Ruthenium-catalyzed cycloaddition of 1,6-diynes with isothiocyanates and carbon disulfide: First transition-metal catalyzed [2 + 2 + 2] cocyclotrimerization involving C=S double bond

Article abstract of DOI:10.1021/ja016510q

In the presence of 10 mol % Cp*Ru(cod)Cl, 1,6-diynes with a tertiary center at 4-position reacted with various isothiocyanates at their C=S double bond to afford bicyclic (2H)-thiopyranimines in 35-88% yields. The (2H)-thiopyran structure was unequivocall

Full text of DOI:10.1021/ja016510q

Published on Web 12/11/2001
Ruthenium-Catalyzed Cycloaddition of 1,6-Diynes with Isothiocyanates and
Carbon Disulfide: First Transition-Metal Catalyzed [2 + 2 + 2]
Cocyclotrimerization Involving CdS Double Bond
Yoshihiko Yamamoto, Hideyuki Takagishi, and Kenji Itoh*
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya UniVersity,
Chikusa, Nagoya 464-8603, Japan
Received June 28, 2001
Despite of continuous efforts, the development of transition-
metal-mediated C-S bond formations have still remained as a
challenging task, due to their difficulty as a result of the strong
coordination of organosulfur compounds deactivating the media-
tors.1 Among such reactions, the cocyclotrimerization of alkynes
with a thiocarbonyl compound is of synthetic significance, because
a C-S single bond as well as two C-C single bonds are
simultaneously formed by a single operation. To the best of our
knowledge, there is only a few example of such an interesting sulfur
ring assembly2,3 whereas thiocarbonyl compounds behave as more
reactive dienophiles for Diels-Alder cycloaddition than the cor-
responding carbonyl compounds.4 Yamazaki and co-workers re-
Figure 1. ORTEP diagram of 7aa at 50% probability level. All hydrogens
are omitted for clarity.
ported that the reaction of a cobaltacyclopentadiene 1 and methyl
isothiocyanate gave a thiopyridone in 10% yield,5 but its structure
was subsequently reassigned to (2H)-thiopyran-2-imine 2 (Scheme
1).6 In addition to the isothiocyanate, carbon disulfide was also
reacted with 1 to furnish a dithiopyrone 3 in 50% yield (Scheme
1).5 To improve these interesting sulfur-heterocycle formations
mediated by a stoichiometric amount of a transition metal into an
environmentally benign catalytic variant, a serious problem might
arise: the oxidative cyclization step to form a metallacyclopenta-
diene key intermediate such as 1 from two alkyne molecules is
inhibited by the strong coordination of the thiocarbonyl components
to the metal center. As a result, the aimed catalytic cycle becomes
totally ineffective. In this context, we envisaged that a solution for
this problem comes from the combination of R,ω-diynes, excellent
precursors of metallacyclopentadienes,7 and ruthenium catalyses,
which have recently been employed for efficient catalytic C-S bond
formations.8 Herein, we wish to report our preliminary study on
the ruthenium-catalyzed cycloaddition of 1,6-diynes 4 with isothio-
cyanates 5 or carbon disulfide 9 (Figure 1).
