Copper-catalyzed intermolecular oxidative [3 + 2] cycloaddition between alkenes and anhydrides: A new synthetic approach to γ-lactones

Article abstract of DOI:10.1021/ja108073k

A new copper-catalyzed oxidative [3 + 2] cycloaddition of alkenes with anhydrides using oxygen as the sole oxidant to afford γ-lactones has been developed. This catalyzed cyclization process has a broad substrate scope and affords γ-lactones in good to excellent yields.

Full text of DOI:10.1021/ja108073k

Published on Web 11/29/2010
Copper-Catalyzed Intermolecular Oxidative [3 + 2] Cycloaddition between
Alkenes and Anhydrides: A New Synthetic Approach to γ-Lactones
Liangbin Huang, Huanfeng Jiang,* Chaorong Qi, and Xiaohang Liu
School of Chemistry and Chemical Engineering, South China UniVersity of Technology,
Guangzhou 510640, P. R. China
Received July 10, 2010; E-mail: jianghf@scut.edu.cn
Table 1. Screening of Reaction Conditionsa
Abstract: A new copper-catalyzed oxidative [3 + 2] cycloaddition
of alkenes with anhydrides using oxygen as the sole oxidant to
afford γ-lactones has been developed. This catalyzed cyclization
process has a broad substrate scope and affords γ-lactones in
good to excellent yields.
entry
catalyst
additive
oxidant
temp (°C)
yield (%)b
The discovery of new transformations through olefin difunc-
tionalization continues to attract broad interest because of their
high potential for application in natural product and bioactive
compound synthesis.1,2 Recent progress in this specific area has
been made with respect to carboamination,3-6 carboetherifica-
tion,7,8 carbohalogenation,9,10 and carboesterification11 of alk-
enes. It is surprising, however, that among these difunctional-
ization reactions, few can achieve the formation of C(sp3)-C(sp3)
bonds,11-13 despite their ubiquitous nature. To address this issue,
we envisioned using cheap acetic anhydride as a carboesterification
agent for the alkene difunctionalization under copper catalysis,14 that
is, copper-mediated intermolecular cycloaddition with subsequent
C(sp3)-H/C-O bond cleavage and C(sp3)-C(sp3)/C-O bond forma-
tion would provide an expedient route to diverse lactone rings from
simple precursors (Scheme 1).12,15,16
1
2
3
4
5
6
7
8
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
-
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
LiBr
NaBr
NBu4Br
-
air
100
100
100
100
100
100
100
120
120
120
120
120
62
57
42
nr
nr
nr
air
air
air
air
air
KI
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
c
-
nr
air
73
88 (86)
0
0
0
9
1 atm O2
TBHP
DDQ
10
11
12d
1 atm O2
a Reaction conditions: All reactions were performed with 1a (1
mmol) and Cu catalyst (10 mol %) under air with NaOAc (1 equiv) and
the additive (30 mol %) in 2 mL of Ac2O for 12 h. b Determined by
GC. The value in parentheses is an isolated yield. c Under a N2
atmosphere. d Using 2 mL of AcOH as the solvent.
Scheme 1
Subsequently, we explored the generality of the reaction with
other alkenes under the optimized conditions. As shown in Table
2, the desired reaction products were synthesized in generally high
yields. A series of para-substituted styrenes, including both electron-
withdrawing groups (Table 2, entries 1-3) and a weakly electron-
donating group (entry 4), were converted into their corresponding
γ-lactones in excellent yields. Moreover, 1-methoxy-4-vinylbenzene
with the strongly electron-donating methoxy group afforded the
corresponding γ-lactone 2f in 76% yield (entry 5). Increasing the
steric demand ortho to the vinyl group by substitution with a methyl
group afforded high yield of 2h (entry 7). Even the slightly sterically
demanding 1,1-disubstituted olefin 1i offered 2i in 79% yield (entry
8). To our delight, highly electron-deficient 1,2,3,4,5-pentafluoro-
6-vinylbenzene also provided a good result (entry 10). It is
especially worth mentioning that when conjugated dienes were
employed as substrates (entries 11 and 12), the desired products 2l
and 2m were isolated in 87 and 93% yield, respectively, with
exclusive selectivity toward the terminal olefin. The generality of
this unique transformation was also demonstrated by the successful
carboesterification of a linear aliphatic alkene (83% yield; entry
13) and 1-(but-3-en-1-ynyl)benzene (71% yield; entry 14). Unfor-
tunately, the nonterminal olefin 1p failed to afford the desired
product (entry 15).
