Synthesis of All Carbon Linked Glycoside Clusters Round Benzene Scaffold via Sonogashira-Heck-Cassar Cross-Coupling of Iodobenzenes with Ethynyl C-Glycosides

Alessandro  Dondoni; Alberto  Marra; Maria Grazia  Zampolli

doi:10.1055/s-2002-34885

LETTER

Synthesis of All Carbon Linked Glycoside Clusters Round Benzene Scaffold via Sonogashira-Heck-Cassar Cross-Coupling of Iodobenzenes with Ethynyl C-Glycosides

Alessandro Dondoni*, Alberto Marra, Maria Grazia Zampolli
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy
Fax: +39(0532)291167; e-Mail: adn@dns.unife.it;

Abstract

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Abstract

The Pd-catalyzed carbon-carbon bond forming reaction between ethynyl C-glycosides and polyiodinated benzenes (Sonogashira-Heck-Cassar coupling) allows the introduction of various ethynylene glycoside chains on the phenyl ring thus creating glycoside clusters wherein the sugar moieties are linked to the benzene ring by an all carbon tether.

Key words

alkynes - clusters - cross-coupling - Sonogashira reaction - sugar acetylenes

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Referenzen

References

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Mp 66-67 °C(pentane), [α] _D²0 = +17.3 (c 2.0, CHCl₃); lit. [9] mp 58 °C, [α]_D ²⁰ = +17.4 (c 1.6, CHCl₃)

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Compound 3: mp 178-180 °C (AcOEt-cyclohexane); [α]_D ²⁰ = +7.4 (c 1.0, CHCl₃); ¹H NMR selected data (C₆D₆): δ = 3.96 (dd, 1 H, J _1,3 = 2.2 Hz, J _3,4 = 9.7 Hz, H-3), 3.76 (dd, 1 H, J _4,5 = 8.8 Hz, J _5,6 = 9.7 Hz, H-5), 1.99 (d, 1 H, H-1).

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Compound 5: mp 150-151 °C(cyclohexane); [α]_D ²⁰ =-54.6 (c 1.0, CHCl₃); ¹H NMR (CDCl₃): δ 7.40-7.25 and 7.17-7.12 (2 m, 44 H, Ar), 5.05 and 4.87 (2 d, 4 H, J = 10.7 Hz, PhCH ₂), 4.96 and 4.87 (2 d, 4 H, J = 11.1 Hz, PhCH ₂), 4.85 and 4.55 (2 d, 4 H, J = 11.0 Hz, PhCH ₂), 4.66 and 4.57 (2 d, 4 H, J = 12.4 Hz, PhCH ₂), 4.33-4.27 (m, 2 H, 2 H-3), 3.81-3.66 (m, 10 H), 3.55-3.49 (m, 2 H); MALDI-TOF MS: 1196.1 (M + Na + 2 H), 1212.4 (M + K + 2 H). Compound 6: mp 180-181 °C (AcOEt-MeOH); [α]²⁰ _D = -33.1 (c 0.8, CH₃OH); ¹H NMR (D₂O): δ 7.12 (s, 4 H, Ar), 3.77 (dd, 2 H, J _7,8a = 0.8 Hz, J _8a,8b = 12.2 Hz, 2 H-8a), 3.58-3.51 (m, 2 H, 2 H-8b), 3.28-3.16 (m, 6 H), 3.11-3.02 (m, 4 H), 2.77-2.52, 2.03-1.90, and 1.65-1.52 (3 m, 8 H, 4 H-1, 4 H-2). Compound 7: mp 279-280 °C (CHCl₃-Et₂O); [α]_D ²⁰ =-58.5 (c 1.1, CHCl₃); ¹H NMR (C₆D₆): δ 7.12 (s, 4 H, Ar), 5.50 (dd, 2 H, J _3,4 = 9.9 Hz, J _4,5 = 9.1 Hz, 2 H-4), 5.32 (dd, 2 H, J _5,6 = 9.3 Hz, 2 H-5), 5.24 (dd, 2 H, J _6,7 = 9.6 Hz, 2 H-6), 4.22 (dd, 1 H, J _7,8a = 4.6 Hz, J _8a,8b = 12.6 Hz, 2 H-8a), 4.07 (d, 2 H, 2 H-3), 4.02 (dd, 2 H, J _7,8b = 2.0 Hz, 2 H-8b), 3.13 (ddd, 2 H, 2 H-7), 1.69, 1.68, 1.66, and 1.64 (4 s, 24 H, 8 Ac); MALDI-TOF MS: 810.2 (M + Na), 826.8 (M + K). Compound 8: mp 254-255 °C (MeOH-AcOEt); [α]_D ²⁰ = 0 (c 0.3, CH₃OH); [α]436²⁰ = -9.0 (c 0.3, CH₃OH); ¹H NMR (CD₃OD): δ 7.45 (s, 4 H, Ar), 4.21-4.15 (m, 2 H, 2 H-3), 3.90 (dd, 2 H, J _7,8a = 0.8 Hz, J _8a,8b = 12.0 Hz, 2 H-8a), 3.72-3.64 (m, 2 H, 2 H-8b), 3.43-3.27 (m, 8 H).

