Phosphazene-Catalyzed Cascade Esterification/Stereoselective Aza-Michael Addition of Chiral β-Trifluoromethyl-α,β-unsaturated N-Acylated Oxazolidin-2-ones

Sasirome Racochote; Chutima Kuhakarn; Pawaret Leowanawat; Vichai Reutrakul; Darunee Soorukram

doi:10.1055/a-2364-6119

Synlett, Table of Contents

Synlett 2025; 36(04): 329-334
DOI: 10.1055/a-2364-6119

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Thieme Chemistry Journals Awardees 2024

Phosphazene-Catalyzed Cascade Esterification/Stereoselective Aza-Michael Addition of Chiral β-Trifluoromethyl-α,β-unsaturated N-Acylated Oxazolidin-2-ones

Sasirome Racochote

^aDepartment of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

,

Chutima Kuhakarn

^aDepartment of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

^bCenter of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

,

Pawaret Leowanawat

^aDepartment of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

^bCenter of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

,

Vichai Reutrakul

^aDepartment of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

^bCenter of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

,

Darunee Soorukram ∗

^aDepartment of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

^bCenter of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

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Abstract

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Abstract

Upon treatment of chiral β-trifluoromethyl-α,β-unsaturated N-acylated oxazolidin-2-ones with a range of alcohols using phosphazene base as a catalyst, the unexpected cascade esterification/stereoselective aza-Michael addition was observed. The reactions proceeded with high diastereoselectivities (up to >99:1) to give a series of enantioenriched aza-Michael addition products in good to high yields. The structure and stereochemistry of the representative aza-Michael adduct were confirmed by X-ray crystal structure analysis. The plausible mechanism was proposed on the basis of the experimental results.The synthetic transformations of chiral aza-Michael addition products were also demonstrated highlighting the synthetic application of the present work.

Key words

aza-Michael addition - oxa-Michael addition - esterification - phosphazene - trifluoromethyl group - cascade reaction

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References

References and Notes
1 Nie J, Guo H.-C, Cahard D, Ma J.-A. Chem. Rev. 2011; 111: 455

2a Hagmann WK. J. Med. Chem. 2008; 51: 4359
2b Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320

3a Besset T, Poisson T, Pannecoucke X. J. Fluorine Chem. 2015; 178: 225
3b Reznikov AN, Klimochkin YN. Synthesis 2020; 52: 781
3c Zheng K, Liu X, Feng X. Chem. Rev. 2018; 118: 7586

4 Chaudhary B, Kulkarni N, Saiyed N, Chaurasia M, Desai S, Potkule S, Sharma S. Adv. Synth. Catal. 2020; 362: 4794

5a Xu X, He Y, Zhou J, Li X, Zhu B, Chang J. J. Org. Chem. 2020; 85: 574
5b Morigaki A, Kawamura M, Arimitsu S, Ishihara T, Konno T. Asian J. Org. Chem. 2013; 2: 239
5c Sanz-Marco A, García-Ortiz A, Blay G, Pedro JR. Chem. Commun. 2014; 50: 2275
5d Morigaki A, Tanaka T, Miyabe T, Ishihara T, Konno T. Org. Biomol. Chem. 2013; 11: 586

6a Volonterio A, Bravo P, Moussier N, Zanda M. Tetrahedron Lett. 2000; 41: 6517
6b Volonterio A, Bravo P, Zanda M. Org. Lett. 2000; 2: 1827
6c Rulev AY, Tyumentsev IA. Adv. Synth. Catal. 2022; 364: 1622
6d Yang X, Chen Z, Cai Y, Huang Y.-Y, Shibata N. Green Chem. 2014; 16: 4530
6e Weiß M, Gröger H. Synlett 2009; 1251
6f Formicola L, Maréchal X, Basse N, Bouvier-Durand M, Bonnet-Delpon D, Milcent T, Reboud-Ravaux M, Ongeri S. Bioorg. Med. Chem. Lett. 2009; 19: 83
6g Volonterio A, Bravo P, Zanda M. Tetrahedron Lett. 2001; 42: 3141
6h Volonterio A, Bravo P, Zanda M. Org. Lett. 2000; 2: 1827
6i Volonterio A, Bellosta S, Bravo P, Canavesi M, Corradi E, Meille SV, Monetti M, Moussier N, Zanda M. Eur. J. Org. Chem. 2002; 428
6j Molteni M, Volonterio A, Fossati G, Lazzari P, Zanda M. Tetrahedron Lett. 2007; 48: 589
6k Molteni M, Volonterio A, Zanda M. Org. Lett. 2003; 5: 3887
6l Molteni M, Bellucci MC, Bigotti S, Mazzini S, Volonterio A, Zanda M. Org. Biomol. Chem. 2009; 7: 2286
6m Bigotti S, Meille SV, Volonterio A, Zanda M. J. Fluorine Chem. 2008; 129: 767
6n Bigotti S, Volonterio A, Zanda M. Synlett 2008; 958

