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Gold catalyzed carbocyclization of phenyl substituted allylic acetates to synthesize benzocycle derivatives
Tetrahedron Letters 52 (2011) 2990–2993
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Gold catalyzed carbocyclization of phenyl substituted allylic acetates to synthesize benzocycle derivatives Heng Liu a, Ya-Hui Wang b, Li-Li Zhu b, Xiao-Xiao Li b, Wen Zhou b, Zili Chen b,c,⇑, Wen-Xiang Hu a,⇑ a
Capital Normal University, Beijing 100048, PR China Department of Chemistry, Renmin University of China, Beijing 100872, PR China c Beijing National Laboratory of Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China b
a r t i c l e
i n f o
Article history: Received 26 January 2011 Revised 21 March 2011 Accepted 30 March 2011 Available online 5 April 2011
a b s t r a c t An efficient and environmentally benign method was developed to synthesize the benzocycles from phenyl substituted allylic acetates through gold catalyzed Friedel–Crafts type carbocyclization reaction. Different substitution patterns were investigated, which gave a series of benzocyclohexane derivatives in moderate to excellent yields. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Gold catalyzed reaction Benzocycle Friedel–Crafts reaction Allylic acetate
Utilizing gold complexes in homogeneous organic catalysis has achieved great progress in recent years. In this regard, most of the reported reactions started from the activation of the substrate’s C– C multiple bonds via forming auric p-complexes, and focused on the transformations involving alkyne-, allene-, or olefin-containing derivatives.1 In the process, the gold complex was usually used as the p-acid catalyst. Allylic esters are important building blocks in organic synthesis. These substrates have been widely utilized in transition metal (especially later transition metal, such as: Ni, Pd, Ir, Rh etc.) catalyzed allyl coupling reactions to provide alkene-containing products of variable structural characteristics and diversities.2 However, the study of employing gold complexes in the reaction of allylic esters, to our knowledge, is very limited.34 This is very notable as compared with the extensive research of propargylic esters in gold chemistry.5 We have recently investigated the gold catalyzed reactions of the allylic acetates.6 In our previous results, it was found that gold catalyzed intramolecular nucleophilic addition of the esters onto the allylic acetates would give c-vinyl butyrolactones with high diastereoselectivities (Scheme 1, Eq. 1).6a As an extension of this reaction, carbocyclization of the dienyl acetates via gold catalysis provided 3-vinyl cyclohexanols and their bicyclic derivatives (Scheme 1, Eq. 2).6c And then, we reported the inter-molecular ⇑ Corresponding authors. Fax: +86 10 62516660 (Z.L.C.); fax: +8610 68904750 (W.-X.H.). E-mail addresses: [email protected] (Z.L. Chen), [email protected] (W.-X. Hu). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.03.142
reaction of the allylic acetates with propargylic alcohols to give multifunctionalized oxygen hetereocycles (Scheme 1, Eq. 3).6b It was proposed that an allylic cation intermediate was formed as the key intermediate from allylic acetate in the condition of gold catalyst, which was then trapped by the intra- or intermolecular nucleophiles to give the desired products. We envisioned that the
O RO
Au(I) or
O
Au(III)
ROOC
O
OAc
(Eq. 1)
RO O
O OAc X
Ph
Au(I) or
R1
RO2C RO2C
O Ph
Au(III) X R1, R2=H or OH
X=NTs or C(COOMe)2
OAc R2 R3
R1 R2
R5 +
R4 OH
OAc Gold catalyst
Au(I)
or MeOOC
(Eq. 2) Ph
Oxygen Hetereocycles
(Eq. 3)
CO2R CO2R
Scheme 1. Gold catalyzed reactions of the allylic acetate derivatives.
2991
H. Liu et al. / Tetrahedron Letters 52 (2011) 2990–2993 Table 1 Carbocyclization of 1a to provide benzocycle 2aa
E E OAc
Solvent
E=CO2Et 1a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
CO2Et CO2Et
catalyst
2a
Catalyst (loading %)
Solvent
Time (h)
Yieldb (%)
AuPPh3Cl/AgOTf (5) AuPPh3Cl/AgBF4(5) AuPPh3Cl/AgPF6(5) AuPPh3Cl/AgSbF6(5) AuPPh3Cl/AgSbF6(2) AuPPh3Cl/AgSbF6(1) AuPPh3Cl/AgSbF6(2) AuPPh3Cl/AgSbF6(2) AuPPh3Cl AgSbF6 AuCl AuCl3 AlCl3 FeCl3 Cu(OTf)2 BF3Et2O TsOH AuPPh3Cl/AgSbF6(2) 1 equiv K2CO3
DCM DCM DCM DCM DCM DCM DCE CH3CN DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM
6 6 6 6 12 12 12 12 6 6 6 3 4 4 4 3 4 24
0 0 32 99 95 72 91 0 0 0 0 93 31 0 0 67 Trace 61
a Unless noted, all reactions were carried out at 0.5 mmol scale in solvent (1 mL) at room temperature. b Isolated yields.
