Novel synthetic route to allyl cyanamides: Palladium-catalyzed coupling of isocyanides, allyl carbonate, and trimethylsilyl azide [6]

Full text of DOI:10.1021/ja016355f

J. Am. Chem. Soc. 2001, 123, 9453-9454
Table 1. Palladium-Catalyzed Formation of Cyanamides 4a
9453
Novel Synthetic Route to Allyl Cyanamides:
Palladium-Catalyzed Coupling of Isocyanides, Allyl
Carbonate, and Trimethylsilyl Azide
Shin Kamijo, Tienan Jin, and Yoshinori Yamamoto*
Department of Chemistry
Graduate School of Science
Tohoku UniVersity, Sendai 980-8578, Japan
ReceiVed June 6, 2001
ReVised Manuscript ReceiVed July 24, 2001
Cyanamides have been attracting many chemists because of
their unique structure and reactivity. They have been used not
only as a building block for heterocyclic compounds in the fields
of organic chemistry1 but also as a ligand for various metals in
the fields of inorganic chemistry and material science.2 Some
cyanamides are found in natural products3 and known to exhibit
biological activities.4 Although cyanamides are one of the
important classes of chemicals, their synthetic routes are quite
limited. The major approaches are as follows:1,5 (1) alkylation of
cyanamide under basic conditions, (2) cyanation of amines by
using cyanogen bromide, and (3) condensation of cyanamide with
carbonyl compounds. We now report a novel synthetic route to
cyanamides via palladium-catalyzed three component coupling
of the isocyanides 1, allyl carbonate 2, and trimethylsilyl azide 3
to give the allyl cyanamides 4 in good to excellent yields (eq 1).
a To a mixture of 1 (0.5 mmol), 2 (1 mmol), and 3 (1 mmol) were
added Pd2(dba)3‚CHCl3 (2.5 mol%) and dppe (10 mol%) in toluene (1
ml). The mixture was stirred at rt for 10 min and then at indicated
temperature for the time shown in table 1. b Isolated yield. c Pd(acac)2
(5 mol%) was used instead of Pd2(dba)3‚CHCl3.
and 3). The isocyanobenzenes having a tert-butyldimethylsilyl-
protecting group 1d, acetyl group 1e, methoxymethyl group 1f,
and mesyl group 1g proceeded smoothly to give the corresponding
cyanamides 4d-g, respectively, in good yields (entries 4-7). In
the case of silyl-protected isocyanide 1d, Pd(acac)2 was used
instead of Pd2(dba)3‚CHCl3 for the ease of separation of the
product 4d.6 The isocyanobenzenes with electron-withdrawing
groups 1h-j reacted even at 40 °C to give the corresponding
products 4h-j in high to good yields (entries 8-10). The
isocyanobenzenes conjugated with vinyl 1k and alkynyl groups
1l-n afforded the cyanamides 4k and 4l-n, respectively, in good
to excellent yields (entries 11-14). Even sterically hindered
isocyanides 1o and 1p underwent the three-component coupling
reaction to give the corresponding cyanamides 4o and 4p in 84
and 65% yields (eq 2). 1,4-Diisocyanobezene 1q gave the
The results are summarized in Table 1. When a mixture of
4-methoxy-1-isocyanobenzene 1a, allyl methyl carbonate 2, and
trimethylsilyl azide 3 in toluene was stirred at room temperature
for 10 min and then heated at 60 °C for 1 h in the presence of
2.5 mol % of Pd2(dba)3‚CHCl3 and 10 mol % of 1,2-bis-
(diphenylphosphino)ethane, N-allyl-N-(4-methoxyphenyl)cyana-
mide 4a was formed in 99% yield (entry 1). In the absence of
the palladium catalyst, no reaction took place even after heating
at 60 °C for 1 h. The regioisomers 1b and 1c also gave the
corresponding products 4b and 4c in excellent yields (entries 2
(1) (a) For a reviews, see: Lantzsch, R. In Methoden der Organischen
Chemie (Houben-Weyl); Hagemann, H., Ed.; Georg Thieme Verlag: Stuttgart,
1983; Vol. E4, pp 974-999. (b) Sandler, S. R.; Karo, W. Organic Functional
Group Preparations; Academic: New York, 1972; Vol. 3, pp 286-287 and
Vol. 2, pp174-178.
