Unexpected Reactions: From (2S,3R)-2-(endo-d-Galacto-pentaacetoxypentyl)-1,4-dimethyl-3-exo-nitro-7-oxabicyclo[2.2.1]hept-5-ene to Chiral Cyclic Ethers

Abstract

The high-pressure Diels-Alder reaction between 2,5-dimethylfuran and d-galacto-3,4,5,6,7-penta-O-acetyl-1,2-dideoxy-1-nitrohept-1-enitol led, after fractional crystallization from the crude product, to pure (2S,3R)-2-(endo-d-galacto-penta­acetoxypentyl)-1,4-dimethyl-3-exo-nitro-7-oxabicyclo[2.2.1]hept-5-ene. The structure was determined through a chemical route and by X-ray powder diffractometry. De-acetylation of the sugar side chain of this adduct caused the ring opening of the bicyclic system, followed by a tandem process of intramolecular nucleophilic additions, thus leading to new chiral bicyclic and tricyclic ethers.

Key words

asymmetric synthesis - carbohydrate nitroalkenes - ­Diels-Alder reaction - heterocycles - ring opening

References and Notes

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9

This ratio was determined from the ¹H NMR spectra of the crude mixture at the end of reaction time, by integration of the signals corresponding to H-5 and H-6 of each stereoisomer.

11

The adduct 3 did not afford suitable crystals for their study by single-crystal X-ray analysis. Hence, this compound was analyzed using X-ray powder diffractometry to determine its crystalline structure. The powder was loaded into the holder (3 mm thick) and pressed slightly with a glass slide to ensure a flat surface and thus the absence of instrumental shift in the position of peaks in the diffractogram. The operating conditions for the data collection were: Cu Kα incident radiation (λ = 1.54183 Å), 5-70° scanning interval, 0.02° step size, and 40 s count time per step, using a Philips PW-1800 diffractometer equipped with a graphite secondary monochromator. The compound crystallized in the monoclinic system, with the space group C2, one molecule in the asymmetric unit giving four molecules in the unit cell (Z = 4), and the following unit cell dimensions: a = 23.8333 (10) Å, b = 10.0745 (4) Å, c = 14.3027 (6) Å, and β = 113.28 (1)°.As starting configuration was used the molecule optimized by molecular modelling with a semiempirical quantum chemistry model [code HyperChem: HYPERCHEM. Release 5. Standalone Version. Computational Chemistry, Hypercube Inc., Publication HC50-00-03-00, October 1996, ISBN 1-896164-17-X].The structure was solved by direct-space methods with a ‘Monte-Carlo/parallel tempering’ search algorithm [code FOX: Favre-Nicolin, V.; Cern, R. FOX: a program for ab initio structure solution from powder diffraction data. Laboratory of Crystallography, University of Geneva, Switzerland, 2000], followed by a final refinement using the Rieltved method [code FullProf: Rodríguez-Carvajal, J. FULLPROF: a program for Rietveld refinement and pattern matching analysis. Abstracts of the Satellite Meeting on powder diffraction of the XV Congress of the International Union of Crystallography, Toulouse, France, 1990].

14

Attempts to prepare the peracetylated derivative of 10 were performed by Ac₂O and pyridine treatment from the evaporated reaction mixture of 3 and aq K₂CO₃, before neutralization with Amberlite IR-120 (H⁺) resin.

