Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2024; 35(20): 2459-2464
DOI: 10.1055/a-2422-1263
DOI: 10.1055/a-2422-1263
letter
Special Issue to Celebrate the 75th Birthday of Prof. B. C. Ranu
Lewis Acid Catalyzed Domino Ring-Opening Cyclization of Azetidines with Alkynes: Synthesis of Tetrahydropyridines
M.K.G. is grateful to the Science and Engineering Research Board (SERB), New Delhi and the Indian Institute of Technology (IIT) Kanpur, India for financial support. D.S., A.B., and R.T. thank the IIT Kanpur. B.S. thanks the Council of Scientific and Industrial Research (CSIR), India; S.S. and A.K.S. thank the University Grants Commission (UGC), India for research fellowships.
Dedicated to Prof. B. C. Ranu on the occasion of his 75th birthday
Abstract
A simple strategy for the synthesis of a variety of tetrahydropyridines in good to excellent yields via a Cu(OTf)2 catalyzed quaternary ammonium salt mediated ring-opening of activated azetidines followed by cyclization with alkynes in a domino ring-opening cyclization (DROC) is described. The formation of the products has been explained by an SN2-type ring-opening of azetidines with alkynes.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2422-1263.
- Supporting Information
Publication History
Received: 02 August 2024
Accepted after revision: 25 September 2024
Accepted Manuscript online:
25 September 2024
Article published online:
25 October 2024
© 2024. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References and Notes
- 1a Dunbar PG, Durant GJ, Rho T, Ojo B, Huzl JJ. III, Smith DA, El-Assadi AA, Sbeih S, Ngur DO, Periyasamy S, Hoss W, Messer WS. Jr. J. Med. Chem. 1994; 37: 2774
- 1b Morale MC, Serra PA, L’Episcopo F, Tirolo C, Caniglia S, Testa N, Gennuso F, Giaquinta G, Rocchitta G, Desole MS, Miele E, Marchetti B. Neuroscience 2006; 138: 869
- 1c Kadieva MG, Oganesyan ÉT, Mutsueva SK. Pharm. Chem. J. 2005; 39: 453
- 1d Xu K, Xu Y, Brown-Jermyn D, Chen J.-F, Ascherio A, Dluzen DE, Schwarzschild MA. J. Neurosci. 2006; 26: 535
- 1e Cawthon D, Soderblom EJ, Xu ZA, Duhart H, Slikker WJr, Ali SF, Goshe MB. Int. J. Neuroprotec. Neuroregener. 2005; 1: 98
- 1f Picon S, Boulahjar R, Hoguet V, Baron M, Duplan I, Vallez E, Hennuyer N, Dumont J, Touche V, Dorchies E, Lasalle M, Descat A, Piveteau C, Biela A, Chaput L, Villoutreix BO, Lipka E, Sevin E, Culot M, Gosselet F, Lestavel S, Roussel P, Deprez-Poulain R, Leroux F, Staels B, Deprez B, Tailleux A, Charton J. J. Med. Chem. 2023; 66: 11732
- 2a Mitch CH, Bymaster FP, Calligaro DO, Quimby SJ, Schoepp DD, Wong DT, Shannon HE. Bioorg. Med. Chem. Lett. 1994; 4: 1721
- 2b Dunbar PG, Durant GJ, Fang Z, Abuh YF, El-Assadi AA, Ngur DO, Periyasamy S, Hoss WP, Messer WS. Jr. J. Med. Chem. 1993; 36: 842
- 2c Olesen PH, Swedberg MD. B, Rimvall K. Bioorg. Med. Chem. 1998; 6: 1623
- 2d Glase SA, Akunne HC, Heffner TG, Jaen JC, MacKenzie RG, Meltzer LT, Pugsley TA, Smith SJ, Wise LD. J. Med. Chem. 1996; 39: 3179
- 2e León LG, Carballo RM, Vega-Hernández MC, Martín VS, Padrón JI, Padrón JM. Bioorg. Med. Chem. Lett. 2007; 17: 2681
- 2f Makarov MV, Hayat F, Graves B, Sonavane M, Salter EA, Wierzbicki A, Gassman NR, Migaud ME. ACS Chem. Biol. 2021; 16: 604
