Hybrid system of metal/Bronsted acid relay catalysis for the intramolecular double hydroarylation and cationic cyclization of diyne diethers and diamines

Article abstract of DOI:10.1021/ol301522y

We have developed a hybrid system of metal/Bronsted acid relay catalysis for the intramolecular double hydroarylation and cationic cyclization of diyne diethers and diamines to give 4,4′-bi(2H-chromene), bi(2H-quinoline), and dioxafluoranthenes starting f

Full text of DOI:10.1021/ol301522y

ORGANIC
LETTERS
2012
Vol. 14, No. 14
3684–3687
Hybrid System of Metal/Brønsted Acid
Relay Catalysis for the Intramolecular
Double Hydroarylation and Cationic
Cyclization of Diyne Diethers and Diamines
Juntae Mo, Dahan Eom, Euichul Lee, and Phil Ho Lee*
Department of Chemistry, Kangwon National University, Chuncheon 200-701,
Republic of Korea
phlee@kangwon.ac.kr
Received June 2, 2012
ABSTRACT
We have developed a hybrid system of metal/Brønsted acid relay catalysis for the intramolecular double hydroarylation and cationic cyclization of
diyne diethers and diamines to give 4,40-bi(2H-chromene), bi(2H-quinoline), and dioxafluoranthenes starting from 2,4-diyne-1,6-diethers and
diamines in one reaction vessel under mild conditions.
Transition metal catalyzed intramolecular hydroaryla-
tion of alkynes, alkenes, and allenes by the addition of an
aryl CꢀH bond across a π-bond has received considerable
attention for its highly useful synthetic applications.1 This
reaction has been demonstrated to be one of the most
effective green chemistry methods because of its ideal atom
economy.2 Since the Pd-catalyzed intramolecular hydro-
arylation of alkynes was first described by Fujiwara,3 a
wide range of transition metal4 and Lewis acid catalyzed5
hydroarylations were reported.6 Recently, we developed
Pt-catalyzed hydroarylation of benzyl allenes through a
(1) (a) Kitamura, T. Eur. J. Org. Chem. 2009, 1111. (b) Harada, H.;
Thalji, R. K.; Bergman, R. G.; Ellman, J. A. J. Org. Chem. 2008, 73,
6772. (c) Tarselli, M. A.; Gagne, M. R. J. Org. Chem. 2008, 73, 2439.
(5) (a) Jean, M.; van de Weghe, P. Tetrahedron Lett. 2011, 52, 3509.
(b) Cacciuttolo, B.; Poulain-Martini, S.; Dunach, E. Eur. J. Org. Chem.
ꢀ
~
(d) Watanabe, T.; Oishi, S.; Fujii, N.; Ohno, H. Org. Lett. 2007, 9, 4821.
(e) Soriano, E.; Marco-Contelles, J. Organometallics 2006, 25, 4542.
(f) Bandini, M.; Emer, E.; Tommasi, S.; Umani-Ronchi, A. Eur. J. Org.
Chem. 2006, 3527. (g) Nevado, C.; Echavarren, A. M. Chem.;Eur. J.
2005, 11, 3155. (h) Nevado, C.; Echavarren, A. M. Synthesis 2005, 167.
(2) (a) England, D. B.; Padwa, A. Org. Lett. 2008, 10, 3631. (b) Yeh,
M.-C. P.; Tsao, W.-C.; Cheng, S.-T. J. Org. Chem. 2008, 73, 2902. (c)
Ferrer, C.; Amijs, C. H. M.; Echavarren, A. M. Chem.;Eur. J. 2007, 13,
2011, 3710. (c) Komeyama, K.; Igawa, R.; Takaki, K. Chem. Commun.
2010, 1748. (d) Hashimoto, T.; Kutubi, S.; Izumi, T.; Rahman, A.;
Kitamura, T. J. Organomet. Chem. 2011, 696, 99. (e) Xie, K.; Wang, S.;
Li, P.; Li, X.; Yang, Z.; An, X.; Guo, C.-C.; Tan, Z. Tetrahedron Lett.
