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DOI: 10.1055/s-0029-1219560
exo-Glycals: Intermediates in the Synthesis of 1,1-Disubstituted C-Glycosides
Publikationsverlauf
Publikationsdatum:
02. März 2010 (online)
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Abstract
The synthesis of 1,1-disubstituted C-glycosides containing amino and ester containing moieties at what is formally the anomeric site is described. Petasis olefination of pyranosyl lactones provided exo-glycals which underwent regioselective azidoselenation and subsequent radical-mediated C-glycoside formation.
Key words
C-glycosides - azidoselenation - Petasis olefination
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1a
Bertozzi CR.Cook DR.Kobertz WR.Gonzalez-Scarano F.Bednarski MD. J. Am. Chem. Soc. 1992, 114: 10639 -
1b
Wei A.Boy KM.Kishi Y. J. Am. Chem. Soc. 1995, 117: 9432 -
1c
Sutherlin DP.Stark TM.Hughes R.Armstrong RW. J. Org. Chem. 1996, 61: 8350 -
2a
Postema MHD. Tetrahedron 1992, 48: 8545 -
2b
Levy D.Tang C. The Chemistry of C-Glycosides Pergamon; Oxford: 1995. -
2c
Nicotra F. Topics Curr. Chem. 1997, 187: 55 -
2d
Togo H.He W.Waki Y.Yokoyama M. Synlett 1998, 700 -
2e
Skrydstrup T.Vauzeilles B.Beau J.-M. In Carbohydrates in Chemistry and Biology. The Chemistry of Saccharides Vol. 1:Ernst B.Hart GW.Sinaÿ P. Wiley-VCH; New York: 2000. Chap. 20. p.495-530 -
3a
San Martin R.Tavassoli B.Walsh KE.Walter DS.Gallagher T. Org. Lett. 2000, 2: 4051 -
3b
Grant L.Liu Y.Walsh KE.Walter DS.Gallagher T. Org. Lett. 2002, 4: 4623 -
3c
Liu Y.Gallagher T. Org. Lett. 2004, 6: 2445 -
4a
Czernecki S.Randriamandimby D. Tetrahedron Lett. 1993, 34: 7915 -
4b
Czernecki S.Ayadi E.Randriamandimby D. J. Chem. Soc., Chem. Commun. 1994, 35 -
4c
Czernecki S.Ayadi E.Randriamandimby D. J. Org. Chem. 1994, 59: 8256 -
4d
Santoyo-Gonzalez F.Calvo-Flores FG.Garcia-Mendoza P.Hernandez-Mateo F.Isac-Garcia J.Robles-Diaz R. J. Org. Chem. 1993, 58: 6122 -
6a
Petasis NA.Bzowej EI. J. Am. Chem. Soc. 1990, 112: 6392 -
6b
Csuk R.Glanzer BI. Tetrahedron 1991, 47: 1655 - 7
Cook MJ.Fleming DW.Gallagher T. Tetrahedron Lett. 2005, 46: 297 -
10a
Trost BM.Van Vranken DL. Chem. Rev. 1996, 96: 395 -
10b
Trost BM.Keinan E. Tetrahedron Lett. 1980, 21: 2591 -
10c
Dunkerton LV.Euske JM.Serino AJ. Carbohydr. Res. 1987, 171: 89 -
10d
Shi G.Huang X.-H.Zhang F.-J. Tetrahedron Lett. 1995, 36: 6305 -
13a
An X-ray diffraction experiment on 16 was carried out at 100 K on a Bruker APEX II diffractometer using MoKα radiation (λ = 0.71073 Å). The data collection was performed using a CCD area detector from a single crystal mounted on a glass fibre. Intensities were integrated (Bruker-AXS SAINT V7.60A) from several series of exposures measuring 0.5˚ in ω or φ. Absorption corrections were based on equivalent reflections using SADABS (Sheldrick, G. M. SADABS V2008/1, University of Göttingen, Germany), and structures were refined against all Fo ² data with hydrogen atoms riding in calculated positions using SHELXL Bruker-AXS SAINT V7.60A.¹³b The Cambridge Crystallographic Data Centre deposition number for 16 is CCDC 763564.
-
13b
Sheldrick GM. Acta Crystallogr., Sect. A 2008, 64: 112 -
14a
Mehta S.Pinto BM. Tetrahedron Lett. 1991, 32: 4435 -
14b
Mehta S.Pinto BM. J. Org. Chem. 1993, 58: 3269 -
14c
Demchenko A. Synlett 2003, 1225 -
14d
France RR.Compton RG.Davis BG.Fairbanks AJ.Rees NV.Wadhawan JD. Org. Biomol. Chem. 2004, 2: 2195
References and Notes
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 decompo-sition) 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).
