Exo -Glycals: Intermediates in the synthesis of 1,1-disubstituted c -glycosides

Synlett

Volumn , Issue 6, 2010, Pages 869-872

  Woodward, Hannah ^a   Smith, Nichola ^b   Gallagher, Timothy ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

Azidoselenation; C glycosides; Petasis olefination

Indexed keywords

GLYCOSIDE; LACTONE DERIVATIVE;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL MODIFICATION; CHEMICAL REACTION; DRUG SYNTHESIS; OLEFINATION;

EID: 77949910423     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-0029-1219560     Document Type: Article

References (34)

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29. Using C1-metalated endo-glycals we have prepared a series of C1-substituted alkyl and aryl glycals (i.e., 1 R = Alk, Ar) and evaluated these as substrates for azidoselenation. Even under forcing conditions, no azidoselenation was observed and this is attributed to the known (and facile) reversible nature of the azidoselenation process. We assume that trapping with Ph2Se2 of the intermediate (a tertiary or benzylic anomeric radical) resulting from initial N3.addition is slow and expulsion of N3.(and its subsequent decomposition) is too efficient. When the C1 substituent carried a pendent alkenyl residue (e.g., allyl), only addition to this less electron-rich alkene was observed (Gallagher, T.; Wang, J.- W. unpublished work).
30. Data for exo-Glycals Conventional carbohydrate numbering (cf. sialic acids) is used. Compound 8b: 1H NMR (400 MHz, CDCl3): d = 1.13, 1.20, 1.23, 1.28 [36 H, 4 11s, 4 ssCOC(CH3)3], 3.994.10 (2 H, m, H7a + H7b), 4.25 (1 H, m, H6), 4.50 (1 H, t, J = 1.5 Hz, =CHH, H1a), 4.77 (1 H, t, J = 1.5 Hz, =CHH, H1b), 5.15 (1 H, dd, J = 10.5, 3.0 Hz, H4), 5.53 (1 H, dd, J = 3.0, 1.0 Hz, H5), 5.76 (1 H, dt, J = 10.5, 1.5 Hz, H3). 13C NMR (100 MHz, CDCl3): d = 27.0, 27.1, 38.7, 38.8, 61.2, 66.6, 67.2, 71.5, 75.8, 95.3, 154.6, 176.7, 176.8, 177.8. ESI-HRMS: m/z calcd for C27H4409 [M + Na]+: 535.2878; found: 535.2868. Compound 9: 1H NMR (400 MHz, CDCl3): d = 1.141.24 [36 H, m, 4 11COC(CH3)3], 3.773.78 (1 H, m, H6), 4.064.26 (2 H, m, H7a + H7b), 4.49 (1 H, t, J = 1.5 Hz, H1a), 4.80 (1 H, t, J = 1.5 Hz, H1b), 5.26 (2 H, dd, J = 7.0, 2.5 Hz, H4 + H5), 5.47 (1 H, m, H3). 13C NMR (100 MHz, CDCl3): d = 27.1, 27.2, 38.8, 38.9, 61.7, 67.6, 69.0, 72.8, 76.6, 96.2, 154.0, 176.4, 176.5, 177.1, 178.1. ESI-HRMS: m/ z calcd for C27H4409 [M + Na]+: 535.2878; found: 535.2902. Compound 10: 1H NMR (400 MHz, CDCl3): d = 1.131.25 [36 H, m, 4 [[COC(CH3)3], 3.87 (1 H, m, H6), 4.234.25 (2 H, m, H7a + H7b), 4.71 (1 H, d, J = 1.0 Hz, H1a), 4.83 (1 H, d, J = 1.0 Hz, H1b), 5.15 (1 H, dd, J = 10.0, 3.5 Hz, H4), 5.62 (1 H, app t, J = 10.0 Hz, H5), 5.69 (1 H, d, J = 3.5 Hz, H3). 13C NMR (100 MHz, CDCl3): d = 27.0, 27.1, 27.1, 38.7, 38.8, 38.9, 61.4, 64.5, 68.9, 71.0, 77.0, 101.4, 152.9, 176.6, 176.9, 177.3, 178.1. ESI-HRMS: m/z calcd for C27H44O9 [M + Na]+: 535.2877; found: 535.2890.
