1818
Y. Ichikawa et al.
LETTER
(8) (a) Ichikawa, Y. Synlett 1991, 238. (b) Ichikawa, Y. Synlett
2007, 2927.
Table 3 Transcarbamoylation Reaction of 3-Methyl-2-cyclohex-
enol
(9) Vaterlaus, B. P.; Kiss, J.; Spiegelberg, H. Helv. Chim. Acta
1964, 47, 381.
O
(10) (a) Loev, B.; Kormendy, M. F. J. Org. Chem. 1963, 28,
3421. (b) Loev, B.; Kormendy, M. F.; Goodman, M. M. Org.
Synth, Coll. Vol. V 1973, 162.
H2N
O
dibutyltin maleate
toluene, 90 °C
(11) (a) Graf, R. Chem. Ber. 1963, 96, 56. (b) Graf, R. Angew.
Chem., Int. Ed. Engl. 1968, 7, 172. (c) Hirama, M.;
Shigemoto, T.; Ito, S. J. Org. Chem. 1987, 52, 3342.
(d) Hirama, M. J. Synth. Org. Chem. Jpn. 1987, 45, 346.
(12) Hirama, M.; Uei, M. Tetrahedron Lett. 1982, 23, 5307.
(13) Kocovsky, P. Tetrahedron Lett. 1986, 27, 5521.
(14) Stryer, L. Biochemistry, 3rd ed.; Freeman and Company:
New York, 1988.
OH
O
NH2
X
OPh
O
18c
O
18a
X = NH and O
18d
Entrya
Catalyst (mol%)
Time (min)
Yield (%)
(15) Although phenyl carbamate (2) is commercially available,
the cost is unacceptably high for us. As a result, this
substance was prepared by treatment of inexpensive phenyl
chloroformate with aq NH3.
1
2
3
10
30
70
100
110
80
61
72
53
Preparation of Phenyl Carbamate (2)
To a biphasic mixture of concd aq NH3 (15 M, 64 mL, 0.80
mol, 2.5 equiv) and CH2Cl2 (120 mL) at 0 °C was added a
solution of phenyl chloroformate (50 g, 0.32 mol) in CH2Cl2
(80 mL) through a dropping funnel, and the dropping funnel
was washed with CH2Cl2 (50 mL). After vigorous stirring at
0 °C for 40 min, the reaction mixture was diluted with H2O.
The separated aqueous layer was extracted with CH2Cl2, and
the combined organic extracts were dried (Na2SO4) and
concentrated in vacuo. The crude product was dissolved in
warm EtOAc (220 mL). Upon cooling the solution, phenyl
carbamate crystallized as white solid, which was separated
by filtration (30.6 g). The mother liquors were concentrated
and then purified by recrystallization to provide additional
product (6.0 g, total yield 84%).
a 2.5 equiv of phenyl carbamate and 0.081 M concentration in toluene
was employed.
mol% catalyst loading decreased the yield to 53% (entry
3), use of 30 mol% catalyst resulted in an acceptable 72%
yield (entry 2).
The studies described above show that the tin-catalyzed
transcarbamoylation reaction serves as a mild and conve-
nient method for the preparation of carbamates from alco-
hols. The main advantages of this process lie in its
experimental simplicity, the use of an inexpensive and
commercially available reagent and catalyst, high yields,
and functional-group compatibility. Other merits result
from the fact that both phenyl carbamate and dibutyltin
maleate are air-stable crystalline compounds, and that tin
catalyst is easily removed after the reaction by using chro-
matography. Overall, the process developed in this study
represents a valuable alternative to known methods that
may find applications in the field of natural product syn-
thesis.
(16) Adams, P.; Hill, M. US 3,161, 676, 1964.
(17) Representative Experimental Procedure
A solution of geraniol (3a, 5.00 g, 32.4 mmol), phenyl
carbamate (6.70 g, 48.6 mmol, 1.50 equiv), and dibutyltin
maleate (337 mg, 0.97 mmol, 3.0 mol%) in toluene was
heated at 90 °C for 150 min. The solution was cooled to 0 °C,
and diluted with 5% aq NaOH (25 mL). After stirring at 0 °C
for 5 min, CH2Cl2 and H2O was added. The organic layer
was separated, washed with 5% aq NaOH, H2O, and brine,
dried over Na2SO4, and then concentrated in vacuo. The
resulting crude product (7.3 g) was subjected to silica gel
chromatography (EtOAc and hexane, stepwise gradient
from 1:5 to 1:0) to afford geranyl carbamate (3b, 6.30 g,
98%).
Acknowledgment
We thank for financial support from Nagase Science and Technolo-
gy Foundation.
(18) (a) Poller, R. C.; Retout, S. P. J. Organomet. Chem. 1979,
173, C7. (b) Otera, J.; Dan-oh, N.; Nozaki, H. J. Org. Chem.
1991, 56, 5307. (c) Baumhof, P.; Mazitschek, R.; Giannis,
A. Angew. Chem. Int. Ed. 2001, 40, 3672.
References and Notes
(19) Relative rate data for solvolysis in 50% aq EtOH of allyl
chlorides shown below demonstrates the unusual methyl
effect. Specifically, 3,3-dimethy allyl chloride is more
reactive than the monosubstituted compound by a factor of
about 103 (Figure 1) This experimental result may explain
why derivatives of 3-methyl-2-cyclohexenol, such as 18b,
are highly prone to undergo solvolysis reactions. See the
reference: Vernon, D. A. J. Chem. Soc. 1954, 423.
(1) (a) Nakatsubo, F.; Cocuzza, A. J.; Keeley, D. E.; Kishi, Y.
J. Am. Chem. Soc. 1977, 99, 4835. (b) Nakatsubo, F.;
Fukuyama, T.; Cocuzza, A. J.; Kishi, Y. J. Am. Chem. Soc.
1977, 99, 8115.
(2) Tanino, H.; Nakata, T.; Kaneko, Y.; Kishi, Y. J. Am. Chem.
Soc. 1977, 99, 2818.
(3) Millar, A.; Kim, K.-H.; Minster, D. K.; Ohgi, T.; Hecht,
S. M. J. Org. Chem. 1986, 51, 189.
(4) Minami, N.; Ko, S. S.; Kishi, Y. J. Am. Chem. Soc. 1982,
104, 1109.
(5) Hirama, M.; Shigemoto, T.; Yamazaki, Y.; Ito, S. J. Am.
Chem. Soc. 1985, 107, 1797.
Cl
Cl
Cl
(6) Donohoe, T. J.; Johnson, P. D.; Cowley, A.; Keenan, M.
J. Am. Chem. Soc. 2002, 124, 12934.
1.0
91
130,000
(7) Espino, C. G.; Du Bois, J. Angew. Chem. Int. Ed. 2001, 40,
598.
Figure 1
Synlett 2010, No. 12, 1815–1818 © Thieme Stuttgart · New York