Sequential Seyferth-Gilbert/CuAAC Reactions: Application to the One-Pot Synthesis of Triazoles from Aldehydes

Delphine Luvino; Camille Amalric; Michael Smietana; Jean-Jacques Vasseur

doi:10.1055/s-2007-990877

LETTER

Sequential Seyferth-Gilbert/CuAAC Reactions: Application to the One-Pot Synthesis of Triazoles from Aldehydes

Delphine Luvino, Camille Amalric, Michael Smietana*, Jean-Jacques Vasseur*
Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-UMI-UMII, Université Montpellier II, Place Eugène Bataillon, 34095 Montpellier, France
Fax: +33(46)7042029; e-Mail: msmietana@univ-montp2.fr; e-Mail: vasseur@univ-montp2.fr;

Abstract

All articles of this category

Abstract

A reliable and operationally simple one-pot reaction for a one-carbon homologation of various aldehydes followed by a Cu-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) is reported. 1,4-Disubstituted 1,2,3-triazoles are obtained in good to excellent yields from a variety of readily available aldehydes without the need for isolation of the alkyne intermediates. The reaction has a broad scope, allows the formation of new bioconjugates and is applied for the synthesis of new boronic acid based fluorescent sensors.

Key words

click chemistry - 1,2,3-triazole - Bestmann-Ohira reagent - bioconjugation - boronic acids

Full Text

References

References and Notes

<A NAME="RG27707ST-1">1</A> Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed. 2002, 41: 2596

<A NAME="RG27707ST-2">2</A> Tornoe CW. Christensen C. Meldal M. J. Org. Chem. 2002, 67: 3057

<A NAME="RG27707ST-3">3</A> Wu P. Fokin VV. Aldrichimica Acta 2007, 40: 7

<A NAME="RG27707ST-4">4</A> Bock VD. Hiemstra H. van Maarseveen JH. Eur. J. Org. Chem. 2005, 51

<A NAME="RG27707ST-5">5</A> Kolb HC. Finn MG. Sharpless KB. Angew. Chem. Int. Ed. 2001, 40: 2004

<A NAME="RG27707ST-6">6</A> Speers AE. Cravatt BF. Chem. Biol. 2004, 11: 535

<A NAME="RG27707ST-7">7</A> Kosiova I. Kovackova S. Kois P. Tetrahedron 2007, 63: 312

<A NAME="RG27707ST-8">8</A> Gierlich J. Burley GA. Gramlich PME. Hammond DM. Carell T. Org. Lett. 2006, 8: 3639

<A NAME="RG27707ST-9">9</A> Bouillon C. Meyer A. Vidal S. Jochum A. Chevolot Y. Cloarec JP. Praly JP. Vasseur JJ. Morvan F. J. Org. Chem. 2006, 71: 4700

<A NAME="RG27707ST-10">10</A> Perez-Balderas F. Ortega-Munoz M. Morales-Sanfrutos J. Hernandez-Mateo F. Calvo-Flores FG. Calvo-Asin JA. Isac-Garcia J. Santoyo-Gonzalez F. Org. Lett. 2003, 5: 1951

<A NAME="RG27707ST-11">11</A> Kuijpers BHM. Groothuys S. Keereweer AR. Quaedflieg P. Blaauw RH. van Delft FL. Rutjes F. Org. Lett. 2004, 6: 3123

<A NAME="RG27707ST-12">12</A> Odlo K. Hoydahl EA. Hansen TV. Tetrahedron Lett. 2007, 48: 2097

<A NAME="RG27707ST-13">13</A> Chittaboina S. Xie F. Wang Q. Tetrahedron Lett. 2005, 46: 2331

<A NAME="RG27707ST-14">14</A> Kacprzak K. Synlett 2005, 943

<A NAME="RG27707ST-15">15</A> Feldman AK. Colasson B. Fokin VV. Org. Lett. 2004, 6: 3897

