Synlett 2014; 25(16): 2265-2270
DOI: 10.1055/s-0034-1378370
cluster
© Georg Thieme Verlag Stuttgart · New York

One-Pot Generation of C≡X Bonds from Methyl 2-Siloxycyclopropane­carboxylates: Simple Syntheses of Functionalized Nitriles and Alkynes

Dorian Reich
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany   Fax: +49(30)83855367   Email: hans.reissig@chemie.fu-berlin.de
,
Dennis S. Müller
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany   Fax: +49(30)83855367   Email: hans.reissig@chemie.fu-berlin.de
,
Luise Schefzig
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany   Fax: +49(30)83855367   Email: hans.reissig@chemie.fu-berlin.de
,
Reinhold Zimmer*
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany   Fax: +49(30)83855367   Email: hans.reissig@chemie.fu-berlin.de
,
Hans-Ulrich Reissig*
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany   Fax: +49(30)83855367   Email: hans.reissig@chemie.fu-berlin.de
› Author Affiliations
Further Information

Publication History

Received: 23 April 2014

Accepted after revision: 28 May 2014

Publication Date:
17 July 2014 (online)


Abstract

Starting from methyl 2-siloxycyclopropanecarboxylates simple and efficient one-pot procedures are described that lead to β-cyanoesters and methoxycarbonyl-substituted terminal alkynes. The prepared functionalized alkynes were subjected to typical transformations such as [3+2] cycloaddition providing triazole derivatives, Sonogashira coupling, Au-catalyzed hydrophosphorylation or a copper-catalyzed coupling of methyl diazoacetate furnishing alkyne 14 and allene derivative 15. The Pauson–Khand reaction of the enyne 4c afforded a diastereomeric mixture of methyl 5-oxohexahydropentalen-2-carboxylate 16 in moderate yield.

