A facile copper(i)-catalyzed homo-coupling of indanone derivatives using diaziridinone under mild conditions

Article abstract of DOI:10.1039/c9ob00901a

A novel and efficient Cu(i)-catalyzed homo-coupling of indanone derivatives using diaziridinone as an oxidant is described. A variety of 1,4-dicarbonyl compounds bearing two adjacent quaternary stereocenters were obtained in high yields with high diastereoselectivities via a base-free and operationally simple process under mild reaction conditions.

Full text of DOI:10.1039/c9ob00901a

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A facile copper(I)-catalyzed homo-coupling of
indanone derivatives using diaziridinone under
mild conditions†
Cite this: DOI: 10.1039/c9ob00901a
Received 19th April 2019,
Accepted 5th July 2019
Wenyong Han,
Yihui Yang, Yingguang Zhu and Yian Shi*
DOI: 10.1039/c9ob00901a
rsc.li/obc
A novel and efficient Cu(I)-catalyzed homo-coupling of indanone 20 : 1 with toluene as solvent (Table 1, entry 3). No oxidative
derivatives using diaziridinone as an oxidant is described. A variety coupling occurred with other metal catalysts, such as FeCl2,
of 1,4-dicarbonyl compounds bearing two adjacent quaternary CoCl2, NiBr2, and Pd(OAc)2 (Table 1, entries 7–10). The best
stereocenters were obtained in high yields with high diastereo- diastereoselectivity was obtained with P(nBu)3 as ligand
selectivities via a base-free and operationally simple process under (Table 1, entries 3, 11–14). No reaction occurred without metal
mild reaction conditions.
catalyst (Table 1, entry 15) or di-t-butyldiaziridinone (Table 1,
entry 16).
Oxidative coupling of enolates and relative derivatives provides
a straightforward approach to 1,4-dicarbonyl functional moi-
eties, which are contained in many biologically and chemically
important molecules.1 Thus far, a variety of effective methods
with various oxidants have been developed.2–11 In our earlier
studies, we have shown that di-t-butyldiaziridinone (1) can
efficiently diaminate olefins in the presence of Pd(0) and Cu(I)
catalysts.12 Recently, we found that di-t-butyldiaziridinone
(1) can also act as an effective oxidant for homo-coupling of
anilines to azo compounds and hydrazines,13 and homo-coup-
ling of terminal alkynes to symmetrical 1,3-diynes14 in the
presence of a Cu catalyst (Scheme 1). In our further exploration
of its reactivity, we discovered that di-t-butyldiaziridinone can
effectively promote the oxidative coupling of indanone deriva-
tives to form 1,4-dicarbonyl compounds bearing two adjacent
quaternary stereocenters in the presence of Cu catalysts.
Herein we wish to report our preliminary studies on this
subject.
The oxidative coupling process can be extended to various
substituted methyl 1-oxo-2-indane-carboxylates in 75–98%
yields with 8 : 1 to 20 : 1 dr (Table 2, entries 1–9). The diasteros-
electivity slightly varied with the substituent on the phenyl
group. Similar diasteroselectivity was obtained with the
corresponding isopropyl ester (Table 2, entry 1 vs. entry 10).
The structures of 3a and 3b were determined by X-ray (see
ESI†).15 2-Phenyl-1H-indene-1,3(2H)-dione (2k) was also
effective for the coupling process, affording the corres-
ponding product 3k10a in 65% yield (Table 2, entry 11).
However, indanones with acyl group at α-position (2-acetyl-
2,3-dihydro-1H-inden-1-one) and tetralone with α-methyl
ester (methyl 1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxy-
late) were found to be poor substrates under the current reac-
tion conditions.
While a precise understanding of the reaction mechanism
awaits further study, a plausible catalytic pathway for the oxi-
dative homo-coupling is proposed in Scheme 2. The CuCl first
reductively cleaved the N–N bond of di-t-butyldiaziridinone (1)
to form Cu(II) nitrogen radical A and/or four-membered Cu(III)
Our initial studies were carried out with methyl 1-oxo-2-
indane-carboxylate 2a as a test substrate. Treating 2a with
5 mol% CuCl-P(nBu)3 and di-t-butyldiaziridinone (1) in CHCl3
at room temperature for 24 h led to the formation of 1,4-dicar-
bonyl compound 3a in 92% yield (Table 1, entry 1).