- 2g Meibom D, Micus S, Andreevski AL, Anlauf S, Bogner P, von Buehler C.-J, Dieskau AP, Dreher J, Eitner F, Fliegner D, Follmann M, Gericke KM, Maassen S, Meyer J, Schlemmer K.-H, Steuber H, Tersteegen A, Wunder F. J. Med. Chem. 2022; 65: 16420
- 2h Lewandowski M, Carmina M, Knümann L, Sai M, Willems S, Kasch T, Pollinger J, Knapp S, Marschner JA, Chaikuad A, Merk D. J. Med. Chem. 2024; 67: 2152
- 3a Ogawa T, Matsumoto K, Yoshimura M, Hatayama K, Kitamura K, Kita Y. Tetrahedron Lett. 1993; 34: 1967
- 3b Taylor MD, Badger EW, Steffen RP, Haleen SJ, Pugsley TA, Shih YH, Weishaar RE. J. Med. Chem. 1988; 31: 1659
- 3c Liu L.-L, Di Y.-T, Zhang Q, Fang X, Zhu F, Chen D.-L, Hao X.-J, He H.-P. Tetrahedron Lett. 2010; 51: 5670
- 3d Krauze A, Vītoliņa R, Garaliene V, Sīle L, Kluša V, Duburs G. Eur. J. Med. Chem. 2005; 40: 1163
- 3e Wang Y, Wang C, Liu J, Sun D, Meng F, Zhang M, Aliper A, Ren F, Zhavoronkov A, Ding X. Bioorg. Med. Chem. 2024; 103: 117662
- 4a Ramachandran PV, Burghardt TE, Bland-Berry L. J. Org. Chem. 2005; 70: 7911
- 4b Han B, Li J.-L, Ma C, Zhang S.-J, Chen Y.-C. Angew. Chem. Int. Ed. 2008; 47: 9971
- 4c Ramachandran R, Jayanthi S, Jeong YT. Tetrahedron 2012; 68: 363
- 4d Maestre L, Fructos MR, Díaz-Requejo MM, Pérez PJ. Organometallics 2012; 31: 7839
- 4e Barber DM, Sanganee HJ, Dixon DJ. Org. Lett. 2012; 14: 5290
- 4f Chen X.-Y, Ye S. Eur. J. Org. Chem. 2012; 5723
- 4g Tong S, Yang X, Wang D.-X, Zhao L, Zhu J, Wang M.-X. Tetrahedron 2012; 68: 6492
- 4h Ramiz MM. M, Abdel Hafiz IS, Elian MA. J. Chin. Chem. Soc. 2012; 59: 758
- 4i Sezer S, Gümrükçü Y, Bakırcı İ, Yağız Ünver M, Tanyeli C. Tetrahedron: Asymmetry 2012; 23: 662
- 4j Pretto LM, Mittersteiner M, Andrade VP, Bonacorso HG, Martins MA. P, Zanatta N. Tetrahedron Lett. 2019; 60: 151336
- 4k He Y, Yang J, Liu Q, Zhang X, Fan X. J. Org. Chem. 2020; 85: 15600
- 5a De Kimpe N, Stevens C. Tetrahedron 1995; 51: 2387
- 5b De Kimpe N, Adams A. Chem. Rev. 2006; 106: 2299
- 5c Verniest G, Surmont R, Hende EV, Deweweire A, Deroose F, Thuring JW, De Kimpe N. J. Org. Chem. 2008; 73: 5458
- 5d Mollet K, D’Hooghe M, De Kimpe N. Mini-Rev. Org. Chem. 2013; 10: 1
- 5e Fujita R, Hanaya K, Sugai T, Higashibayashi S. Sci. Rep. 2021; 11: 24078
- 5f Bastos Braga I, Almir Angnes R, Carlos de Lucca EJr, Carmo Braga AA, Roque Duarte Correia C. Eur. J. Org. Chem. 2022; e202200377
- 5g Xia X.-F, Huang Q, Sun T.-Y, Jiang Y, Ran G. ACS Catal. 2022; 12: 12964
- 5h Terunuma T, Hayashi Y. Nat. Commun. 2022; 13: 7503
- 5i Hu M, Ding H, DeSnoo W, Tantillo DJ, Nairoukh Z. Angew. Chem. Int. Ed. 2023; 62: e202315108
- 5j Muralirajan K, Kancherla R, Maity B, Karuthedath S, Laquai F, Cavallo L, Rueping M. Nat. Commun. 2023; 14: 6622
- 5k Cerveri A, Scarica G, Sparascio S, Hoch M, Chiminelli M, Tegoni M, Protti S, Maestri G. Chem. Eur. J. 2024; 30: e202304010
- 5l Gao P.-S, Pan C.-W, Sui Y, Ye H.-X, Liu C, Liu D.-S, Chen W.-T. Tetrahedron 2024; 155: 133865
- 5m Alizadeh A, Moterassed R. J. Iran. Chem. Soc. 2024; 21: 1635
- 6a Yadav VK, Sriramurthy V. J. Am. Chem. Soc. 2005; 127: 16366
- 6b Van Brabandt W, Van Landeghem R, De Kimpe N. Org. Lett. 2006; 8: 1105
