Synthesis of 2,4-Disubstituted Oxazoles by a Copper-Catalyzed [3+2] Annulation/Olefination Cascade between Amides and I^III/P^V Hybrid Ylides

Abstract

We report a novel and efficient method for oxazole synthesis through a copper-catalyzed [3+2] annulation/olefination cascade between readily available iodonium–phosphonium hybrid ylides and amides. An unprecedented α-phosphonium Cu carbenoid acts as the key intermediate. This method features excellent regioselectivity with mild reaction conditions and a broad substrate scope. Its synthetic utility is demonstrated by its application in late-stage functionalizations and the rapid synthesis of a chiral ligand based on an oxazole motif.

Key words

oxazoles - copper catalysis - carbenoids - [3+2] annulation - cascade reaction - amides

Publication History

Received: 24 August 2023

Accepted after revision: 02 October 2023

Accepted Manuscript online:
02 October 2023

Article published online:
06 November 2023

• References and Notes

• 1a Eicher T, Hauptmann S, Speicher A. The Chemistry of Heterocycles: Structure, Reactions, Synthesis, and Applications, 2nd ed. Wiley-VCH; Weinheim: 2003
• 1b Pozharskii AF, Soldatenkov AT, Katritzky AR. Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry, Biochemistry and Applications, 2nd ed. Wiley; Chichester: 2011
• 2a Davyt D, Serra G. Mar. Drugs 2010; 8: 2755
• 2b Jin Z. Nat. Prod. Rep. 2011; 28: 1143
• 2c Zhang H.-Z, Zhao Z.-L, Zhou C.-H. Eur. J. Med. Chem. 2018; 144: 444
• 2d Kakkar S, Narasimhan B. BMC Chem. 2019; 13: 16
• 3 Oxazoles, Part A: Synthesis, Reactions, and Spectroscopy. Palmer DC. Wiley; New York: 2003

For selected examples, see:
• 4a Merkul E, Müller TJ. J. Chem. Commun. 2006; 4817
• 4b Pan Y.-m, Zheng F.-j, Lin H.-x, Zhan Z.-p. J. Org. Chem. 2009; 74: 3148
• 4c Zheng Y, Li X, Ren C, Zhang-Negrerie D, Du Y, Zhao K. J. Org. Chem. 2012; 77: 10353
• 4d Cheung CW, Buchwald SL. J. Org. Chem. 2012; 77: 7526
• 4e Senadi GC, Hu W.-P, Hsiao J.-S, Vandavasi JK, Chen C.-Y, Wang J.-J. Org. Lett. 2012; 14: 4478
• 4f Hu Y, Yi R, Wang C, Xin X, Wu F, Wan B. J. Org. Chem. 2014; 79: 3052
• 4g Weng Y, Lv W, Yu J, Ge B, Cheng G. Org. Lett. 2018; 20: 1853
• 4h Newar UD, Borra S, Maurya RA. Org. Lett. 2022; 24: 4454

For selected examples, see:
• 5a Wan C, Zhang J, Wang S, Fan J, Wang Z. Org. Lett. 2010; 12: 2338
• 5b Cano I, Álvarez E, Nicasio MC, Pérez PJ. J. Am. Chem. Soc. 2011; 133: 191
• 5c Li X, Huang L, Chen H, Wu W, Huang H, Jiang H. Chem. Sci. 2012; 3: 3463
• 5d Xu Z, Zhang C, Jiao N. Angew. Chem. Int. Ed. 2012; 51: 11367
• 5e Odabachian Y, Tong S, Wang Q, Wang M.-X, Zhu J. Angew. Chem. Int. Ed. 2013; 52: 10878
• 5f Zheng J, Zhang M, Huang L, Hu X, Wu W, Huang H, Jiang H. Chem. Commun. 2014; 50: 3609
• 5g Pan J, Li X, Qiu X, Luo X, Jiao N. Org. Lett. 2018; 20: 2762
• 5h Di Mauro G, Maryasin B, Kaiser D, Shaaban S, González L, Maulide N. Org. Lett. 2017; 19: 3815

