Facile preparation of unsymmetric carbodiimides via in situ tin(II)-mediated heterocumulene metathesis

Full text of DOI:10.1021/ja980173c

J. Am. Chem. Soc. 1998, 120, 5585-5586
5585
Table 1. Isolated Yields of R′NdCdNSiMe3 Obtained from the
Reaction of 2 with R′NCO
Facile Preparation of Unsymmetric Carbodiimides
via in Situ Tin(II)-Mediated Heterocumulene
R′ a
yield (%)
Metathesis
entry
1
2
3
4
5
6
7
t-Bu
Cy
1-Ad
Me3Si
75
82
95
98
b
60
94
Jason R. Babcock and Lawrence R. Sita*
Searle Chemistry Laboratory
Ph
Department of Chemistry, The UniVersity of Chicago
2,6-Me2C6H3
2,6-(i-Pr)2C6H3
5735 South Ellis AVenue, Chicago, IL 60637
a Cy ) cyclohexyl, Ad ) adamantyl. b Complex mixture of products.
ReceiVed January 16, 1998
lylchalcogenolates under mild conditions.9 Given the high yields
of the new heterocumulenes that were observed in these reactions,
we naturally became interested in determining the value of this
process as a practical route to unsymmetric carbodiimides.
However, to achieve this objective, it was first necessary to map
out the steric and electronic requirements of heterocumulene
metathesis with respect to the metal center, the nature of the
silylated amido ligand, and the heterocumulene. Herein, we now
report the successful conclusions of these studies which have
culminated in the development of a simple “one-pot” tin(II)-
mediated synthesis of unsymmetric carbodiimides from readily
available mono-trimethylsilyated amines, (Me3Si)RNH,10 and
R′NCO. This new procedure should serve to expand both the
scope and utility of carbodiimides, and of heterocumulene
metathesis, as tools for organic synthesis.
There is considerable interest in the development of metal-
mediated oxo- and nitrene-transfer processes that can convert
readily available reactants into commodity products.1 Carbodi-
imides, RNdCdNR′, are one such product, as this class of
compound is extremely important for the construction of a wide
variety of chemical structures.2 Surprisingly, however, one still
finds that there is room for improved methods for their production.
In particular, for unsymmetric carbodiimides (R * R′), there
currently exists only two practical routes, and these involve either
the extrusion of the elements of hydrogen sulfide from N,N′-
disubstituted thioureas, RHNC(S)NHR′, or the aza-Wittig reaction
of iminophosphoranes, e.g., Ph3PdNR, with isocyanates, R′NCO.2
Unfortunately, both of these methods suffer from the need to
separately prepare the thiourea and iminophosphorane starting
materials, and in the case of the former process, the use of noxious
reagents such as yellow mercuric oxide,3 phosgene,4 sulfur
dioxide,5 or methanesulfonyl chloride,6 which are not always
general in scope for both alkyl- and aryl-substituted carbodiimides,
has classically been required. Further, although it is known that
group 5 and 6 imido complexes can catalyze the cross-metathesis
of carbodiimides, this process as not yet yielded a viable method
for the synthesis of unsymmetric carbodiimides.7 Finally, there
have been other sporadic reports of a metal-mediated heterocu-
mulene metathesis process providing an isolated example of a
carbodiimide product, but once again, none of these have ever
been developed as practical synthetic methodology.8 Recently,
we have been developing the heterocumulene metathesis of metal
bis(triorganosilyl)amides that proceeds according to MsN(SiR3)2
+ EdCdX (X ) O or NR, E ) O, S and Se) f MsESiR3 +
R3SiNdCdX, as a tool for the synthesis of metal triorganosi-
Wannagat and co-workers8a,b have previously observed that
sodium hexamethyldisilazide (1) cleanly reacts with 2 equiv of
trimethylsilylisocyanate to produce 1,3-bis(trimethylsilyl)carbo-
diimide according to NaN(SiMe3)2 + 2 Me3SiNCO f Me3-
SiNdCdNSiMe3 + Na[NCO] + Me3SisOsSiMe3.11 In this
metathesis reaction, the second equivalent of Me3SiNCO is
required to sacrifically react with the initially formed NaOSiMe3
in order to prevent it from reacting with the desired carbodiimide
product. Unfortunately, it is due to this undesired side reaction
that the Wannagat reaction cannot be extended as a general route
for the synthesis of either RNdCdNSiMe3 from 1 or RNdCdNR′
from other lithium monosilylamides, LiNR(SiMe3), and R′NCO.12
In contrast, we have found that similar metathesis reactions of
isocyanates with divalent tin bis(trimethylsilyl)amido compounds,
and in particular, with the commercially available reagent, Sn-
[N(SiMe3)2]2 (2),13 always proceed in near quantitative yields as
(1) See, for example: (a) Barton, D. H., Martell, A. F., Sawyer, D. T.,
Eds.; The ActiVation of Dioxygen and Homogeneous Catalytic Oxidation;
Plenum Press: New York, 1993. (b) Ayers, W. M., Ed.; Catalytic ActiVation
of Carbon Dioxide; ACS Symposium Series 363; American Chemical
Society: Washington, DC, 1988. (d) Laplaza, C. E.; Cummins, C. C. Science
1995, 268, 861-863. (e) Du Bois, J.; Tomooka, C. S.; Hong, J.; Carreira, E.
