Cerium(IV) Ammonium Nitrate Catalysed Highly Chemoselective ­Deprotection of Ketals and THP Ethers in the Presence of Enol Triflates

Abstract

The chemoselective, catalytic deprotection of a variety of ketals, THP, and selected silyl ethers can be efficiently performed, in the presence of enol triflates, by the action of cerium(IV) ammonium nitrate (CAN).

Key words

cerium(IV) ammonium nitrate - catalysis - deprotection - ketals - enol triflates

References

• For beautiful illustrations of the skilful use of protecting groups in synthesis, see:
• 1a Nicolaou KC. Sorensen EJ. Classics in Total Synthesis   VCH; Weinheim: 1996. 
• 1b Nicolaou KC. Snyder SA. Classics in Total Synthesis II   VCH; Weinheim: 2003. 
• 2a Kocienski PJ. Protecting Groups   Georg Thieme; New York: 1994. 
• 2b Greene TW. Wuts PGM. Protecting Groups in Organic Chemistry   Wiley; New York: 1991. 
• 3 Maulide N. Vanherck J.-C. Markó IE. Eur. J. Org. Chem.  2004,  3962 ; and references cited therein
• 5a Markó IE. Ates A. Gautier A. Leroy B. Plancher J.-M. Quesnel Y. Vanherck J.-C. Angew. Chem. Int. Ed.  1999,  38:  3207 
• 5b Ates A. Gautier A. Leroy B. Plancher J.-M. Quesnel Y. Vanherck J.-C. Markó IE. Tetrahedron  2003,  59:  8989 
• For similar uses of CAN, see:
• 5c Barone G. Bedini E. Iadonisi A. Manzo E. Parrilli M. Synlett  2002,  1645 
• 5d Manzo E. Barone G. Bedini E. Iadonisi A. Mangoni L. Parrilli M. Tetrahedron  2002,  58:  129 
• For deprotection of other functions using CAN, see:
• 6a DattaGupta A. Singh R. Singh VK. Synlett  1996,  69 
• 6b Schreiber SL. Kiesling LL. Tetrahedron Lett.  1989,  30:  433 
• 6c Matsumoto T. Katsuki M. Jona H. Suzuki K. J. Am. Chem. Soc.  1991,  113:  6982 
• 6d Cotelle P. Catteau J.-P. Tetrahedron Lett.  1992,  33:  3855 
• 6e Nair V. Nair LG. Balagopal L. Rajan R. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1999,  38:  1234 
• 6f Hwu JR. Jain ML. Tsai F.-Y. Tsay S.-C. Balakumar A. Hakimelahi GH. J. Org. Chem.  2000,  65:  5077 
• 6g Roy SC. Banerjee B. Synlett  2002,  1677 
• 6h Hwu JR. Jain ML. Tsai F.-Y. Balakumar A. Hakimelahi GH. Tsay S.-C. ARKIVOC  2002,  (ix):  29 
• 6i For the removal of ketals using CeCl₃, see: Marcantoni E. Nobili F. Bartoli G. Bosco M. Sambri L. J. Org. Chem.  1992,  62:  4183 
• For a general review on enol triflates, see:
• 7a Ritter K. Synlett  1993,  735 
• For reviews highlighting the uses of vinyl triflates in metal-mediated coupling reactions see, e.g.:
• 7b Dounay AB. Overman LE. Chem. Rev.  2003,  103:  2945 
• 7c Bolm C. Legros J. Le Paih J. Zani L. Chem. Rev.  2004,  104:  6217 
• 9 For the deprotection of THF and THP ethers by CAN, see: Markó IE. Ates A. Augustyns B. Gautier A. Quesnel Y. Turet L. Wiaux M. Tetrahedron Lett.  1999,  40:  5613 
• 10 This type of behaviour has been recently reported: Tanino K. Aoyagi K. Kirihara Y. Ito Y. Miyashita M. Tetrahedron Lett.  2005,  46:  1168 

4

The successful Fe(III)-catalysed coupling of 2 with MeMgI was initially observed when an impure sample of 1, containing some ketone 2, was found to afford 3 and recovered substrate 1.

8

Readily prepared by deprotonation of the corresponding ketones with NaHMDS in THF, followed by capture with PhNTf₂.

11

Typical Experimental Procedure - Deprotection of 12.
To a one-necked round-bottomed flask fitted with a reflux condenser and containing 100 mg (0.29 mmol, 1 equiv) of protected enol triflate 12 dissolved in 3 mL of MeCN and 3 mL of borate buffer (pH = 8.00), were added with stirring 5 mg (8.8 µmol, 0.03 equiv) of CAN. The resulting yellowish solution was then heated to 60 °C for 2 h, after which the mixture was diluted with H₂O and repeatedly extracted with CH₂Cl₂. The combined organic layers were washed with brine, dried over MgSO₄ and concentrated under reduced pressure. The crude ketone 12a was further purified by column chromatography (silica, PE-EtOAc 2:1) to afford 80 mg (94%) of a colourless oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.50-1.60 (m, 2 H), 1.60-2.14 (m, 6 H), 2.20-2.50 (m, 4 H), 6.00 (t, J = 4.8 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 17.81, 18.90, 24.15, 32.06, 33.38, 37.78, 53.22, 106.37, 120.79, 148.15, 216.74. MS (APCI+, eV): m/z (%) = 299 (10) [M + H] ⁺ , 282 (30), 181 (40), 149 (100). IR (film): 3054, 2987, 2306, 1742, 1420 cm^-1. HRMS (CI+, eV): m/z calcd for C₁₁H₁₄O₄F₃S [M + H]⁺: 299.0558; found: 299.0565.