Carboxylate-Catalyzed C-Silylation of Terminal Alkynes
Anton Bannykh, Petri M. Pihko*
*Department of Chemistry and NanoScience Center, University of Jyväskylä, P.O.B. 35, FI-40014 University of Jyväskylä, Finland,
Email: Petri.Pihko
jyu.fi
A. Bannykh, P. M. Pihko, Org. Lett., 2024, 26, 1991-1995.
DOI: 10.1021/acs.orglett.3c04213
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Abstract
A quaternary ammonium pivalate catalyzes a metal-free C-silylation protocol of terminal alkynes with commercially available N,O-bis(silyl)acetamides like BSA and BTBSA as silylating agents. The reaction proceeds under mild conditions and tolerates a range of functionalities.
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proposed mechanism
Details
This article reports a novel, metal-free, carboxylate-catalyzed C-silylation protocol for terminal alkynes using quaternary ammonium pivalate (TMAP) as the catalyst and N,O-bis(silyl)acetamides (BSA) as silylating agents. The reaction operates under mild conditions, tolerates various functional groups, and allows for the simultaneous O- or N-silylation of acidic OH or NH groups. The process is efficient, yielding high conversions and excellent yields for a range of substrates, including substituted phenylacetylenes, heterocyclic, and aliphatic alkynes. The method also demonstrates scalability and the ability to protect hydroxy and amine groups in situ. Mechanistic studies suggest a turnover-determining deprotonation step, supported by a Hammett ρ value of +1.4 ± 0.1. The protocol's limitations include partial isomerization and decomposition with certain substrates. Overall, this method offers a practical and efficient approach to synthesizing silylated terminal alkynes, with broad substrate scope and potential applications in synthetic organic chemistry. The study was supported by the University of Jyväskylä and the Academy of Finland, with contributions from various researchers for experimental and analytical assistance.
Preparation of the tetramethylammonium pivalate catalyst
For the purposes of this study, the catalyst was prepared as follows: Tetramethylammonium hydroxide solution (25 wt‐% in water, 3.41 mL, 866 mg, 9.5 mmol, 0.95 equiv) was added to a suspension of pivalic acid (1.02 g, 10.0 mmol, 1.0 equiv) in 5 mL of deionized water at room temperature. After 10 min, reaction mixture was concentrated under reduced pressure, and remaining water was removed by heating on the vacuum line using heat gun until the viscous liquid turns to white solid. Final drying was completed overnight under high vacuum at room temperature to give TMAP in quantitative yield (1.74 g) as a white solid. TMAP is slightly hygroscopic, and it was stored in desiccator over silica gel (orange indicator). However, no special precautions were used in handling and weighing the catalyst.
General procedure for the TMAP‐catalyzed silylation of alkynes
General procedure 1 (GP1): To a stirred solution of TMAP (0.1 equiv) in dry MeCN, acetylene (0. 50 - 1.00 mmol, 1 equiv) was added either via syringe or as a solid, followed by addition of N,O‐bis(trimethylsilyl)acetamide (typically 1.5 equiv) via syringe at room temperature. The reaction progress was followed by TLC (UV or KMnO4). After no acetylene remained in the reaction mixture, hexane (10 ml) and water (15 mL) were added, the phases were separated, and the aqueous phase was extracted in hexane (10 ml × 3). The combined organic extracts were dried over Na2SO4, filtered through the 1‐2 cm pad of silica gel, washed the pad with extra portion of hexane (10 ml) and concentrated to give the pure desired product as a colorless oil or solid, unless otherwise noted.
General procedure 2 (GP2): To an cooled solution (0 °C) of TMAP (0.1 equiv) in dry MeCN, acetylene (0.50 - 1.00 mmol, 1 equiv) was added either via syringe or as a solid, followed by addition of N,O‐bis(trimethylsilyl)acetamide (typically 1.5 equiv) via syringe. The reaction progress was followed by TLC (UV or KMnO4). After no acetylene remained in the reaction mixture, hexanes (10 ml) and water (15 mL) were added, the phases were separated, and the aqueous phase was extracted with hexanes (10 ml × 3). The combined organic extracts were dried over Na2SO4, filtered through the 1‐2 cm pad of silica gel, washed the pad with extra portion of hexane (10 ml) and concentrated to give the pure desired product as a colorless oil or solid, unless otherwise noted.
Key Words
ID: J54-Y2024
