoyl peroxide 99 served as oxygenation reagent. The protocol provided an effective and stereoselective oxidative cyclization method for the preparation of γ-lactones, isobenzofuranones, and tetrahydrofurans under mild conditions.…”

Vicinal anti‐Dioxygenation of Alkenes

“…The same research group developed an intramolecular version of this cyclic diacyl peroxide‐mediated anti ‐dioxygenation reaction. Treatment of homoallylic alcohols or carboxylic acids with a cyclic diacyl peroxide furnished various tetrahydrofurans and γ‐lactones in good yields and high anti selectivities (Scheme ) . These reactions also proceed via a cyclic dioxonium ion 54 , which can be trapped intramolecularly by an O‐nucleophile.…”