- 6c Mollet K, Catak S, Waroquier M, Speybroeck VV, D’hooghe M, De Kimpe N. J. Org. Chem. 2011; 76: 8364
- 6d Mollet K, Broeckx L, D’hooghe M, De Kimpe N. Heterocycles 2012; 84: 431
- 6e Fang Y, Rogness DC, Larock RC, Shi F. J. Org. Chem. 2012; 77: 6262
- 6f Shimizu T, Koya S, Yamasaki R, Mutoh Y, Azumaya I, Katagiri K, Saito S. J. Org. Chem. 2014; 79: 4367
- 6g Pawar SK, Vasu D, Liu R.-S. Adv. Synth. Catal. 2014; 356: 2411
- 6h Ishida N, Nečas D, Masuda Y, Murakami M. Angew. Chem. Int. Ed. 2015; 54: 7418
- 6i Shehzadi SA, Kushwaha K, Sterckx H, Abbaspour Tehrani K. Adv. Synth. Catal. 2018; 360: 4393
- 6j Hejiang Luo TC. S. Z. Chin. J. Org. Chem. 2021; 41: 3521
- 6k Dolna M, Narodowiec J, Staszewska-Krajewska O, Szcześniak P, Furman B. React. Chem. Eng. 2023; 8: 784
- 7a Ungureanu I, Klotz P, Schoenfelder P, Mann A. Chem. Commun. 2001; 958
- 7b Mehra V, Kumar V. Tetrahedron 2013; 69: 3857
- 7c Alcaide B, Almendros P, Martín-Montero R, Ruiz MP. Adv. Synth. Catal. 2016; 358: 1469
- 7d Luan L.-B, Song Z.-J, Li Z.-M, Wang Q.-R. Beilstein J. Org. Chem. 2018; 14: 1826
- 7e Nastase AF, Griggs NW, Anand JP, Fernandez TJ, Harland AA, Trask TJ, Jutkiewicz EM, Traynor JR, Mosberg HI. ACS Chem. Neurosci. 2018; 9: 1840
- 7f Suto T, Yanagita Y, Nagashima Y, Takikawa S, Kurosu Y, Matsuo N, Miura K, Simizu S, Sato T, Chida N. Bull. Chem. Soc. Jpn. 2019; 92: 545
- 7g Ham JS, Park B, Son M, Roque JB, Jurczyk J, Yeung CS, Baik M.-H, Sarpong R. J. Am. Chem. Soc. 2020; 142: 13041
- 7h Xiao R.-X, Tian T, Yang T.-Y, Lan M.-X, Lv S, Mou X.-Q, Chen Y.-Z, Cui B.-D. Org. Lett. 2024; 26: 3195
- 7i Shukla D, Kashyap S, Singh B, Sharma AK, Bhattacharyya A, Rahman N, Ghorai MK. Synthesis 2024; in press; DOI: 10.1055/a-2415-1629
- 8a Baeg J.-O, Bensimon C, Alper H. J. Org. Chem. 1995; 60: 253
- 8b Alcaide B, Salgado NR, Sierra MA. Tetrahedron Lett. 1998; 39: 467
- 8c Prasad BA. B, Bisai A, Singh VK. Org. Lett. 2004; 6: 4829
- 8d Couty F, Evano G. Synlett 2009; 3053
- 8e Alcaide B, Almendros P, Aragoncillo C. Curr. Opin. Drug Discovery Dev. 2010; 13: 685
- 8f Barbier V, Marrot J, Couty F, David OR. P. Eur. J. Chem. 2016; 549
- 8g Dao Thi H, Decuyper L, Mollet K, Kenis S, De Kimpe N, Van Nguyen T, D’hooghe M. Synlett 2016; 27: 1100
- 8h Dao Thi H, Danneels B, Desmet T, Van Hecke K, Van Nguyen T, D’Hooghe M. Asian J. Org. Chem. 2016; 5: 1480
- 8i Wang X, Liu C, Zeng X, Wang X, Wang X, Hu Y. Org. Lett. 2017; 19: 3378
- 8j Singh A, Sharma B, Sachdeva D, Mehra V, Singh P, Kumar V. ChemistrySelect 2018; 3: 4764
- 8k Dao Thi H, Le Nhat Thuy G, Catak S, Van Speybroeck V, Van Nguyen T, D’hooghe M. Synthesis 2018; 50: 1439
- 8l Boddy AJ, Cordier CJ, Goldberg K, Madin A, Spivey AC, Bull JA. Org. Lett. 2019; 21: 1818
- 8m Yao Z, Feng H, Xi H, Xi C, Liu W. Org. Biomol. Chem. 2021; 19: 4469
- 9a Ghorai MK, Das K, Kumar A, Das A. Tetrahedron Lett. 2006; 47: 5393
- 9b Ghorai MK, Das K, Kumar A. Tetrahedron Lett. 2007; 48: 4373
- 9c Ghorai MK, Das K, Kumar A. Tetrahedron Lett. 2009; 50: 1105
- 10a Kashyap S, Singh B, Ghorai MK. J. Org. Chem. 2024; 89: 11429
- 10b Singh B, Kashyap S, Singh S, Gupta S, Ghorai MK. J. Org. Chem. 2024; 89: 2247
- 10c Singh B, Kumar M, Goswami G, Verma I, Ghorai MK. J. Org. Chem. 2023; 88: 4504
