Diiodosilane: A Reagent for Mild, Efficient Conversion of Carbamates to Ureas via Isocyanates

Full text of DOI:10.1021/jo9919714

J . Org. Chem. 2000, 65, 3239-3240
3239
Sch em e 1
Diiod osila n e: A Rea gen t for Mild , Efficien t
Con ver sion of Ca r ba m a tes to Ur ea s via
Isocya n a tes
Ste´phane Gastaldi,† Steven M. Weinreb,*,‡ and
Didier Stien§
LCMO-UMR 6517, Universite´ d'Aix-Marseille III,
Avenue Escadrille Normandie-Niemen, 13397 Marseille,
Cedex 20, France, Department of Chemistry,
The Pennsylvania State University,
Ta ble 1. Con ver sion of Ca r ba m a tes to Ur ea s via
Isocya n a tes for m ed w ith SiI2H2
University Park, Pennsylania 16802, and LAPP-UMR 5810,
Universite´ de Montpellier II, Place E. Bataillon,
34095 Montpellier, Cedex 5, France
Received December 28, 1999
About 30 years ago, Greber and Kricheldorf found that
trimethylchlorosilane promotes the conversion of car-
bamates into isocyanates (eq 1).1 Subsequent work by
Pirkle and co-workers demonstrated that highly chlori-
nated silanes are even more effective at inducing this
transformation.2 In addition, some reagents other than
silanes have been shown to effect the reaction.3 Recently,
Petillo et al. have reported a nice systematic study of the
reaction of carbamates with various chlorosilanes.4 It was
found that in general the silane reactivity increases in
the order Me3SiCl < Me2SiCl2 < MeSiCl3 < HSiCl3. In
addition, as the carbamate alkoxyl group becomes bulkier,
the reaction slows down, and with N-Boc carbamates,
isocyanate production is quite sluggish. In the cases
involving O-alkyl carbamates the reactions normally need
to be conducted between room temperature and 70 °C.
It is believed that the transformation probably involves
an initial N-silylated carbamate 1, which presumably
collapses via 2 to the isocyanate 3 and a stable alkoxy-
silane 4, thereby preventing readdition of the alcohol to
3 (Scheme 1).
In the course of a project in alkaloid total synthesis,
we were interested in converting an N-Boc carbamate to
a urea via an isocyanate, but due to the lability of our
substrate were concerned that the usual thermal condi-
tions required for the chlorosilane-induced reaction would
lead to extensive decomposition. We therefore prospected
for alternative reagents which might allow isocyanate
formation under milder reaction conditions, particularly
from N-Boc systems. We now wish to report that com-
a
Cy ) cyclohexyl.
mercially available diiodosilane is a particularly useful
reagent for this transformation.5
Thus, treatment of a carbamate with 1.2 equiv of
Hu¨nig’s base and 1.2 equiv of diiodosilane for 30 min from
-30 to -5 °C in methylene chloride led to complete
disappearance of the starting material as determined by
TLC analysis. Formation of an isocyanate was estab-
lished in the case of N-tert-butoxycarbonyl-4-methoxy-2-
methylaniline (entry 9) by the observation of the char-
acteristic isocyanate IR absorption at 2289 cm-1 (KBr
pellet) in the crude product before the addition of ben-
zylamine. However, in general the isocyanates were not
isolated, but could be trapped in situ with amines
affording ureas in good to excellent yields, depending on
the nature of the starting carbamate as well as the amine
used.6 The generality of the method has been assessed
using a variety of aliphatic and aromatic carbamates,
† Universite´ d'Aix-Marseille III.
‡ The Pennsylvania State University.
§ Universite´ de Montpellier II.
(1) Greber, G.; Kricheldorf, H. R. Angew. Chem., Int. Ed. Engl. 1968,
7, 941.
(2) (a) Pirkle, W. H.; Hoekstra, M. S. J . Org. Chem. 1974, 39, 3904.
(b) Pirkle, W. H.; Hauske, J . R. J . Org. Chem. 1977, 42, 2781. (c)
Mironov, V. F.; Kozyukov, V. P.; Orlov, G. I. J . Gen. Chem. USSR (Engl.
Transl.) 1981, 51, 1555.
(3) (a) Bal’on, Y. G. J . Org. Chem. USSR (Engl. Transl.) 1980, 16,
2233. (b) Valli, V. L. K.; Alper, H. J . Org. Chem. 1995, 60, 257. (c)
Butler, D. C. D.; Alper, H. J . Chem. Soc., Chem. Commun. 1998, 2575.
(4) Chong, P. Y.; J anicki, S. Z.; Petillo, P. A. J . Org. Chem. 1998,
63, 8515 and references cited.
(5) For other synthetic uses of this silane, see: Encyclopedia of
Reagents for Organic Synthesis; Paquette, L. A., Ed.; Wiley: Chi-
chester, U.K., 1995; Vol. 3, p 1905.
(6) For a review on synthesis of ureas, see: Petersen, U. Methoden
Org. Chem. (Houben-Weyl) 1983, E4, 334.
10.1021/jo9919714 CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/12/2000

