Synlett 2019; 30(16): 1895-1898
DOI: 10.1055/s-0037-1611757
letter
© Georg Thieme Verlag Stuttgart · New York

Selective Protection of Secondary Alcohols by Using Formic Acid as a Mild and Efficient Deprotection Reagent for Primary tert-Butyldimethylsilyl Ethers

Krishna Sapkota
,
Faqing Huang*
Department of Chemistry and Biochemistry, University of Southern Mississippi, 118 College drive, Hattiesburg, MS, 39406, USA   Email: Faqing.huang@usm.edu
› Author Affiliations
This work was supported by development fund from the University of Southern Mississippi, Hattiesburg, MS, USA.
Further Information

Publication History

Received: 16 January 2019

Accepted after revision: 27 February 2019

Publication Date:
19 March 2019 (online)


Abstract

A mild, efficient, and environmentally friendly method for the selective protection of secondary hydroxyl groups is described. The method involves the protection of both primary and secondary hydroxyl groups as tert-butyldimethylsilyl (TBDMS) ethers and selective deprotection of the primary TBDMS group with formic acid in acetonitrile/water. The rates of desilylation of primary and secondary TBDMS ethers by different concentrations of formic acid are determined. Formic acid of 5–20% concentration is found to selectively deprotect primary TBDMS ethers while keeping more than 95% of their secondary counterparts intact.

Supporting Information

 
  • References and Notes

  • 1 Corey E, Venkateswarlu A. J. Am. Chem. Soc. 1972; 94: 6190
    • 2a Pilcher AS, DeShong P. J. Org. Chem. 1993; 58: 5130
    • 2b Nicolaou K, Rutjes F, Theodorakis E, Tiebes J, Sato M, Untersteller E. J. Am. Chem. Soc. 1995; 117: 1173
    • 2c Berks AH. Tetrahedron 1996; 52: 331
    • 2d Chandrasekhar S, Mohanty PK, Takhi M. J. Org. Chem. 1997; 62: 2628
    • 2e Kadota I, Takamura H, Sato K, Ohno A, Matsuda K, Yamamoto Y. J. Am. Chem. Soc. 2003; 125: 46
    • 2f Marshall JA, Ellis KC. Org. Lett. 2003; 5: 1729
    • 2g Ghosh AK, Li J. Org. Lett. 2009; 11: 4164
  • 3 Wipf P, Lim S. J. Am. Chem. Soc. 1995; 117: 558
  • 4 Kadota I, Takamura H, Sato K, Ohno A, Matsuda K, Satake M, Yamamoto Y. J. Am. Chem. Soc. 2003; 125: 11893
  • 5 Smith AB, Xian M, Liu F. Org. Lett. 2005; 7: 4613
  • 6 Reiff EA, Nair SK, Henri JT, Greiner JF, Reddy BS, Chakrasali R, David SA, Chiu T.-L, Amin EA, Himes RH. J. Org. Chem. 2009; 75: 86
  • 7 Battistini L, Curti C, Zanardi F, Rassu G, Auzzas L, Casiraghi G. J. Org. Chem. 2004; 69: 2611
  • 8 Sekine M, Aoyagi M, Ushioda M, Ohkubo A, Seio K. J. Org. Chem. 2005; 70: 8400
  • 9 Lee J, Panek JS. Org. Lett. 2009; 11: 4390
    • 10a Reddy CR, Dharmapuri G, Rao NN. Org. Lett. 2009; 11: 5730
    • 10b Ramachandran PV, Srivastava A, Hazra D. Org. Lett. 2007; 9: 157
  • 11 Gu W, Silverman RB. J. Org. Chem. 2011; 76: 8287
  • 12 Yokokawa F, Inaizumi A, Shioiri T. Tetrahedron 2005; 61: 1459
  • 13 Crouch RD. Tetrahedron 2013; 69: 2383
  • 14 Ogilvie KK, Schifman AL, Penney CL. Can. J. Chem. 1979; 57: 2230
    • 15a Zhu X.-F, Williams HJ, Scott AI. J. Chem. Soc., Perkin Trans. 1 2000; 2305
    • 15b Nelson TD, Crouch RD. Synthesis 1996; 1031
  • 16 Feixas J, Capdevila A, Camps F, Guerrero A. J. Chem. Soc., Chem. Commun. 1992; 1451
  • 17 Zhengh X.-A, Kong R, Huang H.-S, Wei J.-Y, Chen J.-Z, Gong S.-S, Sun Q. Synthesis 2019; 51: 944
  • 18 Kawahara S.-i, Wada T, Sekine M. J. Am. Chem. Soc. 1996; 118: 9461
  • 19 Kende AS, Liu K, Kaldor I, Dorey G, Koch K. J. Am. Chem. Soc. 1995; 117: 8258
  • 20 HPLC conditions: Gemini C18 4.6 × 50 mm column, flow-rate 1 mL/min. The column was run in isocratic mode at 40% MeCN and 10% 40 mM KH2PO4 for 1 h. Under these conditions, the retention time for TBDMS-glycolate and TBDMS-lactate were 3.2 min and 3.5 min, respectively. The same amount of each of the reactions at time 0 were injected and used as a control. The area of peaks of 1 and 3 at different time points of reaction were quantified using EZChrom Elite software.
  • 21 Sapkota K, Huang F. Bioorg. Chem. 2018; 76: 23
  • 22 Di-TBDMS-pantethine: 1H NMR (400 MHz, CDCl3): δ = 7.07 (t, J = 6.2 Hz, 4 H), 6.87 (t, J = 5.9 Hz, 4 H), 3.98 (s, 2 H), 3.57 (s, 4 H), 3.44–3.35 (m, 4 H), 2.80 (t, J = 6.5 Hz, 4 H), 1.00 (s, 6 H), 0.95 (s, 18 H), 0.91 (s, 12 H), 0.80 (s, 6 H)