The cascade carbo-carbonylation of unactivated alkenes catalyzed by an organocatalyst and a transition metal catalyst: A facile approach to γ-diketones and γ-carbonyl aldehydes from arylalkenes under air

Article abstract of DOI:10.1039/b921310d

A novel cascade carbo-carbonylation reaction of unactivated arylalkenes with ketones or aldehydes was catalyzed by an organocatalyst and a transition metal catalyst via a SOMO-enamine under air, affording a simple approach to γ-diketones and γ-carbonyl aldehydes. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/b921310d

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The cascade carbo-carbonylation of unactivated alkenes catalyzed
by an organocatalyst and a transition metal catalyst: a facile approach
to c-diketones and c-carbonyl aldehydes from arylalkenes under airw
Jin Xiea and Zhi-Zhen Huang*ab
Received (in Cambridge, UK) 13th October 2009, Accepted 14th December 2009
First published as an Advance Article on the web 13th January 2010
DOI: 10.1039/b921310d
A novel cascade carbo-carbonylation reaction of unactivated
arylalkenes with ketones or aldehydes was catalyzed by an
organocatalyst and a transition metal catalyst via a SOMO-
enamine under air, affording a simple approach to c-diketones
and c-carbonyl aldehydes.
Scheme 1 Organocatalysts 1–4.
chosen as a model reaction. It was found that using 1.0 equiv.
of FeCl3 as a SET reagent, 0.3 equiv. of MacMillan-type
catalyst salt 1 (Scheme 1) could initiate the carbo-carbonylation
reaction of styrene under air in DMF–H2O at 70 1C, giving a
trace amount of g-diketone 7a [entry 1, Table 1, also ESIw for
details]. Under the same conditions, no 7a was obtained using
proline 2 as organocatalyst, and using piperidine salt 3 and
pyrrolidine salt 4a resulted in 7a with 8% and 16% yield,
respectively (entry 1–2, Table 1). After 4a was chosen as an
optimal organocatalyst, we screened the SET salts, and it
was found that using Cu(OTf)2, CuSO4 or Cu(ClO4)2Á6H2O
resulted in the increased yields of 30%, 32% or 40%,
With the great development of organocatalysis in recent years,
a new activation methodology regarded as SOMO (single
occupied molecular orbital)-enamine activation was developed
by MacMillan in 2007.1 In the same year, Sibi et al. revealed
that using a MacMillan-type catalyst and FeCl3 as a single
electron transfer (SET) catalyst, aldehydes reacted with TEMPO
via an electron-deficient enamine radical intermediate, giving
a-oxyamination products of aldehydes in satisfactory yields
with high enantioselectivities.2 In the recent three years,
MacMillan’s research group developed highly stereoselective
a-allylation,3a a-enolation,3b a-alkylation,3c a-vinylation,3d
a-triuoromethylation,3e a-nitroalkylation,3f a-arylation3g
and a-chlorination3h of aldehydes, and carbo-oxidation of
styrene3i via SOMO enamine of aldehydes. In 2009,
Nicolaou et al. reported that in the presence of a MacMillan-
type catalyst and cerium ammonium nitrate (CAN), aldehydes
bearing electron-donating groups on aromatic rings underwent
an intramolecular Friedel–Crafts type arylation with excellent
enantioselectivities.4 It is noteworthy that almost all the above
SOMO-enamines are from aldehydes, only a few literature
reports revealed reactions via SOMO-enamines of ketones.
This prompted us to start our study on the reaction of styrenes
with SOMO-enamines of ketones in the presence of water.
Instead of the expected alcohols, we unexpectedly obtained
g-diketones, which are important synthetic building blocks for
many biologically significant compounds and useful heterocyclic
motifs such as cyclopentenone, furans, pyrroles and thiophene
derivatives.5 Herein, we wish to present a new reaction regarded
as the cascade carbo-carbonylation of unactivated alkenes via
SOMO-enamine under air, which affords a simple approach
to g-diketones or g-carbonyl aldehydes.
Table 1 Screening of reaction conditions for the reaction of cyclo-
hexanone with styrene mediated by organocatalyst 1–4 and transition
metal salta
Organocat.