2010, 51, 4466. (f) Xiao, Y.-P.; Liu, X.-Y.; Che, C.-M. J. Organomet.
Chem. 2009, 694, 494. (g) Zotto, C. D.; Wehbe, J.; Virieux, D.;
Campagne, J.-M. Synlett 2008, 13, 2033. (h) Li, R.; Wang, S. R.; Lu,
W. Org. Lett. 2007, 9, 2219. (i) Yamamoto, H.; Sasaki, I.; Imagawa, H.;
Nishizawa, M. Org. Lett. 2007, 9, 1399. (j) Inoue, H.; Chatani, N.;
Murai, S. J. Org. Chem. 2002, 67, 1414.
ꢀ
ꢀ~
1358. (d) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Commun. 2007,
333. (e) Saito, A.; Kanno, A.; Hanzawa, Y. Angew. Chem., Int. Ed. 2007,
ꢀ
ꢀ
46, 3931. (f) Marion, N.; Dıez-Gonzalez, S.; de Fremont, P.; Noble,
A. R.; Nolan, S. P. Angew. Chem., Int. Ed. 2006, 45, 3647. (g) Ferrer, C.;
Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45, 1105. (h) Trost,
B. M. Science 1991, 254, 1471. (i) Trost, B. M. Angew. Chem., Int. Ed.
1995, 34, 259.
(6) (a) Shibuya, T.; Shibata, Y.; Noguchi, K.; Tanaka, K. Angew.
Chem., Int. Ed. 2011, 50, 3963. (b) Niggemann, M.; Bisek, N. Chem.;
Eur. J. 2010, 16, 11246. (c) Chernyak, N.; Gevorgyan, V. Adv. Synth.
ꢀ
Catal. 2009, 351, 1101. (d) Weber, D.; Gagne, M. R. Org. Lett. 2009, 11,
4962. (e) Jiang, T.-S.; Tang, R.-Y.; Zhang, X.-G.; Li, X.-H.; Li, J.-H.
J. Org. Chem. 2009, 74, 8834. (f) Tang, D.-J.; Tang, B.-X.; Li, J.-H.
J. Org. Chem. 2009, 74, 6749. (g) Menon, R. S.; Findlay, A. D.;
Bissember, A. C.; Banwell, M. G. J. Org. Chem. 2009, 74, 8901. (h)
(3) (a) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.;
Fujiwara, Y. Science 2000, 287, 1992. (b) Jia, C.; Piao, D.; Kitamura,
T.; Fujiwara, Y. J. Org. Chem. 2000, 65, 7516.
ꢀ
(4) (a) Youn, S. W.; Pastine, S. J.; Sames, D. Org. Lett. 2004, 6, 581.
Webber, D.; Tarselli, M. A.; Gagne, M. R. Angew. Chem., Int. Ed. 2009,
€
(b) Mamane, V.; Hannen, P.; Furstner, A. Chem.;Eur. J. 2004, 10, 4556.
48, 5733. (i) Chernyak, N.; Gevorgyan, V. J. Am. Chem. Soc. 2008, 130,
5636. (j) Bajracharya, G. B.; Pahadi, N. K.; Gridnev, I. D.; Yamamoto,
Y. J. Org. Chem. 2006, 71, 6204. (k) Zhang, Z.; Liu, C.; Kinder, R. E.;
Han, X.; Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128,
9066. (l) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 10204.
(m) Thalji, R. K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. J. Am.
Chem. Soc. 2001, 123, 9692.
(c) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669. (d) Nishizawa, M.; Takao,
H.; Yadav, V. K.; Imagawa, H.; Sugihara, T. Org. Lett. 2003, 5, 4563. (e) Li,
Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239. (f) Li, H.-J.; Guillot, R.;
€
Gandon, V. J. Org. Chem. 2010, 75, 8435. (g) Furstner, A.; Mamane, V.