Our initial investigations of Cu-catalyzed carboesterification of
olefins focused on the cycloaddition of acetic anhydride to styrene
(1a). To our delight, when 1a was treated with 10 mol % Cu(OTf)2,
30 mol % LiBr, and 1 equiv of NaOAc in 2 mL of Ac2O,
carboesterification of styrene indeed proceeded readily under 1 atm
air at 100 °C to give the γ-lactone product 2a in moderate yield
(Table 1, entry 1). Further investigation of the additives led to the
discovery that LiBr was the best halide for this reaction (entries
2-5).17 The reaction did not occur without Cu(OTf)2 or O2 (entries
6 and 7). Elevating the temperature to 120 °C and running the
reaction under 1 atm O2 increased the yield to 88% (entries 8 and
9).18 When tert-butylhydroperoxide (TBHP) or 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ) was used as the oxidant, benzaldehyde
was obtained instead of the γ-lactone product 2a and up to 30% of
the styrene was recovered. When the solvent was changed to AcOH,
the yield of 2a dropped to zero. Screening of other copper salts,
solvents, and bases showed that both copper(I) and copper(II) were
effective in the catalysis and that use of the anhydride as the solvent
was essential (see the Supporting Information).
Importantly, when propionic anhydride was used as the substrate,
acceptable yields of γ-lactones were obtained, although the syn/
anti ratio was ∼1:1 (eq 1). This allows the selective synthesis of
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17652 J. AM. CHEM. SOC. 2010, 132, 17652–17654
10.1021/ja108073k  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Substrate Scope of the Carboesterification of Alkenes
In order to obtain information about oxycupration process,
stereospecifically deuterium-labeled styrene (E)-1a-d was prepared
(see the Supporting Information) and then cyclized using acetic
anhydride under the standard conditions (Scheme 2). The reaction
with Acetic Anhydridea
1
afforded a single stereoisomer of product 2a-d, and the H NMR
resonance at J ) 7.2 Hz for the trans isomer was absent while the
1H NMR resonance at J ) 6.8 Hz for the cis isomer was still
present, indicating that oxycupration proceeded with overall cis
selectivity.
Scheme 2. Labeling Experiment Involving Styrene
On the basis of the above results and other experiments,19
a
tentative mechanism for the Cu(II)-catalyzed intermolecular car-
boesterification of alkenes is proposed in Scheme 3. First, the
Cu(OTf)2 coordinates with alkene 1a and the enol of the anhy-
dride.20 Subsequently, a cis oxycupration to form intermediate I is
followed by the formation of II through intramolecular insertion
into the enol.3,4,14e,21 Finally, with the aid of molecular oxygen, II
affords the product 2a and regenerates Cu(II) to complete the
catalytic cycle.
Scheme 3. Tentative Mechanism for the Cu(II)-Catalyzed
Carboesterification of Alkenes
In conclusion, we have developed a new Cu-catalyzed method
for the formation of C(sp3)-C(sp3) and C-O bonds through
carboesterification of alkenes with anhydrides, allowing the facile
synthesis of γ-lactones. This catalyzed cyclization process uses
oxygen as the sole oxidant, has a broad substrate scope, and affords
γ-lactones in good to excellent yields. Ongoing research involves
the extension of carboesterification to other substrates and further
investigations of the synthesis of chiral lactone rings as well as
detailed mechanistic studies. The results will be reported in due
course.
a Reaction conditions: All reactions were performed with 1 (1 mmol),
Cu catalyst (10 mol %), NaOAc (1 equiv), and LiBr (30 mol %) under
1 atm O2 in 2 mL of Ac2O at 120 °C for 12 h. b Isolated yield.
R,γ-disubstituted γ-lactones simply by choosing the correct olefins
and anhydrides.
Acknowledgment. We thank the National Natural Science
Foundation of China (20625205, 20772034, and 20932002), the
National Basic Research Program of China (973 Program)
(2011CB808600), the Doctoral Fund of the Ministry of Education
of China (20090172110014), and the Guangdong Natural Science
Foundation (10351064101000000) for financial support.
Note Added after ASAP Publication. Discussion of yield for
compound 2h has been corrected in the version reposted December 1,
2010.
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C O M M U N I C A T I O N S
(15) (a) Brown, H. C.; Kulkarni, S. V.; Racherla, U. S. J. Org. Chem. 1994, 59,
365. (b) Collins, I. J. Chem. Soc., Perkin Trans. 1 1998, 1869. (c) Collins,
I. J. Chem. Soc., Perkin Trans. 1 1999, 1377. (d) Dohi, T.; Takenaga, N.;
Goto, A.; Maruyama, A.; Kita, Y. Org. Lett. 2007, 9, 3129.
(16) Examples of Mn(III)- and Ce(IV)-mediated γ-lactone annulation: (a) Heiba,
E. H.; Dessau, R. M.; Koehl, W. J., Jr. J. Am. Chem. Soc. 1968, 90, 5905.
(b) Bush, J. B., Jr.; Finkbeiner, H. J. Am. Chem. Soc. 1968, 90, 5903. (c)
Heiba, E. I.; Desaau, R. M.; Rodewald, P. G. J. Am. Chem. Soc. 1974, 96,
7977. (d) Fristad, W. E.; Peterson, J. R. J. Org. Chem. 1985, 50, 10. (e)
Cossy, J.; Bouzide, A.; Leblanc, C. J. Org. Chem. 2000, 65, 7257. (f) Snider,
B. B. Tetrahedron 2009, 65, 10738.
(17) (a) Emmanuvel, L.; Shaikh, T. M. A.; Sudalai, A. Org. Lett. 2005, 7, 5071.