<A NAME="RG27707ST-16">16</A> Andersen J. Bolvig S. Liang XF. Synlett 2005, 2941

<A NAME="RG27707ST-17">17</A> Barral K. Moorhouse AD. Moses JE. Org. Lett. 2007, 9: 1809

<A NAME="RG27707ST-18">18</A> Beckmann HSG. Wittmann V. Org. Lett. 2007, 9: 1

<A NAME="RG27707ST-19">19</A> Nepogodiev SA. Dedola S. Marmuse L. de Oliveira MT. Field RA. Carbohydr. Res. 2007, 342: 529

<A NAME="RG27707ST-20">20</A> Seela F. Sirivolu VR. Helv. Chim. Acta 2007, 90: 535

<A NAME="RG27707ST-21">21</A> Zheng SL. Reid S. Lin N. Wang BH. Tetrahedron Lett. 2006, 47: 2331

A quick search in the Aldrich catalogue (sigma-aldrich.com) found 269 commercial alkynes vs. 870 aldehydes.

<A NAME="RG27707ST-23">23</A> Ohira S. Synth. Commun. 1989, 19: 561

<A NAME="RG27707ST-24">24</A> Muller S. Liepold B. Roth GJ. Bestmann HJ. Synlett 1996, 521

General Experimental Procedure: The aldehyde (2 mmol), 2-oxopropyldiazodimethyl phosphonate (4 mmol) and K₂CO₃ (6 mmol) were suspended in MeOH-THF (1:1; 4 mL) under an argon atmosphere. The reaction mixture was stirred at r.t. until TLC showed the reaction to be complete (2-24 h, in some cases another 0.5 equiv of the reagent was needed to reach completion). When the starting aldehyde was completely converted into the intermediate alkyne, CuI (0.4 mmol) and the azide (2 mmol) were added, and the reaction mixture was stirred at r.t. The progress of the reaction was followed by TLC (2-12 h). The solvents were removed in vacuo and the residue was dissolved in EtOAc (20 mL) and H₂O (20 mL). The aqueous layer was washed with EtOAc (2 × 20 mL). The organic phase was washed with a sat. solution of NH₄Cl (20 mL), brine (20 mL) and dried over anhyd Na₂SO₄. The solvent was removed in vacuo and the crude product was further purified by column chromatography (n-hexane-EtOAc).
Characterization Data for Selected Compounds: 1-{2′-Deoxy-4′-[1-(pyren-1-ylmethyl)-1,2,3-triazol-4-yl]-3′- O - tert -butyldimethylsilyl-β-d -erythrofurano-syl}thymine (Table 1, entry 6): yield: 73%; mp 125-126 °C; R _f 0.53 (n-hexane-EtOAc, 5:5). ¹H NMR (300 MHz, CDCl₃): δ = 0.03 (s, 3 H), 0.13 (s, 3 H), 0.75 (s, 9 H), 1.69 (s, 3 H), 2.20-2.29 (m, 1 H), 2.48-2.57 (m, 1 H), 4.66-4.68 (m, 1 H), 4.79 (d, J = 2.6 Hz, 1 H), 6.29 (s, 2 H), 6.44 (t, J = 5.9 Hz, 1 H), 7.31 (s, 1 H), 7.64 (s, 1 H), 7.99-8.16 (m, 9 H).¹³C NMR (75 MHz, CDCl₃): δ = 4.8, 4.9, 12.4, 25.6, 40.4, 52.5, 75.8, 80.8, 85.7, 111.1, 121.7, 122.4, 124.5, 125.0, 125.2, 125.9, 126.1, 126.2, 126.5, 127.2, 127.8, 128.5, 129.3, 129.4, 130.5, 131.2, 132.3, 136.3, 140.0, 150.2, 163.4. MS (ESI⁺): m/z (%) = 608 (100) [M + H]⁺. HRMS (FAB⁺, NBA): m/z calcd for C₃₄H₃₈N₅O₄Si (M + H⁺): 608.2693; found: 608.2712.
