Intramolecular Cyclization of Vinyldiazoacetates as a Versatile Route to Substituted Pyrazoles

Denis Drikermann; Valerie Kerndl; Helmar Görls; Ivan Vilotijevic

doi:10.1055/s-0040-1707111

Synlett, Table of Contents

Synlett 2020; 31(12): 1158-1162
DOI: 10.1055/s-0040-1707111

letter

Intramolecular Cyclization of Vinyldiazoacetates as a Versatile Route to Substituted Pyrazoles

Denis Drikermann

^aFriedrich-Schiller-University Jena, Institute of Organic and Macromolecular Chemistry, Humboldtstraße 10, 07743 Jena, Germany Email: ivan.vilotijevic@uni-jena.de

,

Valerie Kerndl

^aFriedrich-Schiller-University Jena, Institute of Organic and Macromolecular Chemistry, Humboldtstraße 10, 07743 Jena, Germany Email: ivan.vilotijevic@uni-jena.de

,

Helmar Görls

^bFriedrich-Schiller-University Jena, Institute of Inorganic and Analytical Chemistry, Humboldtstraße 8, 07743 Jena, Germany

,

Ivan Vilotijevic ∗

^aFriedrich-Schiller-University Jena, Institute of Organic and Macromolecular Chemistry, Humboldtstraße 10, 07743 Jena, Germany Email: ivan.vilotijevic@uni-jena.de

› Author Affiliations

Abstract

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In memory of Prof. Dr. Ludwig Knorr, professor at Friedrich-Schiller-University Jena (1889–1921)

Abstract

Vinyldiazo compounds undergo a thermal electrocyclization to form pyrazoles in yields of up to 95%. The reactions are operationally simple, use readily available starting materials, require no intervention of a catalyst, and enable the synthesis of mono-, di- and tri-substituted pyrazoles. With the ability to produce highly substituted pyrazoles and the flexibility in installing various types of substituents, this method constitutes a new entry to this valuable heterocyclic scaffold and may be of interest to all branches of the chemical industry.

Key words

pyrazoles - vinyldiazoacetates - vinyldiazo compounds - cyclization - electrocyclization

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References

References and Notes
1 Knorr L. Ber. Dtsch. Chem. Ges. 1883; 16: 2597

2a Liu J.-J, Zhao M.-y, Zhang X, Zhao X, Zhu H.-L. Mini-Rev. Med. Chem. 2013; 13: 1957
2b Czarnomysy R, Surażyński A, Muszynska A, Gornowicz A, Bielawska A, Bielawski K. J. Enzyme Inhib. Med. Chem. 2018; 33: 1006
2c Hura N, Naaz A, Prassanawar SS, Guchhait KS, Panda D. ACS Omega 2018; 3: 1955
2d Karrouchi K, Radi S, Ramli Y, Taoufik J, Mabkhot YN, Al-aizari FA, Ansar M. Molecules 2018; 23: 134

3a Kidwai M, Jain A, Poddar R. J. Organomet. Chem. 2011; 696: 1939
3b Vaddula RB, Varma SR, Leazer J. Tetrahedron Lett. 2013; 54: 1538
3c Venkateswarlu V, Kour J, Kumar KA. A, Verma KP, Reddy LG, Hussain Y, Tabassum A, Balgotra S, Gupta S, Hudwekar DA, Vishwakarma AR, Sawant DS. RSC Adv. 2018; 8: 26523
3d Wang H, Sun X, Zhang S, Liu G, Wang C, Zhu L, Zhang H. Synlett 2018; 29: 2689
3e Yang G.-P, He X, Yu B, Hu C.-W. Appl. Organomet. Chem. 2018; 32: e4532

4a Kumar V, Kaur K, Gupta KG, Sharma KA. Eur. J. Med. Chem. 2013; 69: 735
4b Pizzuti L, Barschak GA, Stefanello MF, Farias DM, Lencina C, Roesch-Ely M, Cunico W, Moura S, Pereira CM. P. Curr. Org. Chem. 2014; 18: 115
4c Ansari A, Ali A, Asif M. Shamsuzzaman, New J. Chem. 2017; 41: 16

5a Chen B, Zhu C, Tang Y, Ma S. Chem. Commun. 2014; 50: 7677
5b Pires SC, de Oliveira DH, Pontel MR. B, Kazmierczak CJ, Cargnelutti R, Alves D, Jacob GR, Schumacher FR. Beilstein J. Org. Chem. 2018; 14: 2789
5c Preeti, Singh NK. Org. Biomol. Chem. 2018; 16: 9084
5d Mamaghani M, Nia RH. Polycyclic Aromat. Compd. 2019; 1

