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Synlett 2018; 29(14): 1892-1896
DOI: 10.1055/s-0037-1610502
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of Indole Derivatives Containing the Tetrazole Moeity Utilizing an Ugi-Azide Post-Transformation Strategy

Ali Nikbakht
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran   Email: balalaie@kntu.ac.ir
,
Saeed Balalaie  *
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran   Email: balalaie@kntu.ac.ir
b   Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
,
Fatemeh Baghestani
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran   Email: balalaie@kntu.ac.ir
,
Frank Rominger
c   Organisch-Chemisches Institut der Universitaet Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
› Author Affiliations

We thank the National Institute for Medical Research Development (NIMAD, Project No. 963388) for financial support.
Further Information

Publication History

Received: 04 April 2018

Accepted after revision: 29 June 2018

Publication Date:
26 July 2018 (online)

 
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Dedicated to Prof. Bernhard Breit on the occasion of his birthday

Abstract

An efficient strategy has been developed for the synthesis of indole derivatives containing the tetrazole moiety using a AuCl3-catalyzed cyclization reaction. The precursors of the cycloadduct were easily prepared by an Ugi-azide 4-CR in methanol at room temperature. The merit of this protocol lies in its operational simplicity, readily available starting materials, high yields of product, and good functional group tolerance.


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Key words

Ugi-azide post-transformation strategy - metal catalyzed alkyne cyclization - heterocyclization - indole - tetrazole

Indoles have attracted a great deal of interest due to their presence in natural products and pharmaceutical compounds with extensive biological properties such as anticancer, antibacterial, antifungal, and antimicrobial activity.[1] The presence of the indole scaffold in many natural sources such as serotonin, tryptophan, and plant growth hormones underlines the importance of these compounds.[1] Moreover, synthetic indole derivatives possess the potential to be integrated in technical applications, such as ion sensors, organic-light emitting diodes (OLEDs) or organic field-effect transistors (OFETs).[2]

There are several different strategies for the synthesis of indoles.[3] [4] [5] [6] Among these synthetic approaches, the heterocyclization of 2-alkynylanilines to 2-substituted indoles remains the most commonly employed strategy.[7] Different transition metals have exploited in order to carry out this cyclization including Cu,[8,9] Pd,[10] [11] [12] Ag, [13] Au,[14] [15] [16] and In[17] catalysts.

On the other hand, tetrazole derivatives have attracted considerable attention due to their distinct structural features and their notable biological activities.[18] Tetrazoles are bioisosteres of carboxylic acids and are often used as a replacement for carboxylic acid groups. The tetrazole skeleton is a constituent of a range of drugs including losartan and valsartan that demonstrate antihypertensive activities (Figure [1]).[19] It has been reported that the attachment of an indole moiety to the tetrazole nucleus enhances its antimicrobial activity. These hybrid compounds also have peroxisome proliferator-activated receptor (PPAR) activity and can be used for lowering triglycerides and blood sugar (Figure [1]).[20]

Zoom Image
Figure 1 Structure of some bioactive compounds containing tetrazole and indole moieties

Several methods for the synthesis of tetrazoles have been reported in the literature.[21] Synthesis of tetrazoles through the classical Ugi-azide four-component reaction (UA-4CR) has a wide scope with regard to the starting ­materials.[22]

The combination of the Ugi-azide four-component reaction with post-transformational reactions has become a useful tool for generating complex and diverse molecular libraries with novel properties.[23] In a continuation of our previous research work on the design of post-transformation reactions, [24] we report herein an efficient approach to 2-aryl-indoles containing a tetrazole moiety through AuCl3-catalyzed cyclization. The precursors of the cycloadduct were easily prepared through Ugi-azide reaction of 2-(phenylacetylenyl)aniline, trimethylsilylazide, isocyanides, and carbonyl compounds (Scheme [1]).