<A NAME="RD14102ST-14">14</A> Godt A. Franzen C. Veit S. Enkelmann V. Pannier M. Jeschke G. J. Org. Chem. 2000, 65: 7575

Compound 10: mp 133-134 °C (AcOEt-MeOH); [α]_D ²⁰ =
-48.5 (c 1.2, CHCl₃); ¹H NMR (CDCl₃): δ 7.43 (s, 3 H, Ar), 7.39-7.22 and 7.18-7.13 (2 m, 60 H, 12 Ph), 4.96 and 4.82 (2 d, 6 H, J = 10.7 Hz, PhCH ₂), 4.95 and 4.86 (2 d, 6 H, J = 11.0 Hz, PhCH ₂), 4.85 and 4.56 (2 d, 6 H, J = 11.0 Hz, PhCH ₂), 4.65 and 4.56 (2 d, 6 H, J = 12.3 Hz, PhCH ₂), 4.30-4.24 (m, 3 H, 3 H-3), 3.81-3.66 (m, 15 H), 3.54-3.48 (m, 3 H); MALDI-TOF MS: 1742.0 (M + Na), 1758.4 (M + K). Compound 11: mp 234-236 °C (AcOEt); [α]_D ²⁰ = -58.4 (c 0.9, CHCl₃); ¹H NMR (C₆D₆): δ 7.33 (s, 3 H, Ar), 5.46 (dd, 3 H, J _3,4 = 9.8 Hz, J _4,5 = 9.2 Hz, 3 H-4), 5.32 (dd, 3 H, J _5,6 = 9.1 Hz, 3 H-5), 5.24 (dd, 3 H, J _6,7 = 9.6 Hz, 3 H-6), 4.23 (dd, 3 H, J _7,8a = 4.5 Hz, J _8a,8b = 12.5 Hz, 3 H-8a), 4.03 (dd, 3 H, J _7,8b = 2.0 Hz, 3 H-8b), 4.00 (d, 3 H, 3 H-3), 3.14 (ddd, 3 H, 3 H-7), 1.79, 1.68, 1.66, and 1.65 (4 s, 36 H, 12 Ac); MALDI-TOF MS: 1164.3 (M + Na), 1180.7 (M + K). Compound 12: mp 178-180 °C, dec. (MeOH); [α]_D ²⁰ = +5.5 (c 0.2, CH₃OH); ¹H NMR (D₂O): δ 7.55 (s, 3 H, Ar), 4.24-4.17 (m, 3 H, 3 H-3), 3.80 (dd, 3 H, J _7,8a = 0.9 Hz, J _8a,8b = 12.5 Hz, 3 H-8a), 3.60 (dd, 3 H, J _7,8b = 5.0 Hz, 3 H-8b), 3.45-3.28 (m, 12 H). Compound 13: [α]_D ²⁰ = -39.6 (c 0.8, CH₃OH); ¹H NMR (D₂O): δ 6.93 (s, 3 H, Ar), 3.80 (dd, 3 H, J _7,8a = 0.9 Hz, J _8a,8b = 12.2 Hz, 3 H-8a), 3.58 (dd, 3 H, J _7,8b = 5.0 Hz, 3 H-8b), 3.28-3.16 (m, 9 H), 3.13-2.98 (m, 6 H), 2.77-2.54, 2.05-1.91, and 1.69-1.55 (3 m, 12 H, 6 H-1, 6 H-2). Compound 14: mp 116 °C, softening 86 °C(cyclohexane); [α]_D ²⁰ = -10.8 (c 0.5, CHCl₃); ¹H NMR (CDCl₃) selected data: δ 7.41 (s, 3 H, Ar), 7.35-7.15 (m, 105 H, 21 Ph), 4.23-4.18 (m, 3 H, 3 H-3), 3.71-3.59 (m, 18 H), 3.42-3.18 (m, 15 H), 2.22-2.15 and 1.55-1.46 (2 m, 12 H, 6 H-8, 6 H-9); MALDI-TOF MS: 3035.7 (M + Na + 3 H), 3051.7 (M + K + 3 H). Compound 15Ac: mp 245-246 °C (EtOAc); [α]_D ²⁰ =-13.0 (c 0.4, CHCl₃); ¹H NMR (CDCl₃): δ 6.79 (s, 3 H, Ar), 5.20 (dd, 3 H, J _11,12 = J _12,13 = 9.4 Hz, 3 H-12), 5.14 (dd, 3 H, J _4,5 = J _5,6 = 9.3 Hz, 3 H-5), 5.06 (dd, 3 H, J _13,14 = 10.0 Hz, 3 H-13), 4.91 (dd, 3 H, J _10,11 = 9.9 Hz, 3 H-11), 4.86 (dd, 3 H, J _3,4 = 9.9 Hz, 3 H-4), 4.86 (dd, 3 H, J _6,7 = 9.9 Hz, 3 H-6), 4.29 (dd, 3 H, J _14,15a = 5.0, J _15a,15b = 12.2 Hz, 3 H-15a), 4.11 (dd, 3 H, J _14,15b = 2.2 Hz, 3 H-15b), 3.67 (ddd, 3 H, 3 H-14), 3.46-3.33 (m, 9 H, 3 H-3, 3 H-7, 3 H-10), 2.87-2.76, 2.51-2.40, 1.94-1.85, 1.77-1.68, and 1.52-1.39 (5 m, 24 H), 2.12, 2.08, 2.06, 2.02, 2.01, and 1.98 (6 s, 63 H, 21 Ac).

