An Efficient Access to 4-Alkylidene-5,6-dihydro-4H-pyrrolo[1,2-c][1,2,3]triazoles

Wan-li Chen; Chen-liang Su; Xian Huang

doi:10.1055/s-2006-939708

LETTER

An Efficient Access to 4-Alkylidene-5,6-dihydro-4H-pyrrolo[1,2-c][1,2,3]triazoles

Wan-li Chen^a, Chen-liang Su^a, Xian Huang*^a,b
^a Department of Chemistry, Zhejiang University (Campus Xixi), Hangzhou 310028, P. R. of China
Fax: +86(571)88807077; e-Mail: huangx@mail.hz.zj.cn;
^b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China

Abstract

All articles of this category

Abstract

From alkylidenecyclopropanes (MCPs), 4-alkylidene-5,6-dihydro-4H-pyrrolo-[1,2-c][1,2,3]triazoles 6 were prepared in moderate yields through diiodogenation, Cu(I)-catalyzed 1,3-dipolar cycloaddition and subsequent intramolecular Heck reaction.

Key words

1,2,3-trizaole - alkylidenecyclopropanes (MCPs) - 1,3-dipolar cycloaddition - Heck reaction

Full Text

References

References and Notes

<A NAME="RW02106ST-1A">1a</A> Pearson WH. Bergmeier SC. Chytra JA. Synthesis 1990, 156

<A NAME="RW02106ST-1B">1b</A> Dulcere JP. Tawil M. Santelli M. J. Org. Chem. 1990, 55: 571

<A NAME="RW02106ST-1C">1c</A> Pearson WH. Bergmeier SC. Degan S. Lin KC. Poon YF. Schkeryantz JM. Williams JP. J. Org. Chem. 1990, 55: 5719

<A NAME="RW02106ST-1D">1d</A> Marco-Contelles J. Rodríguez-Fernández M. J. Org. Chem. 2001, 66: 3717

<A NAME="RW02106ST-2">2</A> Marei MG. El-Ghanam M. Salem MM. Bull. Chem. Soc. Jpn. 1994, 67: 144

<A NAME="RW02106ST-3A">3a</A> Mukai C. Kobayashi M. Kubota S. Takahashi Y. Kitagaki S. J. Org. Chem. 2004, 69: 2128

<A NAME="RW02106ST-3B">3b</A> Guerin DJ. Miller SJ. J. Am. Chem. Soc. 2002, 124: 2134

<A NAME="RW02106ST-4A">4a</A> Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed. 2002, 41: 2596

<A NAME="RW02106ST-4B">4b</A> Feldman AK. Colasson B. Fokin VV. Org. Lett. 2004, 6: 3897

<A NAME="RW02106ST-4C">4c</A> Appukkuttan P. Dehaen W. Fokin VV. Van der Eycken E. Org. Lett. 2004, 6: 4223

<A NAME="RW02106ST-4D">4d</A> Kacprzak K. Synlett 2005, 943

<A NAME="RW02106ST-4E">4e</A> Akula RA. Temelkoff DP. Artis ND. Norris P. Heterocycles 2004, 63: 2719

<A NAME="RW02106ST-5A">5a</A> Huang X. Chen WL. Zhou HW. Synlett 2004, 329

<A NAME="RW02106ST-5B">5b</A> Huang X. Zhou H. Chen W. J. Org. Chem. 2004, 69: 839

<A NAME="RW02106ST-5C">5c</A> Chen W. Huang X. Zhou H. Synthesis 2004, 1573

<A NAME="RW02106ST-5D">5d</A> Zhou H. Huang X. Chen W. J. Org. Chem. 2004, 69: 5471

<A NAME="RW02106ST-5E">5e</A> Chen W. Huang X. Zhou H. Ren L. Synthesis 2006, 609

<A NAME="RW02106ST-5F">5f</A> For synthesis of MCPs, see: Brandi A. Goti A. Chem. Rev. 1998, 98: 589

For recent reviews, see:

<A NAME="RW02106ST-5G">5g</A> Nakamura I. Yamamoto Y. Adv. Synth. Catal. 2002, 344: 111

<A NAME="RW02106ST-5H">5h</A> Brandi A. Cicchi S. Cordero FM. Goti A. Chem. Rev. 2003, 103: 1213

<A NAME="RW02106ST-5I">5i</A> Nakamura E. Yamago S. Acc. Chem. Res. 2002, 35: 867

See also:

<A NAME="RW02106ST-5J">5j</A> Nakamura I. Oh BH. Saito S. Yamamoto Y. Angew. Chem. Int. Ed. 2001, 40: 1298

<A NAME="RW02106ST-5K">5k</A> Oh BH. Nakamura I. Saito S. Yamamoto Y. Tetrahedron Lett. 2001, 42: 6203

<A NAME="RW02106ST-5L">5l</A> Camacho DH. Nakamura I. Saito S. Yamamoto Y. J. Org. Chem. 2001, 66: 270

<A NAME="RW02106ST-5M">5m</A> Yamago S. Nakamura E. J. Org. Chem. 1990, 55: 5553

<A NAME="RW02106ST-5N">5n</A> Yamago S. Yanagawa M. Nakamura E. Chem. Lett. 1999, 879

<A NAME="RW02106ST-5O">5o</A> Lautens M. Han W. Liu JH.-C. J. Am. Chem. Soc. 2003, 125: 4028

<A NAME="RW02106ST-5P">5p</A> Shi M. Chen Y. Xu B. Org. Lett. 2003, 5: 1225

<A NAME="RW02106ST-5Q">5q</A> Shi M. Xu B. Tetrahedron Lett. 2003, 44: 3839

<A NAME="RW02106ST-5R">5r</A> Chen Y. Shi M. J. Org. Chem. 2004, 69: 426

<A NAME="RW02106ST-6">6</A> Zhou HW. Huang X. Chen WL. Synlett 2003, 2080

<A NAME="RW02106ST-7A">7a</A> Shi M. Shao L.-X. Synlett 2004, 807

<A NAME="RW02106ST-7B">7b</A> Shi M. Liu LP. Tang J. Org. Lett. 2005, 7: 3085

Typical Procedure for the Synthesis of 5.
To a stirred 95% EtOH (2 mL) solution of NaN₃ (0.6 mmol), 2 (0.5 mmol) was added and the reaction mixture was stirred under reflux until the reaction was complete, as monitored by TLC. Then, H₂O (4 mL), ascorbic acid (0.1 g, 0.56 mmol), NaOH (0.022 g, 0.56 mmol), CuSO₄ (0.01 g, 0.04 mmol), and alkyne 4 (0.6 mmol) were added and heated together at 70 °C until the reaction was complete (monitored by TLC). Afterwards, the mixture was cooled to r.t. and H₂O (15 mL) was added. The aqueous layer was extracted with EtOAc (3 × 15 mL). The organic layer was dried over anhyd MgSO₄. After evaporation, the residue was subjected to preparative TLC (eluent: PE-EtOAc, 1:6 to 1:3) to afford 1,4-disub-stituted 1,2,3-triazoles 5.
Selected Spectral Data for 5a.
Solid, mp 70-72 °C. ¹H NMR (400 MHz, CDCl₃): δ = 0.95 (t, 3 H, J = 7.33 Hz), 1.39-1.44 (m, 2 H), 1.64-1.71 (m, 2 H), 2.74 (t, 2 H, J = 7.66 Hz), 3.08 (t, 2 H, J = 6.41 Hz), 4.58 (t, 2 H, J = 6.41 Hz), 6.75 (dd, 2 H, J = 1.75, 7.79 Hz), 7.10-7.32 (m, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.17, 148.27, 146.08, 139.29, 128.50, 128.24, 127.91, 127.60, 127.56, 121.04, 102.68, 49.67, 42.45, 31.77, 25.32, 22.35, 13.85. IR: 2955, 2926, 1437, 1043, 701 cm^-1.