M. Acc. Chem. Res. 1997, 30, 364-372.
(2) (a) Williams, A.; Ibrahim, I. T. Chem. ReV. 1981, 81, 589-636. (b)
Muthyala, R. In ComprehensiVe Organic Functional Group Transformations,
Vol. 5; Katritzky, A., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon: New
York, 1995.
(3) Sheehan, J. C.; Hlavka, J. J. J. Org. Chem. 1956, 21, 439-441.
(4) Ulrich, H.; Sayigh, A. A. R. Angew. Chem., Int. Ed. Engl. 1966, 5,
704-712.
(5) Fujinami, T.; Otani, N.; Sakai, S. Synthesis 1977, 889-890.
(6) Fell, J. B.; Coppola, G. M. Synth. Commun. 1995, 25, 43-47.
(7) (a) Meisel, I.; Hertel, G.; Weiss, K. J. Mol. Catal. 1986, 36, 159-162.
(b) Birdwhistell, K. R.; Boucher, T.; Ensminger, M.; Harris, S.; Johnson, M.;
Toporek, S. Organometallics 1993, 12, 1023-1025.
(8) (a) Wannagat, U.; Pump, J.; Bu¨rgen, H. Mh. Chem. 1964, 94, 1013-
1018. (b) Wannagat, U.; Kuckertz, H.; Kru¨ger, C.; Pump, J. Z. Anorg. Allg.
Chem. 1964, 333, 54-60. (c) Itoh, K.; Lee, I. K.; Matsuda, I.; Sakai, S.; Ishii,
Y. Tetrahedron Lett. 1967, 2667-2670. (d) Bloodworth, A. J.; Davies, A.
G.; Vasishtha, S. C. J. Chem. Soc. C 1968, 2640-2646. (e) Itoh, K.; Kato,
N.; Shizuyoshi, S.; Ishii, Y. J. Chem. Soc. C 1969, 2005-2007. (f) Itoh, K.;
Lee, I. K.; Shizuyoshi, S.; Ishii, Y. J. Chem. Soc. C 1969, 2007-2009. (g)
Itoh, K.; Katsuura, T.; Matsuda, I.; Ishii, Y. J. Organomet. Chem. 1972, 34,
63-73. (h) Itoh, K.; Matsuda, I.; Katsuura, T.; Kato, S.; Ishii, Y. J. Organomet.
Chem. 1972, 34, 75-82. (i) Walsh, P. J.; Hollander, F. J.; Bergman, R. G.
Organometallics 1993, 12, 3705-3723.
1
determined by H NMR spectroscopy. These high yields are
presumably due to the inertness of the formed dimeric tin(II)
products, such as [Sn(µ-OSiMe3)(OSiMe3)]2,9a toward either the
starting isocyanate reactant or the carbodiimide product. Thus,
on a practical scale, as Table 1 reveals, a variety of R′Nd
CdNSiMe3 derivatives can now be conveniently prepared by
adding 2 equiv of R′NCO to a precooled (-78 °C) solution of
2,14 warming the reaction mixture to room temperature, filtering
it through a short column of silica gel to remove the tin-containing
(9) (a) Sita, L. R.; Babcock, J. R.; Xi, R. J. Am. Chem. Soc. 1996, 118,
10912-10913. (b) Weinert, C. S.; Guzei, I. A.; Rheingold, A. L.; Sita, L. R.