Chem. Commun. 2003, 2112. (h) Reetz, M. T.; Sommer, K. Eur. J. Org.
€
Chem. 2003,3485. (i) Furstner, A.; Mamane, V. J. Org. Chem. 2002,67, 6264.
r
10.1021/ol301522y
Published on Web 06/29/2012
2012 American Chemical Society

6-endo mode for the preparation of 1,4-dihydronaphtha-
lenes.7 Because tandem reactions have long been estab-
lished as efficient methods for the rapid synthesis of
complex compounds in relatively short steps starting from
simpleand readily availablesubstrates,8 weenvisionedthat
a tandem process involving transition metal catalyzed
intramolecular hydroarylation of diyne diether and dia-
mine followed by Brønsted acid catalyzed cationic cycliza-
tion of diene in one pot would provide structurally diverse
heterocycles. Herein, we describe the development of
intramolecular Au-catalyzed double hydroarylation of
2,4-diyne-1,6-diethers or diamines followed by cationic
cyclization in one pot.
the use of Ph3PAuCl and AgOTf (5 mol % each) produced
the intramolecular double hydroarylated product 2a in
80% yield in toluene at 30 °C after 2 h (entry 3). The
structure of 2a was unambiguously determined by spectro-
scopy. Dichloromethane was found to be the most optimal
solvent to give a 90% product yield within 0.3 h at the same
temperature (entry 4). Although the employment of AgBF4
(5 mol %) gave 2a in 84% yield at 30 °C for 1 h (entry 5),
AgNTf2 and AgAsF6 (5 mol % each) afforded 2a in 90%
and 88% yields, respectively, after 0.3 h (entries 6 and 7).
Ph3PAuCl and AgSbF6 (5 mol % each) provided 2ain 95%
yield in dichloromethane at 30 °C for 0.3 h (entry 8). The
best result was obtained with Ph3PAuCl and AgSbF6
(2.5 mol % each), producing 2a in 90% yield (entry 9).
Independent use of Ag salt (AgSbF6 and AgOTf, 5 mol %
each) without Ph3PAuCl did not give 2a(entries 10and 11).
To check the possibility of catalysis by a protic acid, we
attempted the double hydroarylation reaction in the
presence of trifluoromethanesulfonic acid (5 mol % and
30 mol %) in dichloromethane at rt. Under these condi-
tions, the reaction did not proceed (entries 12 and 13).
To explore the scope of the present tandem hydroaryla-
tion with respect to diyne diether and diamine 1, we carried
out further reactions in dichloromethane with Ph3PAuCl
and AgSbF6 (2.5 mol % each, Scheme 1). Varying the
electron demand of the substituents on the phenyl ring did
not diminish the efficiency of the tandem hydroarylation
reaction. Under the optimized reaction conditions, treat-
ment of 1,6-di(3,5-dimethylphenoxy)-2,4-hexadiyne 1b
with the Au-catalyst gave 2b in 83% yield in 20 min. The
tandem cyclization of 1,6-di(4-tert-butylphenoxy)-2,4-
hexadiyne 1c proceeded efficiently to provide 2c in 89%
yield in dichloromethane at 30 °C for 30 min. The presence
of a 4- and 3-methoxy group on the phenyl ring had little
effect on either the reaction rate (30 min) or the product
yield (2d, 81% and 2e, 80% yield). When 1,6-diphenoxy-
2,4-hexadiyne 1f having an N-Boc amino group was sub-
jected to the reaction conditions, the corresponding hydro-
arylated product 2f was obtained in 86% yield albeit with
a longer reaction time (7 h). 1,6-Di(2-phenylphenoxy)-2,
4-hexadiyne 1g underwent the Au-catalyzed double hydro-
arylation reaction, producing 2g in 92% yield for 30 min.