8
Data for
exo
-Glycals
Conventional
carbohydrate numbering (cf. sialic acids) is used.
Compound 8b: ¹H NMR (400 MHz,
CDCl3): δ = 1.13, 1.20, 1.23, 1.28 [36
H, 4 × s, 4 × COC(CH3)3],
3.99-4.10 (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): δ = 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): δ = 1.14-1.24 [36
H, m, 4 × COC(CH3)3],
3.77-3.78 (1 H, m, H6), 4.06-4.26 (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): δ = 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): δ = 1.13-1.25 [36
H, m, 4 × COC(CH3)3],
3.87 (1 H, m, H6), 4.23-4.25 (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): δ = 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.
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 sodio-diethyl 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.
11Extensive 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.
12Spectroscopic data are provided for
the galacto series shown in Scheme
[4]
.
Compound 13: ¹H NMR (400 MHz,
CDCl3): δ = 1.12-1.28 [36
H, m, 4 × COC(CH3)3],
3.12 (1 H, d, J = 13.5
Hz, 1 × CH2N3),
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), 7.35-7.44 (3 H, m, ArCH), 7.58-7.61 (2
H, m, ArCH). ¹³C NMR (100 MHz, CDCl3): δ = 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): δ = 1.11-1.27 [36
H, m, 4 × COC(CH3)3],
2.09 (3 H, s, NHCOCH
3), 3.36 (1
H, dd, J = 14.5,
3.5 Hz, 1 × CH
2NHCOCH3),
3.97 (1 H, m, H6a), 4.06-4.15 (2 H, m, H6b + 1 × CH
2NHCOCH3), 4.85
(1 H, m, H5), 5.50-5.53 (2 H, m, H2 + H4), 5.61
(1 H, m, H3), 6.03 (1 H, m, NH), 7.31-7.38 (3 H, m, ArCH),
7.59-7.64 (2 H, m, ArCH). ¹³C
NMR (100 MHz, CDCl3): δ = 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): δ = 1.11-
1.30 [36
H, m, 4 × COC(CH3)3],
1.40-1.55 [2 H, m, CH2CH
2CO2C(CH3)3],
2.06 (3 H, s, NHCOCH
3), 2.17-
2.32 [2
H, m, CH
2CH2CO2C(CH3)3],
3.38-3.44 (2 H, m, CH
2NHCOCH3),
3.62 (1 H, m, H5), 3.97-4.04 (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-d
6): δ = 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-d
6): δ = 1.09-1.22 [36
H, m, 4 × COC(CH3)3],
1.44-1.49 [2 H, m, CH2CH
2CO2C(CH3)3],
2.01 (3 H, s, NHCOCH
3), 2.40-2.42 (2
H, m, CH
2CH2CO2C(CH3)3),
3.26 (1 H, dd, J = 14.5,
4.5, 1 × CH
2NHCOCH3),
3.43 (1 H, dd, J = 14.5,
7.5, 1 × CH
2NHCOCH3),
4.02 (1 H, m, H5), 4.09-4.11 (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-d
6): δ = 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-d
6): δ = 1.10-1.29 [36
H, m, 4 × COC(CH3)3],
1.44-1.50 [2 H, m, CH2CH
2CO2C(CH3)3],
2.12 (3 H, s, NHCOCH
3), 2.29-
2.32 [2
H, m, CH
2CH2CO2C(CH3)3],
3.22 (1 H, m, 1 × CH
2NHCOCH3),
3.40 (1 H, m, 1 × CH
2NHCOCH3), 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-d
6): δ = 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.
Compound 22: ¹H
NMR (400 MHz, acetone-d
6): δ = 1.06, 1.10,
1.16, 1.26 [36 H, 4 × s, 4 × COC(CH3)3],
1.97 (NHCOCH
3), 3.53 (1 H,
dd, J = 15.0,
5.0 Hz, 1 × CH
2NHCOCH3),
3.74 (1 H, dd, J = 15.0,
8.0 Hz, 1 × CH
2NHCOCH3),
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 × CH2Ph), 5.37 (1 H,
app t, J = 2.0
Hz, H2), 5.44-5.46 (2 H, m, H3 + H4), 6.16 (1
H, app t, J = 6.0
Hz, NH), 7.35 (1 H, m, ArCH), 7.40-7.48 (4 H, m, ArCH). ¹³C
NMR (100 MHz, CDCl3): δ = 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): δ = 1.12, 1.14, 1.25,
1.30 [36 H, 4 × s, 4 × COC(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, CH
2Ph), 5.41-5.52
(2 H, m, H3 + H4), 5.58 (1 H, d, J = 3.0
Hz, H2), 7.35-7.45 (5 H, m, ArCH). ¹³C
NMR (100 MHz, CDCl3): δ = 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.