(30 mol%) Time/h Yieldb (%)
Entry SET reagent (mol%)
1
2
3
4
5
6
7
8
FeCl3 (100%)
FeCl3 (100%)
Cu(OTf)2 (100%)
CuSO4 (100%)
1–3
4a
4a
4a
60
48
48
48
48
60
48
60
60
60
60
48
48
0–8
16
30
32
Cu(ClO4)2Á6H2O (100%) 4a
Cu(ClO4)2Á6H2O (100%) 1–3
Cu(ClO4)2Á6H2O (100%) 4b–e
40
0–25
21–30
0
Cu(ClO4)2Á6H2O (100%)
—
4a
9
—
0
0
0
10
61
10c
11d
12e
13f
Cu(ClO4)2Á6H2O (100%) 4a
To screen the conditions for reaction via a SOMO-enamine
FeCl3 (100%) 4a
Cu(ClO4)2Á6H2O (50%) 4a
Cu(ClO4)2Á6H2O (50%) 4a
intermediate, the reaction of cyclohexanone with styrene was
a
a Key Laboratory of Mesoscopic Chemistry of MOE,
College of Chemistry and Chemical Engineering, Nanjing University,
Nanjing, 210093, P.R.China. E-mail: huangzz@nju.edu.cn
b State Key Laboratory of Elemento-organic Chemistry,
Nankai University, Tianjin, 300071, P. R. China
w Electronic supplementary information (ESI) available: Experimental
details and the characterization data for the compounds 7a–k. See
DOI: 10.1039/b921310d
The reaction of styrene (0.5 mmol), cyclohexanone (3.0 mmol),
organocatalyst (30 mol%) and SET reagent in DMF (2.5 mL)–H2O
b
c
(0.15 mL) was performed at 70 1C under air. Isolated yield. The
reaction was performed under nitrogen. There is no water. FeCl3
d
e
was used due to crystallizing water in Cu(ClO4)2Á6H2O. The reaction
f
was carried out under pure oxygen (1 atm). 2.0 equiv. MnO2 was
employed as a co-oxidant.
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respectively (compare entry 2 with 3, 4 or 5, Table 1). When
Cu(ClO4)2Á6H2O was employed as an optimal SET reagent,
organocatalysts 1–3 and various pyrrolidine salts 4b–e were
probed in the reaction, which led to 7a in the lower yields of
0–25% and 21–30% respectively (entry 6 and 7, Table 1; for
details see ESIw). Experiments demonstrated that if there was
an absence of any one of 4a, SET reagent, air or H2O, no 7a
was obtained (entry 8–11, Table 1). These results suggested
that organocatalyst, SET reagent, O2 and protons were
necessary in the reaction. When THF, DCE, 1,4-dioxane or
acetonitrile was employed instead of DMF, the reaction
hardly occurred (see ESIw). If the reaction was performed at
room temperature or 90 1C, only a small amount of 7a was
obtained. It is interesting to note that although the reaction
could not occur without oxygen, only a low yield (10%) of 7a
was obtained when the reaction was performed under pure
oxygen (1 atm) (entry 12, Table 1).6 Besides, some other cheap
co-oxidants were examined in order to decrease the amount of
Cu(ClO4)2Á6H2O. It was found that using KClO3, Na2S2O8, or
MnO2 as the co-oxidant of Cu(ClO4)2Á6H2O (50 mol%)
resulted in the increased yields of 43%, 50% and 61%,
respectively (entry 13, Table 1 and ESIw). Experiments also
indicated that further decreasing the amount of Cu(ClO4)2Á
6H2O was not beneficial to the reaction (see ESIw).
Table 2 The cascade carbo-carbonylation reaction of arylalkenes 5
with ketones or aldehydes 6 catalyzed by 4a and Cu(II)7
Aryl-al- Ketone or
aldehyde
Time/ g-Diketone or g-carbo- Yielda
From the screening of various organocatalysts, solvents,
SET reagents and co-oxidants, the optimized reaction should
be catalyzed by 30 mol% pyrrolidine salt 4a and 50 mol%
Cu(ClO4)2Á6H2O with 2.0 equiv. of MnO2 in DMF–H2O at
70 1C under air. Under the optimal reaction conditions, a
variety of substituted styrenes 5a–f and different ketones or
aldehydes 6a–f were examined in the carbo-carbonylation
reaction. The experimental results showed that except for
strongly electron-deficient arylalkene 5f, both electron-rich
and electron-deficient arylalkenes 5a–e underwent the reaction
smoothly with cyclohexanone to give the desired g-diketones
7a–e in satisfactory yields (entry 1–5, Table 2). On the other
hand, different ketones 6a–c and aldehydes 6d–f could also
perform the reaction readily to furnish the desired g-diketones
7a–h or g-carbonyl aldehydes 7i–k in the yields of 40–71%.