Zoom Image
Scheme 1 Synthesis of 2-aryl-indoles containing tetrazole moieties through Ugi-azide reaction followed by AuCl3-catalyzed cyclization

Table 1 Optimization of the Reaction Conditions for the Synthesis of 6a

Entry

Lewis acid

Yield (%)

1

AuCl3(3%)

78

2

AuCl3(5%)

85

4

InCl3 (10%)

66

5

ZrO2

–

6

AgNO3

–

7

CuI

–

8

Pd(OAc)2

–

The 2-(phenylethynyl)aniline (1) was efficiently prepared by the reported procedure.[25] Next, the four-component reaction of 2-(phenylethynyl)aniline (1), trimethylsilyl azide (2), cyclohexanone (3a), and cyclohexyl isocyanide (4a) was selected as the model reaction for the screening of suitable reaction conditions. The reaction was carried out in methanol at ambient temperature and product 5a was formed in 75% yield (Table [1]). The structure of the Ugi-azide product was confirmed using spectroscopic analysis.

Next, the heterocyclization reaction of 5a was investigated using different Lewis acid catalysts to access the indole skeleton 6a. Different attempts were made at the heterocyclization using copper(I) iodide, silver nitrate, zirconium dioxide, and palladium acetate but the reaction did not proceed. However, performing the reaction using InCl3 (10%) or AuCl3 (5%) resulted in the desired product 6a in 66% and 85% yields, respectively (Table [1], entries 2 and 3). The use of 3% AuCl3 decreased the yield to 78% (Table [1], entry 1). Spectroscopic analysis of 6a confirmed the formation of the indole moiety. The absence of the acetylenic carbons at δ = 85.0 and 95.0 ppm in the 13C NMR spectrum confirmed the cyclization and the C-3 in the indole ring was observed at δ = 108.0 ppm.

With the optimized reaction conditions established, we explored the scope of our methodology using various carbonyl substrates and isocyanides. The reaction conditions were found to be compatible with a range of aromatic aldehydes and ketones (Scheme [2]).

In addition to the spectroscopic analyses, X-ray crystallographic analysis of 6d confirmed the formation of the desired product (Figure [2]).[26] The orientation of the tetrazole ring with the indole ring is interesting, the torsion angle is 54° and the 2-aryl group in position 2 is not coplanar with the indole motif.

Zoom Image
Scheme 2 Scope of the optimized protocol for the synthesis of 2-aryl-indoles containing a tetrazole moiety
Zoom Image
Figure 2 ORTEP structure of 6d

To confirm the importance of this strategy, palladium acetate-catalyzed cyclization of O-(phenylethynyl)-N-ethoxycarbonylanilide for the synthesis of 2-phenylindole was attempted. However, the subsequent Ugi-azide reaction of the 2-phenylindole with cyclohexanone, cyclohexylisocyanide, and trimethylsilyl azide did not take place and the starting materials remained (Scheme [3]). This result confirms the importance of the reaction sequence disclosed herein.

Zoom Image
Scheme 3

A mechanistic rationale for the cyclization reaction is outlined in Scheme [4]. The Lewis acidic Au(III) coordinates to the alkynyl moiety of 5a–i, and the resulting electron-deficient triple bond in I undergoes intramolecular nucleophilic attack by the poorly basic nitrogen atom of the free amine moiety leading to the intermediate II via a 5-endo-dig cyclization in preference to a 4-exo-dig mode of cyclization, the latter being disfavored according to Baldwin’s rules. Finally, protiodemetallation during the workup affords cyclized 6a–i (Scheme [4]).

Zoom Image
Scheme 4 Proposed mechanistic pathway for the gold-catalyzed ­heterocyclization

In conclusion, we have developed an efficient method for the synthesis of functionalized 2-phenyl indoles containing the tetrazole skeleton. The reaction proceeds through AuCl3 catalyzed cyclization of Ugi-azide products containing an alkyne moiety. Good to high yields and simplicity of the reaction are features of the procedure.


