BF₃·OEt₂-Catalyzed Rearrangement of Epoxy-Himachalenes: Access to New Biosourced N-Acetamide-Based Himachalenes

Abstract

Biosourced N-acetamide-based himachalenes were synthesized by Lewis acid catalyzed rearrangement of epoxy-himachalene derived from α-cis- and β-himachalenes, the main component of essential oil of Atlas cedar (Cedrus atlantica). Several new chiral polycyclic N-acetamide compounds were obtained with different selectivities depending on the acid used. Among the Lewis acids used, BF₃·OEt₂ under catalytic and mild conditions is efficient and selective affording the formation of chiral N-acetamides in good yields. Otherwise, using acetonitrile as solvent and reagent was proved as an efficient tool giving access to new N-acetamide-based himachalenes. A mechanism to explain the formation of the different compounds observed in the reaction mixture has also been proposed.

Key words

sesquiterpene - N-acetamides - Atlas cedar - himachalene - Lewis acids

Publikationsverlauf

Eingereicht: 07. Juli 2020

Angenommen nach Revision: 22. September 2020

Artikel online veröffentlicht:
28. Oktober 2020

• References and Notes

• 1a Pfau A, Plattner PL. Helv. Chim. Acta 1934; 17: 129
• 1b Krishna Rao GS, Dev S, Guha PC. J. Indian Chem. Soc. 1952; 29: 721
• 1c Oukhrib A, Zaki M, Ait El Had M, El Karroumi J, Bouamama H, Benharref A, Urrutigoïty M. Rhazes: Green Appl. Chem. 2019; 6: 61
• 2a Ravasio N, Zaccheria F, Guidotti M, Psaro R. Top. Catal. 2004; 27: 157
• 2b Monteiro JL. F, Veloso CO. Top. Catal. 2004; 27: 169
• 3 Daoubi M, Hernandez-Galan R, Benharref A, Collado IG. J. Agric. Food Chem. 2005; 53: 6673
• 4a Chekroun A, Jarid A, Benharref A, Boutalib A. J. Org. Chem. 2000; 65: 4431
• 4b Oukhrib A, Benharref A, Saadi M, Berraho M, El Ammari L. Acta Crystallogr., Sect. E: Struct. Rep. Online 2013; 69: o739
• 5 Oukhrib A, Zaki M, Benharref A. ARKIVOC 2018; (i): 134
• 6a Eljamili H, Auhmani A, Dakir M, Lassaba E, Benharref A, Pierrot M, Chiaroni A, Riche C. Tetrahedron Lett. 2002; 43: 6645
• 6b Ourhriss N, Benharref A, Saadi M, El Ammari L, Berraho M. Acta Crystallogr., Sect. E: Struct. Rep. Online 2013; 69: o275
• 7a Lassaba E, Chekroun A, Benharref A, Chiaroni A, Riche C, Lavergne J.-P. Bull Soc. Chim. Belg. 1997; 106: 281
• 7b Lassaba E, El Jamili H, Chekroun A, Benharref A, Chiaroni A, Riche C, Lavergne J.-P. Synth. Commun. 1998; 28: 2641
• 7c Loubidi M, Agustin D, Benharref A, Poli R. C. R. Chimie 2014; 17: 549
• 8a Joseph TC, Dev S. Tetrahedron 1968; 24: 3853
• 8b Harref AB, Bernardini A, Fkih-Tetouani S, Jacquier R, Viallefont P. J. Chem. Res., Synop. 1981; 5: 372
• 9a Smith JG. Synthesis 1984; 629
• 9b Barluenga J, Vazquez-Villa H, Ballesteros A, Gonzalez JM. Org. Lett. 2002; 4: 2817
• 9c Torborg C, Hughes DD, Buckle R, Robinson MW. C, Bagley MC, Graham AE. Synth. Commun. 2008; 38: 205