<A NAME="RD14102ST-16">16</A> Dondoni A. Giovannini PP. Marra A. J. Chem. Soc., Perkin Trans. 1 2001, 2380

<A NAME="RD14102ST-17">17</A> Mattern DL. J. Org. Chem. 1984, 49: 3051

A solution of 2 (157 mg, 0.44 mmol) and 16 (58 mg, 0.10 mmol) in anhydrous DMF (1.6 mL) and Et₃N (1.6 mL) was degassed by bubbling argon at r.t. for 20 min. To the solution was added commercially available Pd(PPh₃)₄ (23 mg, 0.02 mmol) and the suspension was stirred at 60 °C in an argon atmosphere. After an additional 24 h at 60 °C the red-brown solution was concentrated, then diluted with CH₂Cl₂ (50 mL), washed with 1 M phosphate buffer at pH = 7 (20 mL), dried (Na₂SO₄), and concentrated. The residue was eluted from a column of silica gel with EtOAc-cyclohexane (from 2:1 to 3:1) to give 17 (94 mg) slightly contaminated by uncharacterized byproducts. Trituration of this material with Et₂O (ca. 2 mL) afforded pure 17 (74 mg, 49%) as a white solid; mp 119-120 °C (MeOH); [α]_D ²⁰ = -70.0 (c 1.0, CHCl₃); ¹H NMR (C₆D₆): δ 7.30 (s, 2 H, Ar), 5.58-5.51 (m, 4 H, 4 H-4), 5.42-5.31 (m, 8 H, 4 H-5, 4 H-6), 4.31 (d, 4 H, J _3,4 = 9.8 Hz, 4 H-3), 4.30 (dd, 4 H, J _7,8a = 4.5 Hz, J _8a,8b = 12.3 Hz, 4 H-8a), 4.14 (dd, 4 H, J _7,8b = 1.8 Hz, 4 H-8b), 3.35-3.29 (m, 4 H, 4 H-7), 1.84, 1.74, 1.72, and 1.64 (4 s, 48 H, 16 Ac); MALDI-TOF MS: 1519.3 (M + Na), 1535.8 (M + K).

Compound 18: mp 292-294 °C, dec. (MeOH); [α]_D ²⁰ = -4.1 (c 0.3, H₂O); ¹H NMR (D₂O): δ 7.65 (s, 2 H, Ar), 4.29-4.24 (m, 4 H, 4 H-3), 3.81 (dd, 4 H, J _7,8a = 1.1 Hz, J _8a,8b = 12.5 Hz, 4 H-8a), 3.63 (dd, 4 H, J _7,8b = 5.1 Hz, 4 H-8b), 3.48-3.30 (m, 16 H). Compound 19: [α]_D ²⁰ = -39.6 (c 0.6, H₂O); ¹H NMR (D₂O): δ 6.98 (s, 2 H, Ar), 3.75 (dd, 4 H, J _7,8a = 0.8 Hz,
J _8a,8b = 12.5 Hz, 4 H-8a), 3.54 (dd, 4 H, J _7,8b = 3.8 Hz,
4 H-8b), 3.23-3.12 (m, 12 H), 3.03-2.98 (m, 8 H), 2.71-2.56 (m, 8 H), 1.95-1.83 (m, 4 H), 1.60-1.46 (m, 4 H).