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Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0037-1610502.
  • Supporting Information

  • References and Notes

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  • 3 Li J. Cook JM. In Name Reactions in Heterocyclic Chemistry . Li JJ. Corey E. Wiley and Sons; Hoboken, NJ: 2005
    Search in Google Scholar
  • 4 Gribble GW. Indole Ring Synthesis: From Natural Products to Drug Discovery . Wiley and Sons; New York: 2016
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    Thieme Connect
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  • 17 Sakai N. Annak K. Fujita A. Sato A. Konakahara T. J. Org. Chem. 2008; 73: 4160
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    • 20a Mahindroo N. Huang C.-F. Peng Y.-H. Wang C.-C. Liao C.-C. Lien T.-W. Chittimalla SK. Huang W.-J. Chai C.-H. Prakash E. Chen C.-P. Hsu T.-A. Peng C.-H. Lu I.-L. Lee L.-H. Chang Y.-W. Chen W.-C. Chou Y.-C. Chen C.-T. Goparaju CM. V. Chen Y.-S. Lan S.-J. Yu M.-C. Chen X. Chao Y.-S. Wu S.-Y. Hsieh H.-P. J. Med. Chem. 2005; 48: 8194
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  • 26 HRMS data were collected using an Apex-QC-FT- ICR instrument with ESI. General Procedure for the Synthesis of Compounds 5a–i 2-(Phenylethynyl)aniline in MeOH (5 ml) and cyclohexanone (1 mmol) were stirred at room temperature for 2 h, then the requisite isocyanide (1 mmol) and trimethylsilyl azide were added. The mixture was stirred for 24 h until the reaction was completed. Then, the desired product was either filtered off as a white solid filtered for 5a–e (ketone derivatives) or purified using column chromatography on silica gel (n-hexane/EtOAc, 9:1) for 5f–i (aldehyde derivatives). The yields were in the range of 75–92%. General Procedure for the Synthesis of Compounds 6a–i The products 5a–i (1mmol) and AuCl3 (5 mol%, 15 mg) were added to a reaction flask containing toluene (10 mL). After 12 h the toluene was evaporated under reduced pressure. The crude products were purified by silica gel chromatography (n-hexane/EtOAc, 7:1) to obtain the indole derivatives. N-[4-(tert-Butyl)-1-(1-cyclohexyl-1H-tetrazol-5-yl) cyclohexyl]-2-(phenylethynyl) aniline (5d) Colorless solid; yield 440 mg, (80%); Rf = 0.45 (PE/EtOAc 3:1); mp 142–146 °C. IR (KBr): ν = 1586, 2197, 3377 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.84 (s, 9 H, t-Bu), 1.16–1.34 (m, 4 H, HCyclohexyl), 1.42–1.68 (m, 5 H, HCyclohexyl), 1.73–1.93 (m, 8 H, HCyclohexyl), 2.87–2.91 (m, 2 H, HCyclohexyl), 4.72 (m, 1 H, CHN), 5.07 (s, 1 H, NH), 6.08 (d, 1 H, J = 8.1 Hz, H-Ar), 6.63 (t, 