(2 S ,3 R )- tert -Butyl-2-(benzyloxycarbonylamino)-3-[4-(pyren-1-yl)-1,2,3-triazol-1-yl]butanoate (Table 1, entry 10): yield: 75%; mp 81-83 °C; [α]²⁰ +12° (c = 1, CHCl₃); R _f 0.10 (n-hexane-EtOAc, 8:2). ¹H NMR (300 MHz, CDCl₃): δ = 1.49 (s, 9 H), 1.83 (d, J = 6.8 Hz, 3 H), 4.85-4.89 (dd, J = 4.8, 8.5 Hz, 1 H), 5.11 (m, 1 H), 5.17 (s, 2 H), 5.90 (d, J = 8.3 Hz, 1 H), 7.18-7.31 (m, 3 H), 7.76-7.78 (m, 2 H), 8.00-8.14 (m, 9 H), 8.67 (d, J = 9.3 Hz, 1 H).¹³C NMR (75 MHz, CDCl₃): δ = 21.4, 27.9, 58.3, 58.8, 84.0, 122.0, 124.7, 124.8, 125.2, 125.4, 126.1, 126.3, 127.2, 127.4, 127.8, 128.1, 128.2, 128.3, 128.5, 128.6, 129.6, 130.9, 131.3, 131.4, 139.3, 143.3, 147.2, 155.9, 167.9. MS (ESI⁺): m/z (%) = 561 (100) [M + H]⁺. HRMS (ESI⁺): m/z calcd for C₃₄H₃₃N₄O₄ (M + H⁺): 561.2502; found: 561.2480.
1-{2′-Deoxy-4′-[1-(2′,3′,4′,6′-tetra- O -benzyl-β-d -gluco-pyranosyl)[1,2,3]triazol-4-yl]-3′- O - tert -butyldimethyl-silyl-β-d -erythrofuranosyl}thymine (Table 1, entry 11): yield: 80%; mp 80-83 °C; R _f 0.51 (n-hexane-EtOAc, 5:5). ¹H NMR (300 MHz, CDCl₃): δ = 0.00 (s, 3 H), 0.05 (s, 3 H), 0.88 (s, 9 H), 1.84 (s, 3 H), 2.34-2.63 (m, 2 H), 3.78-3.89 (m, 2 H), 4.05-4.18 (m, 2 H), 4.47-4.96 (m, 10 H), 5.61 (d, J = 9.0 Hz, 1 H), 6.53 (t, J = 6.80 Hz, 1 H), 6.92-6.96 (m, 2 H), 7.16-7.33 (m, 20 H), 7.64 (s, 1 H), 7.82 (s, 1 H), 9.10 (br s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = -4.79, -4.76, 12.5, 17.9, 25.6, 40.4, 68.3, 73.6, 74.8, 75.2, 75.8, 77.2, 77.5, 78.1, 80.2, 80.9, 85.5, 85.8, 87.6, 111.2, 122.1, 127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.4, 128.5, 136.6, 136.8, 137.6, 138.0, 146.1, 150.6, 163.9. MS (ESI⁺): m/z (%) = 916.3 (100) [M + H]⁺. HRMS (ESI⁺): m/z calcd for C₅₁H₆₂N₅O₉Si (M + H⁺): 916.4317; found: 916.4327.
3′-[4-(2′-Deoxy-3′- O - tert -butyldimethylsilyl-1′-thyminyl-β-d -erythrofuranos-4′-yl)-1,2,3-triazol-1-yl]thymidine (Table 1, entry 13): yield: 85%; mp 139-140 °C; R _f 0.09 (CH₂Cl₂-EtOAc, 5:5). ¹H NMR (300 MHz, CDCl₃): δ = 0.06 (2 × s, 6 H), 0.87 (s, 9 H), 1.92 (s, 3 H), 1.95 (s, 3 H), 2.33-2.71 (m, 2 H), 2.94-3.09 (m, 2 H), 3.82-4.12 (m, 2 H), 4.44-4.46 (m, 1 H), 4.71-4.74 (m, 1 H), 4.97 (d, J = 3.01 Hz, 1 H), 5.43-5.49 (m, 1 H), 6.21 (t, J = 6.55 Hz, 1 H), 6.36 (t, J = 6.4 Hz, 1 H), 7.41 (s, 1 H), 7.65 (s, 1 H), 7.80 (s, 1 H), 8.61 (br s, 1 H), 8.64 (br s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 4.83, 12.4, 12.5, 14.2, 25.7, 36.5, 39.8, 59.1, 60.6, 61.2, 76.2, 81.0, 85.3, 87.5, 88.4, 111.2, 122.3, 137.6, 137.7, 146.0, 150.6, 150.8, 164.1, 164.2. MS (ESI⁺): m/z (%) = 618 (100) [M + H]⁺. HRMS (FAB⁺, NBA): m/z calcd for C₂₇H₃₉N₇O₈Si (M + H⁺): 618.2708; found: 618.2682.