For selected examples, see:
• 6a Ohnmacht SA, Mamone P, Culshaw AJ, Greaney MF. Chem. Commun. 2008; 1241
• 6b Besselièvre F, Mahuteau-Betzer F, Grierson DS, Piguel S. J. Org. Chem. 2008; 73: 3278
• 6c Hachiya H, Hirano K, Satoh T, Miura M. Angew. Chem. Int. Ed. 2010; 49: 2202
• 6d Liu B, Qin X, Li K, Li X, Guo Q, Lan J, You J. Chem. Eur. J. 2010; 16: 11836
• 6e Yang F, Xu Z, Wang Z, Yu Z, Wang R. Chem. Eur. J. 2011; 17: 6321
• 6f Yamamoto T, Muto K, Komiyama M, Canivet J, Yamaguchi J, Itami K. Chem. Eur. J. 2011; 17: 10113
• 6g Li Z, Ma L, Xu J, Kong L, Wu X, Yao H. Chem. Commun. 2012; 48: 3763
• 6h Shen X.-B, Zhang Y, Chen W.-X, Xiao Z.-K, Hu T.-T, Shao L.-X. Org. Lett. 2014; 16: 1984
• 6i Zhou P.-X, Shi S, Wang J, Zhang Y, Li C, Ge C. Org. Chem. Front. 2019; 6: 1942
• 6j Shi X, Soulé JF, Doucet H. Adv. Synth. Catal. 2019; 361: 4748
• 6k Choi I, Müller V, Lole G, Köhler R, Karius V, Viöl W, Jooss C, Ackermann L. Chem. Eur. J. 2020; 26: 3509
• 6l Tian Z.-Y, Lin Z.-H, Zhang C.-P. Org. Lett. 2021; 23: 4400