1 H, J = 7.5 Hz, H-Ar), 6.86–6.92 (dt, 1 H, J = 7.2, 1.5 Hz, H-Ar), 7.3(dd, 1 H, J = 8.1, 1.2 Hz, H-Ar), 7.34–7.43(m, 3 H, H-Ar), 7.53–7.56 (m, 2 H, H-Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.7, 24.8, 25.6, 27.5, 32.4, 33.5, 39.0, 47.6, 54.4, 59.2, 85.6, 95.7, 108.8, 111.8, 118.0, 123.0, 128.6, 128.7, 129.9, 131.3, 132.1, 145.4, 153.3 ppm. 1-[4-(tert-Butyl)-1-(1-cyclohexyl-1H-tetrazol-5-yl) cyclohexyl]-2-phenyl-1H-indole (6d) Colorless solid; yield 417.6 mg (87%); Rf = 0.38 (PE/EtOAc, 3:1); mp 178–181 °C. IR (KBr): ν = 1453, 1611, 2940 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.78 (s, 9 H, t-Bu), 0.88–1.56 (m, 17 H, HCyclohexyl), 2.10–2.30 (m, 2 H, HCyclohexyl), 3.10–3.15 (m, 1 H, HCyclohexyl), 6.47 (s, 1 H, H-3 indole), 6.82 (t, 1 H, J = 8.4 Hz, H-Ar), 6.89(dt, 1 H, J = 7.2, 1.2 Hz, H-Ar), 7.01 (t, 1 H, J = 7.2, H-Ar), 7.46–7.59(m, 6 H, H-Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1, 23.9, 24.7, 25.3, 25.4, 26.9, 27.4, 31.2, 32.3, 32.8, 38.1, 38.6, 46.9, 47.0, 58.1, 62.5, 108.1, 112.4, 120.5, 121.3, 122.6, 124.0, 126.0, 128.3, 128.4, 137.1, 137.5, 140.9, 156.4 ppm. HRMS (ESI): m/z calcd for C31H40N5 [M + H]+: 482.3272; found: 482.3288; C31H39N5Na [M + Na]+: 504.3097; found: 504.3106. Colorless crystal (polyhedron), dimensions 0.130 × 0.120 × 0.050 mm3, crystal system triclinic, space group P, Z = 2, a = 10.4530(5) Å, b = 12.9781(6) Å, c = 13.3411(6) Å, α = 108.2879(14)°, β = 112.3234(14)°, γ = 100.5989(14)°, V = 1491.99(12) Å3, ρ = 1.189 g cm–3, T = 200(2) K, θ max= 22.980°, raduiation Mo Kα, λ = 0.71073 Å, 0.5° ω scans with CCD area detector, covering the asymmetric unit in reciprocal space with a mean redundancy of 3.1 and a completeness of 98.3% to a resoltion of 0.91 Å, 12857 reflections measured, 4082 unique (R (int) = 0.0380), 2672 observed (I > 2σ(I)), intensities were corrected for Lorentz and polarization effects, an empirical scaling and absorption correction was applied using SADABS based on the Laue symmetry of the reciprocal space, μ = 0.09 mm–1, T min = 0.93, T max = 0.96, structure refined against F 2 with a full-matrix least-squares algorithm using the SHELXL-2014/7 (Sheldrick, 2014) software, 393 parameters refined, hydrogen atoms were treated using appropriate riding models, goodness of fit 1.05 for observed reflections, final residual values R1(F) = 0.052, wR(F2) = 0.125 for observed reflections, residual electron density –0.21 to 0.14 eÅ–3. 27CCDC 1551544 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 27 Sheldrick GM. Acta Crystallogr., Sect. C: Struct. Chem. 2015; 71: 3
    CrossrefSearch in Google Scholar

