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).

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

References

For beautiful illustrations of the skilful use of protecting groups in synthesis, see:

<A NAME="RD08605ST-1A">1a</A> Nicolaou KC. Sorensen EJ. Classics in Total Synthesis   VCH; Weinheim: 1996. 

<A NAME="RD08605ST-1B">1b</A> Nicolaou KC. Snyder SA. Classics in Total Synthesis II   VCH; Weinheim: 2003. 

<A NAME="RD08605ST-2A">2a</A> Kocienski PJ. Protecting Groups   Georg Thieme; New York: 1994. 

<A NAME="RD08605ST-2B">2b</A> Greene TW. Wuts PGM. Protecting Groups in Organic Chemistry   Wiley; New York: 1991. 

<A NAME="RD08605ST-3">3</A> Maulide N. Vanherck J.-C. Markó IE. Eur. J. Org. Chem.  2004,  3962 ; and references cited therein

<A NAME="RD08605ST-4">4</A>

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.

<A NAME="RD08605ST-5A">5a</A> Markó IE. Ates A. Gautier A. Leroy B. Plancher J.-M. Quesnel Y. Vanherck J.-C. Angew. Chem. Int. Ed.  1999,  38:  3207 

<A NAME="RD08605ST-5B">5b</A> 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:

<A NAME="RD08605ST-5C">5c</A> Barone G. Bedini E. Iadonisi A. Manzo E. Parrilli M. Synlett  2002,  1645 

<A NAME="RD08605ST-5D">5d</A> Manzo E. Barone G. Bedini E. Iadonisi A. Mangoni L. Parrilli M. Tetrahedron  2002,  58:  129 

For deprotection of other functions using CAN, see:

<A NAME="RD08605ST-6A">6a</A> DattaGupta A. Singh R. Singh VK. Synlett  1996,  69 

<A NAME="RD08605ST-6B">6b</A> Schreiber SL. Kiesling LL. Tetrahedron Lett.  1989,  30:  433 

<A NAME="RD08605ST-6C">6c</A> Matsumoto T. Katsuki M. Jona H. Suzuki K. J. Am. Chem. Soc.  1991,  113:  6982 

<A NAME="RD08605ST-6D">6d</A> Cotelle P. Catteau J.-P. Tetrahedron Lett.  1992,  33:  3855 

<A NAME="RD08605ST-6E">6e</A> Nair V. Nair LG. Balagopal L. Rajan R. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1999,  38:  1234 

<A NAME="RD08605ST-6F">6f</A> Hwu JR. Jain ML. Tsai F.-Y. Tsay S.-C. Balakumar A. Hakimelahi GH. J. Org. Chem.  2000,  65:  5077 

<A NAME="RD08605ST-6G">6g</A> Roy SC. Banerjee B. Synlett  2002,  1677 

<A NAME="RD08605ST-6H">6h</A> Hwu JR. Jain ML. Tsai F.-Y. Balakumar A. Hakimelahi GH. Tsay S.-C. ARKIVOC  2002,  (ix):  29 

<A NAME="RD08605ST-6I">6i</A> 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:

<A NAME="RD08605ST-7A">7a</A> Ritter K. Synlett  1993,  735 

For reviews highlighting the uses of vinyl triflates in metal-mediated coupling reactions see, e.g.:

<A NAME="RD08605ST-7B">7b</A> Dounay AB. Overman LE. Chem. Rev.  2003,  103:  2945 

<A NAME="RD08605ST-7C">7c</A> Bolm C. Legros J. Le Paih J. Zani L. Chem. Rev.  2004,  104:  6217 

<A NAME="RD08605ST-8">8</A>

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

<A NAME="RD08605ST-9">9</A> 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 

<A NAME="RD08605ST-10">10</A> This type of behaviour has been recently reported: Tanino K. Aoyagi K. Kirihara Y. Ito Y. Miyashita M. Tetrahedron Lett.  2005,  46:  1168 

<A NAME="RD08605ST-11">11</A>

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.