Nickel-catalyzed regio- and diastereoselective intermolecular three-component coupling of oxabicyclic alkenes with alkynes and organoboronic acids

Article abstract of DOI:10.1039/c2cc38001c

Reaction of oxabicyclic alkenes with alkynes and organoboronic acids in the presence of Ni(cod)₂, P(t-Bu)₃, and CsF in a binary solvent toluene-methanol (1 : 3) at 75 to 85 °C provided exo-5,6-disubstituted 7-oxanorbornene derivatives in good to excellent yields. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c2cc38001c

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Nickel-catalyzed regio- and diastereoselective
intermolecular three-component coupling
of oxabicyclic alkenes with alkynes and
organoboronic acids†
Cite this: Chem. Commun., 2013,
49, 1557
Received 5th November 2012,
Accepted 4th January 2013
DOI: 10.1039/c2cc38001c
Subramaniyan Mannathan and Chien-Hong Cheng*
www.rsc.org/chemcomm
Reaction of oxabicyclic alkenes with alkynes and organoboronic acids in metal-catalyzed p-component coupling reactions9 and bicyclic
in the presence of Ni(cod)2, P(t-Bu)3, and CsF in a binary solvent chemistry,10 we started to explore the possibility of using hetero-
toluene–methanol (1 : 3) at 75 to 85 8C provided exo-5,6-disubstituted bicyclic alkenes in the sequential coupling reaction. Herein, we
7-oxanorbornene derivatives in good to excellent yields.
describe a new nickel-catalyzed intermolecular sequential coupling
of oxanorbornenes with alkynes and organoboronic acids to
Transition-metal-catalyzed domino reactions are versatile and obtain exo-5,6-disubstituted 7-oxanorbornene derivatives11 in
powerful tools for modern organic synthesis.1 Particularly, nickel- high regio- and diastereoselectivity. It is noteworthy that
catalyzed multicomponent reactions have attracted immense inter- 1,2,3,4-tetrahydro-1,4-epoxynaphthalenes are valuable substrates
est due to the facile construction of complex and diverse structures for various transformation reactions.12
from readily accessible starting materials in a one-pot process.2 A
Treatment of oxabenzonorbornadiene (1a) with 1-phenyl-1-
variety of nickel-catalyzed sequential coupling reactions involving propyne (2a) and (E)-styrylboronic acid (3a) in the presence of
two p-systems, including aldehydes, alkenes, alkynes, allylic halides, Ni(cod)2 (10 mol%), P(t-Bu)3 (10 mol%) and CsF (1 equiv.),
imines, dienes, and allenes, with the main group organometallics using a toluene and methanol (1 : 3) binary solvent system, at
was successfully demonstrated.3–6 Among such reactions, sequential 75 1C for 15 min afforded 4a in 92% yield with high diastereo-
coupling involving bicyclic alkene as a p-component is hardly selectivity. The reaction is highly regio- and stereoselective in
studied. In 1998, Ikeda and his co-workers found a diastereo- which the styryl group of 3a and the alkenyl group of 2a are all
differentiative tandem coupling of norbornenes with enones and added very selectively to the exo face of 1a and the C–C bond
alkynyltin.3e Fukuzawa and Ogata described a three-component formation occurred at the alkene carbon of 1a and the methyl
reaction of norbornenes with two alkynes leading to 1,5-enyne substituted alkyne carbon of 2a. Moreover, the phenyl and
via C–H activation of terminal alkynes.7a Very recently, the methyl groups of 2a in the product are cis to each other.
same group disclosed a diastereoselective three-component
To understand the nature of the catalytic reaction and to
coupling reaction between aryl aldehydes, norbornenes, and optimize the reaction conditions, we began our investigation by
silanes to synthesize silylated indanol derivatives.7b Typically, treating 1a (1.00 mmol) and 2a (1.00 mmol) with 3a (1.00 mmol)
these reactions were demonstrated with norbornenes and in the presence of Ni(cod)2 (10 mol%) as the catalyst, using
therefore the application of heterobicyclic alkenes in the multi- methanol as the solvent. The reaction proceeded well at 75 1C
component reactions remains in demand.
affording three component coupling product 4a in 54% yield
Previously, we had demonstrated reductive cyclization8a,b along with [2+2] cycloaddition product8c 5a and ring-opening
and [2+2] cycloaddition8c of oxa- and azabicyclic alkenes with reductive coupling product8b 6a in 22% and 10% yields, respec-
alkynes catalysed by Ni(II) systems. Subsequently, we reported tively (Scheme 1). In order to suppress the formation of 5a and
Ni(cod)2-catalyzed intermolecular three-component coupling 6a, various types of phosphine ligands and additives were
reaction of benzynes (or alkynes) with enones and organoboronic examined under similar reaction conditions (see ESI†). After
acids,8d,e and a borylative coupling of alkynes with enones to the systematic studies, we found that the combination of
synthesize alkenyl boronates.8f As part of our ongoing interest P(t-Bu)3 (10 mol%) as the ligand and CsF (1.00 mmol) as the
additive gave 4a in 82% yield along with 6a in 10% yield. In the
present catalytic reaction, it appears that the use of P(t-Bu)3 as
the ligand limits the formation of 5a to a trace and the presence
of CsF (without CsF, yield of 4a is 62%) remarkably increases the
yield of 4a. A binary solvent system, a 1 : 3 mixture of toluene
and methanol, is also essential to suppress the formation of 6a
Department of Chemistry, National Tsing Hua University, Hsinchu 30043, Taiwan.
E-mail: chcheng@mx.nthu.edu.tw; Fax: +886-3-5724698; Tel: +886-3-5721454
† Electronic supplementary information (ESI) available: General experimental
procedures, spectral data (1H, 13C NMR and HRMS) and copies of 1H and 13C
NMR spectra of all compounds. See DOI: 10.1039/c2cc38001c
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 1557--1559 1557

View Article Online
Communication
ChemComm
Table 2 Results of the three-component coupling of 1a with various alkynes 2
and organoboronic acids 3a
Entry R1
R2
R3
Yieldb (%)
Scheme 1
1
2
3
4
5
6
7
8
9
10
Et
Ph
Ph (2b)
Ph (2c)
E-Styryl (3a)
E-Styryl (3a)
90 (4g)
65c (4h)
92 (4i)
92 (4j)
95 (4k)
90 (4l)
0 (4m)
86 (4n)
n-Propyl 4-MeOC6H4 (2d) E-Styryl (3a)
H
CH2OCH3 Ph (2f)
(CH2)2OH Ph (2g)
CH2CH3 CH2CH3 (2h)
CH2OCH3 CH2OCH3 (2i) E-Styryl (3a)
CH3
CH3
Ph (2e)
E-Styryl (3a)
E-Styryl (3a)
E-Styryl (3a)
E-styryl (3a)
and afforded 4a in 86% yield. Finally, increasing the molar ratio
of 1a (1.50 mmol) and 2a (1.50 mmol) with respect to 3a
(1.00 mmol) provided product 4a in 92% isolated yield.
Under the optimized reaction conditions, the reactions of
various 7-oxanorbornenes 1b–e with 2a and 3a were examined
(see Table 1, footnote a). Thus, 1,4-epoxytriphenylene 1b afforded
the three component coupling product 4b in 75% yield. Similarly,
dimethoxy substituted oxanorbornadienes 1c and 1d effectively
coupled with 2a and 3a to give 4c and 4d in high yields. Aliphatic
functionalized oxanorbornene, 1e, also successfully partici-
pated to give the diastereoselective coupling product 4e in 94%
yield. Gratifyingly, 7-azabenzonorbornadiene 1f underwent three-
component coupling to afford 4f in 88% yield. It is noteworthy that
the present reaction conditions are not suitable for norbornenes.
To broaden the scope of the present sequential coupling
reaction, reactions of various types of alkynes 2 and organo-
boronic acids 3 with 1a were investigated (see Table 2, footnote a).
Thus, 1-phenyl-1-butyne (2b) afforded the corresponding product
4g in high yield (entry 1). In a similar manner, diphenylacetylene
(2c) furnished 4h in 65% yield (entry 2). Electron-rich aromatic
alkyne, 1-methoxy-4-(pent-1-ynyl)benzene (2d), afforded the three-
component coupling product 4i in 92% yield (entry 3). Terminal
alkyne, phenylacetylene (2e), also reacted with 1a and 3a to give
4j in 92% yield (entry 4). Functionalized alkynes, 2f and 2g,
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
E-4-MeC6H4CHQCH (3b) 95 (4o)
Z-CH3CHQCH (3c)
Ph (3d)
2-MeOC6H4 (3e)
4-MeC6H4 (3f)
3-ClC6H4 (3g)
3-FC6H4 (3h)
2-MeC6H4 (3i)
78e (4p)
82 (4q)
89 (4r)
82 (4s)
75 (4t)
70 (4u)
85 (4v)
11d CH3
12d CH3
13d CH3
14d CH3
15d CH3
16d CH3
a
b
Similar to the reactions shown in footnote a, Table 1. Isolated yields.
Reaction was carried out at 85 1C. For entries 11–16 the reaction
c
d
e
time was 0.5 h. Z/E ratio is 88 : 12.
effectively participated to provide 4k and 4l in high yields
(entries 5 and 6). Aliphatic alkyne, 3-hexyne (2h), did not
furnish 4m (entry 7) while 1,4-dimethoxy butyne (2i) gave 4n
in 86% yield (entry 8).
A variety of organoboronic acids was tested in this reaction
(Table 2, entries 9–16). In addition to 3a, 3b and (Z)-prop-1-
enylboronic acid (3c) underwent three-component coupling reaction
effectively with 1a and 2a to give 4o and 4p in 95 and 78% yield,
respectively (entries 9 and 10). Phenylboronic acid (3d) also
successfully participated to give the respective diastereoselective
product 4q in 82% yield (entry 11). In a similar manner, other
arylboronic acids, 3e–i, underwent coupling reaction with 1a
and 2a smoothly to give the corresponding products 4r–v in
70–89% yield, respectively (entries 12–16).
Table 1 Results of the three-component coupling of oxa- and azabenzo-
norbornadiene (1a–f) with alkynes 2a and organoboronic acids 3aa,b
To understand the role of methanol, an isotope-labeling experi-
ment involving 1a, 2a and 3a under standard reaction conditions
using CD3OD as the solvent was carried out (Scheme 2). The reaction
proceeded well and afforded the deuterated product 4a-d1 in 82%
yield with 86% deuterium incorporation.
Furthermore, the sequential coupling of 1a and 2a with
E-styrylboronate (3a0) (Scheme 2) also gave 4a in 92% yield.
These results clearly revealed that the selective protonation of
nickelacyclopentene 9 (Scheme 3) was done by methanol. More-
over, the reaction of 1a and 3a in the absence of 2a results only in
the formation of product 7 from [2+2] dimerization of 1a10e
supporting that the catalytic reaction proceeds via intermediate 9.
Based on the observation in Scheme 2, a possible catalytic
reaction mechanism for the present reaction is shown in
Scheme 3. Highly chemoselective coordination of 1a and 2a
to the Ni(0) center, followed by a regioselective oxidative
cyclometalation, yields nickelacyclopentene intermediate 9.
Selective protonation of 9 by MeOH affords an alkyl(methoxy)-
nickel intermediate 10.8b,c Transmetallation of 10 with styrylboronic
a
Unless otherwise mentioned, all reactions were carried out using
oxanorbornene 1 (1.50 mmol), 1-phenyl-1-propyne 2a (1.50 mmol),
styryl boronic acid 3a (1.00 mmol), Ni(cod)2 (10 mol%), P(t-Bu)3
(10 mol%), CsF (1.0 mmol) and toluene + methanol (1 : 3) (2.0 mL) at
75 1C for 15 min. b Isolated yields; yield in the parentheses was determined
by the 1H NMR method using mesitylene as an internal standard.
c
1558 Chem. Commun., 2013, 49, 1557--1559
This journal is The Royal Society of Chemistry 2013

View Article Online
ChemComm
Communication
Angew. Chem., Int. Ed., 2004, 43, 3890; (e) K. M. Miller, C. Molinaro
and T. F. Jamison, Tetrahedron: Asymmetry, 2003, 14, 3619;
( f ) J. Montgomery and G. J. Sormunen, Top. Curr. Chem., 2007,
279, 1; (g) R. M. Moslin, K. M. Moslin and T. F. Jamison, Chem.
Commun., 2007, 4441; (h) W. Li, A. Herath and J. Montgomery, J. Am.
Chem. Soc., 2009, 131, 17024 and references therein.
3 (a) S. Ikeda and Y. Sato, J. Am. Chem. Soc., 1994, 116, 5975;
(b) S. Ikeda, K. Kondo and Y. Sato, J. Org. Chem., 1996, 61, 8248;
(c) S. Ikeda, H. Yamamoto, K. Kondo and Y. Sato, Organometallics,
1995, 14, 5015; (d) S. Ikeda, D.-M. Cui and Y. Sato, J. Am. Chem. Soc.,
1999, 121, 4712; (e) D.-M. Cui, H. Yamamoto, S. Ikeda, K. Hatano
and Y. Sato, J. Org. Chem., 1998, 63, 2782.
4 Selected references: (a) R. D. Baxter and J. Montgomery, J. Am. Chem.
Soc., 2008, 130, 9662; (b) N. Saito, T. Katayama and Y. Sato, Org. Lett.,
2008, 10, 3829; (c) H. A. Malik, M. R. Chaulagain and J. Montgomery,
Org. Lett., 2009, 11, 5734; (d) H. A. Malik, G. J. Sormunen and
J. Montgomery, J. Am. Chem. Soc., 2010, 132, 6304; (e) W. Li, N. Chen
and J. Montgomery, Angew. Chem., Int. Ed., 2010, 49, 8712; ( f ) W. Li
and J. Montgomery, Chem. Commun., 2012, 48, 1114.
Scheme 2 Mechanistic studies.
5 (a) S.-S. Ng and T. F. Jamison, J. Am. Chem. Soc., 2005, 127, 14194;
(b) C.-Y. Ho and T. F. Jamison, Angew. Chem., Int. Ed., 2007, 46, 782;
(c) W.-S. Huang, J. Chan and T. F. Jamison, Org. Lett., 2000, 2, 4221;
(d) S. J. Patel and T. F. Jamison, Angew. Chem., Int. Ed., 2003, 42, 1364.
6 Selected references: (a) K. Shimizu, M. Takimoto and M. Mori, Org.
Lett., 2003, 5, 2323; (b) K. Saibata, M. Kimura, M. Shimizu and
Y. Tamura, Org. Lett., 2001, 3, 2181; (c) M. Kimura, A. Ezoe,
K. Shibata and Y. Tamura, J. Am. Chem. Soc., 1998, 120, 4033;
(d) Y. Sato, R. Sawaki, N. Saito and M. Mori, J. Org. Chem., 2002,
67, 656; (e) S.-K. Kang and S.-K. Yoon, Chem. Commun., 2002, 2634;
( f ) R. Shintani, A. Tsurusaki, K. Okamoto and T. Hayashi, Angew.
Chem., Int. Ed., 2005, 44, 3909.
7 (a) K. Ogata, J. Sugasawa, Y. Atsuumi and S.-I. Fukuzawa, Org. Lett.,
2010, 12, 148; (b) K. Ogata, Y. A. Atsuumi, D. Shimada and
S.-I. Fukuzawa, Angew. Chem., Int. Ed., 2011, 50, 5896.
Scheme 3 Proposed mechanistic pathway.
8 (a) D. K. Rayabarapu, T. Sambaiah and C.-H. Cheng, Angew. Chem.,
Int. Ed., 2001, 40, 1286; (b) D. K. Rayabarapu and C.-H. Cheng,
Chem.–Eur. J., 2003, 9, 3164; (c) D.-J. Huang, D. K. Rayabarapu, L.-P. Li,
T. Sambaiah and C.-H. Cheng, Chem.–Eur. J., 2000, 6, 3706; (d) T. T.
Jayanth and C.-H. Cheng, Angew. Chem., Int. Ed., 2007, 46, 5921;
(e) C.-M. Yang, M. Jeganmohan, K. Parthasarathy and C.-H. Cheng,
Org. Lett., 2010, 12, 3610; ( f ) S. Mannathan, M. Jeganmohan and
C.-H. Cheng, Angew. Chem., Int. Ed., 2009, 48, 2192.
9 (a) M. Jeganmohan and C.-H. Cheng, Chem. Commun., 2008, 3101;
(b) M. Jeganmohan, S. Bhuvaneswari and C.-H. Cheng,
Angew. Chem., Int. Ed., 2009, 48, 77; (c) M. Jeganmohan and C.-H.
Cheng, Chem.–Eur. J., 2008, 14, 10876; (d) S. Mannathan and
C. H. Cheng, Chem.–Eur. J., 2012, 18, 11771; (e) S. Mannathan and
C.-H. Cheng, Chem. Commun., 2010, 46, 1923; ( f ) C.-H. Wei,
S. Mannathan and C.-H. Cheng, J. Am. Chem. Soc., 2011, 133, 6942.
acid 3a gives nickel–styryl intermediate 11. Reductive elimination
affords product 4a and regenerates the Ni(0) catalyst for further
catalytic cycles. The highly regioselective oxidative cyclometalation
in the present catalytic reaction might be controlled by both
electronic and steric effects of alkyne and alkene.9c Moreover,
the phenyl group from alkyne 2 favoring to stay at the position
close to the Ni(II) center of nickelacyclopentene 9 is probably to
stabilize the intermediate via an Z3-benzyl–Ni coordination.13
In conclusion, we have developed a highly regio- and
diastereoselective nickel-catalyzed three-component reductive
coupling of oxanorbornenes with alkynes and organoboronic 10 (a) D. K. Rayabarapu and C.-H. Cheng, Acc. Chem. Res., 2007, 40, 971;
(b) C.-S. Li, C.-H. Cheng, F.-L. Liao and S.-L. Wang, J. Chem. Soc.,
Chem. Commun., 1991, 710; (c) J.-P. Duan and C.-H. Cheng, Organo-
metallics, 1995, 14, 1608; (d) J.-P. Duan and C.-H. Cheng, Tetrahedron
acids to obtain exo-5,6-disubstituted 7-oxanorbornene deriva-
tives in good to excellent yields. The wide scope of the three
substrates was successfully demonstrated. Further extension to
the coupling of two different p-components with an organo-
metallic reagent is in progress.
We thank the National Science Council of Republic of China
(NSC-101-2628-M-007-004) for support of this research.
Lett., 1993, 34, 4019; (e) D.-J. Huang and C.-H. Cheng, J. Organomet.
Chem., 1995, 490; ( f ) D. K. Rayabarapu, C.-F. Chiou and
C.-H. Cheng, Org. Lett., 2002, 4, 1679.
11 (a) S. Ito, T. Itoh and M. Nakamura, Angew. Chem., Int. Ed., 2011,
50, 454; (b) R. C. Larock and P. L. Johnson, J. Chem. Soc., Chem.
Commun., 1989, 1368; (c) C.-J. Kuo, S.-J. Cheng, S.-T. Chang and
C.-H. Liu, Eur. J. Org. Chem., 2008, 485.
12 (a) Y. Guindon, M. Therien, Y. Girard and C. Yoakim, J. Org. Chem.,
1987, 52, 1680; (b) U. Azzena, S. Demartis and G. Melloni, J. Org.
Chem., 1996, 61, 4913; (c) R. Caple, G. M.-S. Chen and J. D. Nelson,
J. Org. Chem., 1971, 36, 2874; (d) Y. Guindon, M. Therien, Y. Girard
and C. Yoakim, J. Org. Chem., 1987, 52, 1680.
Notes and references
1 (a) T.-L. Ho, Tandem Organic Reactions, Wiley-Interscience,
New York, 1992; (b) T.-L. Ho, Tactics of Organic Synthesis, Wiley-
Interscience, New York, 1994, p. 79.
13 (a) P. Liu, P. McCarren, P. H.-Y. Cheong, T. F. Jamison and
K. N. Houk, J. Am. Chem. Soc., 2010, 132, 2050; (b) A. Nishimura,
M. Ohashi and S. Ogoshi, J. Am. Chem. Soc., 2012, 134, 15692.
2 Reviews and selected references: (a) J. Montgomery, Acc. Chem. Res.,
2000, 33, 467; (b) S. Ikeda, Acc. Chem. Res., 2000, 33, 511; (c) S. Ikeda,
Angew. Chem., Int. Ed., 2003, 42, 5120; (d) J. Montgomery,
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 1557--1559 1559