Novel Photolabile Protecting Group for Phosphate Compounds

Abstract

A novel photolabile protecting group, thiochromone S,S-dioxide, containing the diazomethyl group for protection of phosphate derivatives is described. Deprotection of the successfully protected phosphate derivatives proceeded smoothly under photoirradiation using an ultrahigh-pressure mercury lamp to recover the corresponding phosphates quantitatively, and the photoproduct derived from the thiochromone derivative showed high fluorescence intensity.

Key words

thiochromone - diazomethyl - photolabile protecting groups - phosphates - photochemistry

References and Notes

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• 3e Mayer G. Heckel A. Angew. Chem. Int. Ed.  2006,  45:  4900 
• 3f Wang PF. Hu HY. Wang Y. Org. Lett.  2007,  9:  1533 
• 4 Givens RS. Kueper LW. Chem. Rev.  1993,  93:  55 
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• 7 In this step, we observed an interesting side reaction and for details, see: Zhang Y. Tanimoto H. Nishiyama Y. Morimoto T. Kakiuchi K. Heterocycles  2011,  83:  2337 

8

Analytical and Spectral Data of 6 Yellow solid; mp 213.7-214.2 ˚C. IR (KBr): 1685, 1310 cm^-¹. ^¹H NMR (500 MHz, CDCl₃/TMS): δ = 9.54 (1 H, s), 8.24 (1 H, d, J = 6.7 Hz), 8.15 (1 H, d, J = 7.9 Hz), 7.97 (1 H, dd, J = 7.9, 7.9 Hz), 7.83 (1 H, dd, J = 6.7, 7.9 Hz), 7.63 (1 H, dd, J = 7.3, 7.9 Hz), 7.56 (2 H, dd, J = 7.9, 7.3 Hz), 7.37 (2 H, d, J = 6.7 Hz). ^¹³C NMR (125 MHz, CDCl₃/TMS): δ = 185.3, 179.5, 148.7, 141.8, 141.2, 135.7, 133.4, 131.5, 131.1, 129.0, 128.7, 128.5, 128.1, 123.4. HRMS (EI): m/z calcd for C₁₆H₁₀O₄S [M⁺]: 298.0300; found: 298.0298.

9

Analytical and Spectral Data of 7 Yellow solid; mp 165.5-167.8 ˚C. IR (KBr): 3420, 2359 cm^-¹. ^¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.20 (3 H, m), 7.92 (1 H, dd, J = 7.9 Hz), 7.81 (2 H, d, J = 8.5 Hz), 7.78 (1 H, dd, J = 7.9 Hz), 7.50 (3 H, m), 7.32 (2 H, d, J = 8.5 Hz), 7.19 (2 H, d, J = 7.0 Hz), 5.30 (1 H, s), 2.42 (3 H, s). ^¹³C NMR (125 MHz, CDCl₃/TMS): δ = 178.1, 145.0, 144.3, 143.4, 142.2, 142.1, 136.8, 135.0, 134.5, 133.0, 130.8, 129.9, 129.8, 128.6, 128.6, 128.3, 128.2, 123.4, 21.7. HRMS-FAB: m/z calcd for C₂₃H_{1 8}N₂O₅S₂ [M + H]⁺: 467.0735; found: 467.0742.

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Analytical and Spectral Data of 1b
Yellow solid; mp 122.3-123.5 ˚C. IR (KBr): 3433, 2359 cm^-¹. ^¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.26 (1 H, d, J = 7.9 Hz), 8.06 (1 H, d, J = 7.9 Hz), 7.85 (1 H, dd, J = 7.9 Hz), 7.79 (1 H, dd, J = 7.9 Hz), 7.48 (3 H, m), 7.27 (2 H, d, J = 7 Hz), 4.95 (1 H, s). ^¹³C NMR (125 MHz, CDCl₃/TMS): δ = 175.0, 139.6, 133.5, 133.5, 132.5, 129.8, 129.6, 129.1, 128.9, 128.8, 128.7, 127.4, 122.7, 47.5. HRMS-ESI: m/z calcd for C₃₂H₂₀O₆S₂Na [2 M - 2 N₂ + Na]⁺: 587.0599; found: 587.0600.

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Treatment of 8h with 2.5 equiv of 1b in the presence of a catalytic amount of 10% HCl aq in CHCl₃ at 60 ˚C afforded diprotection product in 81% yield. The complete experi-mental procedures and analytical data are shown in the Supporting Information.