31. To determine whether the carbohydrate substrates were reactive towards Pd(0), a series of control experiments were carried using cinnamyl acetate as a standard. Exposure of cinnamyl acetate and exo-glycal 8b (or 9 or 10) to sodiodiethyl malonate in the presence of a catalytic quantity of Pd(0) (Pd2dba3/dppe) led to the expected substituted cinnamyl adduct as the only product observed and galacto 8b was recovered unchanged. With the gluco substrates 9 essentially the same outcome was observed: cinnamyl acetate reacted but exo-glycal 9 did not. In the case of the manno variant 10, and under the same reaction conditions, none of the cinnamyl substitution product was detected, suggesting that coordination of Pd(0) to 10 occurred [to sequester Pd(0)] but any resulting complex (e.g., 11) was then unreactive towards the external malonate nucleophile.
32. Extensive attempts (varying ligands, reaction temperatures, solvents and catalysts, including use of palladium and nickel) to carry out the allylic displacement chemistry using manno substrate 10 were all unsuccessful.
33. Spectroscopic data are provided for the galacto series shown in Scheme 4. Compound 13: 1H NMR (400 MHz, CDCl3): d = 1.121.28 [36 H, m, 4 [[COC(CH3)3], 3.12 (1 H, d, J = 13.5 Hz, 1 11CH2N3), 3.62 (1 H, d, J = 13.5 Hz, 1 ==CH2N3), 3.94 (1 H, dd, J = 11.0, 9.0 Hz, H6a), 4.03 (1 H, dd, J = 11.0, 6.0 Hz, H6b), 4.71 (1 H, m, H5), 5.48 (1 H, dd, J = 10.5, 3.0 Hz, H3), 5.59 (1 H, dd, J = 3.0, 1.0 Hz, H4), 5.87 (1 H, d, J = 10.5 Hz, H2), 7.357.44 (3 H, m, ArCH), 7.58 7.61 (2 H, m, ArCH). 13C NMR (100 MHz, CDCl3): d = 26.9, 27.0, 27.1, 38.7, 38.8, 38.9, 39.0, 56.1, 60.3, 66.5, 66.7, 70.5, 70.5, 91.9, 124.5, 129.3, 137.6, 176.3, 177.9, 180.4, 180.5. ESI-HRMS: m/z calcd for C33H49N3O9Se [M + Na]+: 734.2526; found: 734.2556. Compound 14: 1H NMR (400 MHz, CDCl3): d = 1.111.27 [36 H, m, 4 [[COC(CH3)3], 2.09 (3 H, s, NHCOCH3), 3.36 (1 H, dd, J = 14.5, 3.5 Hz, 1 ==CH2NHCOCH3), 3.97 (1 H, m, H6a), 4.064.15 (2 H, m, H6b + 1 44CH2NHCOCH3), 4.85 (1 H, m, H5), 5.505.53 (2 H, m, H2 + H4), 5.61 (1 H, m, H3), 6.03 (1 H, m, NH), 7.317.38 (3 H, m, ArCH), 7.59 7.64 (2 H, m, ArCH). 13C NMR (100 MHz, CDCl3): d = 20.7, 26.9, 27.0, 27.1, 27.2, 27.2, 38.7, 38.8, 39.0, 45.0, 60.4, 66.4, 67.1, 70.2, 71.1, 91.6, 124.7, 129.1, 129.2, 129.2, 137.4, 169.3, 176.4, 177.2, 177.9, 178.1. ESI-HRMS: m/z calcd for C35H53NO10Se [M + Ma]+: 750.2727; found: 750.2712. Compound 15: 1H NMR (300 MHz, CDCl3): d = 1.11 1.30 [36 H, m, 4 11COC(CH3)3], 1.401.55 [2 H, m, CH2CH2CO2C(CH3)3], 2.06 (3 H, s, NHCOCH3), 2.17 2.32 [2 H, m, CH2CH2CO2C(CH3)3], 3.383.44 (2 H, m, CH2NHCOCH3), 3.62 (1 H, m, H5), 3.974.04 (2 H, m, H6a + H6b), 5.08 (1 H, dd, J = 10.5, 3.0 Hz, H4), 5.20 (1 H, d, J = 10.0 Hz, H2), 5.48 (1 H, dd, J = 10.0, 3.0 Hz, H3), 6.05 (1 H, d, J = 5.0 Hz, NH). 