Interestingly, the reaction proceeded with high diastereo-
selectivity (12 : 1 dr). The selectivity was further improved to
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523,
USA. E-mail: Yian.Shi@colostate.edu; Fax: +(1)-970-4911801; Tel: +(1)-970-4917424
†Electronic supplementary information (ESI) available: Experimental pro-
cedures, characterization data, crystallographic data, and NMR spectra. CCDC
1904252 (3a) and 1904257 (3b). For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c9ob00901a
Scheme 1 Cu(I)-catalyzed oxidative homo-coupling of anilines and
alkynes.
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Table 1 Optimization of the reaction conditionsa
Table 2 Substrate scopea
Yieldb (%)
drc
Entry
Substrate
Product
Yieldb (%)
drc
Entry
Catalyst
Solvent
1
2
3
4
5
6
7
8
CuCl-P(nBu)3
CuCl-P(nBu)3
CuCl-P(nBu)3
CuI-P(nBu)3
CuCl2-P(nBu)3
CuBr2-P(nBu)3
FeCl2-P(nBu)3
CoCl2-P(nBu)3
NiBr2-P(nBu)3
Pd(OAc)2-P(nBu)3
CuCl-PPh3
CHCl3
92
91
94
92
92
93
0
0
0
0
92
94
0
93
0
12 : 1
6 : 1
20 : 1
7 : 1
9 : 1
9 : 1
—
CH3CN
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
1d
2e
3d
2a, X = H
2b, X = Me
2c, X = F
3a (X-ray)
3b (X-ray)
3c
94
98
95
20 : 1
14 : 1
10 : 1
—
—
9
10
11
12
13
14
15
16d
—
10 : 1 4e
2d, X = Me
2e, X = OMe
2f, X = Cl
3d
3e
3f
87
93
88
75
12 : 1
8 : 1
10 : 1
14 : 1
CuCl-P(OPh)3
CuCl-phen
7 : 1
5
6
—
CuCl
12 : 1 7e
2g, X = Br
3g
P(nBu)3
—
—
CuCl-P(nBu)3
0
a The reaction was carried out with 2a (0.50 mmol), di-t-butyldiaziri-
dinone (1) (0.60 mmol), catalyst (0.025 mmol), and ligand
(0.025 mmol) in solvent (0.8 mL) at room temperature for 24 h unless
otherwise stated. b Isolated yield of both diastereomers. c The dr value
was determined by 1H NMR analysis of the crude reaction mixture.
8
2h, X = Me
2i, X = Cl
3h
3i
90
80
77
10 : 1
10 : 1
20 : 1
9
10d
d In the absence of di-t-butyldiaziridinone (1). phen
= 1,10-
phenanthroline.
11d
65
—
a The reaction was carried out with 2 (0.50 mmol), di-t-butyldiaziridi-
none (1) (1.00 mmol), CuCl (0.025 mmol), and P(n-Bu)3 (0.025 mmol)
in toluene (0.8–1.0 mL) at room temperature for 48 h unless otherwise
species B, which reacted with methyl 1-oxo-2-indane-carboxy-
late 2a to form radical intermediate C. Dimerization of C gave
coupling product 3a. When the reaction was carried out in the
presence TEMPO, compound 4 was isolated in 74% yield,
which supports the involvement of radical intermediate C
(Scheme 3).16
1
stated. b Isolated yield. c The dr value was determined by H NMR ana-
lysis of the crude reaction mixture. d With di-t-butyldiaziridinone (1)
(0.60 mmol) for 24 h. e For 72 h.
When ethyl 3-oxo-3-phenylpropanoate (5) was treated with
10 mol% CuCl, 20 mol% P(nBu)3, and 4.0 equiv. di-t-butyldia-
ziridinone in CDCl3 at 65 °C for 24 h, tetrasubstituted olefin 6
was obtained in 74% yield as two isomers with a ratio of 4.6 : 1
(Scheme 4). Compound 6 was likely formed by the dehydro-
genation of intermediate 7,17 which resulted from the dimeri-
zation of radical D. Compound 6 was also formed in good
yield when the preformed 79c was subjected to the reaction
conditions, which is consistent with the proposed reaction
mechanism (Scheme 5).18
Scheme 2 Proposed catalytic cycle.
In summary, we have developed a mild and efficient
method for the oxidative coupling of indanone derivatives
with CuCl catalyst and di-t-butyldiaziridinone (1) as an
oxidant, giving the corresponding 1,4-dicarbonyl com-
pounds containing vicinal quaternary carbons in 65–98%
yields with high diastereoselectivities (8 : 1 to 20 : 1 dr).
The reaction is base-free and operationally simple.
Further development of other oxidative coupling processes
with diaziridinones and related compounds are currently
underway.
Scheme 3 Trapping of radical intermediate with TEMPO.
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A. T. McPhail, Tetrahedron Lett., 1993, 34, 4457;
(h) T. Langer, M. IIIich and G. Helmchen, Tetrahedron Lett.,
1995, 36, 4409; (i) S. Mao, Y.-R. Gao, S.-L. Zhang, D.-D. Guo
and Y.-Q. Wang, Eur. J. Org. Chem., 2015, 876.
3 For leading references with Mn(OAc)3 as oxidant, see:
(a) R. M. Dessau and E. I. Heiba, J. Org. Chem., 1974, 39,
3457; (b) B. B. Snider, J. J. Patricia and S. A. Kates, J. Org.
Chem., 1988, 53, 2137.
4 For leading references with Fe(III) as oxidant, see:
(a) R. H. Frazier Jr. and R. L. Harlow, J. Org. Chem., 1980, 45,
5408; (b) P. S. Baran and M. P. DeMartino, Angew. Chem., Int.
Ed., 2006, 45, 7083; (c) M. P. DeMartino, K. Chen and
P. S. Baran, J. Am. Chem. Soc., 2008, 130, 11546.
5 For leading references with CAN or CeCl3·7H2O as oxidant,
see: (a) E. Raciocchi, A. Casu and R. Ruzziconi, Tetrahedron
Lett., 1989, 30, 3707; (b) M. D. Clift, C. N. Taylor and
R. J. Thomson, Org. Lett., 2007, 9, 4667; (c) J. Song,
H. Zhang, X. Chen, X. Li and D. Xu, Synth. Commun., 2010,
40, 1847; (d) P. Tisovský, M. Mečiarová and R. Šebesta, Org.
Biomol. Chem., 2014, 12, 9446; (e) I. Geibel, A. Dierks,
M. Schmidtmann and J. Christoffers, J. Org. Chem., 2016,
81, 7790; (f) E. E. Robinson and R. J. Thomson, J. Am.
Chem. Soc., 2018, 140, 1956.
Scheme 4 The formation of tetrasubstituted olefin 6.
Scheme 5 The dehydrogenation of compound 7.
6 For leading references with AgO as oxidant, see:
(a) S. E. Drewes, C. J. Hogan, P. T. Kaye and G. H. P. Roos,
J. Chem. Soc., Perkin Trans. 1, 1989, 1585; (b) J.-C. Jung and
O.-S. Park, Synth. Commun., 2007, 37, 1665.
Conflicts of interest
7 For leading references with VO(OR)Cl2 as oxidant, see:
(a) T. Fujii, T. Hirao and Y. Ohshiro, Tetrahedron Lett., 1992,
33, 5823; (b) K. Ryter and T. Livinghouse, J. Am. Chem. Soc.,
1998, 120, 2658; (c) T. Amaya, T. Masuda, Y. Maegawa and
T. Hirao, Chem. Commun., 2014, 50, 2279; (d) T. Amaya,
Y. Maegawa, T. Masuda, Y. Osafune and T. Hirao, J. Am.
Chem. Soc., 2015, 137, 10072; (e) T. Amaya, Y. Osafune,
Y. Maegawa and T. Hirao, Chem. – Asian J., 2017, 12, 1301.
8 For leading references with TiCl4 as oxidant, see:
(a) N. Kise, K. Tokioka and Y. Aoyama, J. Org. Chem., 1995,
60, 1100; (b) T. Langer, M. IIIich and G. Helmchen, Synlett,
1996, 1137; (c) N. Kise, K. Kumada, Y. Terao and N. Ueda,
Tetrahedron, 1998, 54, 2697.
There are no conflicts to declare.
Acknowledgements
We are grateful for generous financial support from the
General Medical Sciences of the National Institutes of Health
(GM083944-08).
Notes and references
1 For reviews on oxidative coupling of enolates and relative
derivatives, see: (a) A. G. Csákÿ and J. Plumet, Chem. Soc.
Rev., 2001, 30, 313; (b) F. Guo, M. D. Clift and
R. J. Thomson, Eur. J. Org. Chem., 2012, 4881;
(c) S. Murarka and A. P. Antonchick, Synthesis, 2018, 50,
2150.
2 For leading references with Cu(II) as oxidant, see:
(a) M. W. Rathke and A. Lindert, J. Am. Chem. Soc., 1971,
93, 4605; (b) Y. Ito, T. Konoike and T. Saegusa, J. Am. Chem.