6a Aggarwal KV, de Vicente J, Bonnert VR. J. Org. Chem. 2003; 68: 5381
6b Vuluga D, Legros J, Crousse B, Bonnet-Delpon D. Green Chem. 2009; 11: 156
6c Pramanik MM. D, Kant R, Rastogi N. Tetrahedron 2014; 70: 5214

7a Chandanshive ZJ, Bonini FB, Gentili D, Fochi M, Bernardi L, Franchini CM. Eur. J. Org. Chem. 2010; 6440
7b Voronin VV, Ledovskaya SM, Gordeev GE, Rodygin SK, Ananikov PV. J. Org. Chem. 2018; 83: 3819
7c Yavari I, Taheri Z, Naeimabadi M, Bahemmat S, Halvagar RM. Synlett 2018; 29: 918

8a Nájera C, Sansano MJ, Yus M. Org. Biomol. Chem. 2015; 13: 8596
8b Bakthadoss M, Agarwal V. ChemistrySelect 2018; 3: 6960

9a Brewbaker LJ, Hart H. J. Am. Chem. Soc. 1969; 91: 711
9b Padwa A, Kulkarni SY, Zhang Z. J. Org. Chem. 1990; 55: 4144
9c Supurgibekov BM, Cantillo D, Kappe OC, Surya Prakash GK, Nikolaev AV. Org. Biomol. Chem. 2014; 12: 682
9d O’Connor NR, Bolgar P, Stoltz MB. Tetrahedron Lett. 2016; 57: 849
9e Bien J, Davulcu A, DelMonte AJ, Fraunhoffer JK, Gao Z, Hang C, Hsiao Y, Hu W, Katipally K, Littke A, Pedro A, Qiu Y, Sandoval M, Schild R, Soltani M, Tedesco A, Vanyo D, Vemishetti P, Waltermire ER. Org. Process Res. Dev. 2018; 22: 1393

10a Ito K, Maruyama J. Heterocycles 1984; 22: 1057
10b Ito K, Maruyama J. J. Heterocycl. Chem. 1988; 25: 1681
10c Davies HM. L, Hougland WP, Cantrell WR. Jr. Synth. Commun. 1992; 22: 971
10d Antos MJ, Francis BM. J. Am. Chem. Soc. 2004; 126: 10256
10e Qian Y, Xu X, Wang X, Zavalij JP, Hu W, Doyle PM. Angew. Chem. Int. Ed. 2012; 51: 1
10f Cui S, Zhang Y, Wang D, Wu Q. Chem. Sci. 2013; 4: 3912
10g Supurgibekov BM, Prakash GK. S, Nikolaev AV. Synthesis 2013; 45: 1215
10h Guo H, Zhang D, Zhu C, Li J, Xu G, Sun J. Org. Lett. 2014; 16: 3110
10i Deng Y, Jing C, Doyle PM. Chem. Commun. 2015; 51: 12924
10j Xu G, Zhu C, Gu W, Li J, Sun J. Angew. Chem. Int. Ed. 2015; 54: 883
10k Martin CS, Vohidov F, Wang H, Knudsen ES, Marzec AA, Ball TZ. Bioconjugate Chem. 2017; 28: 659
10l Roizen LJ, Jones CA, Smith CR, Virgil CS, Stoltz MB. J. Org. Chem. 2017; 82: 13051
10m Zhao M.-N, Zhang M.-N, Ren Z.-H, Wang Y.-Y, Guan Z.-H. Sci. Bull. 2017; 62: 493
10n Craig AR, Smith CR, Roizen LJ, Jones CA, Virgil CS, Stoltz MB. J. Org. Chem. 2018; 83: 3467
10o Zhang X, Zheng Y, Qiu L, Xu X. Org. Biomol. Chem. 2018; 16: 70