presence of the allylic cation intermediate might also promote the intramolecular C–C bond formation between phenyl group and allylic acetates to provide the benzocycle derivatives (Scheme 1). Benzocycles appear frequently as common structural units in natural and unnatural products with biological potentials.7 The
classical routes to prepare these compounds have recourse to the cyclic radical addition and carbopalladation of the 2-alkenyl/alkynyl aryl halides, in which, the tedious preparation of the aryl halide reactants was needed.8a In 2002, Ma and Zhang reported the acid catalyzed cyclic Friedel–Crafts reaction of 6-acetoxy-4-alkenyl arenes to construct the benzocycle derivatives.8 However, the synthetic utility of this reaction was dwarfed by the high reaction temperature and the use of the acidic solvent (TFA/HOAc = 3:1). In this Letter, we will report an efficient and environmentally benign method to synthesize these important structural entities via gold catalyzed carbocyclization of the phenyl substituted allylic acetates. In this reaction, gold complex was used as the strong lewis acid catalyst. The readily available 4-acetoxy-2-isopentene substituted benzylmalonate 1a was chosen as the model system for our initial investigation. When compound 1a was treated with 5% mol equiv of AuPPh3Cl/AgOTf or AuPPh3Cl/AgBF4 in DCM at rt, no product was obtained (Table 1, entries 1 and 2). To enhance the catalyst’s lewis acidity, the silver source was changed from AgOTf and AgBF4 to AgPF6 and AgSbF6. To our delight, the reaction occurred when 5% mol equiv of AuPPh3Cl/AgPF6 was employed, giving product 2a in 32% yield (Table 1, entry 3), while combination of AuPPh3Cl/AgSbF6 (5% mol equiv) afforded the desired product in nearly quantitative yield (Table 1, entry 4). The effect of the catalyst loading on the reaction yield was then tested. 2% mol equiv of catalyst also gave a high reaction yield, though with a long reaction time (Table 1, entry 5). However, further reducing the gold catalyst amount to 1% led to a much less yield (Table 1, entry 6). In solvent screening experiments, no reaction occurred in CH3CN. The effect of dichloroethane (DCE) was similar to DCM (Table 1, entries 7 and 8). AuPPh3Cl or AgSbF6 alone failed to catalyze the reaction at all. (Table 1, entries 9 and 10). Among the non-phosphine-ligated gold catalysts, AuCl3 had the highest catalytic activity (Table 1, entry 12). Lewis acids such as BF3Et2O, Cu(OTf)2, AlCl3, FeCl3 were also examined. BF3Et2O, and
Table 2 Gold catalyzed carbocyclization of phenyl substituted allylic acetates 1 to synthesize benzocycle derivatives 2a
E E
R2
R3 OAc
catalyst
R1
CO2Et CO2Et
Solvent R2
E=CO2Et or CO2Me R1 Entry
Substrate
1
EtO2C EtO2C
1
2 % Cat.
Time (h)
R3
CO2Et CO2Et
OAc
2
12
95
1a
2 3
4
2a OAc
MeO2C MeO2C
R
1b, R= tBu 1c, R= F
2 5
E
2 6 R
87 23
CO2Me CO2Me
2
4
95 2d
1d Ph MeO2C MeO2C
E 2b, R= tBu 2c, R= F E=CO2Me
OAc
MeO2C MeO2C
5 6
Yield (%)b
Product
OAc 1e, R = H 1f, R = tBu R
2 2
4 2
99 97
E E 2e, R = H 2f, R = tBu E=CO2Me
R
Ph
(continued on next page)
2992
H. Liu et al. / Tetrahedron Letters 52 (2011) 2990–2993
Table 2 (continued) Entry
Substrate
% Cat.
Time (h)
Yield (%)b
Product
Ph
7
CO2Me CO2Me
OAc
MeO2C MeO2C
2
0.5
99 2g Ph
1g Ph
8
OAc
MeO2C MeO2C
2
1
1h
Ph
E E
2h
MeO2C CO2Me
9
OAc E=CO2Me
2
2
75
1i E E
2i CO2Me CO2Me
OAc
10
91
CO2Me CO2Me
1j
E=CO2Me
MeO2C MeO2C
2
4
2
24
65
2j anti/syn = 1/1
OAc EE NTs
OAc
11
TsN
72 2k
1k a b
Unless noted, all reactions were carried out at 0.5 mmol scale in 1 mL DCM at room temperature with the addition of 2% mol equiv of Ph3PAuCl/AgSbF6. Isolated yields.