• 9d Izquierdo J, Rodríguez S, González FV. Org. Lett. 2011; 13: 3856
• 9e Xu C, Xu J. Org. Biomol. Chem. 2020; 18: 127
• 10a Xu C, Xie W, Xu J. Org. Biomol. Chem. 2020; 18: 2661
• 10b Xu C, Lu Y, Xu K, Xu J. Synthesis 2020; 52: 602
• 11a Joseph TC, Dev S. Tetrahedron 1968; 24: 3853
• 11b Ait El Had M, Oukhrib A, Zaki M, Urrutigoity M, Benharref A, Chauvin R. Chin. Chem. Lett. 2020; 31: 1851
• 12a Auhmani A, Kossareva E, Eljamili H, Reglier M, Pierrot M, Benharref A. Synth. Commun. 2002; 32: 699
• 12b Oukhrib A, Benharref A, Saadi M, Berraho M, El Ammari L. Acta Crystallogr., Sect. E: Struct. Rep. Online 2013; 69: o589
• 12c Ourhriss N, Giorgi M, Mazoir N, Benharref A. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2005; 61: o699
• 12d Benharref A, Oukhrib A, Ait Elhad M, Daran JC, Berraho M. IUCrData 2016; 1: x160554
• 13a Chaudhary A, Das P, Mishra A. Mol. Diversity 2012; 16: 357
• 13b Chaudhary A, Sood S, Das P, Kaur P, Mahajan I, Gulati A, Singh B. EXCLI Journal 2014; 13: 1216
• 14 El Haib A, Benharref A, Parres-Maynadie S, Manoury E, Urrutigoity M, Gouygou M. Tetrahedron: Asymmetry 2011; 22: 101
• 15 Chekroun A, Jarid A, Benharref A, Boutalib A. J. Org. Chem. 2000; 65: 4431
• 16 Eljamili H, Auhmani A, Dakir M, Lassaba E, Benharref A, Pierrot M, Chiaroni A, Riche C. Tetrahedron Lett. 2002; 43: 6645
• 17 Tantillo DJ. J. Phys. Org. Chem. 2008; 21: 561
• 18 El Haib A, Benharref A, Parres-Maynadie S, Manoury E, Urrutigoity M, Gouygou M. Tetrahedron: Asymmetry 2010; 21: 1272
• 19 Mazoir N, Benharref A, Daran JC, Oukhrib A, Ait Elhad M, Berraho M. IUCrData 2017; 2: x170805
• 20 Smith J.-RL, Norman RO. C, Stillings MR. J. Chem. Soc., Perkin Trans. 1 1975; 1202
• 21 Ait Elhad M, Benharref A, El Ammari L, Saadi M, Oukhrib A, Berraho M. IUCrData 2017; 2: x170275
• 22 Benharref A, Ait Elhad M, Mazoir N, Daran JC, Oukhrib A, Berraho M. IUCrData 2017; 2: x170970
• 23 All purchased solvents and chemicals were of analytical grade and used without further purification. Thin-layer chromatography (TLC) was performed using F254 precoated plates (0.25 mm) and visualized by UV fluorescence quenching and phosphomolybdic acid solution staining. Flash chromatography was performed on silica gel (230–400 mesh). Chromatography separations were carried out by a conventional column on silica gel 60 (230–400 mesh), using hexanes–EtOAc (EtOAc–hexane) mixtures of increasing polarity. ¹H NMR and ¹³C NMR spectra were recorded at 600 and 500 MHz, and at 150 and 125 MHz, respectively in CDCl₃. Chemical shifts (δ_H) are quoted in parts per assigned utilizing DEPT experiments and based on heteronuclear correlations. Infrared spectra (IR) were recorded as thin films or as solids on a FTIR spectrophotometer with samples frequency of absorption (cm^–1). [α]_D ²⁵ measurements were carried out in a polarimeter; utilizing a 1 dm length cell and CHCl₃ as a solvent. Concentration is expressed