corresponding silyl triflates (especially, TBDMS, TIPS, and
TBDPS), 1c–e are considerably moisture-insensitive. Without
catalyst 2, the reaction did not proceed. Namely, Si-BEZA (1),
itself, is adequately stable and 2 acts as a useful trigger. An
analogous pyridinium salt, PPTS did not promote the silylation.
Diphenylammonium triflate6 is also a good catalyst, we chose 2
due to its convenience. Careful NMR experiments of 1c
revealed that the structure was not an N-TBDMS amide but a O-
TBDMS imidate. The high silylation potential originated from
the strong driving force of the reactive O-silyl imidate
transformed into thermodynamically stable benzamide with the
release of the silyl moiety. Table 2 lists the results of the
silylation of sterically crowded (silylation-resistant) and/or
functionalized alcohols.‡ Indeed, silylation-resistant terpinen-
4-ol (3), linalool (4), and 2,4-di-tert-butylphenol (5) were
successfully silylated in excellent yield under mild conditions.
In the case of 5, BTF solvent was more suitable than THF.
Several functionalized alcohols, i.e., allylic 4, tetrahydropyr-
anyl 6, ester 7 and aldol 8 tolerated the present conditions. To
our knowledge, this is the first example of the bulky TBDPS
group being practically introduced into a tertiary alcohol 9.7
The present method has another practical merit of easy work-
up procedure. After the reaction was completed, solid benzani-
lide was easily filtered from the mixture containing the desired
silyl ester and/or separated by standard column chromatog-
raphy. Two parallel experiments for silylations using TIPS-
BEZA (1d) with linalool (4) and o-cresol (10) demonstrate that
the ability of 1d is considered to rival or surpass the most
powerful method using SiOTfs–2,6-lutidine8 under standard
conditions (Figs. 1 and 2). Small amounts of polymerization
was found to occur, when linalool (4) was subjected to silylation
using TIPSOTf–2,6-lutidine (Fig. 1).
In conclusion, this original reagent, Si-BEZA (1), with
catalytic PyH+·OTf2 (2) is structurally simple, yet, exhibits
powerful and highly efficient silylations.
This research was partially supported by a Grant-in-Aid for
Scientific Research on Priority Areas (A) ‘Exploitation of
Multi-Element Cyclic Molecules’ and on Basic Areas (C) from
the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Notes and references
† Benzanilide was added to a stirred suspension of NaH (1.0 equiv.) in
MeCN (ca. 0.5 M) at 0–5 °C and stirred at rt for 1 h. To the mixture was
added silyl chloride (1.0 equiv.) at 0–5 °C, followed by stirring at room
temp. for 2–10 h. After evaporation of MeCN, the residue was extracted
with hexane, and NaCl and the small amount of benzanilide remaining were
removed. Hexane was evaporated to give crude Si-BEZA (1a–e), which was
purified by distillation (TMS, TES), recrystallization from hexane
(TBDMS), or neutral alumina column chromatography with hexane–ether
(ca. 20+1) (TIPS, TBDPS). TfOH was added to a stirred solution of pyridine
(1.0 equiv.) in toluene at 0–5 °C and stirred at rt for 15 min. Toluene was
evaporated to give the crude solid, which was washed with ether to give pure
PyH·OTf2. TMS-BEZA (1a); yellow oil; 190 °C (oven temp.) at 0.2
1
mmHg; H NMR (300 MHz, CDCl3) d 20.26–0.69 (9H, br s), 6.62–8.16
(10H, m); 13C NMR (75 MHz, CDCl3) d 0.22, 120.21—123.89 (br),
126.98—131.48 (br), 148.01. TES-BEZA (1b); yellow oil; 200 °C (oven
1
temp.) at 0.2 mmHg; H NMR (300 MHz, CDCl3) d 0.07–1.41 (15H, m),
6.50–8.12 (10H, m); 13C NMR (75 MHz, CDCl3)
d 5.01, 6.56,
120.17–131.78 (br), 148.00. TBDMS-BEZA (1c); Colorless crystals; mp
1
73–74 °C; H NMR (300 MHz, 240 °C, CDCl3) d 20.29 (3.7H, s), 0.39
(2.3H, s), 0.79 (5.6H, s), 0.99 (3.4H, s), 6.68–7.99 (10H, m); (20 °C, CDCl3)
d 20.52–1.57 (15H, m), 6.53–8.36 (10H, m); (140 °C, d7-DMF) 0.16 (6H,
s), 0.94 (9H, s), 6.78–6.86 (2H, m), 6.91–6.99 (1H, m), 7.15–7.24 (2H, m),
7.27–7.40 (3H, m), 7.54–7.65 (2H, m). 13C NMR (100 MHz; 240 °C,
CDCl3) d 24.89, 24.23, 17.87, 18.19, 25.36, 25.73, 120.88, 122.14,
122.51, 123.34, 127.62, 128.00, 128.26, 128.33, 128.89, 129.56, 129.77,
130.74, 131.51, 135.16, 146.95, 148.29, 154.28, 156.40; (20 °C, CDCl3) d
24.28, 18.26, 25.79, 120.18–123.72 (br), 126.61–130.79 (br), 147.87 (not
amide but imidate). 29Si NMR (80 MHz; 240 °C, TMS) d 23.10, 23.25.