Organometallics 1998, 17, 498-500. (c) Xi, R.; Sita, L. R. Inorg. Acta Chim.
1998, 270, 118-122. (d) Babcock, J. R.; Zehner, R. W.; Sita, L. R. Chem.
Mater. 1998, 10, In press.
(10) (a) Hardy, J. P.; Cumming, W. D. J. Am. Chem. Soc. 1971, 93, 928-
932. (b) Courtois, G.; Miginiac, L. Tetrahedron Lett. 1987, 28, 1659-1660.
(11) LiN(SiMe3)2 works equally well in this reaction.
(12) As determined by NMR spectroscopy, metathesis between LiNR-
(SiMe3) and R′NCO does appear to occur; however, only trace amounts of
the carbodiimide product are obtained due to its apparent subsequent reaction
with LiOSiMe3.
(13) Harris, D. H.; Lappert, M. F. J. Chem. Soc., Chem. Commun. 1974,
895.
(14) A variety of aprotic solvents can be used (e.g., hexane, toluene, Et2O,
tetrahydrofuran, dichloromethane); however, pentane is preferred for volatile
carbodiimide products.
S0002-7863(98)00173-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/22/1998

5586 J. Am. Chem. Soc., Vol. 120, No. 22, 1998
Communications to the Editor
Table 2. Isolated Yields of RNdCdNR′ Obtained According to
Scheme 1
Scheme 1
entry
R
R′
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
n-Bu
Cy
t-Bu
Cy
i-Pr
n-Bu
Ph
2,6-Me2C6H3
2,6-(i-Pr)2C6H3
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
84
84
75
61
83
83
97
72
86
60
80
31
a
material, and then isolating the product by distillation. Of the
isocyanates utilized, only PhNCO failed to produce an appreciable
amount of carbodiimide product, and in this case, following the
course of the reaction by NMR spectroscopy revealed that
secondary reactions were occurring to produce a complex mixture
from which the product could not be separated. However, as
can be seen, an increase in the steric bulk of the isocyanate appears
to retard these secondary reactions as manifested in the higher
yields obtained for 2,6-dimethyl- and 2,6-diisopropylphenyl
isocyanate. Further, noting that the reaction of PhNCO with 2
was extremely rapid even at -78 °C, we prepared the more
sterically hindered tin(II) reagent, Sn[N(SiMe2Ph)2]2 (3),15 and
now found by NMR that reaction of this compound with PhNCO
proceeded smoothly at 50 °C to provide the desired carbodiimide,
PhNdCdNSiMe2Ph, as the sole organic product.16 Accordingly,
by using either 2 or 3, it should be possible to expand the range
of mono-silylated carbodiimides that can be prepared by metath-
esis.
A key question that we wished to answer next was whether
this heterocumulene metathesis could be extended for the produc-
tive synthesis of nonsilylated carbodiimides. To probe this, we
first utilized the known monomeric tin(II) bisamide, Sn[N(SiMe3)-
(t-Bu)]2 (4),13 and gratifyingly found that a 94-95% isolated yield
of 1,3-bis(tert-butyl)carbodiimide could be obtained at room
temperature either by reacting a pentane solution of 4 with 2 equiv
of t-BuNCO or by reacting it with CO2 (60 psi) in a pressure
reaction vessel. On a NMR scale, 4 was also found to react
cleanly with the range of isocyanates used in Table 1 to provide
the corresponding unsymmetric carbodiimides, t-BuNdCdNR′,
and this time, even in the case where R′ ) Ph. Unfortunately,
were the success of this methodology as a general synthetic tool
to depend on the availability of well-characterized Sn[N(SiMe3)-
(R)]2 derivatives, it would fail as few other than 4 are known,
and these all incorporate “bulky” R groups to aid in the kinetic
stabilization of these monomeric tin(II) species.17 Indeed, in an
attempt to explore this chemistry further, we prepared the new
derivative 5 where R ) 2,6-diisopropylphenyl,15 but this com-
pound proved unreactive toward both isocyanates and CO2, most
likely as a result of too much kinetic stablization. Given these
limitations, we next turned to determining whether high yields
of unsymmetric carbodiimide products could be obtained if the
tin(II) bisamides were simply prepared and reacted in situ
according to Scheme 1. Fortunately, as Table 2 reveals, this idea
worked exceedingly well. Thus, deprotonation of (Me3Si)RNH
in diethyl ether (Et2O) with n-butyllithium at 0 °C, followed by
addition of slightly more than half an equivalent of tin dichloride,
Ph
i-Pr
Me3Si
2,6-(i-Pr)2C6H3
i-Pr
t-Bu
i-Pr
50
a No reaction.