<A NAME="RG27707ST-26">26</A> Yang W. Gao X. Wang B. Boronic Acids Hall DG. Wiley-VCH; Weinheim: 2005. Chap. 13.

<A NAME="RG27707ST-27">27</A> James TD. Boronic Acids Hall DG. Wiley-VCH; Weinheim: 2005. Chap. 12.

<A NAME="RG27707ST-28">28</A> Luvino D. Smietana M. Vasseur JJ. Tetrahedron Lett. 2006, 47: 9253

Characterization Data for Selected Compounds: 1-Benzyl-4-[3-(4,4,5,5-tetramethyl-1,3-dioxa-2-borolan-2-yl)phenyl]-1,2,3-triazole (Table 2, entry 1): yield: 30%; white solid; mp 172-173 °C; R _f 0.24 (n-hexane-EtOAc, 8:2). ¹H NMR (300 MHz, CDCl₃): δ = 1.22 (s, 12 H), 5.44 (s, 2 H), 7.14-7.33 (m, 5 H), 7.25 (s, 1 H), 7.59 (s, 1 H), 7.64 (m, 1 H), 7.92 (m, 1 H), 7.97 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 22.6, 52.0, 81.7, 117.4, 125.8, 126.1, 126.4, 126.5, 126.9, 127.8, 129.7, 132.3, 132.5, 146.0. MS (ESI⁺): m/z (%) = 362.2 (100) [M + H]⁺. HRMS (ESI⁺): m/z calcd for C₂₁H₂₅BN₃O₂ (M + H⁺): 362.2040; found: 362.2037.
1-(Pyren-1-ylmethyl)-4-[4-(4,4,5,5-tetramethyl-1,3-dioxa-2-borolan-2-yl)phenyl]-1,2,3-triazole (Table 2, entry 4): yield: 55%; mp 168-170 °C; R _f 0.14 (n-hexane-EtOAc, 8:2). ¹H NMR (400 MHz, CDCl₃): δ = 1.23 (s, 12 H), 6.21 (s, 2 H), 7.22 (d, J = 7.9 Hz, 2 H), 7.44-7.74 (m, 3 H), 7.92-8.19 (m, 8 H), 8.17 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 24.8, 55.3, 83.8, 119.9, 121.9, 124.8, 125.9, 126.0, 126.5, 127.2, 127.8, 128.4, 128.7, 129.2, 129.4, 130.6, 131.2, 132.3, 132.9, 135.2, 139.1, 143.6, 147.9. MS (ESI⁺): m/z (%) = 486 (100) [M + H]⁺. HRMS (ESI⁺): m/z calcd for C₃₁H₂₉BN₃O₂ (M + H⁺): 486.2353; found: 486.2378.