Supporting Information

 
  • References and Notes


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  • 26 Typical Procedure for Methyl 3-Cyano-2,3-dimethyl-butanoate (2c): A mixture of cyclopropane 1c (1.15 g, 5.00 mmol) and NH2OH·HCl (486 mg, 7.00 mmol) in formic acid (5 mL) was heated at 100 °C for 6 h. After cooling to r.t. the solution was neutralized with 2 N NaOH solution followed by extraction with CH2Cl2 (3 × 30 mL). Purification by kugelrohr distillation (80 °C, 1.3 mbar) afforded β-cyanoester 2c (524 mg, 68%) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ = 1.28 (d, J = 7.2 Hz, 3 H, Me), 1.34, 1.39 (2 × s, 2 × 3 H, Me), 2.51 (q, J = 7.2 Hz, 1 H, CH), 3.67 (s, 3 H, OMe). 13C NMR (125.8 MHz, CDCl3): δ = 13.7 (q, Me), 24.0, 25.3 (2 × q, Me), 34.5 (s, CMe2), 47.1 (d, CH), 51.8 (q, OMe), 123.2 (s, CN), 172.9 (s, CO2Me). IR (ATR): 2985–2845 (C–H), 2240 (C≡C), 1740 (C=O) cm–1. HRMS (ESI–TOF): m/z [M + Na]+ calcd for C8H13NNaO2: 178.0838; found: 178.0839. Typical Procedure for Methyl 3-Methylpent-5-yne-carboxylate (4a): To a suspension of K2CO3 (819 mg, 5.93 mmol) in MeOH (6 mL) reagent 3 (452 mg, 2.35 mmol) and siloxycyclopropane 1a (684 mg, 3.56 mmol) were added at r.t. After stirring overnight, 5% aq NaHCO3 solution (10 mL) and Et2O (50 mL) were added. After separation of the phases, the aqueous phase was extracted with Et2O (3 × 50 mL). The combined organic layers were dried with Na2SO4, filtered and carefully concentrated. Column chromatography (silica gel, Et2O) followed by careful removal of the solvent (ca 500 mbar; bath temp: 35 °C) provided 4a 16b (362 mg, 98%) as a pale yellow liquid. 1H NMR (400 MHz, CDCl3): δ = 1.21 (d, J = 7.0 Hz, 3 H, Me), 2.03 (d, J = 2.5 Hz, 1 H, 5-H), 2.36 (dd, J = 6.0, 12.5 Hz, 1 H, 2-H), 2.52 (dd, J = 5.7, 12.5 Hz, 1 H, 2-H), 2.87–2.95 (m, 1 H, 3-H), 3.65 (s, 3 H, OMe). 13C NMR (125.8 MHz, CDCl3): δ = 20.6 (q, Me), 22.7 (d, C-3), 41.2 (t, C-2), 51.7 (q, OMe), 68.9 (s, C-4), 87.1 (d, C-5), 171.8 (s, C-1). Typical Procedure for Methyl 3-(1-Benzyl-1H-1,2,3-triazol-4-yl)-3-butanoate (5a): To a solution of the alkyne 4a (0.072 g, 0.571 mmol) in MeCN (10 mL) benzyl azide (0.051 g, 0.380 mmol), TBTA (0.028 g, 0.053 mmol), Et3N (5 μL, 0.053 mmol), and CuI (0.010 g, 0.053 mmol) were added at r.t. and stirred overnight. After filtration of the mixture (silica gel), concentration in vacuo and purification by column chromatography (silica gel, hexanes–EtOAc, 8:1 → 2:1) afforded the product 5a (0.071 g, 72%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ = 1.30 (d, J = 7.0 Hz, 3 H, Me), 2.51 (dd, J = 7.6, 15.8 Hz, 1 H, 2-H), 2.78 (dd, J = 7.0, 15.8 Hz, 1 H, 2-H), 3.42 (sextet, J = 7.0 Hz, 1 H, 3-H), 3.59 (s, 3 H, OMe), 5.45 (s, 2 H, NCH2), 7.20–7.23, 7.31–7.34 (2 × m, 2 × 3 H, =CH, Ph). 13C NMR (100.5 MHz, CDCl3): δ = 20.1 (q, Me), 27.8 (d, CH), 40.9 (t, CH2), 51.4 (q, OMe), 53.9 (t, CH2Ph), 120.0 (d, =CH), 127.9, 128.5, 129.0, 134.8 (3 × d, s, Ph), 151.9 (s, =C), 172.6 (s, C=O). IR (ATR): 3140–2845 (=C–H, C–H), 1735 (C=O) cm–1. HRMS (ESI–TOF): m/z [M + Na]+ calcd for C14H17N3NaO2: 282.1213; found: 282.1222. Diphenyl 4-(Diphenoxyphosphoryloxy)-3-methylpent-4-enoate (12): Alkyne 4a (0.051 g, 0.405 mmol) was dissolved in toluene (2 mL) and diphenyl phosphate 11 (0.084 g, 0.338 mmol), AgPF6 (0.004 g, 0.017 mmol) and Ph3AuCl (0.008 g, 0.017 mmol) were added. The solution was stirred at r.t. overnight. After filtration through a pad of silica gel (EtOAc), the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, hexanes–EtOAc, 6:1 → 2:1) to afford 12 (0.095 g, 75%) as a yellow oil. 1H NMR (500 MHz, CDCl3): δ = 1.08 (d, J = 6.8 Hz, 3 H, Me), 2.23 (dd, J = 8.2, 15.3 Hz, 1 H, CH2), 2.53 (dd, J = 6.2, 15.3 Hz, 1 H, CH2), 2.79–2.87 (m, 1 H, CH), 3.65 (s, 3 H, OMe), 4.66, 5.02 (mc, 2 × 1 H, =CH2), 7.16–7.25, 7.32–7.36 (2 × m, 2 × 3 H, 2 × 2 H, Ph). 13C NMR (125.8 MHz, CDCl3): δ = 17.6 (q, Me), 35.5 (dd, 3 J CP = 7.3 Hz, CH), 38.4 (t, CH2), 51.6 (q, OMe), 96.9 (td, 3 J CP = 2.1 Hz, =CH2), 120.1 (dd, 3 J CP = 5.2 Hz, Ph), 125.5 (d, Ph), 129.8 (d, Ph), 150.4 (d, 2 J CP = 7.3 Hz, Ph), 157.7 (d, 2 J CP = 9.3 Hz, =C), 172.1 (s, CO2). IR (ATR): 2955–2850 (=C–H, C–H), 1740 (C=O), 1665 (C=C), 1300 (P–O) cm–1. HRMS (ESI–TOF): m/z [M + H]+ calcd for C19H22O6P: 377.1149; found: 377.1127. HRMS (ESI–TOF): m/z [M + Na]+ calcd for C19H21NaO6P: 399.0968; found: 399.0946. HRMS (ESI–TOF): m/z [M + K]+ calcd for C19H21KO6P: 415.0707; found: 415.0682. Methyl 5-Oxo-1,2,3,3a,4,5-hexahydropentalen-2-carboxylate (16): Enyne 4e (0.177 g, 1.16 mmol) was dissolved in Et2O (16 mL). After addition of Co2(CO)8 (0.398 g, 1.16 mmol), the solution was stirred for 15 h at r.t. under an Ar atmosphere. The solution was then filtrated through neutral alumina (Et2O) and the filtrate was concentrated to dryness. The resulting crude product was dissolved in CH2Cl2 (10 mL) and NMO (0.178 g, 2.37 mmol) was added in one portion at 0 °C. The solution was stirred at this temperature for 18 h and then treated with 10% HCl solution (1 mL). The separated organic phase was washed with brine (2 × 3 mL) and dried (Na2SO4). After removal of the solvent under reduced pressure, the residue was purified by column chromatography (hexanes–EtOAc, 4:1) to afford bicyclic product 16 (0.104 g, 50%; 2 diastereomers = 60:40) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.37–1.52 (m, 2 H, CH2), 2.04 (dd, J = 3.1, 18.1 Hz, 0.6 H, CH2), 2.12 (dd, J = 3.4, 18.1 Hz, 0.4 H, CH2), 2.42–2.50, 2.57–2.65, 2.84–3.11, 3.19–3.29 (4 × m, 0.6 H, 0.4 H, 3 H, 1 H, CH, CH2), 3.69, 3.72 (2 × s, 1.2 H, 1.8 H, OMe), 5.89, 5.91 (2 × mc, 0.6 H, 0.4 H, =CH). 13C NMR (125.8 MHz, CDCl3): δ = 30.0*, 30.3, 34.4, 35.2*, 42.0*, 42.2 (6 × t, CH2), 43.3, 44.0*, 44.4, 46.6* (4 × d, CH), 52.1*, 52.2 (2 × q, OMe), 125.1, 125.6* (2 × d, =CH), 174.6*, 175.8 (2 × s, CO2Me), 187.3*, 188.1 (2 × s, =C), 209.8*, 210.2 (2 × s, C=O); signals of the minor diastereomer are marked with *. IR (ATR): 3140–2860 (=C–H, C–H), 1730 (C=O) cm–1. HRMS (ESI–TOF): m/z [M + H]+ calcd for C10H13O3: 181.0859; found: 181.0860. HRMS (ESI–TOF): m/z [M + Na]+ calcd for C10H12NaO3: 203.0679; found: 203.0685. HRMS (ESI–TOF): m/z [M + K]+ calcd for C10H12KO3: 219.0418; found: 219.0426.