C O M M U N I C A T I O N S
Table 2. Synthesis of Bis-Carbene Complex 1
cyclization of the intermediate carbene complex 7, it is not
surprising that it is sensitive to the concentration. The yield drops
to 16% at 0.025 M. It was surprising that the yield could not be
improved when a mixture of 1c and 2c was added via syringe pump
to hot 1,2-dichloroethane. Given the effects of solvent that we have
seen on other macrocyclizations of carbene complexes,2 it was
surprising to find little solvent effect on this reaction. The yields
of 3c in THF, acetonitrile, benzene, and 1,4-dioxane were all in
the range of 26-30%. Higher temperature is optimal: the reaction
at 83 °C gives a 33% yield of 3c with a reaction time of 90 min,
but this falls to 25% yield at 50 °C with a reaction time of 2 days.
The benzannulation reaction of Fischer carbene complexes with
alkynes provides for a highly regiocontrolled synthesis of unsym-
metrical calix[4]arenes in a process that constructs two of the
benzene rings of the calixarene simultaneously with the macrocy-
clization event that creates the 16-membered ring of the calixarene.
Furthermore, the overall yields from commercially available
materials of the unsymmetrical calixarenes so generated are
comparable with the overall yields of existing methods via either
the 2 + 2 or the 3 + 1 strategies that have been previously
developed.5
R2
R4
6
% yield 6
R1
R3
1
% yield 1
Me
Me
Me
Ph
Ph
6a
6b
6c
6d
73
77
86
78
Me
Me
Me
Ph
Ph
1a
1b
1c
1d
47
44
36
32
n-C6H13
OMe
OMe
n-C6H13
OMe
OMe
Table 3. Triple Benzannulation of Complex 1 and Diyne 2a
entry
complex 1
R1
R3
arene 2
R2
R4
3
% yield 3
Acknowledgment. This work was supported by a grant from
the NIH.
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1c
1d
1c
1b
1c
Me Ph
2a
2b
2c
2d
2a
2a
2b
2d
2d
Me Ph
Me n-C6H13 3b
Me OMe
Ph OMe
Me Ph
Me Ph
Me n-C6H13 3g
Ph OMe
Ph OMe
3a
35b
22
36
Me n-C6H13
Me OMe
Ph OMe
Me OMe
Ph OMe
Me OMe
Me n-C6H13
Me OMe
3c
3d
3e
3f
Supporting Information Available: Experimental procedures and
spectral data for all new compounds, 1H NMR spectra for calixarenes
3a-3i; X-ray structural data for 3a-I, 3a-II, and 3c (PDF); X-ray
crystallographic data (CIF). This material is available free of charge
41
31c
35d
22e
35e
40
3h
3i
References
a All reactions were carried out in 1,2-dichloroethane at 100 °C at 2.5
mM in 1 with 1.0 equiv of alkyne 2 for 20-40 min. b Isolated as a separable
1.7:1 mixture of two conformers. c Isolated as a nonseparable 3.8:1 mixture
of two conformers. d Isolated as a nonseparable 3.3:1 mixture of two
conformers. e Isolated as a nonseparable 7.9:1 mixture of two conformers.
(1) (a) CalixarenessA Versatile Class of Macrocyclic Compounds; Vicens,
J., Bohmer, V., Eds.; Kluwer: Norwell, MA, 1991. (b) Calixarenes
ReVisited; Gutsche, C. D., Ed.; Royal Society of Chemistry: Cambridge,
UK, 1998. (c) Calixarenes 2001; Asfari, Z., Bohmer, V., Harrowfield, J.,
Vicens, J., Eds.; Kluwer: Norwell, MA, 2001.
(2) Wang, H.; Huang, J.; Wulff, W. D.; Rheingold, A. L. J. Am. Chem. Soc.
2003, 125, 8980 and references therein.
(3) Sarandeses, L. A.; Sestelo, J. P.; Perez, I. J. Am. Chem. Soc. 2001, 123,
4155.
We were delighted to find that the reaction of the carbene
complex 1c with diyne 2c gave the unsymmetrical calixarene 3c
in 36% yield. While all but two of the yields in Table 3 are in the
30-40% range, this is well above the yields normally seen for the
cyclization event for either the 2 + 2 or 3 + 1 strategies.5 Since it
is well known that the synthesis of phenols via the benzannulation
reaction of Fischer carbene complexes and alkynes can be very
sensitive to the reaction conditions,6 an optimization regimen was
explored for the reaction of bis-complex 1c with diyne 2c (entry
3). Since this macrocyclization likely involves the intramolecular
(4) Rossi, R.; Carpita, A.; Lippolis, V.; Benetti, M. Gazz. Chim. Ital. 1990,
120, 783.
(5) Reference 1a, page 44, and ref 1c, page 15.
(6) For recent reviews on carbene complexes in organic chemistry, see: (a)
Wulff, W. D. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W., Stone, R. G. A., Wilkinson, G., Eds.; Pergemon Press: 1995, Vol.
12, p 469. (b) Hegedus, L. S. Tetrahedron 1997, 53, 4105. (c) de Meijer,
A.; Schirmer, H.; Duetsch, M. Angew. Chem., Int. Ed. 2000, 39, 3964.
(d) Do¨tz, K. H.; Tomuschatt, P. Chem. Soc. ReV. 1999, 28, 187. (e)
Herndon, J. W. Coord. Chem. ReV. 1999, 181, 177. (f) Metal Carbenes
in Organic Synthesis; Do¨rwald, F. Z., Ed.; Wiley-VCH: New York, 1999.
JA0454236
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