7a Su Y, Ling J-B, Zhang S, Xu P.-F. J. Org. Chem. 2013; 78: 11053
7b Hu W.-F, Zhao J.-Q, Chen X.-Z, Zhou M.-Q, Zhang X.-M, Xu X.-Y, Yuan W.-C. Tetrahedron 2019; 75: 2206
7c Chen W, Jing Z, Chin KF, Qiao B, Zhao Y, Yan L, Tan C.-H, Jiang Z. Adv. Synth. Catal. 2014; 356: 1292

8 Jiang Q, Guo T, Yu Z. J. Org. Chem. 2017; 82: 1951
9 Shibatomi K, Narayama A, Abe Y, Iwasa S. Chem. Commun. 2012; 48: 7380
10 Ratner VG, Lork E, Pashkevich KI, Röschenthaler G.-V. J. Fluorine Chem. 2000; 102: 73
11 Racochote S, Pohmakotr M, Kuhakarn C, Leowanawat P, Reutrakul V, Soorukram D. Eur. J. Org. Chem. 2019; 2212
12 Racochote S, Naweephattana P, Surawatanawong P, Kuhakarn C, Leowanawat P, Reutrakul V, Soorukram D. Org. Biomol. Chem. 2023; 21: 7180

For oxa-Michael addition, see:

13a Ivanovs I, Bērziņa S, Lugiņina J, Belyakov S, Rjabovs V. Heterocycl. Commun. 2016; 22: 95
13b Adderley NJ, Buchanan DJ, Dixon DJ, Lainé DI. Angew. Chem. Int. Ed. 2003; 42: 4241
13c Nising CF, Bräse S. Chem. Soc. Rev. 2008; 37: 1218
13d Nising CF, Bräse S. Chem. Soc. Rev. 2012; 41: 988
13e Wang Y, Du D.-M. Org. Chem. Front. 2020; 7: 3266
13f Thiyagarajan S, Krishnakumar V, Gunanathan C. Chem. Asian J. 2020; 15: 518
13g Csókás D, Ho AX. Y, Ramabhadran RO, Bates RW. Org. Biomol. Chem. 2019; 17: 6293

14a Onyeagusi CI, Malcolmson SJ. ACS Catal. 2020; 10: 12507
14b Chen M.-W, Yang Q, Deng Z, Ding Q, Peng Y. J. Org. Chem. 2019; 84: 10371 ; see also ref. 6

15a Punirun T, Soorukram D, Kuhakarn C, Reutrakul V, Pohmakotr M. Eur. J. Org. Chem. 2014; 4162
15b Phae-nok S, Kuhakarn C, Leowanawat P, Reutrakul V, Soorukram D. Synthesis 2024; 56: 1941
15c Luo C, Bandar JS. J. Am. Chem. Soc. 2018; 140: 3547
15d Kondoh A, Yamaguchi S, Watanabe Y, Terada M. Synlett 2022; 33: 1853
15e Kondoh A, Oishi M, Tezuka H, Terada M. Angew. Chem. Int. Ed. 2020; 59: 7472
15f Puleo TR, Sujansky SJ, Wright SE, Bandar JS. Chem. Eur. J. 2021; 27: 4216
15g Imahori T, Hori C, Kondo Y. Adv. Synth. Catal. 2004; 346: 1090
15h Kondoh A, Ando K, Terada M. Chem. Commun. 2013; 49: 10254
15i Kondoh A, Ma C, Terada M. Chem. Commun. 2020; 56: 10894
15j Kondoh A, Terada M. Chem. Eur. J. 2021; 27: 585

16 Schwesinger R, Schlemper H. Angew. Chem., Int. Ed. Engl. 1987; 26: 1167 ; Angew. Chem. 1987, 99, 1212
17 Tshepelevitsh S, Kütt A, Lõkov M, Kaljurand I, Saame J, Heering A, Plieger PG, Vianello R, Leito I. Eur. J. Org. Chem. 2019; 6735

18a Seebach D, Beck AK. Modern Synthetic Methods, Vol. 7. Ernst B, Leumann C. Wiley-VCH; Weinheim: 1995: 48
18b Mamdani HT, Hartley RC. Tetrahedron Lett. 2000; 41: 747
18c Fischer SM, Kaschnitz P, Slugovc C. Catal. Sci. Technol. 2022; 12: 6204