provided, in each case, an orange to orange-brown reaction
mixture when warmed to room temperature. Addition of 1.1
equiv of an isocyanate at this stage then resulted in bleaching of
this color with time, and after the usual workup, a range of
carbodiimide products could be obtained in very good to excellent
yields.18 Surprisingly, however, as entry 12 in Table 2 shows, a
notable exception was found for the in situ generation of 2 which
failed to give as high of a yield of carbodiimide as that obtained
by working with isolated 2. Why this should be is not clear at
this time; however, a possibility exists that complexation of 2
with lithium salts might be interfering with the course of the
reaction.19 We finally note that unsymmetric carbodiimides
bearing small organic groups, such as n-butyl or isopropyl, can
also be successfully prepared by having this group placed on either
the amine starting component or the isocyanate (cf., entries 4 and
8 in Table 2).
In conclusion, we have developed a simple one-step synthesis
of unsymmetric carbodiimides that is based on a facile in situ
tin(II)-mediated heterocumulene metathesis process. Since this
new methodology appears to offer complimentary advantages over
existing routes, we are now in the process of defining the full
extents and limitations of this chemistry as a tool for organic
synthesis.
Acknowledgment. This work was supported by the donors of the
Petroleum Research Fund, administered by the American Chemical
Society, for which we are grateful.
JA980173C
(18) RepresentatiVe procedure: To a solution of 1.03 g (7.05 mmol) of
N-tert-butyltrimethylsilylamine in 20 mL of Et2O, precooled to 0 °C, was
added 2.74 mL of n-butyllithium (2.57 M in hexanes). The reaction mixture
was warmed to room temperature and stirred for 2 h, whereupon, it was
transferred, via cannula, to a suspension of 0.67 g (3.88 mmol, 0.55 equiv) of
tin(II) chloride in 20 mL of Et2O that was cooled to 0 °C. The resultant orange
mixture was allowed to warm to room temperature and stir for 2 h; at which
time, it was cooled back down to 0 °C, and a solution of 0.77 g (7.75 mmol,
1.1 equiv) of tert-butyl isocyanate in 10 mL of Et2O added. The mixture was
warmed to room temperature and stirred for 12 h until the orange color faded.
The volatiles were then removed under reduced pressure (200 mmHg); the
crude mixture was taken up in a minimial amount of Et2O and filtered through
a 1 × 5 cm pad of silica gel on a glass frit. Removal of the volatiles provided
the final crude product which was bulb-to-bulb distilled at 75 °C/35 mmHg
to provide 0.918 g (5.92 mmol, 84%) of pure 1,3-bis(tert-butyl)carbodiimide
as a colorless oil.
(15) The preparation and crystal structure of this compound will be reported
elsewhere.
(16) The controlled reactivity of 3 with para-substituted arylisocyanates,
X-C6H4NCO (X ) OMe, Me, F, Cl, CF3), has been used to conduct a Hammett
study which revealed that the rate of heterocumulene metathesis is enhanced
by electron-donating groups, and thus, these rates also parallel the nucleo-
philicities of these isocyanates.
(17) (a) Veith, M.; Recktenwald, O. Top. Curr. Chem. 1981, 1-55. (b)
Lappert, M. F.; Power, P. P.; Sanger, A. R.; Srivastava, R. C. Metal and
Metalloid Amides; Ellis Horwood Limited: Chichester, 1980, and references
therein.
(19) Divalent tin(II) compounds have been observed in the solid state as
LiCl complexes, see: Arif, A. M.; Cowley, A. H.; Elkins, T. M. J. Organomet.
Chem. 1987, 325, C11-C13.