Transition-metal-catalyzed cocyclotrimerization of two molecules
of an alkyne and an isocyanate leading to a substituted pyridone
has been accomplished using Co,9 Ni,10 and Rh11 catalysts. Recently,
we also reported the first example of the ruthenium-catalyzed
cycloaddition of 1,6-diynes 4 with isocyanates furnishing bicyclic
pyridones.12 In contrast to isocyanates, corresponding sulfur
analogues, isothiocyanates, has been scarcely employed for such a
cocyclotrimerization with alkynes.5 On the basis of our previous
studies on the ruthenium catalyses,12,13 we attempted the cycload-
dition of a diyne 4a (X ) C(CO2Me)2) and an isothiocyanate 5a
(RdCO2Et) using a ruthenium(II) complex, Cp*Ru(cod)Cl (6a) as
a catalyst (Figure 1). In the presence of 10 mol % 6a, a solution of
4a and 1.2 equiv 5a in 1,2-dichloroethane was heated at 90 °C for
3 h. The purification by silica gel chromatography afforded a
product 7aa along with a small amount of a diyne dimer 8 (Table
1, run 1). The 1H and 13C NMR spectra (see Supporting Information)
Scheme 1
Table 1. Ruthenium-Catalyzed Cycloaddition of 1,6-Diyne 4a with
Isothiocyanates 5a-da
isothiocyanate 5
yieldb (%)
run
R (equiv)
catalyst/mol %
t (h)
7
8
1
2
3c
4
5
6
7
8
9
5a/CO2Et (1.2)
5a/CO2Et (2)
5a/CO2Et (1.2)
5a/CO2Et (1.2)
5a/CO2Et (1.2)
5b/COPh (1.2)
5c/Ph (1.2)
6a/10
6a/10
6a/10
6b/10
6c/10
6a/10
6a/10
6a/5
3
1.5
3
3.5
21
24
5
24
24
7aa, 71
7aa, 79
7aa, 72
7aa, 68
7aa, 6
7ab, 76
7ac, 88
7ac, 51
7ad, 50
5
trace
10
9
5
trace
3
trace
15
5c/Ph (1.2)
5d/Cy (1.2)
6a/10
a All reactions were carried out with a dyne 4a and isothiocyanates 5a-d
in 1,2-dichloroethane at 90 °C. b Isolated yields. c The reaction was carried
out in benzene.
as well as the molecular ion peak (MH+ m/z ) 340) of its FAB
mass spectrum indicated that 7aa is a 1:1 adduct of 4a and 5a.
The formation of the (2H)-thiopyran ring was unequivocally
determined by X-ray analysis as shown in Figure 1.14 The S1-C1
and S1-C8 single bond distances are 1.722(3) and 1.758(3) Å,
respectively, which are consistent with the typical Csp2-S single
bond distance (1.75 Å). The N1-C8 bond is a typical CdN double
bond of 1.319(3) Å, and the ethoxycarbonyl group on the nitrogen
atom is oriented toward the sulfur atom (vide infra).
It is noteworthy that only 1.2 equiv of 5a chemoselectively gave
7aa in good yield, suppressing the concomitant formation of 8
(Table 1, run 1). This is in contrast to the cycloaddition of 4 with
isocyanates, in which 4 equiv of isocyanates were required to realize
the chemoselective pyridone annulation.12 The increased amount
9
28 VOL. 124, NO. 1, 2002 J. AM. CHEM. SOC.
10.1021/ja016510q CCC: $22.00 © 2002 American Chemical Society

C O MMU N I C A T I O N S
Table 2. Cp*Ru(cod) Cl-Catalyzed Cycloaddition of 1,6-Diynes
4a-e with Phenylisothiocyanate 5ca
Scheme 2
ruthenium center to form a ruthenacyclopentadiene 11. Subse-
quently, an isothiocyanate 5 was inserted into the Ru-C bond in
such a way that the strongly coordinating sulfur atom is oriented
toward the ruthenium center (in 12). At this stage, the R group on
the nitrogen atom is placed far from the ruthenacycle to minimize
the steric repulsion between them. The reductive elimination of a
[Cp*RuCl] fragment from an intermediate 13 affords a thiopyra-
nimine 7. The Diels-Alder cycloaddition of 11 with an isothio-
cyanate via 14 might be an alternative route to 7.16
a All reactions were carried out with 10 mol % 6a, diynes 4a-e and an
isothiocyanate 5c (1.2 equiv) in 1,2-dichloroethane at 90 °C. b Isolated yields.
c The reaction was carried out in benzene.