Certain labile functional groups commonly employed in
organic synthesis such as bromo or iodo moieties substi-
tuted on the phenyl ring were tolerated under these re-
action conditions. The presence of a strong electron-
withdrawing group such as 4-acetyl and 4-ethoxycarbonyl
had little effect on the product yield (2k, 88% and 2l, 91%)
although the reaction rate was found to be decreased to
some extent. Encouraged by these results, we carried out
an intramolecular Au-catalyzed double hydroarylation
reaction of diyne diamines. We were pleased to find that
substrates derived from N-sulfonyl substituted anilines
were successfully applied to the cyclization conditions,
thus greatly expanding the scope of our synthetic method.
For example, when bis(N-phenyl-N-tosyl)hexa-2,4-diynyl-
1,6-diamine (1m) was subjected to the optimized condi-
tions, the desired product (2m) was obtained in 84% yield
albeit requiring a longer reaction time when compared to
Table 1. Optimization of Intramolecular Catalytic Double
Hydroarylationa
entry
cat (mol %)
solvent time (h) yield (%)b
1
2
3
4
5
6
7
8
9
AuCl3 (5)/AgOTf (15)
toluene
toluene
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
4
0
AuCl (5)/AgOTf (5)
4
0
Ph3PAuCl (5)/AgOTf (5)
Ph3PAuCl (5)/AgOTf (5)
Ph3PAuCl (5)/AgBF4 (5)
Ph3PAuCl (5)/AgNTf2 (5)
Ph3PAuCl (5)/AgAsF6 (5)
Ph3PAuCl (5)/AgSbF6 (5)
2
80
90
84
90
88
95
90
0
0.3
1
0.3
0.3
0.3
0.3
18
4
Ph3PAuCl (2.5)/AgSbF6 (2.5) CH2Cl2
10 AgSbF6 (5)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
11
AgOTf (5)
0
12 TfOH (5)
13 TfOH (30)
24
24
0
0
a Reactions were carried out with 1a (0.2 mmol) in the presence of
catalyst. b Isolated yield.
At the outset of our studies, we attempted to optimize the
reaction conditions for the intramolecular Au-catalyzed
double hydroarylation reaction of 1,6-diphenoxy-2,4-hex-
adiyne (1a) readily prepared by Cu-catalyzed oxidative
coupling of phenyl propargyl ether (Table 1).9 When 1a
was treated with AuCl3 or AuCl (5 mol % each) in the
presence of AgOTf (5 mol %) in toluene at 30 °C, the
desired reaction did not proceed (entries1 and 2). However,
(7) Mo, J.; Lee, P. H. Org. Lett. 2010, 12, 2570.
(8) (a) Mo, J.; Kim, S. H.; Lee, P. H. Org. Lett. 2010, 12, 424. (b)
ꢀ
ꢀ
ꢀ
Fustero, S.; Jimenez, D.; Sanchez-Rosello, M.; del Pozo, C. J. Am.
Chem. Soc. 2007, 129, 6700. (c) Camm, K. D.; Castro, N. M.; Liu, Y.;
Czechura, P.; Snelgrove, J. L.; Fogg, D. E. J. Am. Chem. Soc. 2007, 129,
4168. (d) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem.,
Int. Ed. 2006, 45, 7134. (e) Seigal, B. A.; Fajardo, C.; Snapper, M. L.
J. Am. Chem. Soc. 2005, 127, 16329. (f) Ajamian, A.; Gleason, J. L. Angew.
Chem., Int. Ed. 2004, 43, 3754. (g) Tietze, L. F.; Rackelmann, N. Pure Appl.
Chem. 2004, 76, 1967. (h) Sutton, A. E.; Seigal, B. A.; Finnegan, D. F.;
Snapper, M. L. J. Am. Chem. Soc. 2002, 124, 13390. (i) Louie, J.; Bielawski,
C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 11312.