15N-enriched TBDMS-BEZA (1c) was prepared from 15N-aniline ( > 99%
purity). 15N NMR of this sample (40 MHz; 240 °C, CH3NO2) d 2123.43,
2123.29. TIPS-BEZA (1d); pale yellow oil; 1H NMR (300 MHz, CDCl3) d
0.84–1.61 (21H, m), 6.63–7.62 (10H, m); 13C NMR (75 MHz, CDCl3) d
12.43, 18.16, 120.73–122.81 (br), 127.80, 128.90, 129.46, 129.81, 148.47.
TBDPS-BEZA (1e); pale yellow viscous oil; 1H NMR (300 MHz, CDCl3)
d 0.83–1.46 (9H, m), 6.24–7.90 (20H, m); 13C NMR (75 MHz, CDCl3) d
19.59, 27.30, 120.78, 122.49, 127.39, 127.86, 128.70, 129.40, 129.51,
130.01, 133.08, 135.17, 135.54, 147.60, 154.76.
‡ A typical procedure. TBDMS-BEZA (1c; 476 mg, 1.5 mmol) was added
to a stirred solution of terpinen-4-ol (3; 154 mg, 1.0 mmol) and PyH·OTf2
(46 mg, 0.2 mmol) in THF (2.0 cm3) at 20–25 °C. After stirring at 50 °C for
2.5 h, the mixture was quenched with water and extracted twice with ether.
The combined organic phase was washed with water, brine, dried (Na2SO4)
and concentrated. The obtained crude oil was purified by SiO2-column
chromatography (hexane) to give 1-(tert-butyldimethylsiloxy)-1-isopropyl-
4-methyl-3-cyclohexene (257 mg, 96%). Colorless oil. 1H NMR (300 MHz,
CDCl3) d 0.03 (3H, s), 0.06 (3H, s), 0.87 (9H, s), 0.88 (3H, d, J 6.7 Hz), 0.89
(3H, d, J 6.7 Hz), 1.61–2.30 (10H, m), 5.20–5.25 (1H, m). 13C NMR (75
MHz, CDCl3) d 22.33, 22.04, 17.06, 17.15, 18.65, 23.07, 26.00, 28.78,
32.23, 33.79, 35.92, 75.72, 119.40, 133.49.
Fig. 1 Comparable experiments of triisopropylsilylation of linalool (4)
conversion (GC%) -: TIPS-BEZA (1d; 1.5 equiv.)–PyH+·OTf2 (2; 0.2
equiv.)–THF, 50 °C. :: TIPSOTf (1.5 equiv.)–2,6-lutidine (2.5 equiv.)–
DMF, 50 °C.
1 T. W. Green and P. G. M. Wuts, Protective Groups in Organic Synthesis,
3rd. edn., Wiley, New York, 1999, pp. 113–148.
2 P. Kocienski, Protecting Groups, Thieme, Stuttgart, 1994, p. 28.
3 B. A. DASa and J. G. Verkade, J. Am. Chem. Soc., 1996, 118, 12832.
4 Y. Tanabe, M. Murakami, K. Kitaichi and Y. Yoshida, Tetrahedron Lett.,
1994, 35, 8409; Y. Tanabe, H. Okumura, A. Maeda and M. Murakami,
Tetrahedron Lett., 1994, 35, 8413.
5 D. A. Johnson and L. M. Taubner, Tetrahedron Lett., 1996, 37, 605.
6 K. Wakasugi, T. Misaki, K. Yamada and Y. Tanabe, Tetrahedron Lett.,
2000, 41, 5249; J. Otera, Angew. Chem., Int. Ed., 2001, 40, 2044.
7 Fluka Fine Chemical Co. Ltd., Chemika, Silylating Agents, 1995.
8 E. J. Corey, H. Cho, C. Rücker and D. H. Hua, Tetrahedron Lett., 1981,
22, 3455.
Fig. 2 Comparable experiments of triisopropylsilylation of o-cresol (10)
conversion (GC%) -: TIPS-BEZA (1d; 1.5 equiv.)–PyH+·OTf2 (2; 0.2
equiv.)–BTF, 25 °C. :: TIPSOTf (1.5 equiv.)–2,6-lutidine (2.5 equiv.)–
CH2Cl2, 25 °C
Chem. Commun., 2001, 2478–2479
2479