- 10d Wani IA, Sk S, Mal A, Sengupta A, Ghorai MK. Org. Lett. 2022; 24: 7867
- 10e Pradhan S, Chauhan N, Shahi CK, Bhattacharyya A, Ghorai MK. Org. Lett. 2020; 22: 7903
- 10f Bhattacharyya A, Das S, Chauhan N, Biswas PK, Ghorai MK. Synlett 2020; 708 For azetidines, see
- 10g Goswami G, Singh B, Wani IA, Mal A, Ghorai MK. J. Org. Chem. 2024; 89: 11576
- 10h Goswami G, Chauhan N, Mal A, Das S, Das M, Ghorai MK. ACS Omega 2018; 3: 17562
- 10i Ghorai MK, Kumar A, Das K. Org. Lett. 2007; 9: 5441
- 11a Ghorai MK, Shukla D, Bhattacharyya A. J. Org. Chem. 2012; 77: 3740
- 11b Ghorai MK, Kumar A, Tiwari DP. J. Org. Chem. 2010; 75: 137
- 11c Bhattacharyya A. Synlett 2012; 23: 2142
For aziridines see:
(A) General procedure for DROC of azetidine with alkynes in the presence of catalytic Cu(OTf)2 and stoichiometric TBAFP and characterization data of compounds 6a–h and 10a–13a′A solution of azetidine (1.0 equiv), TBAFP (1.0 equiv), and alkyne (3.0 equiv) in dichloromethane was added to anhydrous Cu(OTf)2 (20 mol%) at 0 °C under an argon atmosphere. The reaction mixture was stirred for the appropriate time, then quenched with saturated NaHCO3 at the same temperature. The aqueous layer was extracted with CH2Cl2 (3 × 5.0 mL) and dried over anhydrous Na2SO4. The crude compound was purified by flash column chromatography on neutral alumina (ethyl acetate/petroleum ether) to provide the corresponding cyclized product.During the temperature-dependence studies, the reaction was performed at the appropriate temperature. When the reaction was performed with BF3·OEt2 as the Lewis acid, it was added to the reaction mixture after the addition of all other reagents. These compounds were unstable, and some amount of the product was hydrolyzed during workup or column chromatographic purification or during the preparation of the analytical sample.(B) Racemization studies of (S)-2-phenyl-N-tosylazetidine 4a in the presence of Cu(OTf)2 in dichloromethane (Ref. 11a)We studied the racemization of enantiopure (S)-2-phenyl-N tosylazetidine 4a by performing the reaction with a stoichiometric amount of Cu(OTf)2 in CH2Cl2 at room temperature, as well as at 0 °C without adding nucleophile. The aliquots were taken from the reaction mixture at defined time intervals and analyzed by chiral HPLC (Chiralpak AD-H column, flow rate 1 mL/min; hexane-isopropanol, 95:5). At room temperature, the ee of (S)-4a was found to decrease with increasing time and the compound racemized completely within 5 minutes (Table 2, Figure 2)Table 1 Racemization study of (S)-4a (1.0 equiv) in the Presence of Cu(OTf)2 (1.0 equiv) at RT and 0 °C in CH2Cl2 When the reaction was carried out at 0 °C, the racemization occurred within 1.5 h (Table 2, Figure 3). Racemization of (S)-4a during the course of the reaction is responsible for the reduced ee of the product. When the racemization of (S)-2-phenyl-N-tosylazetidine 4a was studied in the presence of a catalytic amount of Cu(OTf)2 (30 mol%) and stoichiometric TBAHS (1.0 equiv) in CH2Cl2 at 0 °C without adding a nucleophile, the ee of (S)-4a did not decrease with increasing reaction time in dichloromethane.