  • References and Notes

  • 2 Janosik T. Wahlström N. Bergman J. Tetrahedron 2008; 64: 9159
    CrossrefSearch in Google Scholar
  • 3 Li J. Cook JM. In Name Reactions in Heterocyclic Chemistry . Li JJ. Corey E. Wiley and Sons; Hoboken, NJ: 2005
    Search in Google Scholar
  • 4 Gribble GW. Indole Ring Synthesis: From Natural Products to Drug Discovery . Wiley and Sons; New York: 2016
    Search in Google Scholar
  • 5 Krüger K. Tillack A. Beller M. Adv. Synth. Catal. 2008; 350: 2153
    CrossrefSearch in Google Scholar
  • 8 Ye Y. Cheung KP. S. He L. Tsui GC. Org. Lett. 2018; 20: 1676
    CrossrefPubMedSearch in Google Scholar
  • 9 Song S. Huang M. Li W. Zhu X. Wan Y. Tetrahedron 2015; 71: 451
    CrossrefSearch in Google Scholar
  • 10 Li J. Li C. Yang S. An Y. Wu W. Jiang H. J. Org. Chem. 2016; 81: 2875
    CrossrefSearch in Google Scholar
  • 11 Sheng J. Li S. Wu J. Chem. Commun. 2014; 50: 578
    CrossrefSearch in Google Scholar
  • 15 Arcadi A. Bianchi G. Marinelli F. Synthesis 2004; 610
    Thieme Connect
  • 16 Brand JP. Chevalley C. Waser J. Beilstein J. Org. Chem. 2011; 7: 565
    CrossrefPubMedSearch in Google Scholar
  • 17 Sakai N. Annak K. Fujita A. Sato A. Konakahara T. J. Org. Chem. 2008; 73: 4160
    CrossrefSearch in Google Scholar
  • 18 Ostrovskii VA. Trifonov RE. Popova EA. Russ. Chem. Bull. 2012; 61: 768
    CrossrefSearch in Google Scholar
    • 20a Mahindroo N. Huang C.-F. Peng Y.-H. Wang C.-C. Liao C.-C. Lien T.-W. Chittimalla SK. Huang W.-J. Chai C.-H. Prakash E. Chen C.-P. Hsu T.-A. Peng C.-H. Lu I.-L. Lee L.-H. Chang Y.-W. Chen W.-C. Chou Y.-C. Chen C.-T. Goparaju CM. V. Chen Y.-S. Lan S.-J. Yu M.-C. Chen X. Chao Y.-S. Wu S.-Y. Hsieh H.-P. J. Med. Chem. 2005; 48: 8194
      CrossrefPubMedSearch in Google Scholar
    • 20b Mahindroo N. Wang C.-C. Liao C.-C. Huang C.-F. Lu I.-L. Lien T.-W. Peng Y.-H. Huang W.-J. Lin Y.-T. Hsu M.-C. Lin C.-H. Tsai C.-H. Hsu JT.-A. Chen X. Lyu P-C. Chao Y.-S. Wu S.-Y. Hsieh H.-P. J. Med. Chem. 2006; 49: 1212
      CrossrefPubMedSearch in Google Scholar
  • 25 Reactions and Syntheses: In the Organic Chemistry Laboratory . 2nd ed. Tietze LF. Eicher T. Diederichsen U. Speicher A. Schützenmeister N. Wiley-VCH; Weinheim: 2015
    Search in Google Scholar
  • 26 HRMS data were collected using an Apex-QC-FT- ICR instrument with ESI. General Procedure for the Synthesis of Compounds 5a–i 2-(Phenylethynyl)aniline in MeOH (5 ml) and cyclohexanone (1 mmol) were stirred at room temperature for 2 h, then the requisite isocyanide (1 mmol) and trimethylsilyl azide were added. The mixture was stirred for 24 h until the reaction was completed. Then, the desired product was either filtered off as a white solid filtered for 5a–e (ketone derivatives) or purified using column chromatography on silica gel (n-hexane/EtOAc, 9:1) for 5f–i (aldehyde derivatives). The yields were in the range of 75–92%. General Procedure for the Synthesis of Compounds 6a–i The products 5a–i (1mmol) and AuCl3 (5 mol%, 15 mg) were added to a reaction flask containing toluene (10 mL). After 12 h the toluene was evaporated under reduced pressure. The crude products were purified by silica gel chromatography (n-hexane/EtOAc, 7:1) to obtain the indole derivatives. N-[4-(tert-Butyl)-1-(1-cyclohexyl-1H-tetrazol-5-yl) cyclohexyl]-2-(phenylethynyl) aniline (5d) Colorless solid; yield 440 mg, (80%); Rf = 0.45 (PE/EtOAc 3:1); mp 142–146 °C. IR (KBr): ν = 1586, 2197, 3377 