Notes and references
1 P. G. M. Wuts and T. W. Greene, Greene’s Protective Groups in Organic
Synthesis, 4th edn., John Wiley & Sons, Hoboken, NJ, 2007.
2 (a) K. K. Ogilvie, K. L. Sadana, E. A. Thompson, M. A. Quilliam and
J. B. Westmore, Tetrahedron Lett., 1974, 15, 2861; (b) K. K. Ogilvie,
E. A. Thompson, M. A. Quilliam and J. B. Westmore, Tetrahedron
Lett., 1974, 15, 2865.
3 For a comprehensive review of TIPS in organic synthesis, see C.
Ru¨cker, Chem. Rev., 1995, 95, 1009.
Scheme 1 Comparison of desilylation methods: recyclability of the
silicon byproducts.
4 J. J. Landi, Jr. and K. Ramig, Synth. Commun., 1991, 21, 167.
5 (a) J. C.-Y. Cheng, U. Hacksell and G. P. Daves, Jr., J. Org. Chem.,
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P. W. Glunz and S. J. Danishefsky, J. Am. Chem. Soc., 1999, 121,
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Islam and C. Gatz, Chem.–Eur. J., 2008, 14, 3670.
desilylations which yield TIPSF, a non-convertible waste. Hence
our protocol renders TIPS a recyclable silyl protective group for
solution-phase synthesis.
As alkali acetates exhibited different trends of activity in
the deprotection of aryl TBS12 and TIPS ethers, respectively,
we reasoned that for the latter, Lewis base-catalysis was the
predominant mechanism. The unique structural character of
TIPS contributed to its vulnerability◦toward Lewis bases. The
extraordinarily large cone angle (160 , typical 118–145◦)16 and
17
˚
˚
long Si–C bond (1.919 A, typical 1.870 A) of TIPS render
the silicon atom geometrically exposed to external nucleophiles.
Thus, a mechanism involving direct attack of the Si center by
acetoxy anion, possibly with the assistance of hydrogen bonding
between water and the outgoing aryloxy anion, is plausible
(Fig. 1).
6 (a) R. F. Cunico and L. Bedell, J. Org. Chem., 1980, 45, 4797; (b) P.
Magnus, M. Giles, R. Bonnert, G. Johnson, L. McQuire, M. Deluca,
A. Merritt, C. S. Kim and N. Vicker, J. Am. Chem. Soc., 1993, 115,
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J. Am. Chem. Soc., 1990, 112, 7659; (d) C. Eisenberg and P. Knochel,
J. Org. Chem., 1994, 59, 3760.
7 G. A. Olah and D. A. Klumpp, Synthesis, 1997, 744.
R
8 A rough search for aryl TIPS ethers by SciFinderꢀ in March 2009
returned 2683 hits, while aryl TBS ethers amounted to 14454 hits.
9 Conventional glassware was reportedly detrimental to HF-mediated
de-silylation, and teflon reaction vessel was required, see ref. 5e.
10 For excellent reviews, see: (a) T. D. Nelson and R. D. Crouch,
Synthesis, 1996, 1031; (b) R. D. Crouch, Tetrahedron, 2004, 60, 5833;
(c) For selected examples, see: S. R. Chemler and S. J. Danishefsky,
Org. Lett., 2000, 2, 2695; (d) I. Kadota and Y. Yamamoto, J. Org.
Chem., 1998, 63, 6597; (e) I. Kadota, J.-Y. Park, N. Koumura, G.
Pollaud, Y. Matsukawa and Y. Yamamoto, Tetrahedron Lett., 1995,
36, 5777.
Fig. 1 Plausible catalytic cycle and transition state.
In summary, we have developed a green deprotection protocol
for phenolic TIPS protection using catalytic amount of KOAc
under fluoride-free conditions.18 The solvent, catalyst, and
silanol byproduct can all be recycled, minimising waste pro-
duction. Other notable benefits include operational simplicity,
economy and environmental friendliness. Excellent functional
group compatibility and chemoselectivity have been achieved.
In particular, aryl TIPS ethers are orthogonally cleaved in the
presence of alkyl silyl ethers, acetates, carbamates and epoxides.
We believe that our protocol would significantly expand the
utility of TIPS in both academia and industry. More detailed
mechanistic study is in progress, and extension of Lewis base
catalysis to other aspects of silicon chemistry is currently being
pursued in this laboratory.
11 B. M. Trost, Science, 1991, 254, 1471.
12 B. Wang, H.-X. Sun and Z.-H. Sun, J. Org. Chem., 2009, 74, 1781.
13 The half-lives of p-MeC6H4OSiR3 in 5% NaOH–MeOH at 25 ◦C were
3.5, 6.5 and 188 min for SiR3 = TBS, TBDPS and TIPS, respectively,
see: J. S. Davies, C. L. Higginbotham, E. J. Tremeer, C. Brown and
R. C. Treadgold, J. Chem. Soc., Perkin Trans. 1, 1992, 3043.
14 NaHCO3/MeOH/RT/45 min removes phenolic Ac protections, see:
G. Bu¨chi and S. M. Weinreb, J. Am. Chem. Soc., 1971, 93, 746.
15 M. Shin, T. Banno and I. Mitsuo, J. Organomet. Chem., 2006, 691,
174.
16 J. S. Panek, A. Prock, K. Eriks and W. P. Giering, Organometallics,
1990, 9, 2175.
17 D. G. Anderson, D. W. H. Rankin, H. E. Robertson, C. M. F. Frazao
and H. Schmidbauer, Chem. Ber., 1989, 122, 2213.
18 General procedure: To a solution of aryl TIPS ether (1.0 mmol) in
DMF–H2O (20 : 1, 4 mL) was added KOAc (10 mg, 0.10 mmol),
and the mixture was stirred at appropriate temperature until all
the starting material had been consumed (TLC). The mixture was
diluted with ether (20 ml), washed with water (twice) and brine, dried
(Na2SO4) and concentrated under reduced pressure. The residue was
purified by silica gel flash column chromatography. For details of a
large-scale reaction, see ESI†.
Acknowledgements
Financial support from the NSFC (20602008, 20832005) is
gratefully acknowledged.
1114 | Green Chem., 2009, 11, 1112–1114
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