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


    • The term donor–acceptor cyclopropane was introduced in this report:
    • 1a Reissig H.-U, Hirsch E. Angew. Chem., Int. Ed. Engl. 1980; 19: 813 ; Angew. Chem. 1980 , 92, 839

    • Earlier examples of this class of cyclopropanes are certainly known. See:
    • 1b Cram DJ, Ratajczak A. J. Am. Chem. Soc. 1968; 90: 2198
    • 1c Cram DJ, Yankee EW. J. Am. Chem. Soc. 1970; 92: 6329

    • For first synthetic applications also see:
    • 1d Wenkert E. Acc. Chem. Res. 1980; 13: 27

      For reviews on d–a cyclopropanes, see:
    • 2a Reissig H.-U. Top. Curr. Chem. 1988; 144: 73
    • 2b Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
    • 2c Gnad F, Reiser O. Chem. Rev. 2003; 103: 1603
    • 2d Yu M, Pagenkopf BL. Tetrahedron 2005; 61: 321
    • 2e De Simone F, Waser J. Synthesis 2009; 3353
    • 2f Carson CA, Kerr MA. Chem. Soc. Rev. 2009; 38: 3051
    • 2g Schneider TF, Kaschel J, Awan SL, Dittrich B, Werz DB. Chem. Eur. J. 2010; 16: 11276
    • 2h Mel’nikov MYa, Budynina EM, Ivanova OA, Trushkov IV. Mendeleev Commun. 2011; 21: 293
    • 2i Cavitt MA, Phun LH, France S. Chem. Rev. Soc. 2014; 43: 804
    • 2j Schneider TF, Kaschel J, Werz DB. Angew. Chem. Int. Ed. 2014; 53: 5504 ; Angew. Chem. 2014, 126, 5608

    • For a seminal theoretical study on d–a cyclopropanes, see:
    • 2k Schneider TF, Werz DB. Org. Lett. 2011; 13: 1848
  • 3 Grimm EL, Reissig H.-U. J. Org. Chem. 1985; 50: 242
  • 4 Reichelt I, Reissig H.-U. Synthesis 1984; 786
    • 5a Beyzavi MH, Lentz D, Reissig H.-U, Wiehe A. Eur. J. Org. Chem. 2013; 269
    • 5b Beyzavi MH, Nietzold C, Reissig H.-U, Wiehe A. Adv. Synth. Catal. 2013; 355: 1409
    • 6a Özbek H, Veljkovic IS, Reissig H.-U. Synlett 2008; 3145
    • 6b Ngo TH, Berndt H, Lentz D, Reissig H.-U. J. Org. Chem. 2012; 77: 9676
    • 6c Ngo TH, Berndt H, Wilsdorf M, Lentz D, Reissig H.-U. Chem. Eur. J. 2013; 19: 15155
  • 7 Zimmer R, Ziemer A, Gruner M, Brüdgam I, Hartl H, Reissig H.-U. Synthesis 2001; 1649
  • 8 Veljkovic I, Zimmer R, Reissig H.-U, Brüdgam I, Hartl H. Synthesis 2006; 2677

    • For other selected publications dealing with in situ generation of 1,4-dicarbonyl compounds from d–a cyclopropanes and their functionalizations in one-pot procedures, see:
    • 9a Brückner C, Reissig H.-U. J. Org. Chem. 1988; 53: 2440
    • 9b Brückner C, Reissig H.-U. Liebigs Ann. Chem. 1988; 465
    • 9c Brückner C, Suchland B, Reissig H.-U. Liebigs Ann. Chem. 1988; 471
    • 9d Ullmann A, Schnaubelt J, Reissig H.-U. Synthesis 1998; 1052
    • 9e Patra PK, Reissig H.-U. Eur. J. Org. Chem. 2001; 4195

      For a comprehensive overview on the use of nitriles in organic chemistry, see:
    • 11a Science of Synthesis . Vol. 19. Murahashi S.-I. Georg Thieme Verlag; Stuttgart: 2004

    • For selected recent publications dealing with the nitrile synthesis from aldoximes, see:
    • 11b Bad MN. S, Behrouz S, Nekoei A.-R. Synlett 2012; 23: 1191
    • 11c Dev D, Palakurthy NB, Kumar N, Mandal B. Tetrahedron Lett. 2013; 54: 4397
    • 11d Patil UB, Shendage SS, Nagarkar JM. Synthesis 2013; 45: 3295
    • 11e Yu L, Li H, Zhang X, Ye J, Liu J, Xu Q, Lautens M. Org. Lett. 2014; 16: 1346 ; and references cited in these reports
  • 12 The subsequent formation of the corresponding amidoximes from nitriles and hydroxylamine was not observed. For a related reference, see: Lin C.-C, Hsieh T.-H, Liao P.-Y, Liao Z.-Y, Chang C.-W, Shih Y.-C, Yeh W.-H, Chien T.-C. Org. Lett. 2014; 16: 892