(b) Rodebaugh, R.; Debenham, J. S.; Fraser-Reid, B.; Snyder, J. P. J. Org.
Chem. 1999, 64, 1758.
(18) Recent examples of the use of molecular oxygen as the sole oxidant: (a)
Wang, A. Z.; Jiang, H. F.; Chen, H. J. J. Am. Chem. Soc. 2009, 131,
3846. (b) Zhu, M.-K.; Zhao, J.-F.; Loh, T.-P. J. Am. Chem. Soc. 2010,
132, 6284. (c) Schmidt, V. A.; Alexanian, E. J. Angew. Chem., Int. Ed.
2010, 49, 4491.
(19) Use of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2ꢀ-di-tert-butyl-
4-methylphenol (BHT) as a radical quenching agent made a tiny impact
on this reaction, and 2-bromo-1-phenylethyl acetate failed to generate the
corresponding product under the standard conditions. See the Supporting
Information.
(20) (a) Song, J. H.; Lei, Y. X.; Rappoport, Z. J. Org. Chem. 2007, 72, 9152.
(b) Frey, J.; Rappoport, Z. J. Am. Chem. Soc. 1996, 118, 5169.
(21) (a) Taylor, J. G.; Whittall, N.; Hill, K. K. Chem Commun. 2005, 5103. (b)
Chemler, S. R.; Fuller, P. H. Chem. Soc. ReV. 2007, 36, 1153. (c) Fuller,
P. H.; Kim, J. K.; Chemler, S. R. J. Am. Chem. Soc. 2008, 130, 17638. (d)
Sherman, E. S.; Fuller, P. H.; Kasi, D.; Chemler, S. R. J. Org. Chem. 2007,
72, 3896.
Supporting Information Available: Experimental procedures and
characterization of compounds 2a-o and 3a-e. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
(1) Jensen, K. H.; Sigman, M. S. Org. Biomol. Chem. 2008, 6, 4083.
(2) Hojo, M.; Murakami, C.; Ohno, K.; Kuboyama, J.; Nakamura, S.-y.; Ito,
H.; Hosomi, A. Heterocycles 1998, 47, 97.
(3) Zeng, W.; Chemler, S. R. J. Am. Chem. Soc. 2007, 129, 12948.
(4) Fuller, P. H.; Chemler, S. R. Org. Lett. 2007, 9, 5477.
(5) Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 1474.
(6) Houlden, C. E.; Bailey, C. D.; Ford, J. G.; Gagne, M. R.; Lloyd-Jones,
G. C.; Booker-Milburn, K. I. J. Am. Chem. Soc. 2008, 130, 10066.
(7) (a) Nakhla, J. S.; Kampf, J. W.; Wolfe, J. P. J. Am. Chem. Soc. 2006, 128,
2893. (b) Hay, M. B.; Wolfe, J. P. Angew. Chem., Int. Ed. 2007, 46, 6492.
(8) Wang, Y. Z.; Du, H. F. J. Org. Chem. 2010, 75, 3503.
(9) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5538.
(10) Kalyani, D.; Satterfield, A. D.; Sanford, M. S. J. Am. Chem. Soc. 2010,
132, 8419.
(11) Li, Y.; Jardine, K. J.; Tan, R. Y.; Song, D. T.; Dong, V. M. Angew. Chem.,
Int. Ed. 2009, 48, 9690.
(12) Nguyen, R.-V.; Li, C.-J. J. Am. Chem. Soc. 2005, 127, 17184.
(13) Urkalan, K. B.; Sigman, M. S. J. Am. Chem. Soc. 2009, 131, 18042.
(14) Recent examples of copper-catalyzed reactions: (a) Brasche, G.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2008, 47, 1932. (b) Hein, J. E.; Tripp, J. C.;
Krasnova, L. B.; Sharpless, K. B.; Fokin, V. V. Angew. Chem., Int. Ed.
2009, 48, 8018. (c) Nakamura, I.; Araki, T.; Terada, M. J. Am. Chem. Soc.
2009, 131, 2804. (d) Fuller, P. H.; Kim, J. W.; Chemler, S. R. J. Am. Chem.
Soc. 2008, 130, 17638. (e) Sequeira, F. C.; Turnpenny, B. W.; Chemler,
S. R. Angew. Chem., Int. Ed. 2010, 49, 6365. (f) Hamada, T.; Ye, X.; Stahl,
S. S. J. Am. Chem. Soc. 2008, 130, 833. (g) Li, Y.; Yu, Z. K.; Wu, S. Z.
J. Org. Chem. 2008, 73, 5647.
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