1,6‐C‐H and 1,5‐O‐Si Insertion Reactions of Alkylidenecarbene Derivatives of Monosaccharides*

* This work is dedicated to the memory of Professor Jacques H. van Boom.

Abstract

A new protocol has been developed for the generation of alkylidenecarbene derivatives of monosaccharides based on the reaction of trimethylsilylazide and Bu₂SnO with α‐cyanomesylates derived from uloses. When this method is applied to conveniently functionalized carbohydrate derivatives it provides novel heterocyclic ring systems by the rare 1,6‐C‐H or 1,5‐O‐Si insertion reactions.

* This work is dedicated to the memory of Professor Jacques H. van Boom.

Keywords:

• Alkylidenecarbenes
• α‐Cyanomesylates
• Trimethylsilylazide
• Dibutyltin oxide
• Sugar templates
• 1,6‐C‐H Insertion
• 1,5‐O‐Si Insertion

Acknowledgments

RL thanks the MECD (Spain) for a short‐term grant to visit Laboratoire des Glucides, Université de Picardie‐Jules Verne; Faculté des Sciences, Amiens (France), and for a predoctoral fellowship. DP thanks the Conseil Régional de Picardie (France) and the Ministère Français de la Recherche for financial support. MCC thanks the Portuguese FCT for a short‐term sabbatical grant to visit the Radical Chemistry Laboratory in the Instituto de Química Orgánica General (CSIC), Madrid.

Notes

* This work is dedicated to the memory of Professor Jacques H. van Boom.

^aIn a typical experiment, to a solution of compound 1b (400 mg, 1.04 mmol) in dry toluene (16 mL) under argon, dibutyltin oxide (260 mg, 1.04 mmol) and TMSN₃ (0.21 mL, 1.56 mmol) were added. The reaction was heated to 98°C and stirred for 16 hr and then the solvent was removed under vacuo. The crude product was submitted to flash chromatography (EtOAc: petroleum ether, 18∶82) to give successively compound 3β (26 mg) and 3α (105 mg). Total 3β+3α (131 mg, 45%, 1∶4 ratio).

^bAll new compounds showed excellent analytical data. Selected spectroscopic data. 3β: pale yellow solid: mp 100–102°C; [α]_D ²⁰ +29 (c 0.18, CHCl₃); IR (ATR) ? 2921, 2351, 2110, 1452, 1370, 1244, 1162, 1040, 1011 cm⁻¹; ¹H NMR (CDCl₃, 300 MHz) δ 7.37 (m, 5 H, C₆H₅), 6.20 (t, J _6,4=2.0 Hz, J _6,7=2.0 Hz, 1 H, H‐6), 5.90 (d, J _1,2=3.7 Hz, 1 H, H‐1), 5.30 (t, J _7,4=2.0 Hz, 1 H, H‐7), 5.03 (d, 1 H, H‐2), 4.73 (m, 1 H, H‐4), 4.08 (dd, J _4,5a=6.0 Hz J _5a,5b=10.4 Hz, 1 H, H‐5a), 3.29 (dd, J _4,5b=8.6 Hz, 1 H, H‐5b), 1.61 (s, 3 H, CH₃), 1.41 (s, 3 H, CH₃); ¹³C NMR (CDCl₃, 75 MHz) δ 139.5–127.8 (C‐3, C₆H₅), 125.3 (C‐6), 113.4 [OC(CH₃)₂], 105.8 (C‐1), 80.0 (C‐2), 73.9 (C‐7), 70.2 (C‐4), 62.5 (C‐5), 27.4 (CH₃), 27.0 (CH₃); MS (ES): 297.1 [M+Na]⁺. 3α: pale yellow solid: mp 93–94°C; [α]D²⁰+176 (c 0.16, CHCl₃); IR (ATR) ? 2981, 2932, 2104, 1441, 1370, 1216, 1161, 1047, 1017 cm⁻¹; ¹H NMR (CDCl₃, 300 MHz) δ 7.34 (m, 5 H, C₆ H ₅), 5.99 (t, J _6,4=J _6,7=2.0 Hz, 1 H, H‐6), 5.87 (d, J _1,2=3.7 Hz, 1 H, H‐1), 5.08 (t, J _7,4=2.0 Hz, 1 H, H‐7), 4.97 (d, 1 H, H‐2), 4.81 (m, 1 H, H‐4), 4.45 (dd, J _4,5a=5.9 Hz, J _5a,5b=10.0 Hz, 1 H, H‐5a), 3.35 (dd, J _4,5b=9.1 Hz, 1 H, H‐5b), 1.61 (s, 3 H, CH₃), 1.40 (s, 3 H, CH₃); ¹³C NMR (CDCl₃, 75 MHz) δ 139.6–127.8 (C‐3, C₆H₅), 126.2 (C‐6), 113.4 [OC(CH₃)₂], 105.3 (C‐1), 80.3 (C‐2), 77.4 (C‐7), 70.3 (C‐4), 69.0 (C‐5), 27.5 (CH₃), 27.0 (CH₃); MS (ES): 297.1 [M+Na]⁺. 16: ¹H NMR (CDCl₃, 300 MHz) δ 7.68 (d, J _4,5=1.8 Hz, 1 H, H‐4), 6.63 (d, 1 H, H‐5), 4.64 (dd, J _1a,OH=4.6 Hz, J _1a,1b=19.8 Hz, 1 H, H‐1a), 4.57 (dd, J _1b,OH=4.6 Hz, 1 H, H‐1b), 3.45 (t, 1 H, OH), 0.97 [s, 9 H, SiC(CH₃)₃], 0.36 (s, 6 H, 2×SiCH₃); ¹³C NMR (CDCl₃, 75 MHz) δ 194.6 (C=O), 167.3 (C‐6), 147.4 (C‐5), 132.3 (C‐3), 108.6 (C‐4), 67.0 (C‐1), 27.0 [Si(CH₃)₂C(CH₃)₃], 18.4 [Si(CH₃)₂ C(CH₃)₃], –5.8 [Si(CH₃)₂C(CH₃)₃].