11 Drikermann D, Mößel SR, Al-Jammal WK, Vilotijevic I. Org. Lett. 2020; 22: 1091

12a Miyamoto T, Matsumoto J. Chem. Pharm. Bull. 1988; 36: 1321
12b Miyamoto T, Matsumoto J. Chem. Pharm. Bull. 1990; 38: 3211
12c Nikolaev AV, Zakharova MV, Hennig L, Sieler J. J. Fluorine Chem. 2007; 128: 507
12d Supurgibekov BM, Zakharova MV, Sieler J, Nikolaev AV. Tetrahedron Lett. 2011; 52: 341
12e Bel Abed H, Mammoliti O, Bande O, Van Lommen G, Herdewijn P. J. Org. Chem. 2013; 78: 7845
12f Nikolaev AV, Cantillo D, Kappe OC, Medvedev JJ, Prakash GK. S, Supurgibekov BM. Chem. Eur. J. 2016; 22: 174
12g Moslin R, Zhang Y, Wrobleski TS, Lin S, Mertzman M, Spergel S, Tokarski SJ, Strnad J, Gillooly K, McIntyre KW, Zupa-Fernandez A, Cheng L, Sun H, Chaudhry C, Huang C, D’Arienzo C, Heimrich E, Yang X, Muckelbauer KJ, Chang C, Tredup J, Mulligan D, Xie D, Aranibar N, Chiney M, Burke RJ, Lombardo L, Carter HP, Weinstein SD. J. Med. Chem. 2019; 62: 8953

13 Pavlyuk O, Teller H, McMills MC. Tetrahedron Lett. 2009; 50: 2716
14 Ye F, Qu S, Zhou L, Peng C, Wang C, Cheng J, Hossain LM, Liu Y, Zhang Y, Wang Z.-X, Wang J. J. Am. Chem. Soc. 2015; 137: 4435
15 Green PS, Wheelhouse MK, Payne DA, Hallett PJ, Miller WP, Bull AJ. Org. Process Res. Dev. 2020; 24: 67
16 Methyl 5-Phenyl-1H-pyrazole-3-carboxylate (2a); Typical Procedure A mixture of cinnamic alcohol (3.35 g, 25.0 mmol, 1.00 equiv), formic acid (2.83 mL, 75.0 mmol, 3.00 equiv), acetic anhydride (7.09 mL, 75.0 mmol, 3.00 equiv), tris(dibenzylideneacetone)dipalladium(0) (114 mg, 0.5 mol%) and Xantphos (289 mg, 2.0 mol%) was suspended in toluene (15 mL) and heated to 80 °C for 12 h.¹⁷ The mixture was filtered through a short pad of silica and washed with ethyl acetate. The volatiles were removed under reduced pressure to give a crude product. The product could be purified by column chromatography (dry loading, 10–20% v/v ethyl acetate/petroleum ether) and isolated as a yellow solid (3.45 g, 85% yield). A suspension of the crude carboxylic acid from the previous step (3.00 g, 18.5 mmol, 1.00 equiv), Cs₂CO₃ (3.01 g, 9.25 mmol, 0.50 equiv) and MeI (2.30 mL, 37.0 mmol, 2.00 equiv) in acetone (150 mL) was heated at 80 °C for 3 h.^[18] Silica gel was added and the solvent was evaporated. After column chromatography purification (dry loading, 5–20% v/v ethyl acetate/petroleum ether), methyl (E)-4-phenylbut-3-enoate (3a) was isolated as a yellow oil (2.29 g, 70% yield). To a solution of p-ABSA (4.09 g, 17.0 mmol, 1.50 equiv) and ester 3a (2.00 g, 11.3 mmol, 1.00 equiv) in dry acetonitrile (0.10 M) at 0 °C under a N₂ atmosphere was slowly added DBU (3.37 mL, 22.6 mmol, 2.00 equiv) over a period of 30 min. After the addition was complete, the mixture was allowed to warm to RT overnight and then quenched by addition of sat. NH₄Cl solution. The aqueous layer was extracted with ethyl acetate (3 × 150 mL), and the combined organic phase was dried over MgSO₄, concentrated and the crude residue purified by column chromatography (5–20% v/v ethyl acetate/petroleum ether) to give methyl (E)-2-diazo-4-phenylbut-3-enoate (1a) as a dark red oil (2.29 g, 72% yield).^[13] A solution of vinyldiazo compound 1a (101 mg, 0.50 mmol, 1.00 equiv) in benzotrifluoride (0.42 mL, 1.20 M) was heated to reflux until complete consumption of the vinyldiazo compound was observed (<10 min). Silica gel was then added and the solvent was evaporated. The product was purified by column chromatography (dry loading, 50–70% v/v ethyl acetate/petroleum ether) and pyrazole 2a was isolated as an off-white solid (95.2 mg, 94%). The analytical data matched with the literature.^[10d]
1H NMR (250 MHz, CDCl₃): δ = 7.89–7.76 (m, 2 H), 7.51–7.37 (m, 3 H), 7.14 (s, 1 H), 3.97 (s, 3 H).
17 Fu M.-C, Shang R, Cheng W.-M, Fu Y. Chem. Eur. J. 2017; 23: 8818
18 Eissler S, Nahrwold M, Neumann B, Stammler H.-G, Sewald N. Org. Lett. 2007; 9: 817

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