3240 J . Org. Chem., Vol. 65, No. 10, 2000
Notes
The solution was recooled to -50 °C, and the amine was added
(2.5 mmol). The mixture was then allowed to warm to room
temperature. The solution was diluted with AcOEt, washed with
1 N HCl solution and brine, and dried over Na2SO4. The crude
product was purified by flash chromatography. All compounds
in Table 1 are known except for those listed below.
some bearing other functional groups potentially reactive
toward electrophiles (Table 1). As can be seen, the
reaction proceeds rapidly with all types of carbamates,
including N-Boc derivatives. The ethyl ester functionality
in the example in entry 7 proved compatible with the
reagent. Carbamates of secondary amines are not af-
fected under the reaction conditions (entry 10).
A tertiary alkylamine base is required to effect the
desired transformation. When pyridine is used, the
reaction simply affords the parent amine from the
carbamate instead of the isocyanate.7 Since in exploratory
runs with the model carbamate N-Boc-cyclohexylamine
slightly better yields of urea were produced with Hu¨nig’s
base compared to triethylamine, which is the common
base in the chlorosilane reactions, the former base was
generally used in our work.
1-Allyl-1-ben zyl-3-cycloh exylu r ea (en tr y 1b): 1H NMR
(CDCl3) δ 0.80-1.90 (m, 10H), 3.58 (m, 1H), 3.77 (d, 2H, J )
5.3 Hz), 4.22 (d, 1H, J ) 7.3 Hz), 4.40 (s, 2H), 5.12 (m, 2H), 5.71
(m, 1H), 7.20 (m, 5H); 13C NMR (CDCl3) δ 24.8, 25.6, 33.7, 49.3,
49.6, 50.2, 116.8, 127.3, 127.4, 128.7, 134.1, 138.2, 157.7.
1-Ben zyl-3-cyclop r op ylu r ea (en tr y 5): 1H NMR (CDCl3) δ
0.65 (m, 2H), 0.73 (m, 2H), 2.42 (m, 1H), 4.42 (d, 2H, J ) 5.9
Hz), 5.00 (bs, 1H), 5.40 (bs, 1H), 7.25 (m, 5H);13C NMR (CDCl3)
δ 7.5, 22.4, 44.2, 127.3, 127.4, 130.9, 139.4, 159.1.
2-(3-Ben zylu r eid o)-3-p h en yla la n in e eth yl ester (en tr y
7): 1H NMR (CDCl3) δ 1.11 (t, 3H, J ) 7.0 Hz), 2.99 (m, 2H),
4.02 (q, 2H, J ) 7.0 Hz), 4.27 (AB of ABX, 2H, J AB ) 15.2 Hz),
4.75 (q, 1H, J ) 6.0 Hz), 5.30 (m, 2H), 7.05 (m, 2H), 7.22 (m,
8H); 13C NMR (CDCl3) δ 14.1, 38.7, 44.3, 54.0, 61.3, 126.9, 127.2,
127.4, 128.4, 128.5, 129.4, 136.3, 139.1, 157.4, 173.1.
In conclusion, isocyanates are formed under very mild
low temperature reaction conditions from a wide variety
of carbamates by treatment with commercially available
SiI2H2 and Hu¨nig’s base. In situ trapping of the iso-
cyanate with primary or secondary amines efficiently
leads to ureas.
1-Ben zyl-3-(4-m eth oxy-2-m eth ylp h en yl)u r ea (en tr y 9):
1H NMR (DMSO-d6) δ 2.11 (s, 3H), 3.39 (d, 1H, J ) 5.1 Hz),
3.69 (s, 3H), 4.28 (d, 2H, J ) 5.1 Hz), 6.71 (m, 3H), 7.29 (m,
4H), 7.55 (m, 2H); 13C NMR (DMSO-d6) δ 18.0, 42.9, 55.1, 111.1,
115.3, 123.7, 126.7, 127.1, 128.9, 130.5, 130.9, 140.5, 155.0, 155.9.
Exp er im en ta l Section
Ack n ow led gm en t. We are grateful to the National
Science Foundation (CHE-97-32038) for financial sup-
port of this research. We also thank the Ministry of
Foreign Affairs (France) for a Lavoisier Postdoctoral
Fellowship to D.S.
Gen er a l Exp er im en ta l P r oced u r e. Diiodosilane (0.6 mmol,
Aldrich) was added to a -30 °C solution of the carbamate (0.5
mmol) and DIPEA (0.6 mmol) in 3 mL of dichloromethane. The
reaction temperature was then slowly elevated to -5 °C (30 min).
Su p p or tin g In for m a tion Ava ila ble: Copies of proton and
carbon NMR spectra of new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
(7) It should be noted that iodotrimethylsilane cleaves Boc carbam-
ates to amines: J ung, M. E.; Lyster, M. A. J . Chem. Soc., Chem.
Commun. 1978, 315. Lott, R. S.; Chauhan, V. S.; Stammer, C. H. J .
Chem. Soc., Chem. Commun. 1979, 495. Sakaitani, M.; Ohfune, Y.
Tetrahedron Lett. 1985, 26, 5543.
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