Geminal Difunctionalization of Vinylarenes: Concise Synthesis of 1,3-Dioxolan-4-ones

Abstract

We report a straightforward method for the synthesis of five-membered 1,3-dioxolan-4-ones by an unprecedented oxidative alkene geminal difunctionalization strategy using α-hydroxy carboxylic acids. Under the geminal oxidative addition conditions, various substituted α-hydroxy carboxylic acids and styrenes containing a variety of substituents, including β-substituted styrenes, were effectively coupled regioselectively (anti-Markovnikov) with an isobutyl-substituted chiral α-hydroxy carboxylic acid, providing an annulation with excellent dia­­stereoselectivity. An aryl migration in the semipinacol rearrangement leading to geminal oxidative addition of the α-hydroxy carboxylic acids was confirmed by deuterium-labelling and control studies.

Key words

dioxolanones - geminal difunctionalization - regioselectivity - rearrangement - aryl migration

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• 17 Because the observed diastereoselectivities in Table 1 (including 3f) are essentially highly substrate controlled, a more robust and comprehensive catalyst-controlled protocol for the highly enantio- and diastereoselective synthesis of 1,3-dioxolan-4-ones through geminal dioxygenation of alkenes is being currently pursued in the authors’ laboratory, the results of which will be disclosed in a separate article in the future.
• 18 1,3-Dioxolan-4-ones 3a–s; General Procedure NBS (0.60 mmol) and AgOTf (0.70 mmol) were added to a well-stirred colorless solution of the appropriate α-hydroxy carboxylic acid 1 (0.50 mmol) and the appropriate styrene 2 (0.75 mmol) in CH₂Cl₂ (5 mL) at rt (25 °C) under argon in a dry Schlenk flask. The mixture initially changed from colorless to cloudy white, then to colorless with a pale-yellow suspension, and finally to colorless with a pale-gray precipitate after 1 h. The progress of the reaction was monitored by TLC. The mixture was stirred for 1 h at rt, then H₂O (3 mL), sat. aq NaHCO₃ (4 mL), and sat. aq Na₂S₂O₃ (4 mL) were added successively. The mixture was extracted with CH₂Cl₂ (3 × 5 mL), and the combined organic layers were dried (Na₂SO₄), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography [silica gel, pentane–Et₂O (25:1)]. (5R)-2-Benzyl-5-phenyl-1,3-dioxolan-4-one (3a) Yield: 97 mg (76%). Diastereomer A: white solid; mp 82–84 °C; [α]_D ²⁴ –89.7 (c 1.0, CHCl₃). IR (thin film): 3032, 2924, 1796, 1496, 1454, 1401, 1274, 1214 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.21 (m, 10 H), 5.86 (t, J = 4.5 Hz, 1 H), 5.19 (s, 1 H), 3.30–3.20 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 171.3, 133.5, 133.0, 130.2, 129.2, 128.6, 128.5, 127.3, 127.0, 103.9, 76.8, 40.5. HRMS (ESI-QTOF): m/z [M + Na]⁺ calcd for C₁₆H₁₄NaO₃: 277.0841; found: 277.0843. Diastereomer B: white solid; mp 53–54 °C; [α]_D ²⁴ –38.2 (c 1.0, CHCl₃). IR (thin film): 3031, 2924, 1797, 1495, 1454, 1215, 1177, 1109, 992, 934 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.38–7.25 (m, 10 H), 6.02 (t, J = 3.9 Hz, 1 H), 5.11 (s, 1 H), 3.21 (d, J = 4.2 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.1, 126.6, 126.0, 123.2, 122.0, 121.9, 121.6, 120.4, 118.9, 97.9, 68.3, 34.3. HRMS (ESI-QTOF): m/z [M + Na]⁺ calcd for C₁₆H₁₄NaO₃: 277.0841; found: 277.0850. 2-Benzyl-5,5-dimethyl-1,3-dioxolan-4-one-d ₂ (3s) Colorless oil; yield: 66 mg (63%). IR (thin film): 2984, 2926, 1798, 1387, 1281, 1183, 1008, 986 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.34–7.25 (m, 5 H), 5.72 (s, 1 H, HCCD₂Ph), 1.38 (s, 3 H), 1.34 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 175.4, 133.3, 130.1, 128.4, 127.2, 101.9, 77.2, 40.4 (quint, ³ J _C–D = 19.6 Hz), 24.4, 21.8. HRMS (ESI-QTOF): m/z [M + Na]⁺ calcd for C₁₂H₁₂D₂NaO₃: 231.0966; found: 231.0969.