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Synlett 2020; 31(02): 189-193
DOI: 10.1055/s-0039-1691491
DOI: 10.1055/s-0039-1691491
letter
One-Pot Deprotonative Synthesis of Biarylazacyclooctynones
This work was financially supported by the Japan Society for the Promotion of Science (JSPS KAKENHI, Grant Numbers JP16K05774 in Scientific Research (C), JP19H02717 in Scientific Research (B), JP16H01153 and JP18H04413 in the Middle Molecular Strategy) and the Japan Society for the Promotion of Science (JSPS) predoctoral fellowship (for Y.H.).Further Information
Publication History
Received: 10 October 2019
Accepted after revision: 04 November 2019
Publication Date:
04 December 2019 (online)
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Abstract
Deprotonative formation of biarylazacyclooctynone (BARAC) from the corresponding enol triflate is described. The reaction furnished the azacyclooctynone within one hour at –78 °C. This process could be performed in one pot from the starting ketone to provide a range of BARAC derivatives in moderate to excellent yields. The protocol enabled the gram-scale formation of the BARAC skeleton by reducing the number of reaction steps. Furthermore, the established method was applied to the synthesis of the BARAC derivative bearing a coumarin moiety.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691491.
- Supporting Information
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References and Notes
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- 11 Experimental Procedures and Characterization Data A flame-dried 500 mL two-necked flat-bottomed flask equipped with a Teflon-coated magnetic stirring bar, a rubber septum, and an inlet adapter with a three-way stopcock was charged with ketolactam 4a (1.65 g, 6.56 mmol) and PhNTf2 (2.35 g, 6.56 mmol) in THF (39 mL). After the resulting solution was cooled to –78 °C, KHMDS (0.50 M in toluene, 32.8 mL, 16 mmol) was added dropwise over 6 min. After stirring at –78 °C for 1 h, the reaction mixture was treated with water (80 mL) and diluted with diethyl ether (30 mL). The mixture was allowed to warm to room temperature for 15 min. The aqueous layer was extracted twice with diethyl ether (2 × 15 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give a crude material, which was purified by silica gel column chromatography (hexane/diethyl ether = 1:3) to afford N-methyl BARAC 6a (1.45 g, 6.22 mmol, 95%) as a brown solid. Rf = 0.38 (hexane/diethyl ether = 1:3); mp decomp. (120 °C). IR (ATR): 2924, 1657, 1468, 1447, 1333, 1214, 1180, 1079, 1039, 761, 715, 630 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.65–7.58 (m, 2 H), 7.50–7.35 (m, 6 H), 2.73 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 176.9, 156.6, 149.4, 130.0, 129.5, 129.4, 128.9, 128.2, 127.6, 126.5, 125.6, 122.31, 122.27, 109.5, 108.7, 38.8. HRMS (DART+): m/z calcd for C16H12NO: 234.0919 [M + H]+; found: 234.0928.
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BARAC:
OCT:
DIBO:
DIFO:
BCN:
DIBAC:
DIMAC:
Sondheimer diyne:
DACN:
PYRROC:
SNO-OCT: