Novel palladium-catalyzed cascade carboxylative annulation to construct functionalized γ-lactones in ionic liquids

Article abstract of DOI:10.1039/c3cc48052f

A novel palladium-catalyzed, one-pot, four-step cascade method has been developed to afford functionalized γ-lactones in moderate to good yields. This novel and general methodology represents a rare instance of carbonylation of the C(sp³)-palladium bond. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc48052f

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Novel palladium-catalyzed cascade carboxylative
annulation to construct functionalized c-lactones
in ionic liquids†
Cite this: Chem. Commun., 2014,
50, 1381
Received 20th October 2013,
Accepted 26th November 2013
Jianxiao Li, Shaorong Yang,* Wanqing Wu and Huanfeng Jiang*
DOI: 10.1039/c3cc48052f
www.rsc.org/chemcomm
A novel palladium-catalyzed, one-pot, four-step cascade method accessible substrates continues to attract broad interest. More
has been developed to afford functionalized c-lactones in moderate recently, some representative strategies have been exploited for
to good yields. This novel and general methodology represents a rare the preparation of these types of compounds as well.10 Moreover,
instance of carbonylation of the C(sp3)–palladium bond.
we reported an intermolecular carboesterification to construct
saturated g-lactones through copper-catalyzed oxidative [3+2]
Motivated by the increasing requirements for sustainable chemistry, cycloaddition reactions between alkenes and anhydrides.11
green and atom-economic synthesis has attracted great attention.1 Despite the significant progress that has been achieved along
Toward this end, carbonylation processes using carbon monoxide these lines, there are only a few methods that exist for the effective
(CO) as a C1 building block have been studied extensively, because synthesis of functionalized saturated g-lactones in an efficient,
of the direct formation of complicated molecules from readily safer and green way. As part of our research program on nucleo-
accessible starting materials.2 In particular, transition metal- palladation12 and Pd-catalyzed cross-coupling reactions in ionic
catalyzed carbonylation of aromatic halides with CO in the presence liquids (ILs),13 herein, we wish to present the first example of
of various nucleophiles has undergone rapid development,3 since palladium-catalyzed intermolecular carbonylation of alkynes with
the pioneering work of Heck and co-workers in 1974.4 During homoallylic alcohols in [C2O2mim]X to selectively construct satu-
the past decade, Pd-catalyzed aromatic C–H functionalization/ rated g-lactones with high regio- and stereoselectivity.
carbonylation simultaneously has attracted more and more
interest.5 However, carbonylation of the C(sp3)–palladium bond propiolate (1a) with homoallyl alcohol (2) in the presence of
remains an outstanding challenge.6
1 atm CO/O2 (Table 1). Firstly, when 1a and 2 were treated with
Our experiment was initiated by treating ethyl 3-phenyl-
On the other hand, the saturated g-lactones are important PdCl2 (3 mol%) and CuCl2Á2H2O (2 equiv.) in [Bmim]Cl, no
moieties in organic synthesis because of their ability to serve as desired product 3a was obtained. Subsequently, the reaction
building blocks in a wide variety of functional group transforma- was further investigated by replacing [Bmim]Cl with other ionic
tions.7 They have also been found as a substructure in numerous liquids, such as [C2O2mim]Cl and [C2OHmim]Cl, and
bioactive natural products and potential pharmaceutically [C2O2mim]Cl was found to be the most suitable medium for
interesting compounds.8 Transition metal-catalyzed reactions this process (entries 2 and 3). Optimization of the reaction
have emerged as a powerful tool for the construction of saturated conditions showed that O2 played a crucial role in the success
g-lactones and have become one of the most attractive methodo- of this transformation (entries 4–6). Gratifyingly, when the
logies in the last decade.9 However, all these elegant develop- carbonylation was conducted under mixed gas outside the
ments suffer from certain limitations such as multiple steps, CO/O2 explosion limits (CO/O2 = 3 : 1), 93% yield of desired
troublesome operation, harsh reaction conditions or low yields, (Z)-3a was obtained (entry 7). The configuration was elucidated
making them less attractive in organic synthesis. Thus, the by interpreting NOESY spectra.14 Furthermore, other palladium
development of methods that can construct these classes of catalysts were also examined. Except for PdCl2, other Pd
compounds in an efficient and practical manner from readily sources, including Pd(OAc)2, Pd(PPh3)2Cl2, Pd(MeCN)2Cl2,
Pd(PhCN)2Cl2 and PdBr2, showed low efficiencies (entries 8–12).
School of Chemistry and Chemical Engineering, South China University of
Finally, various conventional solvents were examined, such as
CH3CN, THF, 1,4-dioxane and DMF, which significantly decreased
the yields and stereoselectivities (entries 13–16).
With the optimal conditions in hand, we further investi-
gated the scope and limits of this reaction. Representative
Technology, Guangzhou, 510640, China. E-mail: jianghf@scut.edu.cn;
Fax: +86-20-87112906; Tel: +86-20-87112906
† Electronic supplementary information (ESI) available: Experimental section,
characterization of all compounds, and copies of 1H and 13C NMR spectra for
isolated compounds. See DOI: 10.1039/c3cc48052f
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Table 1 Optimization of the reaction conditionsa
excellent yields of the desired products were obtained (3b–3f).
Pleasingly, all the reactions exhibited high functional-group
tolerance and smoothly and cleanly occurred with both
electron-withdrawing and electron-donating substituents on
the aromatic ring. When 2 reacted with alkynoates with
electron-donating groups, the corresponding products 3g–3m
were obtained in moderate yields (63–80%). Notably, the vinyl
group was tolerated under the standard reaction conditions,
providing 3l in 63% yield with high stereoselectivity. Substitution
at the 4-position or 3-position of the aromatic ring had a slight
impact (3e, 3g and 3f). Moreover, the di-electron-donating group
substituted substrate also gave moderate yield (3m). Thus,
this result indicated that these reactions were not considerably
inhibited by the steric hindrance of alkynoates. Alkynoates with
halide substituents remained intact in these coupling reactions.
For example, alkynoates with the –Cl, –F, or –Br substituent at the
4-position reacted with 2 to give 3n, 3o, and 3q in 76%, 78%, and
83% yields, respectively. Alkynoates with a strong electron-
Entry
Catalyst
Solvent
Yieldb
Z/E
1
2
3
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Pd(OAc)2
PdCl2(PPh3)2
Pd(PhCN)2Cl2
Pd(MeCN)2Cl2
PdBr2
PdCl2
PdCl2
[Bmim]Cl
—
—
81
37
31
24
93 (86)
47
26
43
35
61
80
83
18
74
—
—
[C2OHmim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
[C2O2mim]Cl
CH3CN
>98/2
98/2
94/6
94/6
>98/2
98/2
98/2
98/2
98/2
98/2
78/22
70/30
54/46
4c
5d
6e
7 f
8
9
10
11
12
13
14
15
16
1,4-Dioxane
DMF
THF
PdCl2
PdCl2
79/21 withdrawing group at the 4-position, such as –COOMe, –CN, or
–CF3, gave products 3r, 3s, and 3t in 83%, 83%, and 85% yields,
a
Unless otherwise noted, all reactions were performed with 1a
(0.25 mmol), 2 (0.3 mmol), Pd catalyst (0.03 mol) and CuCl2Á2H2O (2 equiv.)
under CO/O2 = 1 : 1 (1 atm) in the indicated solvent (1.0 mL) at room
temperature for 12 h. [Bmim]Cl: 1-butyl-3-methylimidazolium chloride;
[C2OHmim]Cl: 1-hydroxyethyl-3-methylimidazolium chloride; [C2O2mim]Cl:
1-carboxymethyl-3-methylimidazolium chloride. b Determined by GC using
dodecane as the internal standard. Data in parentheses are the isolated
respectively. In addition, naphthalene alkynoate exhibited excellent
reactivity under the standard reaction conditions and gave the
desired product 3u in 78% yield. Disappointingly, heterocyclic
alkynoate, such as ethyl 3-(thiophen-2-yl)propiolate (1v), failed to
react with 2 to afford the desired products. In terms of the
stereoselectivity, all the products obtained in the presence of an
excess of chloride ions and acid in a polar solvent resulted from
trans additions.15 The site of halogen addition to asymmetric
acetylenes was controlled by electronic factors.16
yields. Without O2. d Instead of O2, 2 equiv. K2S2O8 was used. e Instead of
c
f
O2, 2 equiv. DDQ was used. CO/O2 = 3:1.
Table 2 Substrate scope of the carbonylation of alkynoates with 2 in
[C2O2mim]Cla
(1)
(2)
(3)
Inspired by these results, we further examined other types of
alkynes for this transformation under the standard reaction
conditions. Unfortunately, alkynone (4) and alkynamides (5)
failed to afford the desired products (eqn (1) and (2)). It
is noteworthy that the reaction of 1a with 2 in [C2O2mim]Br
(1-carboxymethyl-3-methylimidazolium bromide) under similar
reaction conditions provided 6 in 81% yield (eqn (3)).
To further demonstrate the utility of the present reaction in
synthesizing various saturated g-lactone derivatives, the trans-
formations of the resultant 3a were investigated (Scheme 1). For
instance, 3a underwent the Suzuki–Miyaura coupling to produce the
a
Reaction conditions: 1 (0.25 mmol), 2 (0.30 mmol), PdCl2 (3 mol%),
O2 (1 atm) and [C2O2mim]Cl (1 mL) at room temperature. The comple-
tion of the reaction was monitored by TLC. Yields refer to isolated yields.
results are summarized in Table 2. As expected, ethyl, allyl and highly functionalized g-lactone 7 in 70% yield.17 To our satisfaction,
phenyl alkynoates and substituted phenylpropiolic acid were the Negishi coupling of 3a occurred uneventfully as well, providing
allowed to react under the optimal conditions, and good to the stereodefined tetrasubstituted alkene 8 in 63% yield.17
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Guangdong Natural Science Foundation (10351064101000000 and
S2012040007088) for financial support.
Notes and references
´
1 For selective examples, see: (a) I. T. Horvath and P. T. Anastas, Chem.
Rev., 2007, 107, 2169; (b) C. Gunanathan and D. Milstein, Acc. Chem.
Res., 2011, 44, 588; (c) B. Sundararaju, M. Achard and C. Bruneau,
Chem. Soc. Rev., 2012, 41, 4467; (d) R. A. Sheldon, Chem. Soc. Rev.,
2012, 41, 1437.
2 For selective examples, see: (a) R. F. Heck, in Synthesis via Metal
Carbonyls, ed. I. Wender and P. Pino, New York, 1968; (b) H. M.
Colquhoun, D. J. Thompson and M. V. Twigg, Carbonylation: Direct
Synthesis of Carbonyl Compounds, Plenum Press, New York, 1991;
(c) Y. Zhao, L. Jin, P. Li and A. Lei, J. Am. Chem. Soc., 2008, 130, 9429.
3 For selective examples, see: (a) C. F. J. Barnard, Organometallics,
2008, 27, 5402; (b) A. Brennfu¨hrer, H. Neumann and M. Beller,
Angew. Chem., Int. Ed., 2009, 48, 4114; (c) X.-F. Wu, H. Neumann and
M. Beller, Chem. Soc. Rev., 2011, 40, 4986.
Scheme 1 Synthetic transformations of 3a.
4 (a) A. Schoenberg, I. Bartoletti and R. F. Heck, J. Org. Chem., 1974,
39, 3318; (b) A. Schoenberg and R. F. Heck, J. Org. Chem., 1974, 39, 3327.
5 For selective examples, see: (a) J. Magano and J. R. Dunetz, Chem.
Rev., 2011, 111, 2177; (b) H. Zhang, R. Shi, P. Gan, C. Liu, A. Ding,
Q. Wang and A. Lei, Angew. Chem., Int. Ed., 2012, 51, 5204; (c) R. Shi,
L. Lu, H. Zhang, B. Chen, Y. Sha, C. Liu and A. Lei, Angew. Chem., Int.
Ed., 2013, 52, 10582; (d) X.-F. Wu, H. Neumann and M. Beller, Chem.
Rev., 2013, 113, 1.
6 (a) E. J. Yoo, M. Wasa and J.-Q. Yu, J. Am. Chem. Soc., 2010,
132, 17378; (b) P. Xie, Y. Xie, B. Qian, H. Zhou, C. Xia and
H. Huang, J. Am. Chem. Soc., 2012, 134, 9902.
7 For selected examples recently, see: (a) L. H. Powell, P. H. Docherty,
D. G. Hulcoop, P. D. Kemmittc and J. W. Burton, Chem. Commun.,
2008, 2559; (b) L. J. Gooßen, D. M. Ohlmanna and M. Dierker, Green
Chem., 2010, 12, 197; (c) D. A. Devalankar, P. U. Karabal and
A. Sudalai, Org. Biomol. Chem., 2013, 11, 1280.
8 For selected examples, see: (a) R. Bandichhor, B. Nosse and
O. Reiser, Top. Curr. Chem., 2005, 243, 43; (b) R. R. A. Kitson,
A. Millemaggi and R. J. K. Taylor, Angew. Chem., Int. Ed., 2009,
48, 9426; (c) D. A. Devalankar, P. U. Karabal and A. Sudalai, Org.
Biomol. Chem., 2013, 11, 1280.
Scheme 2 Proposed mechanism.
9 For selected examples, see: (a) S. Shimada, Y. Hashimoto and K. Saigo,
Based on the current results and previous literature,12,13,18
the postulated mechanism is depicted in Scheme 2. The Pd
complex is initially formed in situ in ILs,13 and vinylpalladium
intermediate A is formed by trans-chloropalladation of the
alkyne in a polar solvent system15 in the presence of excess
chloride ions.19 Then, intermediate A could undergo alkene
insertion. Simultaneously, the vinylpalladium species coordinates
to both the oxygen atoms of OR2 and the hydroxyl group to generate
a Pd–alkyl intermediate B. Subsequently, migratory insertion of CO
J. Org. Chem., 1993, 58, 5226; (b) R. B. Chhor, B. Nosse, S. Sorgel,
¨
¨
C. Bohm, M. Seitz and O. Reiser, Chem.–Eur. J., 2003, 9, 260; (c) B. W.
Greatrex, M. C. Kimber, D. K. Taylor, G. Fallon and E. R. T. Tiekink, J. Org.
Chem., 2002, 67, 5307; (d) G. Liu and X. Lu, Tetrahedron Lett., 2003,
44, 127; (e) M. He, A. Lei and X. Zhang, Tetrahedron Lett., 2005, 46, 1823.
10 (a) L. Zhou, C. K. Tan, X. Jiang, F. Chen and Y.-Y. Yeung, J. Am.
Chem. Soc., 2010, 132, 15474; (b) C. Shu, M.-Q. Liu, Y.-Z. Sun and
L.-W. Ye, Org. Lett., 2012, 14, 4958; (c) C. G. Kokotos, Org. Lett., 2013,
15, 2406; (d) C. C. Oliveira, R. A. Angnes and C. R. D. Correia, J. Org.
Chem., 2013, 78, 4373.
11 L. Huang, H. Jiang, C. Qi and X. Liu, J. Am. Chem. Soc., 2010, 132, 17652.
12 W. Wu and H. Jiang, Acc. Chem. Res., 2012, 45, 1736.
into the palladium–carbon s bond produced intermediate C.18 13 (a) S.-R. Yang, H.-F. Jiang, Y.-Q. Li, H.-J. Chen, W. Luo and Y.-B. Xu,
Tetrahedron, 2008, 64, 2930; (b) J. Li, S. Yang, L. Huang, H. Chen and
H. Jiang, RSC Adv., 2013, 3, 11529.
14 See the ESI† for details.
Finally, a reductive elimination gives the target product and Pd(II)
was regenerated in the presence of an oxidant for the next cycle.
In conclusion, we have developed a practical, efficient, and 15 For selected examples, see: (a) L. Zhao, X. Lu and W. Xu, J. Org.
Chem., 2005, 70, 4059; (b) W. Wu, A. Kong and X. Lu, J. Org. Chem.,
2006, 71, 3854.
16 K. Kaneda, T. Uchiyama, Y. Fujiwara, T. Imanaka and S. Teranishi,
J. Org. Chem., 1979, 44, 55.
17 A. F. Littke and G. C. Fu, Angew. Chem., Int. Ed., 2002, 41, 4176.
18 (a) A. Cowell and J. K. Stille, J. Am. Chem. Soc., 1980, 102, 4193;
versatile method for the synthesis of functionalized saturated
g-lactones. This novel and general methodology may open up a
new viewpoint on the carbonylation of the C(sp3)–palladium
bond. Further investigation of the reaction mechanism as well as
the synthetic applications of this protocol for the construction of
functionalized g-lactones are currently in progress.
´
(b) C. Coperet, T. Sugihara, G. Wu, I. Shimoyama and E. Negishi,
J. Am. Chem. Soc., 1995, 117, 3422.
19 For selected examples, see: (a) Z. Zhang, X. Lu and G. Zhu, J. Org.
Chem., 1995, 60, 1087; (b) X. Lu, Z. Xu, Q. Zhang and X. Han,
Organometallics, 2001, 20, 3724; (c) Q. Zhang, W. Xu and X. Lu,
J. Org. Chem., 2005, 70, 1505.
We thank the National Natural Science Foundation of China
(21102047, 21172076 and 21202046), the National Basic Research
Program of China (973 Program) (2011CB808600), and the
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Chem. Commun., 2014, 50, 1381--1383 | 1383