Soc., 1975, 97, 2912; (c) Y. Kobayashi, T. Taguchi and
E. Tokuno, Tetrahedron Lett., 1977, 18, 3741; (d) Y. Ito,
T. Konoike, T. Harada and T. Saegusa, J. Am. Chem. Soc.,
9 For leading references with halogen reagents as oxidant,
see: (a) P. Renaud and M. A. Fox, J. Org. Chem., 1988, 53,
3745; (b) C. Alvarez-Ibarra, A. G. Csákÿ, B. Colmenero and
M. L. Quiroga, J. Org. Chem., 1997, 62, 2478; (c) A. Wu,
Y. Zhao, N. Chen and X. Pan, Synth. Commun., 1997, 27,
331; (d) N. Kise, A. Fujimoto and N. Ueda, Tetrahedron:
Asymmetry, 2002, 13, 1845; (e) T. Saitoh, S. Yoshida and
J. Ichikawa, J. Org. Chem., 2006, 71, 6414; (f) Z. Wang,
G. Yin, A. Chen, S. Hu and A. Wu, Synth. Commun., 2007,
37, 4399; (g) K. Xu, Y. Fang, Z. Yan, Z. Zha and Z. Wang,
Org. Lett., 2013, 15, 2148; (h) P. Mizar and T. Wirth, Angew.
Chem., Int. Ed., 2014, 53, 5993.
1977, 99, 1487; (e) S. K. Chung and L. B. Dunn Jr., J. Org. 10 For leading references with O2 as oxidant, see:
Chem., 1983, 48, 1125; (f) T. Kawabata, K. Sumi and
T. Hiyama, J. Am. Chem. Soc., 1989, 111, 6843;
(g) N. A. Porter, Q. Su, J. J. Harp, I. J. Rosenstein and
(a) Y. Monguchi, T. Takahashi, Y. Iida, Y. Fujiwara,
Y. Inagaki, T. Maegawa and H. Sajiki, Synlett, 2008, 2291;
(b) N. A. Lozinskaya, S. E. Sosonyuk, Y. N. Firsova,
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M. V. Proskurnina and N. S. Zefirov, Russ. Chem. Bull., 13 Y. Zhu and Y. Shi, Org. Lett., 2013, 15, 1942.
2009, 58, 152; (c) H.-Q. Do, H. Tran-Vu and O. Daugulis, 14 Y. Zhu and Y. Shi, Org. Biomol. Chem., 2013, 11, 7451.
Organometallics, 2012, 31, 7816.
15 The stereochemistry of 3c–j was tentatively assigned by
11 For leading references with other oxidants, see:
analogue.
(a) A. A. Hagedorn III and D. G. Farnum, J. Org. Chem., 16 For some examples of radical-based oxidative coupling of
1977, 42, 3765 (di-t-butyl peroxide); (b) H. Irie,
J. Maruyama, M. Shimada, Y. Zhang, I. Kouno,
K. Shimamoto and Y. Ohfune, Synlett, 1990, 421 (K2S2O8);
(c) S. Imachi and T. Mukaiyama, Chem. Lett., 2007, 36, 718
carbonyl systems, see: (a) P. Finkbeiner and
B. J. Nachtsheim, Synthesis, 2013, 45, 979; (b) X.-F. Wu,
J.-L. Gong and X. Qia, Org. Biomol. Chem., 2014, 12, 5807;
(c) S. R. Chowdhury, I. U. Hoque and S. Maity, Chem. –
Asian J., 2018, 13, 2824.
(pentavalent
biphenyl-2,2′-ylenebismuth
reagents);
(d) E. Dinca, P. Hartmann, J. Smrček, I. Dix, P. G. Jones and 17 T. A. Ramirez, B. Zhao and Y. Shi, Tetrahedron Lett., 2010,
U. Jahn, Eur. J. Org. Chem., 2012, 4461 (TEMPO); 51, 1822.
(e) M. Arisawa, G. Li and M. Yamaguchi, Tetrahedron Lett., 18 Little home-coupling product could be isolated when ethyl
2013, 54, 1298 (α-thioketone).
12 Y. Zhu, R. G. Cornwall, H. Du, B. Zhao and Y. Shi, Acc.
2-ethyl-3-oxo-3-phenylpropanoate was treated with 5 mol%
CuCl-P(nBu)3 and 1.2 equiv. of di-t-butyldiaziridinone (1) in
toluene at 60 °C for 72 h.
Chem. Res., 2014, 47, 3665.
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