The plausible mechanism for the direct carbo-carbonylation
reaction of styrene is depicted in Scheme 2. Pyrrolidine as an
organocatalyst initially reacts with cyclohexanone to form
enamine 8, followed by the oxidation with SET reagent
to generate a eletrophilic three-p-electron radical cationic
enamine 9. Then the cationic enamine 9 undergoes the electro-
philic addition with styrene to form the radical cationic imine
10. The a-carbon radical and imine cation in 10 is respectively
reacted with oxygen8 and hydrolyzed to give intermediate 11,
Entry kene
h
nyl aldehyde 7
(%)
1
2
3
5a
5b
5c
6a
48
61
6a
6a
48
48
58
64
4
5
6
5d
5e
5f
6a
6a
6a
48
48
48
62
71
40
7
5a
5a
5a
6b
6c
6d
50
72
16
43
55
50
8b
9b
10b 5a
6e
24
24
62
56
11b 5a
6f
a
b
Isolated yield. The temperature was decreased to 55 1C due to the
low b.p. of acetone or high activities of aldehydes.
Scheme 2 Plausible mechanism.
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which is oxidized further under the catalysis of copper,9
affording g-diketone 7a ultimately.
and D. W. C. MacMillan, J. Am. Chem. Soc., 2009, 131, 11332;
(g) J. C. Conrad, J. Kong, B. N. Laforteza and D. W.
C. MacMillan, J. Am. Chem. Soc., 2009, 131, 11640;
(h) M. Amatore, T. D. Beeson, S. P. Brown and D. W.
C. MacMillan, Angew. Chem., Int. Ed., 2009, 48, 5121;
(i) T. H. Graham, C. M. Jones, N. T. Jui and D. W.
C. MacMillan, J. Am. Chem. Soc., 2008, 130, 16494.
In conclusion, we have developed a novel carbo-carbonylation
reaction of unactivated arylalkenes by cascade SOMO catalysis
and oxidation. Both ketones and aldehydes react directly with
the arylalkenes without any prefunctionalization under the
catalysis of pyrrolidine and Cu(ClO4)2Á6H2O in the presence of
MnO2 and air, affording a novel approach to g-diketones
and g-carbonyl aldehydes. Further studies about the cascade
carbo-carbonylation reaction are currently underway.
We thank the National Natural Science Foundation of
China for its financial support of the project 20872059.
4 K. C. Nicolaou, R. Reingruber, D. Sarlah and B. Stefan, J. Am.
Chem. Soc., 2009, 131, 2086.
5 (a) Y. Yamamoto, H. Maekawa, S. Goda and I. Nishiguchi, Org.
Lett., 2003, 5, 2755; (b) M. Rossle, T. Werner, A. Baro, W. Frey and
J. Christoffers, Angew. Chem., Int. Ed., 2004, 43, 6547.
6 A similar phenomenon, in which the yield of a reaction performed
under pure oxygen atmosphere was decreased remarkably as
compared to the reaction under air was also reported in Y. Nobe,
K. Arayama and H. Urabe, J. Am. Chem. Soc., 2005, 127,
18006.
7 General procedure: The mixture of ketone or aldehyde 6a–f
(3.0 mmol), organocatalyst 4a (0.15 mmol, 30 mol%) in a mixed
solvent (2.5 mL DMF and 0.15 mL H2O) was stirred at 70 1C for
5–10 min. Then, Cu(ClO4)2Á6H2O (0.25 mmol, 50 mol%), activated
MnO2 (1.0 mmol, 2.0 equiv.) and arylalkene 5a–f (0.5 mmol) were
added and the reaction mixture was stirred at 70 1C for the time
indicated in Table 2 under air. Normal work-up afforded the desired
g-diketones or g-carbonyl aldehydes 7a–k.
Notes and references
1 S. Bertelsen, M. Nielsen and K. A. Jørgensen, Angew. Chem., Int.
Ed., 2007, 46, 7356.
2 M. P. Sibi and M. Hasegawa, J. Am. Chem. Soc., 2007, 129, 4124.
3 (a) T. D. Beeson, A. Mastracchio, J.-B. Hong, K. Ashton and D. W.
C. MacMillan, Science, 2007, 316, 582; (b) H.-Y. Jang, J.-B. Hong
and D. W. C. MacMillan, J. Am. Chem. Soc., 2007, 129, 7004;
(c) D. A. Nicewicz and MacMillan, Science, 2008, 322, 77;
(d) H. Kim and D. W. C. MacMIllan, J. Am. Chem. Soc., 2008,
130, 398; (e) D. A. Nagib, M. E. Scott and D. W. C. MacMillan,
J. Am. Chem. Soc., 2009, 131, 10875; (f) J. E. Wilson, A. D. Casarez
8 H. Nakayama and A. Itoh, Tetrahedron Lett., 2007, 48, 1131.
9 K. Cheng, L.-H. Huang and Y.-H. Zhang, Org. Lett., 2009, 11,
2908.
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This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 1947–1949 | 1949