in mg/mL. Epoxidation of α-cis- and β-Himachalene – General Procedure m-Chloroperbenzoic acid (1 equiv, 1.7 g, 10 mmol) is added to a stirred mixture of α-cis and β-himachalene (2.1 g, 10 mmol) in CH₂Cl₂ (30 mL) at 0 °C. The reaction mixture was stirred at room temperature for 2 h. Then, the mixture was quenched with saturated solution of NaHCO₃ (20 mL) and washed with water (2 × 30 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The two epoxides 1 and 2 were separated by chromatography on silica gel with EtOAc/hexane (2:98) as eluent. (1S,2S,3R,6R)-2,3-Epoxy-3,7,11,11-tetramethylbicyclo[5,4,0]-undec-7,13-ene (1) Oily; R_f = 0.5 (EtOAc/hexane, 2:98). ¹H NMR (500 MHz, CDCl₃): δ = 0.95 (3 H, s), 1.1 (3 H,s), 1.65–1.45 (2 H, m), 1.35–1.55 (2 H, m), 1.72 (2 H, m), 1.75 (3 H, s), 2.41 (1 H, q), 2.66 (1 H, dd, J = 4.0, 11.0 Hz), 2.95 (1 H, d, J = 4.5 Hz), 4.78 (2 H, d, J = 6.5 Hz) ppm. ¹³C NMR (126 MHz, CDCl₃): δ = 22.71 (CH₃), 23.20 (CH₃), 24.8 (CH₂), 26.60 (CH₂), 28.11 (CH₂), 30.8 (CH₂), 32.09 (CH₃), 36.9 (C), 37.80 (C), 39.31 (CH₂), 47.50 (C), 58.8 (C), 62.59 (CH), 111.90 (CH₂), 155.61 (C) ppm. MS (DCI, NH₃): m/z (%) = 221 (100%) [M + H]⁺. IR (film): 890 (C–O–C) cm^–1. (1S,6S,7R)-6,7-Epoxy-3,7,11,11-tetramethylbicyclo[5,4,0]-undec-2-ene (2) Oily; R_f = 0.4 (EtOAc/hexane, 2:98). ¹H NMR (500 MHz, CDCl₃): δ = 0.98 (3 H, s), 1.35 (3 H, s), 1.65 (3 H, s), 1.53 (2 H, m), 1.75 (3 H, s), 1.97 (2 H, dt), 2.2–1.95 (2 H, m), 2.01 (1 H, d, J = 4.5 Hz), 4.41 (1 H, d, J = 4.5 Hz) ppm. ¹³C NMR (126 MHz, CDCl₃): δ = 18.30 (CH₂), 20.71 (CH₂), 23.82 (CH₃), 24.80 (CH₃), 25.39 (CH₃), 27.58 (CH₂), 29.91 (CH₃), 36.30 (CH₂), 36.52 (CH₂), 44.11 (C), 48.81 (CH), 65.0 (C), 65.15 (C), 124.32 (CH), 134.81 (C) ppm. MS (DCI, NH₃): m/z (%) = 220 (100%) [M + H]⁺. IR (film): 1034 (C–O–C) cm^–1. Diepoxy β-Himachalene (3) – General Procedure Epoxy-β-himachalene (2, 1 g, 45 mmol) dissolved in CH₂Cl₂ (15 mL) and stirred at 0 °C. Then, one equivalent of m-chloroperbenzoic acid (780 mg, 45 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 2 h. After completion of the reaction, the mixture was quenched with saturated solution of NaHCO₃ (10 mL) and then washed with water (2 × 30 mL). The organic layer was combined, dried over sodium sulfate, and then concentrated under reduced pressure. The diepoxide 3 was separated by chromatography on silica gel with EtOAc/hexane (4:96) as eluent. (1S,2R,3S,6S,7R)-2,3,6,7-Diepoxy-3,7,11,11 tetramethylbicyclo[5,4,0]undecane (3) White solid; mp 68–69 °C; R_f = 0.4 (EtOAc/hexane, 4:96). ¹H NMR (500 MHz, CDCl₃): δ = 1.01 (3 H, s), 1.09 (3 H, s), 1.24 (3 H, s), 1.37 (3 H, s), 3.01 (1 H, d, J = 2.0 Hz) ppm. ¹³C NMR (126 MHz, CDCl₃): δ = 60.38 (C), 60.36 (C), 59.62 (C), 55.45 (C), 47.01 (CH), 28.5 (CH₂), 24.5 (CH₂), 21.32 (CH₂), 43.40 (CH₂), 27.0 (C), 23.6 (CH₂), 20.61 (C), 27.29 (2 × CH₂) ppm. MS (DCI, NH₃): m/z (%) = 236 (100%) [M + H]⁺. Rearrangement Reaction of Epoxides – General Procedure Epoxy-himachalene (1 mmol) was dissolved in CH₃CN (15 mL) and stirred at the desired temperature. Then, the acid (20%) was gently added to the solution. The reaction mixture was stirred at room temperature for 2 h. After completion of the reaction, the mixture was quenched with NaHCO₃ (10 mL) saturated solution, and then brine (9ml) was added, the resulting aqueous phase was extracted with CH₂Cl₂ (3 × 20 mL). The organic layer was combined, dried over sodium sulfate, and then concentrated under reduced pressure. The crude was separated by chromatography on silica gel with EtOAc/hexane as eluent. (1S,3R,7S) 3,11,11-Trimethyltricyclo [5.4.1^(3,7).0]dodecan-2-one (4) Oily; [α]_D ²⁵ = + 9.1 (c 3.8, CHCl₃); R_f = 0.6 (EtOAc/hexane, 5:95). ¹H NMR (500 MHz, CDCl₃): δ = 1.03 (s, 3 H), 1.07 (s, 3 H), 1.12 (td, J = 13.6, 1.43 Hz, 2 H), 1.22 (s, 3 H), 1.24 (td, J = 13.4 Hz, 1 H), 1.32 (d, J = 13.0 Hz, 1 H), 1.38 (d, J = 11.3 Hz, 1 H), 1.41 and 1.71 (m, 2 H), 1.44 and 1.59 (m, 2 H), 1.53–1.69 (m, 2 H), 1.62 (d, J = 11.3 Hz, 1 H), 1.63 (s, 1 H), 1.76 (d, J = 13.0 Hz, 1 H), 2.14 (m, 1 H) ppm. ¹³C NMR (126 MHz, CDCl₃): δ = 19.39 (CH₂), 20.47 (CH₂), 20.69 (CH₃), 21.59 (CH₃), 31.89 (CH₃), 32.63 (CH₂), 33.25 (C), 38.88 (CH₂), 39.51 (CH₂), 40.82 (C), 43.34 (CH₂), 48.23 (C), 53.21 (CH₂), 66.68 (CH), 220.70 (C=O) ppm. IR (film): 2923, 2854, 1730, 1699, 1454, 1384, 1363, 1350, 1109, 962, 909, 893, 771, 744 cm^–1. N-[(1R,2S,3S)-1,4,4-Trimethyltricyclo[6.3.1.0^3,9]dodec-8(12)-en-2-yl]acetamide (5) White solid; mp 145–146 °C; [α]_D ²⁵ + 6.4 (c 1.5, CHCl₃); R_f = 0.3 (EtOAc/hexane, 15:85). ¹H NMR (500 MHz, CDCl₃): δ = 0.80 (s, 3 H), 0.82–0.95 (m, 1 H), 0.96 (s, 3 H), 0.99 (m, 1 H), 1.02 (s, 3 H), 1.10 (m, 1 H), 1.26 (s, 1 H), 1.34 (m, 1 H), 1.44–1.55 (m, 2 H), 1.56–1.64 (m, 2 H), 1.96 (dd, J = 8.2, 4.6 Hz,1 H), 1.99 (s, 3 H), 2.30 (m, 1 H), 2.42 (dq, J = 3.1, 1.5 Hz, 1 H), 3.53 (ddd, J = 10.2, 4.9, 2.0 Hz, 1 H), 5.40 (br, 1 H), 5.58 (s, 1 H) ppm. ¹³C NMR (126 MHz, CDCl₃): δ = 19.96 (CH₂), 21.91 (CH₂), 23.70 (CH₃), 26.22 (CH₂), 26.27 (CH₂), 27.50 (CH₃), 28.23 (CH₃), 32.40 (CH₃), 34.65 (CH₂), 34.79 (CH), 36.83 (C), 39.40 (C), 55.47 (CH), 56.72 (CH), 131.47 (CH), 145.76 (C), 169.09 (C=O) ppm. HRMS (ES+/TOF): m/z calcd for C₁₇H₂₇NO [M + H⁺]: 262.2171; found: 262.2168. IR (film): 3293, 2927, 2866, 1648, 1552, 1464, 1370, 805, 771, 606, 513, 475 cm^–1. N-{(3aR*,3bS*)-1,3b,7,7-Tetramethyl-3a,3b,4,5,6,7,7a,7b-octahydro-3H-cyclopenta[3,4]-cyclobuta[1,2]benzen-3a-yl}acetamide (6) White solid; mp 158–159 °C; [α]_D ²⁵ –41.9 (c 1.4, CHCl₃); R_f = 0.3 (EtOAc/hexane, 10:90). ¹H NMR (500 MHz, CDCl₃): δ = 0.82 (s, 3 H), 0.89 (s, 3 H), 1.10–1.28 (m, 3 H), 1.32 (s, 3 H), 1.37–1.56 (m, 4 H), 1.71 (m, 3 H), 1.91 (s, 3 H), 2.27–2.35 (m, 1 H), 2.50 (ddd, J = 17.7, 2.7, 1.8 Hz, 1 H), 2.99 (d, J = 2.8 Hz, 1 H), 