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.84 (s, 9 H, t-Bu), 1.16–1.34 (m, 4 H, HCyclohexyl), 1.42–1.68 (m, 5 H, HCyclohexyl), 1.73–1.93 (m, 8 H, HCyclohexyl), 2.87–2.91 (m, 2 H, HCyclohexyl), 4.72 (m, 1 H, CHN), 5.07 (s, 1 H, NH), 6.08 (d, 1 H, J = 8.1 Hz, H-Ar), 6.63 (t, 1 H, J = 7.5 Hz, H-Ar), 6.86–6.92 (dt, 1 H, J = 7.2, 1.5 Hz, H-Ar), 7.3(dd, 1 H, J = 8.1, 1.2 Hz, H-Ar), 7.34–7.43(m, 3 H, H-Ar), 7.53–7.56 (m, 2 H, H-Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.7, 24.8, 25.6, 27.5, 32.4, 33.5, 39.0, 47.6, 54.4, 59.2, 85.6, 95.7, 108.8, 111.8, 118.0, 123.0, 128.6, 128.7, 129.9, 131.3, 132.1, 145.4, 153.3 ppm. 1-[4-(tert-Butyl)-1-(1-cyclohexyl-1H-tetrazol-5-yl) cyclohexyl]-2-phenyl-1H-indole (6d) Colorless solid; yield 417.6 mg (87%); Rf = 0.38 (PE/EtOAc, 3:1); mp 178–181 °C. IR (KBr): ν = 1453, 1611, 2940 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.78 (s, 9 H, t-Bu), 0.88–1.56 (m, 17 H, HCyclohexyl), 2.10–2.30 (m, 2 H, HCyclohexyl), 3.10–3.15 (m, 1 H, HCyclohexyl), 6.47 (s, 1 H, H-3 indole), 6.82 (t, 1 H, J = 8.4 Hz, H-Ar), 6.89(dt, 1 H, J = 7.2, 1.2 Hz, H-Ar), 7.01 (t, 1 H, J = 7.2, H-Ar), 7.46–7.59(m, 6 H, H-Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1, 23.9, 24.7, 25.3, 25.4, 26.9, 27.4, 31.2, 32.3, 32.8, 38.1, 38.6, 46.9, 47.0, 58.1, 62.5, 108.1, 112.4, 120.5, 121.3, 122.6, 124.0, 126.0, 128.3, 128.4, 137.1, 137.5, 140.9, 156.4 ppm. HRMS (ESI): m/z calcd for C31H40N5 [M + H]+: 482.3272; found: 482.3288; C31H39N5Na [M + Na]+: 504.3097; found: 504.3106. Colorless crystal (polyhedron), dimensions 0.130 × 0.120 × 0.050 mm3, crystal system triclinic, space group P, Z = 2, a = 10.4530(5) Å, b = 12.9781(6) Å, c = 13.3411(6) Å, α = 108.2879(14)°, β = 112.3234(14)°, γ = 100.5989(14)°, V = 1491.99(12) Å3, ρ = 1.189 g cm–3, T = 200(2) K, θ max= 22.980°, raduiation Mo Kα, λ = 0.71073 Å, 0.5° ω scans with CCD area detector, covering the asymmetric unit in reciprocal space with a mean redundancy of 3.1 and a completeness of 98.3% to a resoltion of 0.91 Å, 12857 reflections measured, 4082 unique (R (int) = 0.0380), 2672 observed (I > 2σ(I)), intensities were corrected for Lorentz and polarization effects, an empirical scaling and absorption correction was applied using SADABS based on the Laue symmetry of the reciprocal space, μ = 0.09 mm–1, T min = 0.93, T max = 0.96, structure refined against F 2 with a full-matrix least-squares algorithm using the SHELXL-2014/7 (Sheldrick, 2014) software, 393 parameters refined, hydrogen atoms were treated using appropriate riding models, goodness of fit 1.05 for observed reflections, final residual values R1(F) = 0.052, wR(F2) = 0.125 for observed reflections, residual electron density –0.21 to 0.14 eÅ–3. 27CCDC 1551544 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 27 Sheldrick GM. Acta Crystallogr., Sect. C: Struct. Chem. 2015; 71: 3
    CrossrefSearch in Google Scholar

   Permissions and Reprints All articles of this category
Zoom Image
Figure 1 Structure of some bioactive compounds containing tetrazole and indole moieties
Zoom Image
Scheme 1 Synthesis of 2-aryl-indoles containing tetrazole moieties through Ugi-azide reaction followed by AuCl3-catalyzed cyclization
Zoom Image
Scheme 2 Scope of the optimized protocol for the synthesis of 2-aryl-indoles containing a tetrazole moiety
Zoom Image
Figure 2 ORTEP structure of 6d
Zoom Image
Scheme 3
Zoom Image
Scheme 4 Proposed mechanistic pathway for the gold-catalyzed ­heterocyclization