Asymmetric Allenylation of N-Acylhydrazones with Propargyltrichlorosilane Catalyzed by Helical Chiral 2,2′-Bipyridine N-Monoxide

Dedicated to Professor Hisashi Yamamoto on his 80^th birthday

Abstract

(M)-Helicene-derived 2,2′-bipyridine N-monoxide catalyzed the allenylation of N-acylhydrazones with propargyltrichlorosilane with excellent regioselectivity and moderate-to-good enantioselectivity. This study represents the first catalytic asymmetric allenylation of acylhydrazones.

Key words

azahelicene - organocatalysis - asymmetric synthesis - propargyltrichlorosilane - acylhydrazone

Publication History

Received: 30 May 2023

Accepted after revision: 03 July 2023

Article published online:
09 August 2023

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• 15 Representative ProcedureA test tube was charged with a magnetic stir bar, flame-dried in vacuo, and cooled to room temperature under an atmosphere of nitrogen. To this was added acylhydrazone 4a (36 mg, 0.1 mmol), a solution of (M)-7 in CH₂Cl₂ (0.05 M, 200 μL), and i-Pr₂NEt (87 μL, 0.5 mmol). The resulting heterogeneous mixture was cooled to –78 °C, treated with a solution of propargyltrichlorosilane in CH₂Cl₂ (1.5 M, 100 μL) drop-by-drop through the sidewall of the test tube. The reaction test tube was transferred to the isopropanol bath at –20 °C and kept therein for 20 h. The reaction mixture was cooled back to –78 °C, quenched with 50% Et₃N in MeOH (400 μL), allowed to warm up to room temperature, and washed with saturated aqueous NaHCO₃ solution (1 mL). The aqueous layer was extracted with CH₂Cl₂ (1 mL) three times, and the combined organic layers were dried over Na₂SO₄, filtered, and concentrated in vacuo to provide the crude reaction mixture. ¹H NMR yield was determined with the crude reaction mixture by using 1,1,2,2-tetrachloroethane as an internal standard; 5a (57%) and 6a (3%). The crude reaction mixture was purified by preparative TLC using 10% EtOAc in toluene as eluent to afford 5a (20 mg, 50%) as a white solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.08 (s, 2 H), 8.01 (s, 1 H), 7.53 (d, J = 7.2 Hz, 1 H), 7.45 (d, J = 7.2 Hz, 2 H), 7.40 (t, J = 7.5 Hz, 2 H), 7.36 (d, J = 7.0 Hz, 1 H), 5.41 (q, J = 7.0 Hz, 1 H), 5.24–5.21 (m, 1 H), 4.91 (dd, J = 6.6, 2.0 Hz, 2 H), 4.77–4.75 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 208.5, 164.5, 139.9, 135.1, 132.4 (q, ² J_C–F = 33.8 Hz), 128.8, 128.3, 127.8, 127.2 (br s), 125.4 (t, ³ J_C–F = 3.5 Hz), 122.8 (q, ¹ J_C–F = 271.4 Hz), 91.8, 77.3, 63.8. HRMS (ESI): exact mass calcd for C₁₉H₁₅F₆N₂O [M + H]⁺: 401.1083; found: 401.1073. er = 75:25; t _R (+) = 17.87 min; t _R (–) = 23.12 min (Daicel Chiralcel^® OJ-H with an OJ-H guard column, hexane/2-propanol = 90:10, 0.5 mL/min). [α]_D ²² = –72.8 (c 0.33, CHCl₃)