(2) (a) Miyasaka, H.; Cle´rac, R.; Campos-Ferna´ndez, C. S.; Dunbar, K. R.
Inorg. Chem. 2001, 40, 1663-1671. (b) Letcher, R. J.; Zhang, W.; Bensimon,
C.; Crutchley, R. J. Inorg. Chim. Acta 1993, 210, 183-191. (c) Zhang, W.;
Bensimon, C.; Crutchley, R. J. Inorg. Chem. 1993, 32, 5808-5812. (d)
Hollebone, B. R.; Nyholm, R. S. J. Chem. Soc. A 1971, 332-337. (e)
Pomberio, A. J. L. Inorg. Chim. Acta 1992, 198-200, 179-186.
(3) (a) Echavarren, A. M.; Tamayo, N.; Frutos, OÄ . D.; Garc´ıa, A.
Tetrahedron 1997, 53, 16835-16846. (b) Kno¨lker, H.-J.; O’Sullivan, N.
Tetrahedron 1994, 50, 10893-10908. (c) Dmitrienko, G. I.; Nielsen, K. E.;
Steingart, C.; Ming, N. S.; Wilson, J. M.; Weeratunga, G. Tetrahedron Lett.
1990, 31, 3681-3684.
corresponding dicyanamide 4q in 93% yield (eq 3). The structures
of the products 4 were determined by spectroscopic data and
elemental analysis. Furthermore, the structure of 4n was unam-
biguously confirmed by X-ray crystallographic analysis (Figure
1). It is clear that the obtained product 4n is an allyl cyanamide
and not an allyl carbodiimide.
(4) (a) Falgueyret, J.-P.; Oballa, R. M.; Okamoto, O.; Wesolowski, G.;
Aubin, Y.; Rydzewski, R. M.; Praist, P.; Reindeau, D.; Ridab, S. B.; Percival,
M. D. J. Med. Chem. 2001, 44, 94-104. (b) Atwal, K. S.; Grover, G. J.;
Ahmed, S. Z.; Sleph, P. G.; Dzwonczyk, S.; Baird, A.; Normandin, D. E. J.
Med. Chem. 1995, 38, 3236-3245. (c) Manley, P. W.; Quast, U. J. Med.
Chem. 1992, 35, 2327-2340. (d) Yanagisawa, I.; Hirata, Y.; Ishii, Y. J. Med.
Chem. 1984, 27, 849-857. (e) Shimada, K.; Fujisaki, H.; Oketani, K.;
Murakami, M.; Shoji, T.; Wakabayashi, T.; Ueda, K.; Ema, K.; Hashimoto,
K.; Tanaka, S. Chem. Pharm. Bull. 1984, 32, 4893-4906.
(5) Palladium-catalyzed reactions, see: (a) Cerezo, S.; Corte´s, J.; Moreno-
Man˜as, M.; Pleixats, R.; Roglans, A. Tetrahedron 1998, 54, 14869-14884.
(b) Cerezo, S.; Corte´s, J.; Lo´pez-Romero, J.-M.; Moreno-Man˜as, M.; Parella,
T.; Pleixats, R.; Roglans, A. Tetrahedron 1998, 54, 14885-14904.