For selected examples, see:
• 7a Meyers AI, Tavares FX. J. Org. Chem. 1996; 61: 8207
• 7b Williams DR, Lowder PD, Gu Y.-G, Brooks DA. Tetrahedron Lett. 1997; 38: 331
• 7c Phillips AJ, Uto Y, Wipf P, Reno MJ, Williams DR. Org. Lett. 2000; 2: 1165
• 7d Huang Y, Ni L, Gan H, He Y, Xu J, Wu X, Yao H. Tetrahedron 2011; 67: 2066
• 7e Li X, Li C, Yin B, Li C, Liu P, Li J, Shi Z. Chem. Asian J. 2013; 8: 1408
• 8a Graham TH. Org. Lett. 2010; 12: 3614
• 8b Saito A, Taniguchi A, Kambara Y, Hanzawa Y. Org. Lett. 2013; 15: 2672
• 8c Selvi T, Srinivasan K. Chem. Commun. 2014; 50: 10845
• 8d Wang B, Chen Y, Zhou L, Wang J, Tung C.-H, Xu Z. J. Org. Chem. 2015; 80: 12718
• 8e Zeng T.-T, Xuan J, Ding W, Wang K, Lu L.-Q, Xiao W.-J. Org. Lett. 2015; 17: 4070
• 8f Chatterjee T, Cho JY, Cho EJ. J. Org. Chem. 2016; 81: 6995
• 8g Hu J, Hong H, Qin Y, Hu Y, Pu S, Liang G, Huang Y. Org. Lett. 2021; 23: 1016
• 9a Doyle MP, Forbes DC. Chem. Rev. 1998; 98: 911
• 9b de Frémont P, Marion N, Nolan SP. Coord. Chem. Rev. 2009; 253: 862
• 9c Ford A, Miel H, Ring A, Slattery CN, Maguire AR, McKervey MA. Chem. Rev. 2015; 115: 9981
• 9d Xia Y, Qiu D, Wang J. Chem. Rev. 2017; 117: 13810
• 9e Wentrup C. Angew. Chem. Int. Ed. 2018; 57: 11508
• 9f Zhu D, Chen L, Fan H, Yao Q, Zhu S. Chem. Soc. Rev. 2020; 49: 908
• 10a Davies HM. L, Manning JR. Nature 2008; 451: 417
• 10b Davies HM. L, Morton D. Chem. Soc. Rev. 2011; 40: 1857
• 10c Zhu S.-F, Zhou Q.-L. Acc. Chem. Res. 2012; 45: 1365
• 10d Guo X, Hu W. Acc. Chem. Res. 2013; 46: 2427
• 11a Lebel H, Marcoux J.-F, Molinaro C, Charette AB. Chem. Rev. 2003; 103: 977
• 11b Degennaro L, Trinchera P, Luisi R. Chem. Rev. 2014; 114: 7881
• 12a West TH, Spoehrle SS. M, Kasten K, Taylor JE, Smith AD. ACS Catal. 2015; 5: 7446
• 12b Bach R, Harthong S, Lacour J. In Comprehensive Organic Synthesis, 2nd ed., Vol. 3, Chap. 3.20. Knochel P, Molander GA. Elsevier; Amsterdam: 2014: 992
• 13a Connell RD, Tebbe M, Gangloff AR, Helquist P, Åkermark B. Tetrahedron 1993; 49: 5445
• 13b Doyle KJ, Moody CJ. Tetrahedron 1994; 50: 3761
• 14a Clapham B, Spanka C, Janda KD. Org. Lett. 2001; 3: 2173
• 14b Clapham B, Lee S.-H, Koch G, Zimmermann J, Janda KD. Tetrahedron Lett. 2002; 43: 5407
• 15a Shi B, Blake AJ, Campbell IB, Judkins BD, Moody CJ. Chem. Commun. 2009; 3291
• 15b Shi B, Blake AJ, Lewis W, Campbell IB, Judkins BD, Moody CJ. J. Org. Chem. 2010; 75: 152
• 15c Reddy MR, Reddy GN, Mehmood U, Hussein IA, Rahman SU, Harrabi K, Subba Reddy BV. Synthesis 2015; 47: 3315
• 15d Honey MA, Pasceri R, Lewis W, Moody CJ. J. Org. Chem. 2012; 77: 1396
• 16a Doyle MP, McKervey MA, Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides. Wiley;  New York: 1998
• 16b Wang J. Tetrahedron Lett. 2022; 108: 154135
• 17a He W, Li C, Zhang L. J. Am. Chem. Soc. 2011; 133: 8482
• 17b Yang W, Zhang R, Yi F, Cai M. J. Org. Chem. 2017; 82: 5204
• 17c Zimin DP, Dar’in DV, Kukushkin VY, Dubovtsev AY. J. Org. Chem. 2020; 86: 1748
• 18a Yusubov MS, Yoshimura A, Zhdankin VV. ARKIVOC 2016; (i): 342
• 18b Mi X, Pi C, Feng W, Cui X. Org. Chem. Front. 2022; 9: 6999
• 19a Müller P. Acc. Chem. Res. 2004; 37: 243
• 19b Kumar S, Borkar V, Mujahid M, Nunewar S, Kanchupalli V. Org. Biomol. Chem. 2023; 21: 24
• 19c Zhu C, Yoshimura A, Ji L, Wei Y, Nemykin VN, Zhdankin VV. Org. Lett. 2012; 14: 3170
• 19d Mo S, Li X, Xu J. J. Org. Chem. 2014; 79: 9186
• 19e Jiang Y, Li P, Zhao J, Liu B, Li X. Org. Lett. 2020; 22: 7475
• 19f Mayakrishnan S, Tamizmani M, Maheswari NU. Chem. Commun. 2020; 56: 15462
• 20 Moriarty RM, Prakash I, Prakash O, Freeman WA. J. Am. Chem. Soc. 1984; 106: 6082
• 21 Song K, Wen M, Shen K, Fan C, Yang Z, Lin S, Pan Q. Tetrahedron Lett. 2021; 72: 153057
• 22 2-(4-Methylphenyl)-4-phenyl-1,3-oxazole (3a); Typical Procedure A dry clean test-tube equipped with a stirrer bar was charged with p-methylbenzamide 2a (16.2 mg, 0.12 mmol), Na₂CO₃ (25.4 mg, 0.24 mmol), I^III/P^V hybrid ylide 1a (67.0 mg, 0.1 mmol), Cu(acac)₂ (1.31 mg, 5 mol%), and 3 Å MS (50 mg). DCE (1.0 mL) was then added from a syringe under a N₂ atmosphere. The resulting mixture was stirred for 3 h at 40 °C (water-bath temperature), then cooled to r.t. After removal of the volatiles under reduced pressure, the residue was purified by column chromatography [silica gel, PE–EtOAc (20:1)] to give a white solid; yield: 21.2 mg (90%). ¹H NMR (400 MHz, CDCl₃): δ = 8.01 (d, J = 7.3 Hz, 2 H), 7.95 (s, 1 H), 7.83 (d, J = 7.9 Hz, 2 H), 7.43 (t, J = 7.5 Hz, 2 H), 7.34 (dd, J = 6.8 Hz, 1 H), 7.29 (d, J = 7.9 Hz, 2 H), 2.42 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 162.3, 142.0, 140.8, 133.3, 131.4, 129.6, 128.9, 128.2, 126.6, 125.8, 125.0, 21.7. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₆H₁₄NO: 236.1070; found: 236.1069.