13C NMR (100 MHz, acetone-d6): d = 20.2, 23.5, 26.5, 26.6, 26.7, 26.8, 27.1, 27.5, 27.5, 27.6, 27.6, 38.4, 38.8, 39.5, 42.5, 61.3, 66.5, 67.8, 72.5, 77.0, 106.9, 172.1, 172.9. ESI-HRMS: m/z calcd for C36H61NO12 [M + Na]+: 722.4086; found: 722.4098. Compound 18: 1H NMR (300 MHz, acetone-d6): d = 1.09 1.22 [36 H, m, 4 11COC(CH3)3], 1.441.49 [2 H, m, CH2CH2CO2C(CH3)3], 2.01 (3 H, s, NHCOCH3), 2.40-2.42 (2 H, m, CH2CH2CO2C(CH3)3), 3.26 (1 H, dd, J = 14.5, 4.5, 1 11CH2NHCOCH3), 3.43 (1 H, dd, J = 14.5, 7.5, 1 11CH2NHCOCH3), 4.02 (1 H, m, H5), 4.094.11 (2 H, m, H6a + H6b), 5.00 (1 H, app t, J = 10.0 Hz, H4), 5.17 (1 H, d, J = 10.0 Hz, H2), 5.49 (1 H, app t, J = 10.0 Hz, H3), 6.42 (1 H, br s, NH). 13C NMR (100 MHz, acetone-d6): d = 20.2, 23.3, 26.5, 26.6, 26.7, 27.5, 27.0, 27.6, 29.5, 29.3, 42.4, 62.7, 68.6, 70.1, 71.2, 104.1, 169.2, 172.0, 176.8, 177.3, 177.3. ESI-HRMS: m/z calcd for C36H61NO12 [M + Na]+: 722.4086; found: 722.4109. Compound 21: 1H NMR (400 MHz, acetone-d6): d = 1.10 1.29 [36 H, m, 4 11COC(CH3)3], 1.441.50 [2 H, m, CH2CH2CO2C(CH3)3], 2.12 (3 H, s, NHCOCH3), 2.29 2.32 [2 H, m, CH2CH2CO2C(CH3)3], 3.22 (1 H, m, 1 11CH2NHCOCH3), 3.40 (1 H, m, 1 ))CH2NHCOCH3), 3.90 (1 H, m, H5), 4.12 (1 H, dd, J = 12.0, 4.5 Hz, H6a), 4.24 (1 H, d, J = 12.0, 2.0 Hz, H6b), 5.14 (1 H, dd, J = 10.0, 3.5 Hz, H3), 5.36 (1 H, d, J = 10.0 Hz, H2), 5.41 (1 H, dd, J = 3.5, 1.0 Hz, H4). 13C NMR (100 MHz, acetone-d6): d = 20.0, 26.4, 26.5, 26.6, 26.7, 27.0, 27.5, 27.6, 27.7, 38.3, 38.5, 39.0, 42.0, 42.3, 61.9, 65.6, 68.1, 72.4, 76.2, 100.0, 173.2, 176.9, 177.1, 179.8. ESI-HRMS: m/z calcd for C36H61NO12 [M + Na]+: 722.4086; found: 722.4087.
34. Compound 22: 1H NMR (400 MHz, acetone-d6): d = 1.06, 1.10, 1.16, 1.26 [36 H, 4 11s, 4 ssCOC(CH3)3], 1.97 (NHCOCH3), 3.53 (1 H, dd, J = 15.0, 5.0 Hz, 1 = CH2NHCOCH3), 3.74 (1 H, dd, J = 15.0, 8.0 Hz, 1 = CH2NHCOCH3), 4.09 (1 H, m, H5), 4.16 (1 H, dd, J = 12.0, 4.5 Hz, H6a), 4.32 (1 H, dd, J = 12.0, 2.0 Hz, H6b), 4.67 (1 H, d, J = 12.0 Hz, 1 ==CH2Ph), 4.90 (1 H, d, J = 12.0 Hz, 1 11CH2Ph), 5.37 (1 H, app t, J = 2.0 Hz, H2), 5.445.46 (2 H, m, H3 + H4), 6.16 (1 H, app t, J = 6.0 Hz, NH), 7.35 (1 H, m, ArCH), 7.407.48 (4 H, m, ArCH). 13C NMR (100 MHz, CDCl3): d = 20.3, 26.5, 26.5, 26.6, 26.8, 37.7, 38.3, 38.5, 38.6, 38.7, 59.7, 61.6, 62.7, 65.0, 68.1, 70.1, 101.4, 127.7, 127.8, 128.7, 138.0, 170.0, 176.3, 176.6, 177.1, 177.3. ESI-HRMS: m/z calcd for C36H55NO11 [M + Na]+: 700.3667; found: 700.3679 Compound 23: 1H NMR (400 MHz, CDCl3): d = 1.12, 1.14, 1.25, 1.30 [36 H, 4 11s, 4 ssCOC(CH3)3], 3.26 (1 H, d, J = 13.5 Hz, 1 ==CH2N3), 3.70 (1 H, d, J = 13.5 Hz, 1 = CH2N3), 3.92 (1 H, app dq, J = 10.0, 2.0 Hz, H5), 4.12 (1 H, app d, J = 3.5 Hz, H6a), 4.14 (1 H, app d, J = 3.5 Hz, H6b), 4.62 (2 H, ABq, J = 12.0 Hz, CH2Ph), 5.415.52 (2 H, m, H3 + H4), 5.58 (1 H, d, J = 3.0 Hz, H2), 7.357.45 (5 H, m, ArCH). 13C NMR (100 MHz, CDCl3): d = 27.0, 27.1, 38.3, 38.8, 49.5, 61.8, 63.3, 64.7, 68.4, 70.1, 70.6, 100.8, 127.2, 128.7, 131.5, 136.4, 176.7, 177.1, 178.0. ESI-HRMS: m/z calcd for C34H51N3O11 [M + Na]+: 684.3467; found: 684.3478.