Reductive Ring-Opening 1,3-Difunctionalizations of Arylcyclopropanes with Sodium Metal

Abstract

Sodium dispersion promotes reductive ring opening of arylcyclopropanes. The presence of a reduction-resistant electrophile, such as methoxypinacolatoborane, epoxide, oxetane, paraformaldehyde, or chlorotrimethylsilane, during the reductive ring opening event leads to the formation of 1,3-difunctionalized 1-arylalkanes by immediate trappings of the resulting two reactive carbanions. In particular, the ring-opening 1,3-diborylations of arylcyclopropanes afford 1,3-diborylalkanes with high syn selectivity.

Key words

carbanions - cleavage - diastereoselectivity - electron transfer - metalation - reduction - ring opening - sodium

Publication History

Received: 27 August 2020

Accepted after revision: 16 September 2020

Article published online:
22 October 2020

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• 9 Experimental ProcedureAn oven-dried 20 mL Schlenk tube was charged with 4,4′-di-tert-butylbiphenyl (DTBB, 53.3 mg, 0.200 mmol), THF (4.0 mL), and trans-1a (191 mg, 0.983 mmol). After the mixture was cooled to –78 °C, MeOBpin (0.97 mL, 6.0 mmol) was added. Sodium dispersion (10.0 M, 0.40 mL, 4.0 mmol) was then added dropwise, and the resulting suspension was stirred at –78 °C for 1.5 h. The resulting mixture was warmed to 0 °C, and the reaction was then quenched with i-PrOH (0.31 mL, 4.0 mmol) and then aqueous NH₄Cl (5 mL). The resulting biphasic solution was extracted with EtOAc (4 × 10 mL). The combined organic layer was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (hexane to hexane/EtOAc = 30:1) on silica gel to provide 2a as a white solid (81% yield, 359 mg, 0.801 mmol, syn/anti = 89:11); mp 120–130 °C. ¹H NMR (600 MHz, CDCl₃): δ = 7.21 (dd, J = 7.5, 7.5 Hz, 0.89 × 4 H + m, 0.11 × 4 H), 7.13 (d, J = 7.5 Hz, 0.89 × 4 H + m, 0.11 × 4 H), 7.10 (t, J = 7.5 Hz, 0.89 × 2 H + m, 0.11 × 2 H), 2.36 (ddd, J = 14.4, 7.8, 7.8 Hz, 0.89 × 1 H), 2.30 (t, J = 7.8 Hz, 0.89 × 2 H), 2.25 (dd, J = 9.6, 6.6 Hz, 0.11 × 2 H), 2.21 (t, J = 6.6 Hz, 0.11 × 2 H), 2.02 (ddd, J = 14.4, 7.8, 7.8 Hz, 0.89 × 1 H), 1.20 (s, 0.89 × 12 H), 1.18 (s, 0.89 × 12 H), 1.15 (s, 0.11 × 12 H), 1.14 (s, 0.11 × 12 H). ¹³C NMR (151 MHz, CDCl₃): δ (syn isomer) = 143.3, 128.6, 128.4, 125.3, 83.3, 35.2, 31.3 (br), 24.8. ¹¹B NMR (192 MHz, CDCl₃): δ = 33.1 (br). HRMS (APCI-MS, positive): m/z = 448.2957. Anal. Calcd for C₂₇H₃₈B₂O₄: 448.2960 [M]⁺.
• 10 The relative stereochemistry of 2a was unambiguously assigned after oxidation to the corresponding diol with retention of the stereochemistry.

Organolithium compounds can react with electrophiles with either retention or inversion of the stereochemistry of the nu­cleophilic carbon center, which depends on the electrophiles used. See:
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