5.43 (dt, J = 2.6, 1.6 Hz, 1 H), 5.79 (br, 1 H) ppm. ¹³C NMR (126 MHz, CDCl₃): δ = 15.82 (CH₃), 18.28 (CH₂), 23.19 (CH₃), 23.50 (CH₃), 28.67 (CH₃), 29.72 (CH₃), 29.73 (C), 31.36 (CH₂), 36.85 (CH₂), 40.71 (CH₂), 41.23 (C), 53.94 (CH), 57.30 (CH), 66.09 (C), 127.96 (CH), 141.94 (C), 169.38 (C=O) ppm. HRMS (ES+/TOF): m/z calcd for C₁₇H₂₇NO [M + H⁺]: 262.2171; found: 262.2169. IR (film): 3287, 3034, 2953, 2917, 1635, 1542, 1441, 1368, 1318, 1300, 1253, 1212, 1012, 790, 598, 536 cm^–1. N-{(1R,3aR,3bS,7aR,7bS)-1-Hydroxy-1,3b,7,7-tetramethyldecahydro-3aH-cyclopenta[3,4]cyclobuta[1,2]benzen-3a-yl}acetamide (7) White solid; mp 163–164 °C; [α]_D ²⁵ –19.3 (c 1.1, CHCl₃); R_f = 0.2 (EtOAc/hexane, 15:85). ¹H NMR (600 MHz, CDCl₃): δ = 0.83 (s, 3 H), 0.91 (s, 3 H), 1.10 (s, 3 H), 1.18 (d, J = 8.4 Hz, 1 H), 1.22 (s, 3 H), 1.28 (t, J = 6.3 Hz, 2 H), 1.55–1.41 (m, 3 H), 1.65–1.58 (m, 1 H), 1.91–1.78 (m, 2 H), 1.97 (s, 3 H), 2.17–2.10 (m, 2 H), 2.53 (d, J = 8.4 Hz, 1 H), 5.99 (s, 1 H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = 18.18 (CH₂), 23.88 (CH₃), 24.17 (CH₃), 24.23 (CH₃), 29.68 (CH₃), 30.30 (C), 31.03 (CH₂), 31.22 (CH₃), 32.25 (CH₂), 36.48 (CH₂), 39.23 (C), 40.56 (CH₂), 49.11 (CH), 55.89 (CH), 66.63 (C), 80.67 (C), 170.15 (C=O) ppm. HRMS (ES+/TOF): m/z calcd for C₁₇H₂₉NO₂ [M + H⁺]: 279.2198; found: 279.2193. IR (film): 3283, 3075, 2945, 2865, 1626, 1546, 1460, 1369, 1301, 1276, 1224, 1190, 1147, 1111, 912, 769, 691, 593 cm^–1. Arylhimachalene (8) Oily; [α]_D ²⁵ +0.4 (c 1.6, CHCl₃). R_f = 0.7 (hexane). ¹H NMR (600 MHz, CDCl₃): δ = 1.22 (s, 3 H), 1.24 (s, 3 H), 1.31 (d, J = 6.8 Hz, 3 H), 2.23 (s, 3 H), 3.18 (m, 1 H), 6.82 (d, J = 7.9 Hz, 2 H), 6.91 (d, 7.9 Hz, 1 H), 7.04 (s, 1 H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = 22.09 (CH₃), 22.14 (CH₃), 25.97 (CH₃), 30.03 (CH₃), 33.27 (CH₂), 33.36 (CH₂), 3966 (C), 37.55 (CH₂), 41.24, 126,65 (CH), 126.30 (CH), 127.50 (CH), 134.76 (C), 140.70 (C), 147.36 (C) ppm. (1R,2R,7S,8R,9R)-N-{2-Hydroxy-2,6,6,9-tetramethyl-12-oxatricyclo[7.2.1.0^1,7] dodecan-8-yl}- acetamide (9) White solid; mp 181–182 °C; [α]_D ²⁵ –56.5 (c 0.3, CHCl₃); R_f = 0.2 (EtOAc/hexane, 20:80). ¹H NMR (500 MHz, CDCl₃): δ = 0.96 (s, 3 H), 1.13 (s, 3 H), 1.24 (m, 1 H), 1.31 (s, 3 H), 1.31 (s, 3 H), 1.35 (m, 1 H), 1.55 (dd, J = 14.4, 8.7 Hz, 1 H), 1.69 (m, 1 H), 1.97–1.78 (m, 5 H), 2.06 (s, 3 H), 2.77 (dd, J = 11.7, 2.4 Hz, 1 H), 4.44 (td, J = 11.5, 1.8 Hz, 1 H), 5.53 (d, J = 11.2 Hz, 1H ) ppm. ¹³C NMR (126 MHz, CDCl₃): δ = 17.90 (CH₂), 19.62 (CH₃), 24.11 (CH₃), 26.17 (CH₃), 27.26 (CH₃), 29.01 (CH₂), 32.33 (CH₃), 32.63 (CH₂), 33.47 (C), 41.66 (CH₂), 45.60 (CH), 47.32 (CH₂), 58.01 (CH), 73.50 (C), 82.90 (C), 94.65 (C), 169.49 (C=O) ppm. HRMS (ES+/TOF): m/z calcd for C₁₇H₂₉NO₃ [M + H⁺]: 296.2226; found: 296.2224. IR (film): 3291, 2918, 2853, 1657, 1546, 1472, 1452, 1378, 1317, 1297, 1219, 1131, 1064, 1048, 911, 772 cm^–1.