A proposed mechanism is shown in Scheme 1. First, Pd(0)
reacts with allyl carbonate 2 and TMSN3 3 to give π-allylpalla-
dium azide along with CO2 and TMSOMe. Then the reaction of
isocyanide 1 with the π-allylpalladium azide would give the
π-allylpalladium intermediate A. Elimination of N2 followed by
the 1,2-migration of π-allylpalladium group from the carbon to
10.1021/ja016355f CCC: $20.00 © 2001 American Chemical Society
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9454 J. Am. Chem. Soc., Vol. 123, No. 38, 2001
Communications to the Editor
mide 4. A key step for the proposed mechanism is the formation
of π-allylpalladium carbodiimide complex and its isomerization
to π-allylpalladium cyanamide complex. To obtain strong support
for this interesting isomerization, we synthesized the allyl
carbodiimide 59 and examined the isomerization under the
conditions similar to those of Table 1 (eq 4). As expected, the
Figure 1. X-ray structure of 4n
allyl cyanamide 4a was obtained in 88% yield.10 When 5 was
heated in toluene (0.5 M)/10 mol % dppe at 100 °C for 1 h, no
reaction took place, and 5 was recovered.11 Accordingly, it is very
probable that the π-allylpalladium complexes B-D intervene in
the catalytic cycle of the three-component coupling process.
We are now in a position to synthesize allyl aryl cyanamides
in very high to good yields through the palladium-catalyzed three-
component coupling reaction between isocyanides 1, allyl carbon-
ate 2, and trimethylsilyl azide 3. In addition, we pointed out that
a π-allylpalladium mimic of the Curtius rearrangement intervenes
in the catalytic cycle. Further studies on the synthetic application
of this novel reaction and on the mechanistic detail are in progress
in our laboratory.
Scheme 1. Proposed Mechanism for the Formation of Allyl
Cyanamides 4
Acknowledgment. We thank faculties in Instrumental Analysis Center
for Chemistry at Tohoku University for measurement of compound data.
S.K. also thanks the fellowship support from the Japan Society of
Promotion of Science for Young Scientists.
Supporting Information Available: Experimental procedures and
spectroscopic and analytical data for relevant compounds (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
R-nitrogen atom in A would afford the palladium-carbodiimide
complex B.7 It should be noted that the conversion from A to B
is a π-allylpalladium mimic of the Curtius rearrangement. The
palladium-carbodiimide complex B could be in equilibrium with
the palladium-cyanamide complex C, or more probably could
be represented as a heteroatom containing bis-π-allylpalladium
analogue D.8 Reductive elimination of Pd(0) from the palladium-
cyanamide intermediate C gives the corresponding allyl cyana-
JA016355F
(8) For the chemistry on bis-π-allylpalladium, see: (a) Nakamura, H.;
Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 6641-6647. (b)
Nakamura, H.; Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120,
4242-4243. (c) Nakamura, H.; Shim, J.-G.; Yamamoto, Y. J. Am. Chem.
Soc. 1997, 119, 8113-8114. (d) Shim, J.-G.; Nakamura, H.; Yamamoto, Y.
J. Org. Chem. 1998, 63, 8470-8474.
(9) Shi, C.; Zhang, Q.; Wang, K. K. J. Org. Chem. 1999, 64, 925-932.
(10) It is well-known that a π-allylpalladium complex is formed by the
oxidative addition of Pd(0) to CH2dCHCH2Y (Y: halide, OCO2R, OAc, OP-
(O)(OR2), NR2, etc.). However, to the best of our knowledge, there is no report
for the oxidative addition of Pd(0) to allyl carbodiimide (Y: NdCdNR).
See: Tsuji, J. Transition Metal Reagents and Catalysts; Wiley: New York,
2000; Chapter 4.
(6) It is difficult to separate the cyanamide 4d and dibenzylideneacetone
derived from Pd2(dba)3‚CHCl3.
(7) Stoichiometric reaction of palladium-azido complexes with isocyanides,
see: (a) Kim, Y.-S.; Kwak, Y.-S.; Lee, S.-W. J. Organomet. Chem. 2000,
603, 152-160. (b) Beck, W.; Burger, K.; Fehlhammer, W. P. Chem. Ber.
1971, 104, 1816-1825.
(11) Yamamoto, N.; Isobe, M. Chem. Lett. 1994, 2299-2302.