of 5a gave a similar result (run 2). The cycloaddition also proceeded
similarly in benzene (run 3), but the catalyst appeared to be
deactivated in acetonitrile. Among various ruthenium complexes,
Cp*Ru(cod)Cl (6a) exhibited the highest catalytic efficiency. A
similar ruthenium(III) complex, [Cp*RuCl2]2 (6b), proved to
catalyze the cycloaddition, but the yield was slightly lowered (run
4). On the other hand, a Ru(II) complex without the Cp* ligand,
RuCl2(CH3CN)2(cod) (6c), hardly catalyzed the cycloaddition, and
other complexes such as [RuCl2(cod)]n and C6Me6Ru(cod) were
totally ineffective toward the present cycloaddition.
Under the optimized reaction conditions, several isothiocyanates
were subjected to the cycloaddition with 4a. Upon heating a solution
of 4a and benzoyl isothiocyanate (5b) for 24 h, the desired
cycloadduct 7ab was almost exclusively obtained in 76% yield (run
6). Similarly, phenyl isothiocyanate (5c) gave 7ac in the highest
yield of 88% (run 7). The reaction, however, did not complete
within 24 h and the yield was lowered to 51% with a reduced
catalyst loading of 5 mol % (run 8). Cyclohexyl isothiocyanate (5d)
also gave the corresponding thiopyranimine 7ad albeit in moderate
yield, accompanying the formation of 8 in 15% yield (run 9).
Exceptionally, tert-butyl isothiocyanate gave no cycloadduct under
the same reaction conditions.
The generality of the novel [2 + 2 + 2] cycloaddition involving
a CdS double bond was subsequently examined with regard to
the diyne substrate as summarized in Table 2. In the same manner
for 4a (run 1), a cyclic diester analogue 4b was reacted with 5c for
9 h to afford 7bc in 35% yield (run 2). Similarly, 1,2-diketones 4c
and 4d, or a malononitrile derivative 4e gave the corresponding
thiopyranimines 7cc, 7dc, and 7ec in 58-74% yields (runs 3-5).
These results demonstrated the wide functional group compatibility
of the ruthenium catalysis. On the contrary, a tosylamide 4f (X )
NTs) and an ether 4g (X ) O) failed to undergo cycloaddition
with 5c. Accordingly, the thiopyran annulation cannot proceed
without the aid of the Thorpe-Ingold effect induced by the tertiary
center at 4-position of the diynes,15 which facilitates the oxidative
cyclization of the diynes on the ruthenium center (vide infra).
In addition to the isothiocyanates, carbon disulfide (9) can be
involved in the cycloaddition with the diyne (Figure 1). In the
presence of 10 mol % 6a, a solution of 4a in CS2/1,2-dichloroethane
(2:3 v/v) was heated at 90 °C for 6 h to furnish the expected bicyclic
dithiopyrone 10 in 50% yield along with a recovered 4a (24%).
A plausible mechanism for the catalytic formation of the
thiopyranimines 7 was outlined in Scheme 2. The catalytic cycle
starts with the oxidative cyclization of a 1,6-diyne 4 on the
Acknowledgment. We gratefully acknowledge financial support
(09750947, 09305059, 10132222, 12450360, and 13875174) from
the Ministry of Education, Science, Sports, and Culture, Japan.
Supporting Information Available: Experimental procedures and
analytical data for 7 and 10 (PDF). An X-ray crystallographic file (CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(1) For a review, see: Kondo, T.; Mitsudo, T. Chem. ReV. 2000, 100, 3205-
3220 and references therein.
(2) (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-92. (b)
Ojima, I.; Tzamarioudaki, M.; Donovan, R. J. Chem. ReV. 1996, 96, 635-
662.
(3) A noncatalyzed cocyclotrimerization involving a CdS double bond, see:
Bianchini, C.; Meli, A. J. Organomet. Chem. 1982, 236, C75-C77.
(4) Weinreb, S. M.; Staib, R. R. Tetrahedron 1982, 38, 3087-3128, and
references therein.