AlCl3 gave 2a in moderate yields, together with a mixture of elimination products (Table 1, entries 13 and 16). In the control experiments, TsOH afforded trace amount of 2a. Treating 1a in the basic condition gave 2a in 61% yield after a prolonged reaction time (Table 1, entry 18). By using the condition from entry 5 in Table 1, the scope and limitations of this reaction were then explored.9 A number of cyclic and linear substrates with different substitution patterns at the phenyl group as well as at the allylic acetate moiety were prepared from the simple starting materials by utilizing –C(COOMe) or TsN– as the linker group. Table 2 showed some representative examples for the preparation of the benzocycle derivatives 2 using a variety of differently substituted substrates 1a–1k. The influence of the substituent R1 on the phenyl group (Table 2’s Scheme) was first studied by using terminal 4-acetoxy-2-isopentene as the electrophile. It was found that substrates 1b and 1d, bearing an electrorich phenyl group (Table 2, entries 2 and 4), worked better than their electro-deficient analogue 1c. Compound 2c was obtained only in 23% yield, even in the condition of 5% mol equiv of gold catalyst. Compound 2d was formed as the para-selective product, without formation of the ortho isomer. The substituents at the double bond and at the ally carbon also affected the reaction yield. As compared with the results of 2a, 2b, and 2d, product 2e, 2f, and 2g can be obtained in slightly higher reaction yields (Table 2, entries 5–7). In the reaction of naphthyl containing substrate 1h, only ortho-selective product 2h was separated in 91% yield (Table 2, entry 8). This means the electric effect is more favored. The cyclic substrate 1i can be transformed into tricyclic product 2i, with a slightly lower yield (75%, Table 2, entry 9). Substrate 1j, which contained two allylic acetate units, was also investigated. It provided the corresponding tricyclic product 2j in 65% yield with a ratio of anti/syn = 1:1 (Table 2, entry 10). Substrate with –NTs as the linker group was then studied. As compared with the result obtained from 1a, TsN– containing substrate 1k gave the desired products in relative low yield (72%, Table 2, entry 11).
To determine the effect of the substrate’s stereochemistry on the reaction yield, we turned to investigate the reactions of compound 3 (regioisomer of 1e) and trans-1h. Treating 3 with Ph3PAuCl/AgSbF6 in DCM gave 2e in 97% yield (Scheme 2, Eq. 4), while the reaction of trans-1h afforded 2h in 79% yield (Scheme 2, Eq. 5). These results were similar to those of 1e, 1h (Table 2, entry 5, 9). Nevertheless, when the alcoholic analogue 4 underwent the same transformation in the condition of gold catalyst, the corresponding product 2e was obtained only in 56% yield, which is considerably lower than that of 1e. A plausible mechanism started from the formation of an allylic cation intermediate, which was then trapped by the intramolecular electrophilic substitution reaction to give the desired product. This conforms to the similar reactivities exhibited by compound 3 (regioisomer of 1e) and trans-1h. Ph OAc
MeO2C MeO2C
CO2Me CO2Me
Ph3PAuCl/ AgSbF6 (2%)
(Eq. 4)
DCM, rt
3
2e, 97%
MeO2C CO2Me
Ph3PAuCl/ AgSbF6 (2%) OAc
Ph
MeO2C CO2Me (Eq. 5)
DCM, rt
Trans-1h
2h, 79%
MeO2C CO2Me Ph OH
CO2Me CO2Me (Eq. 6)
Ph3PAuCl/ AgSbF6 (2%) DCM, rt
4
2e, 56%
Ph
Scheme 2. Investigation of the reaction of compound 3, trans-1h, and compound 4.
H. Liu et al. / Tetrahedron Letters 52 (2011) 2990–2993
Eq. 6’s result means that the presence of the acetate would favor the formation of the allylic cation intermediate. In summary, we herein have developed an efficient and environmentally benign new method for the preparation of the benzocycles via a gold catalyzed carbocyclization. Different substitution patterns were investigated, which gave a series of benzocyclohexane derivatives in moderate to excellent yields. The reaction proceeded via a Friedel–Crafts type carbocyclization process, in which, the gold catalyst exhibited high lewis acidity.
3.
4.
5.
Acknowledgment
6.
Support of this work by the grant from the National Sciences Foundation of China (Nos. 20872176 and Nos. 21072224) is gratefully acknowledged.
7.
Supplementary data 8.
Supplementary data (a brief experimental details and the spectra data for all the products) associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.03.142. References and notes 1. For recent general reviews, see: (a) Krause, N.; Winter, C. Chem. Rev. 2011, 111, 1994; (b) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49, 5232; (c) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Soc. Rev. 2009, 38, 3208; (d) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395; (e) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239; (f) Arcadi, A. Chem. Rev. 2008, 108, 3266; (g) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395; (h) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180; (i) Fürstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410; (j) Skouta, R.; Li, C.-J. Tetrahedron 2008, 64, 4917. 2. (a) Trost, B. M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford, 1982; pp 799– 938. Vol. 8; (b) Godelski, S. A. In Comprehensive Organic Synthesis; Trost, B. M.,
9.