19a Lucet D, Toupet L, Gall TL, Mioskowski C. J. Org. Chem. 1997; 62: 2682
19b Sabelle S, Lucet D, Gall TL, Mioskowski C. Tetrahedron Lett. 1998; 39: 2111
19c Lucet D, Sabelle S, Kostelitz O, Gall TL, Mioskowski C. Eur. J. Org. Chem. 1999; 2583
19d Lucet D, Heyse P, Gissot A, Gall TL, Mioskowski C. Eur. J. Org. Chem. 2000; 3575
19e Feroci M, Inesi A, Palombi L, Rossi L. Tetrahedron: Asymmetry 2001; 12: 2331
19f Turconi J, Lebeau L, Paris J.-M, Mioskowski C. Tetrahedron 2006; 62: 8109
19g Shankar PS, Sani M, Terraneo G, Zanda M. Synlett 2009; 1341
19h Capra J, Gao B, Hemmery H, Thuéry P, Gall TL. ARKIVOC 2015; 60

20a Mayr H, Breugst M, Ofial AR. Angew. Chem. Int. Ed. 2011; 50: 6470
20b Endo A, Danishefsky SJ. J. Am. Chem. Soc. 2005; 127: 8298

21a Pal KB, Guo A, Das M, Báti G, Liu X.-W. ACS Catal. 2020; 10: 6707
21b Jardel D, Davies C, Peruch F, Massip S, Bibal B. Adv. Synth. Catal. 2016; 358: 1110

22 Cascade Esterification/Stereoselective aza-Michael Addition Reaction of 1aA flame-dried round-bottom flask equipped with a magnetic stirring bar, an argon inlet, and a rubber septum was charged with 1a (58.3 mg, 0.20 mmol), benzyl alcohol (2a, 24 μL, 0.22 mmol), and dry MeCN (1 mL). The resulting solution was cooled at 0 °C then P₂-t-Bu solution (2.0 M in THF, 10 μL, 0.02 mmol) was added. After stirring at 0 °C for 6 h, the reaction mixture was quenched with 10% HCl solution (10 mL) and extracted with EtOAc (3 × 20 mL). The combined organic layer was washed with a saturated aqueous NaCl solution (30 mL), brine, and dried over anhydrous Na₂SO₄. After removal of the solvent in vacuo, the residue was purified by column chromatography (70% CH₂Cl₂ in hexanes) to afford (S,R)-3a (60.1 mg, 75% yield, dr 97:3, ¹⁹F NMR analysis) as a white solid.Compound (S,R)-3a: R_f = 0.30 (70% CH₂Cl₂ in hexanes); mp 85–87 °C (70% CH₂Cl₂ in hexanes); [α]_D ²³ –31.5 (c 1.1, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.43–7.31 (m, 8 H, ArH), 7.30–7.23 (m, 2 H, ArH), 5.15 (ABq, J = 12.1 Hz, 2 H, CHH), 4.75 (dd, J = 8.2, 8.2 Hz, 1 H, CHN), 4.50–4.38 (m, 2 H, CHHO, CH), 4.11 (dd, J = 7.6, 8.5 Hz, 1 H, CHHO), 3.21 (dd, J = 10.5, 16.6 Hz, 1 H, CHH), 2.86 (dd, J = 4.4, 16.6 Hz, 1 H, CHH). ¹³C NMR (100 MHz, CDCl₃): δ = 168.6 (CO), 157.5 (CO), 136.4 (C), 135.2 (C), 129.6 (CH), 129.2 (2 × CH), 128.7 (2 × CH), 128.6 (CH), 128.5 (2 × CH), 127.7 (2 × CH), 124.4 (q, ¹ J_CF = 282.4 Hz, CF₃), 70.5 (CH₂), 67.3 (CH₂), 59.9 (CH), 52.7 (q, ² J_CF = 32.2 Hz, CH), 30.4 (CH₂). ¹⁹F NMR (376 MHz, CDCl₃): δ = –72.4 (CF₃). IR (ATR): λ_max = 1757, 1496, 1479, 1361, 1243, 1184, 1124 cm^–1. MS: m/z (%) relative intensity 394 [(M + H)⁺, 92], 286 (100), 216 (30), 91 (30). HRMS (ESI-TOF): m/z calcd for C₂₀H₁₈F₃NO₄Na⁺ [M + Na]⁺: 416.1080; found: 416.1082.
23 Katz SJ, Bergmeier SC. Tetrahedron Lett. 2002; 43: 557 ; see also ref. 19
24 Sun F, Van der Eycken EV, Feng H. Adv. Synth. Catal. 2021; 363: 5168

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