(9) (a) Chernykh, A.; Agag, T.; Ishida, H. Polymer 2009, 50, 3153. (b)
Huerta, G.; Fomina, L.; Rumsh, L.; Zolotukhin, M. G. Polym. Bull.
2006, 57, 433.
Org. Lett., Vol. 14, No. 14, 2012
3685

Scheme 1. Intramolecular Au-Catalyzed Double Hydroaryla-
tion of Dialkynyl Diethersa
Scheme 2. Intramolecular Au-Catalyzed Double Hydroaryla-
tion of 3a
a Reactions were carried out with 3 (0.2 mmol) in the presence of
catalyst. Percentage indicates isolated yield.
cascade reaction consisting of an intramolecular double
hydroarylation and a cationic cyclization might occur
in one pot. Unfortunately, the subsequent cyclization reac-
tion of 2a with Ph3PAuCl and AgSbF6 (2.5 mol % each)
in dichloromethane did not proceed (Table 2, entry 1).
Although exposure of 2a to trifluoromethanesulfonic acid
(TfOH, 5 mol %) afforded 5a in 3% yield (entry 2), we
were delighted to observe that TfOH (30 mol %) gave the
cationic cyclized product 5a in 80% yield in dichloro-
methane at 30 °C for 0.5 h (entry 3). The fact that
intramolecular double hydroarylation proceeds only with
a Au catalyst (Table 1, entry 9 vs 13) and the cationic
cyclization of its product 2a is just achieved by TfOH
catalyst(Table 2, entry 1 vs3) indicates thatthese two types
of cyclization reactions could be combined as a cascade
reaction in one pot. Althoughsubjecting1atothe optimum
conditions in the presenceof TfOH (10 and 20mol %) gave
the desired product5ain15% and 49% yields, respectively,
the second reaction, cationic cyclization of 1,3-diene
2a, was not completed (Table 3, entries 1 and 2). How-
ever, when 1a was treated with Ph3PAuCl and AgSbF6
(2.5 mol % each) in the presence of TfOH (30 mol %), the
cascade reaction consisting of a Au-catalyzed intramo-
lecular double hydroarylation and cationic cyclization
proceeded smoothly without the interference of two types
of catalyst, producing 5a in 79% yield in dichloromethane
at 30 °C for 2 h in one pot (entry 3).
a Reactions were carried out with 1 (0.2 mmol) in the presence of
catalyst. Percentage indicates isolated yield. bPh3PAuCl and AgSbF6
(5 mol % each) was used as a catalyst.
substrates bearing an aryl ether unit. The structure of 2m
was unambiguously characterized by a X-ray crystallo-
graphy.10 Likewise, bi-(2H-quinoline) (2n and 2o) could be
obtained in high yields under the same conditions.
We were pleased to find that diyne 3a having both an
ether and amine functional group underwent the desired
reaction with Ph3PAuCl and AgSbF6 (5 mol % each) in
dichloromethane at 30 °C, producing the corresponding
cyclic compound 4a in 88% yield through an intramo-
lecular double hydroarylation reaction (Scheme 2). More-
over, under the optimum reaction conditions, diynes 3b
and 3c bearing mutually different substituents on each
phenyl ring were smoothly converted to the cyclic com-
pounds (4b and 4c) in 89% and 82% yields, respectively.
Next, we envisioned that 1,3-dienes 2 might be further
cyclized by either a Au or Brønsted acid catalyst, produ-
cing dioxafluoranthene. Moreover, if this catalytic cationic
cyclization could be accomplished, we envisaged that the
Table 2. Cationic Cyclization of 1,3-Dienesa
entry
cat. (mol %)
time (h)
yield (%)b
1
2
3
Ph3PAuCl (2.5)/AgSbF6(2.5)
TfOH (5)
10
12
0.5
0
3
TfOH (30)
80
a Reactions were carried out with 2a (0.2 mmol) in the presence of
catalyst. b Isolated yield.