(5) Wakatsuki, Y.; Yamazaki, H. J. Chem. Soc., Chem. Commun. 1973, 280.
(6) Yamazaki, H. J. Synth. Org. Chem., Jpn. 1987, 45, 244-257.
(7) Mu¨ller, E. Synthesis 1974, 761-774.
(8) (a) Koelle, U.; Rietmann, C.; Tjoe, J.; Wagner, T.; Englert, U. Organo-
metallics 1995, 14, 703-713. (b) Kondo, T.; Uenoyama, S.; Fujita, K.;
Mitsudo, T. J. Am. Chem. Soc. 1999, 121, 482-483. (c) Kondo, T.;
Morisaki, Y.; Uenoyama, S.; Wada, K.; Mitsudo, T. J. Am. Chem. Soc.
1999, 121, 8657-8658.
(9) (a) Hong, P.; Yamazaki, H. Tetrahedron Lett. 1977, 1333-1336. (b) Hong,
P.; Yamazaki, H. Synthesis 1977, 50-52. (c) Earl, R. A.; Vollhardt, K.
P. C. J. Org. Chem. 1984, 49, 4786-4800. (d) Diversi, P.; Ingrosso, G.;
Lucherini, A.; Malquori, S. J. Mol. Catal. 1987, 40, 267-280.
(10) (a) Hoberg, H.; Oster, B. W. Synthesis 1982, 324-325. (b) Hoberg, H.;
Oster, B. W. J. Organomet. Chem. 1982, 234, C35-C38. (c) Hoberg, H.;
Oster, B. W. J. Orgnomet. Chem. 1983, 252, 359-364.
(11) Flynn, S. T.; Hasso-Henderson, S. E.; Parkins, A. W. J. Mol. Catal. 1985,
32, 101-105.
(12) Yamamoto, Y.; Takagishi, H.; Itoh, K. Organic Lett. 2001, 4, 2117-
2119.
(13) (a) Yamamoto, Y.; Ogawa, R.; Itoh, K. Chem. Commun. 2000, 549-
550. (b) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Kawaguchi, H.; Tatsumi,
K.; Itoh, K. J. Am. Chem. Soc. 2000, 122, 4310-4319. (c) Yamamoto,
Y.; Okuda, S.; Itoh, K. Chem. Commun. 2001, 1102-1103. (d) Yamamoto,
Y.; Ogawa, R.; Itoh, K. J. Am. Chem. Soc. 2001, 123, 6189-6190.
(14) Crystallographic data for C15H17NO6S (7aa): The space group is P21/n,
monoclinic, with unit-cell demensions a ) 6.9808(10) Å, b ) 11.2342-
(16) Å, c ) 20.146(3) Å, â ) 90.057 °, V ) 1579.9(4) Å3, Z ) 4, Dcalc
) 1.427 Mg/m3. Intensity data were collected at 293 K on a Bruker
SMART APEX diffractometer with Mo KR radiation and graphite
monochromator. The structure was solved by direct methods and refined
by the full-matrix least-squares on F2 (SHELXTL). A total 7657 reflections
were measured and 2279 were independent. Final R1 ) 0.0541, wR2
)
0.1460 (I > 2σ(I)), and GOF ) 0.637 (for all data, R1 ) 0.05921, wR2 )
0.1556). Full details are described in the Supporting Information.
(15) (a) Beesley, R. M.; Ingold, C. K.; Thorpe, J. F. J. Chem. Soc. 1915, 107,
1080-1106. (b) Jung, M. E.; Gervay, J. J. Am. Chem. Soc. 1991, 113,
224-232.
(16) Diercks, R.; Eaton, B. E.; Gu¨rtzgen, S.; Jalisatgi, S.; Matzger, A. J.; Radde,
R. H.; Vollhardt, K. P. C. J. Am. Chem. Soc. 1998, 120, 8247-8248.
JA016510Q
9
J. AM. CHEM. SOC. VOL. 124, NO. 1, 2002 29