    • Alkylated methyl cyclopropanecarboxylates 1 are easily accessible by deprotonation at C-1 followed by reaction with suitable alkyl halides such as MeI or allyl bromide. See:
    • 13a Reissig H.-U, Böhm I. J. Am. Chem. Soc. 1982; 104: 1735
    • 13b Reichelt I, Reissig H.-U. Chem. Ber. 1983; 116: 3895
    • 13c Reichelt I, Reissig H.-U. Liebigs Ann. Chem. 1984; 531
  • 14 Gilbert JC, Weerasooriya U. J. Org. Chem. 1982; 47: 1837
    • 16a Brimioulle R, Bach T. Science 2013; 342: 840
    • 16b Barbero A, Cuadrado P, Fleming I, González AM. J. Chem. Soc., Perkin Trans. 1 1993; 1657
    • 16c Cordes C, Prelog V, Troxler E, Westen HH. Helv. Chim. Acta 1968; 51: 1663

      For selected applications of alkynoic acid derivatives, see:
    • 17a Ojima I. Pure Appl. Chem. 2002; 74: 159
    • 17b Ji X, Zhou Y, Wang J, Zhao L, Jiang H, Liu H. J. Org. Chem. 2013; 78: 4312
    • 17c Nagendiran A, Verho O, Haller C, Johnston EV, Bäckvall J.-E. J. Org. Chem. 2014; 79: 1399
    • 17d For a total synthesis of (+)-lupinine using alkyne 4d, see ref. 16a.
  • 18 For the enyne ring-closing metathesis of 4d leading to exo-methylene-functionalized cyclohexene product, see: Lee Y.-J, Schrock RR, Hoveyda AH. J. Am. Chem. Soc. 2009; 131: 10652
    • 19a Chan TR, Hilgraf R, Sharpless KB, Fokin VV. Org. Lett. 2004; 6: 2853

    • For a recent review, see:
    • 19b Berg R, Straub BF. Beilstein J. Org. Chem. 2013; 9: 2715
  • 20 El Meslouti A, Beaupère D, Demailly G, Uzan R. Tetrahedron Lett. 1994; 35: 3913
  • 21 Moinizadeh N, Klemme R, Kansy M, Zimmer R, Reissig H.-U. Synthesis 2013; 45: 2752
    • 22a Lee PH, Kim S, Park A, Chary BC, Kim S. Angew. Chem. Int. Ed. 2010; 49: 6806 ; Angew. Chem. 2010, 122, 6958

    • For a similar hydrophosphorylation of terminal alkynes, see:
    • 22b Nun P, Egbert JD, Oliva-Madrid M.-J, Nolan SP. Chem. Eur. J. 2012; 18: 1064

      For reviews on synthesis and recent application of enol phosphates, see:
    • 23a Lichtenthaler FW. Chem. Rev. 1961; 61: 607
    • 23b Occhiato EG. Mini-Rev. Org. Chem. 2004; 1: 149
    • 23c Protti S, Fagnoni M. Chem. Commun. 2008; 3611
    • 23d Knappke CE. I, Jacobi von Wangelin A. Chem. Soc. Rev. 2011; 40: 4948
    • 23e Sellars JD, Steel PG. Chem. Soc. Rev. 2011; 40: 5170
    • 23f Li B.-J, Yu D.-G, Sun C.-L, Shi Z.-J. Chem. Eur. J. 2011; 17: 1728
    • 23g Song R.-J, Liu Y.-Y, Wu J.-C, Xie Y.-X, Deng G.-B, Yang X.-H, Liu Y, Li J.-H. Synthesis 2012; 44: 1119

    • For recent contributions on enol phosphates, see:
    • 23h Krawczyk E, Mielniczak G, Owsianik K, Luczak J. Tetrahedron: Asymmetry 2012; 23: 1480
    • 23i Barthes N, Grison C. Bioorg. Chem. 2012; 40: 48
  • 24 Kumaraswamy G, Jayaprakash N, Balakishnan G. Org. Biomol. Chem. 2011; 9: 7913

    • For reviews, see:
    • 25a Pauson PL. Tetrahedron 1985; 41: 5855
    • 25b Schore NE. Chem. Rev. 1988; 88: 1081
    • 25c Rodríguez Rivero M, Adrio J, Carretero JC. Synlett 2005; 26 ; and references cited herein

    • For selected examples, see:
    • 25d Paquette LA, Borrelly S. J. Org. Chem. 1995; 60: 6912
    • 25e Zimmer R, Buchholz M, Collas M, Angermann J, Homann K, Reissig H.-U. Eur. J. Org. Chem. 2010; 4111
  • 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.