(10) Supporting Information.
3686
Org. Lett., Vol. 14, No. 14, 2012

Table 3. Double Hydroarylation and Cationic Cyclization of
1,3-Diynesa
Scheme 3. Intramolecular Au-Catalyzed Double Hydroaryla-
tion and Cationic Cyclization of Dialkynyl Diethersa
entry
cat. (mol %)
time (h) yield (%)b
1
2
3
Ph3PAuCl (2.5)/AgSbF6 (2.5)/TfOH (10)
Ph3PAuCl (2.5)/AgSbF6 (2.5)TfOH (20)
Ph3PAuCl (2.5)/AgSbF6 (2.5)/TfOH (30)
24
8
15 (68)c
49 (28)c
79
2
a Reactions were carried out with 1a (0.2 mmol) in the presence of
catalyst. b Isolated yield. c Isolated yield of 2a.
We next investigated the scope and functional group
tolerance of the above double hydroarylation followed by
cationic cyclization (Scheme 3). Treatment of 1b with
Ph3PAuCl and AgSbF6 (2.5 mol % each) in the presence
of TfOH (30 mol %) gave the desired product 5b in 89%
yield in dichloromethane at 30 °C for 2 h. Under the
optimum reaction conditions, the tandem reaction perfor-
med equally well with diynes 1c and 1d having a methoxy
and phenyl group, producing 5c and 5d in 76% and 92%
yields, respectively. Treatment of 1,6-di(2-bromophenoxy)-
2,4-hexadiyne (1e) with Ph3PAuCl and AgSbF6 (5 mol %
each) in the presenceof 30mol % TfOH afforded 5e in 86%
yield. The reaction of 1f with a Au-catalyst followed by
TfOH produced 5f in 89% yield. 1,6-Di(4-iodophenoxy)-
2,4-hexadiyne (1g) underwent the tandem reaction to af-
ford 5g in 74% yield under the present conditions. How-
ever, in the case of substrates (2f, 2m, 2n, and 2o) having a
nitrogen atom, the cationic cyclization of 1,3-diene in the
cascade reaction did not proceed after intramolecular Au-
catalyzed double hydroarylation.
a Reactions were carried out with 1 (0.2 mmol) in the presence of
catalyst. Percentage indicates isolated yield. Ph3PAuCl and AgSbF6
(5 mol % each) was used as a catalyst.
b
Scheme 4. Plausible Mechanism
Although the mechanism of the present reaction has not
been fully established at the present stage, a possible reaction
pathway is shown in Scheme 4. Coordination of a gold
catalyst to triple bond in diyne diether 1a results in the
formation of the intermediate A which, upon nucleophilic
attack of the carbon on the aromatic ring, is cyclized leading to
a σ-gold complex B. Subsequent aromatization followed by
protodeauration of B might afford the chromene derivative C
to release the gold catalyst back into the catalytic cycle. The
repeated intramolecular hydroarylation of intermediate C
with a Au-catalyst would give double hydroarylation product
2a. 1,3-Diene 2a is expected to be protonated to produce
tertiary benzylic carbocation E, and then, an electrocycliza-
tion process followed by aromatization finally will furnish 5a.
In conclusion, we presented herein the development
of Au-catalyzed intramolecular double hydroarylation
followed by cationic cyclization that allows the rapid
synthesis of 4,40-bi(2H-chromene), bi(2H-quinoline), and
dioxafluoranthene starting from 2,4-diyne-1,6-diether and
diamine in one reaction vessel.
Acknowledgment. Dedicated to Professor Chang Kiu
Lee, Kangwon National University, on the occasion of his
honorable retirement. We thank the CRI (2012-0001245)
program funded by the National Research Foundation of
Korea. P. H. Lee thanks Prof. S. Chang for helpful discussion.
Supporting Information Available. Experimental pro-
cedure and spectral data (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 14, 2012
3687