Y. Saito et al. / Tetrahedron Letters 51 (2010) 6915–6917
6917
3c (5 mol%)
OBoc
OH
OH
OBoc
OBoc
Boc2O (100 mol%)
OH
rt, CH2Cl2
2x
4
pyrocatechol (1x)
3c (5 mol%)
BocO
HO
BocO
OBoc
HO
Boc2O (100 mol%)
OH
OBoc
OH
rt, CH2Cl2
2y
6
2-tert-butylbenzene-1,4-diol
5
(1y)
Scheme 2.
advantages over other catalysts use for this purpose in that the cat-
alyst is reusable and can be used at very low catalyst loadings. In
addition, since the recent Letter of the Suzuki–Miyaura coupling
of aryl tert-butylcarbonates,10 functionalized O-Boc phenols would
be expected to be in widespread use as precursors to polysubstitut-
ed aromatic compounds.
Table 5
tert-Butoxycarbonylation of 1a with 3c in CH2Cl2 at room temperature
Entry
Catalytic loading (mol %)
Time (h)
Yielda (%)
1
2
3
4
5
1
0.5
0.1
10
31
72
96
93
91
94
88
2. Typical experimental procedures
a
Isolated yields.
In
a flask were placed phenol (1a) (2.0 mmol), Boc2O
(2.4 mmol), and 6,7-dimethoxyisoquinoline 3c (0.1 mmol) under
an argon atmosphere. Anhydrous CH2Cl2 (3 mL) was added and
the resulting solution was stirred at room temperature for 10 h.
Ethyl acetate (80 mL) was then added and the mixture was succes-
sively washed twice with 5% HCl (10 mL), brine (20 mL), twice with
10% NaOH (10 mL), and brine (20 mL). The solution was then dried
over anhydrous Na2SO3 and evaporated. The residue was purified
by flash column chromatography on silica gel to give O-Boc-phenol
2a (361 mg, 93%) as a colorless oil.
Table 6
tert-Butoxycarbonylation of 1a reusing 3c (5 mol %)in CH2Cl2 at room temperature
Entry
The number of times (reuses)
Time (h)
Yielda (%)
1
2
3
4
5
1
2
3
4
5
10
10
14
14
14
92
92
92
93
92
a
Isolated yields.
Acknowledgment
2x (88%) and 2y (95%), respectively, with no contamination by di-
O-Boc derivative 4 and mono-O-Boc regioisomers 5 and 6 due to
sterically hindered substituents, such as O-Boc and tert-butyl
groups at the ortho position (Scheme 2). However, attempts to O-
butoxycarbonylate of resorcinol and hydroquinone provided gave
This study was financially supported by a Grant-in-Aid, no.
30364409, for Scientific Research from the Japan Society for the
Promotion of Science (JSPS).
References and notes
a
mixture of mono- and di-O-Boc products under similar
conditions.
Next, catalytic loading with 3c was examined for the O-butoxy-
1. (a) Wuts, P. G. M.; Green, T. W. Greene’s Protective Groups in Organic Synthesis,
4rd ed.; Wiley: New York, NY, 2007; (b) Parrish, J. P.; Salvatore, R. N.; Jung, K.
W. Tetrahedron 2000, 56, 8207; (c) Kocienski, P. J. Protecting Groups; Stuttgart:
George Thieme, 2000.
2. (a) Ouchi, H.; Saito, Y.; Yamamoto, Y.; Takahata, H. Org. Lett. 2002, 4, 585; (b)
Saito, Y.; Ouchi, H.; Takahata, H. Tetrahedron 2006, 62, 11599.
3. Houlihan, F.; Bouchard, F.; Frchet, J. M. J.; Willson, C. G. Can. J. Chem. 1985, 63,
153.
4. (a) Basel, Y.; Hassner, A. J. Org. Chem. 2000, 65, 6368; (b) Hansen, M.; Riggs, J. R.
Tetrahedron Lett. 1998, 39, 2705.
5. Bartoli, G.; Bosco, M.; Carlone, A.; Dalpozzo, R.; Locatelli, M.; Melchiorre, P.;
Palazzi, P.; Sambri, L. Synlett 2006, 2104.
6. Suryakiran, N.; Prabhakar, P.; Venkateswarlu, Y. Synth. Commun. 2008, 38, 177.
7. (a) Chebolu, R.; Chankeshwara, S. V.; Chakraborti, A. K. Synthesis 2008, 1448;
(b) Chankeshwara, S. V.; Chebolu, R.; Chakraborti, A. K. J. Org. Chem. 2008, 73,
8615.
8. Even though reflux and the use of excess Boc2O, di-Boc compound of 1g was
not detected.
9. The catalyst 3c was recovered and reused as follows; ethyl acetate was added
to the reaction, and the mixture was extracted twice with 5% HCl. The extracts
were made basic by the addition of 10% NaoH and the mixture was extracted
with ethyl acetate. The extract was washed with brine, dried over anhydrous
Na2SO3 and evaporated to yield 3c (ꢀ95%). This procedure was repeated in
future runs.
carbonylation of 1a in CH2Cl2 at room temperature and the results
are shown in Table 5. A very low catalyst loading (0.1 mol %) can be
used, although the reaction time is long (entry 4). To our knowl-
edge, this value of 0.1 mol % as an organocatalyst is quite small.
Lastly, the reuse of the organocatalyst was tested. After work-
up, the aqueous layer, including 6,7-dimethoxyisoquinoline as
the hydrochloride salt, was made basic by the addition of 10%
NaOH, the solution extracted with ethyl acetate, and evaporated
to yield the recovered 6,7-dimethoxyisoquinoline, which was then
reused in subsequent reactions without further purification. The
results are summarized in Table 6.9 Although the reaction has been
repeated only five times in this stage, it was expected that this pro-
cedure would be done in additional runs. In general, the reuse of a
condensing reagent is difficult due to its transformation. Therefore,
this operation is valuable and remarkable.
In summary, the chemoselective O-tert-butoxycarbonylation of
phenols using 6,7-dimethoxyisoquinoline as a novel organocata-
lyst under mild condition was developed. This procedure has novel
10. Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg, N. K. J. Am. Chem. Soc. 2009,
131, 17748.