The temperature (70 °C) is required for the triazole synthesis step in our reaction by trial and error. At higher temperature 1,5-regioisomers can be formed and at lower temperature the reaction was not complete after several hours.

<A NAME="RW02106ST-10A">10a</A> Heck RF. J. Am. Chem. Soc. 1968, 90: 5518

<A NAME="RW02106ST-10B">10b</A> Tsuji J. Palladium Reagents and Catalysts Wiley; New York: 1995.

Reviews:

<A NAME="RW02106ST-10C">10c</A> de Meijere A. Meyer FE. Angew. Chem., Int. Ed. Engl. 1994, 33: 2379

<A NAME="RW02106ST-10D">10d</A> Cabri W. Candiani I. Acc. Chem. Res. 1995, 28: 2

<A NAME="RW02106ST-10E">10e</A> Crisp GT. Chem. Soc. Rev. 1998, 27: 427

<A NAME="RW02106ST-10F">10f</A> Geret JP. Savignac MJ. J. Organomet. Chem. 1999, 576: 305

<A NAME="RW02106ST-10G">10g</A> Beletskaya IP. Cheprakov AV. Chem. Rev. 2000, 100: 3009

<A NAME="RW02106ST-10H">10h</A> For a recent mechanistic study on Heck-type reaction see: Amatorc C. Jutand A. J. Organomet. Chem. 1999, 576: 254

Typical Procedure for the Synthesis of 6.
Compound 5 (0.25 mmol), Pd(OAc)₂ (0.025 mmol), tetrabutylammonium chloride (TBAC, 0.25 mmol), NaHCO₃ (0.5 mmol), and N,N-dimethylformamide (DMF, 1 mL) were added into a Schlenk tube at r.t. The reaction mixture was stirred at 100 °C until the reaction was complete, as monitored by TLC. Then the reaction mixture was cooled and H₂O (15 mL) was added. The aqueous layer was extracted with EtOAc (3 ¥ 15 mL). The organic layer was dried over anhyd MgSO₄. After evaporation, the residue was subjected to preparative TLC (eluent: PE-EtOAc, 1:6 to 1:3) to afford 4-alkylidene-5,6-dihydro-4H-pyrrolo-[1,2-c][1,2,3]-triazoles 6.
Selected Data. Compound 6a: solid, mp 124-126 °C. IR: 2948, 2924, 1440, 764, 703 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.74 (t, 3 H, J = 7.26 Hz), 0.92-1.00 (m, 2 H), 1.20-1.28 (m, 2 H), 1.49 (t, 2 H, J = 7.45 Hz), 3.51 (t, 2 H, J = 6.89 Hz), 4.36 (t, 2 H, J = 6.89 Hz), 7.18-7.38 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 141.97, 141.94, 141.30, 138.43, 137.67, 129.92, 129.18, 128.72, 128.21, 127.86, 127.70, 123.51, 45.24, 37.50, 31.62, 25.35, 22.28, 13.76. MS (EI, 70 eV): m/z (%) = 329 (19) [M⁺]. Anal. Calcd for C₂₂H₂₃N₃: C, 80.21; H, 7.04; N, 12.76. Found: C, 80.00; H, 7.16; N, 12.83.
Compound 7a: solid, mp 126-128 °C. IR: 2926, 1486, 1086, 828 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.91 (t, 3 H, J = 7.33 Hz), 1.34-1.40 (m, 2 H), 1.61-1.68 (m, 2 H), 2.73 (t, 2 H, J = 7.58 Hz), 2.99 (t, 2 H, J = 6.71 Hz), 4.54 (t, 2 H, J = 6.71 Hz), 7.27 (s, 4 H), 7.40 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 148.35, 134.24, 132.75, 128.61, 121.27, 120.96, 86.01, 82.23, 48.65, 31.55, 25.28, 22.22, 21.63, 13.78. MS (EI, 70 eV): m/z (%) = 287 (29.08) [M⁺]. Anal. Calcd for C₁₆H₁₈ClN₃: C, 66.78; H, 6.30; N, 14.60. Found: C, 66.90; H, 6.21; N, 14.65.