19

Selected Data for Compound 3White solid; 43% yield; [α]_D ²⁰ -27.2 (c 0.51, CHCl₃); mp 189-190 °C. ¹H NMR (400 MHz, CDCl₃): δ = 6.40 (d, 1 H, J _5,6 = 5.6 Hz, H-6), 6.24 (d, 1 H, H-5), 4.77 (dd, 1 H, J _{1 ′ ,2} = 11.3 Hz, H-1′), 4.35 (d, 1 H, J _2,3 = 3.4 Hz, H-3), 2.97 (dd, 1 H, H-2). ¹³C NMR (100 MHz, CDCl₃): δ = 143.1 (C-6), 136.6 (C-5), 92.8 (C-3), 88.5, 87.9 (C-1, C-4), 51.3 (C-2). HRMS (CI): m/z calcd for C₂₃H₃₁NO₁₃Na [M + Na]⁺: 552.1693; found: 552.1689.Selected Data for Compound 7dPale yellow oil; 60% yield; [α]_D ²⁰ +29.4 (c 0.54, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 5.57 (dd, 1 H, J _{1 ′ ,2 ′} = 2.4 Hz, H-1′), 5.37 (ddd, 1 H, H-2′), 5.11 (dd, 1 H, J _7,8 = 1.6 Hz, J _{1 ′ ,8} = 9.6 Hz, H-8), 4.76 (dd, 1 H, J _{1 ′′ a,6} = 6.8 Hz, H-1′′a), 4.49 (dd, 1 H, J _{1 ′′ a,1 ′′ b} = 13.6 Hz, J _{1 ′′ b,6} = 6.0 Hz, H-1′′b), 4.41 (dd, 1 H, J _3b,4 = 4.4 Hz, H-4), 4.29 (dd, 1 H, J _{2 ′ , 3 ′ a} = 5.6 Hz, H-3′a), 4.27 (dd, 1 H, J _6,7 = 8.8 Hz, H-7), 3.93 (dd, 1 H, J _{3 ′ a,3 ′ b} = 11.2 Hz, J _{2 ′ , 3 ′ b} = 7.2 Hz, H-3′b), 2.58 (ddd, 1 H, H-6), 2.29 (br d, 1 H, J _3a,3b = 14.8 Hz, H-3a), 2.09 (dd, 1 H, H-3b). ¹³C NMR (100 MHz, CDCl₃): δ = 106.8 (C-2), 91.7 (C-5), 88.8 (C-4), 79.0 (C-8), 72.7 (C-1′′), 68.9, 68.6, 67.9 (C-1′, C-2′, C-7), 62.0 (C-3′), 47.3 (C-6), 44.1 (C-3). HRMS-FAB: m/z calcd for C₂₁H₃₀NO₁₂Na [M - OH + Na]⁺: 528.1693; found: 528.1706.Selected Data for Compound 8aPale yellow oil; 20% yield; [α]_D ²⁰ +68.0 (c 0.50, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 5.45 (ddd, 1 H, H-2′), 5.23 (dd, 1 H, J _{1 ′ ,2 ′} = 1.6 Hz, H-1′), 4.74 (dd, 1 H, J _{1 ′′ a,1 ′′ b} = 13.6 Hz, J _{1 ′′ a,6} = 4.8 Hz, H-1′′a), 4.56 (dd, 1 H, J _{1 ′′ b,6} = 9.6 Hz, H-1′′b), 4.48 (br d, 1 H, J _3b,4 = 4.0 Hz, J _3a,4 = 1.0 Hz, H-4), 4.23 (dd, 1 H, J _{3 ′ a,3 ′ b} = 12.0 Hz, J _{2 ′ ,3 ′ a} = 4.8 Hz, H-3′a), 4.09 (br d, 1 H, J _6,7 = 6.4 Hz, J _7,8 = 1.0 Hz, H-7), 4.06 (dd, 1 H, J _{2 ′ ,3 ′ b} = 8.0 Hz, H-3′b), 3.34 (d, 1 H, J _{1 ′ ,8} = 9.2 Hz, H-8), 3.05 (ddd, 1 H, H-6), 2.29 (br d, 1 H, J _3a,3b = 14.4 Hz, H-3a), 2.04 (dd, 1 H, H-3b). ¹³C NMR (100 MHz, CDCl₃): δ = 106.7 (C-2), 92.3 (C-5), 89.4 (C-4), 81.1 (C-7), 74.8 (C-1′′), 70.8, 70.2, 69.6 (C-1′, C-2′, C-8), 62.6 (C-3′), 47.9 (C-6), 43.8 (C-3). HRMS (CI): m/z calcd for C₁₉H₂₈NO₁₁ [M + H]⁺: 446.1662; found: 446.1642.Selected Data for Compound 9ePale yellow oil; 15% yield; [α]_D ²⁰ +25.4 (c 0.51, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 5.21 (dd, 1 H, J _{1 ′ ,2} = 9.6 Hz, H-2), 4.87 (br s, 1 H, H-7), 4.63 (dd, 1 H, J _{1 ′′ a,4} = 7.6 Hz, H-1′′a), 4.59 (br s, 1 H, J _6,Me-8 = 1.2 Hz, J _6,7 = 1.0 Hz, H-6), 4.45 (dd, 1 H, J _{1 ′′ a,1 ′′ b} = 14.4 Hz, J _{1 ′′ b,4} = 4.4 Hz, H-1′′b), 3.66 (dd, 1 H, J _2,3 = 2.4 Hz, J _3,4 = 10.8 Hz, H-3), 2.60 (ddd, 1 H, H-4). ¹³C NMR (100 MHz, CDCl₃): δ = 160.5 (C-8), 95.1 (C-7), 91.7 (C-5), 90.4 (C-6), 75.1 (C-2), 71.4 (C-1′′), 68.7, 68.1, 66.3 (C-1′, C-2′, C-3), 47.1 (C-4). HRMS (CI): m/z calcd for C₂₁H₃₀NO₁₂ [M + H]⁺: 488.1768; found: 488.1754.