2993
Fleming, I., Eds.; Pergamon: Oxford, 1991; pp 585–661. Vol. 4; (c) Hegedus, L. S. In Organometallics in Synthesis; Schlosser, M., Ed.; Wiley: Chichester, 1994; pp 427–444; (d) Hegedus, L. S. Organische Synthesemit übergangsmetallen; VCH: Weinhein, 1995. (a) Marion, N.; Gealageas, R.; Nolan, S. P. Org. Lett. 2007, 9, 2653; (b) Gourlaouen, C.; Marion, N.; Nolan, S. P.; Maseras, F. Org. Lett. 2009, 11, 81; (c) Porcel, S.; López-Carrillo, V.; Garci9 a-Yebra, C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2008, 47, 1883. The reaction of allenyl carbinol esters or allyl alcohol: (a) Buzas, A. K.; Istrate, F. M.; Gagosz, F. Org. Lett. 2007, 9, 985; (b) Aponick, A.; Li, C.-Y.; Biannic, B. Org. Lett. 2008, 10, 669. For reviews, see: (a) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750; (b) Marco-Contelles, J.; Soriano, E. Chem. Eur. J. 2007, 13, 1350. (a) Wang, Y. H.; Zhu, L. L.; Zhang, Y. X.; Chen, Z. Chem. Commun. 2010, 46, 577; (b) Chen, Z.; Zhang, Y.-X.; Wang, Y.-H.; Zhu, L.-L.; Liu, H.; Li, X.-X.; Guo, L. Org. Lett. 2010, 12, 3468; (c) Zhu, L.-L.; Wang, Y.-H.; Zhang, Y.-X.; Li, X.-X.; Liu, H.; Chen, Z. J. Org. Chem. 2011, 76, 441. (a) Kuramoto, M.; Yamada, K.; Shikano, M.; Yazawa, K.; Arimoto, H.; Okamura, T.; Uemura, D. Chem. Lett. 1997, 885; (b) Buckingham, J., Ed. Dictionary of Natural Products; Chapman & Hall, London, 1994, Vol. 1, pp. 812–813.; (c) Palmer, D. C.; Strauss, M. J. Chem. Rev. 1977, 77, 1–36; (d) Shiotani, S.; Kometani, T.; Mitsuhashi, K.; Nozawa, T.; Kurobe, A.; Futsukaichi, O. J. Med. Chem. 1976, 19, 803. (a) Ma, S.; Zhang, J. Tetrahedron Lett. 2002, 43, 3435. and references therein; (b) Ma, S.; Zhang, J. Tetrahedron 2003, 59, 6273. General Procedure for the gold catalyzed Friedel–Crafts type carbocyclization reaction of allylic acetate: The gold catalyst was generated in a oven-dried schlenk tube containing a magnetic stir bar under N2 by addition of AgSbF6 (0.02 equiv), AuPPh3Cl (0.02 equiv), and 0.5 mL CH2Cl2. After stirring the catalyst mixture at room temperature for 2 min, a solution of substrate 1a (0.5 mmol) in 0.5 mL CH2Cl2 was added. The resulting mixture was allowed to stand at room temperature until complete consumption of starting material monitored by TLC analysis, then the solvent was removed by rotary evaporation, and the residue was purified by column chromatography on silica gel to afford the described compound 2a in 95% yield. The spectral data of diethyl 3,4-dihydro-4-methyl-4vinylnaphthalene-2,2(1H)-dicarboxylate 2a: 1H NMR (400 MHz, CDCl3): d 7.18– 7.15 (m, 4H), 5.85 (dd, J = 17.3,10.5 Hz, 1H), 4.93 (d, J = 10.6 Hz, 1H), 4.63 (d, J = 17.2 Hz, 1H), 4.17 (q, J = 7.1 Hz, 2H), 4.08 (q, J = 7.1 Hz, 2H), 3.33 (d, J = 16.0 Hz, 1H), 3.12 (d, J = 16.1 Hz, 1H), 2.52 (d, J = 14.3 Hz, 1H), 2.38 (d, J = 14.2 Hz, 1H), 1.39 (s, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 171.9, 170.9, 147.0, 139.7, 133.7, 128.8, 127.7, 126.4, 126.1, 112.5, 61.4, 61.1, 52.3, 40.8, 40.5, 35.0, 29.3, 14.0, 13.8.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Gold catalyzed carbocyclization of phenyl substituted allylic acetates to synthesize benzocycle derivatives Heng Liu a, Ya-Hui Wang b, Li-Li Zhu b, Xiao-Xiao Li b, Wen Zhou b, Zili Chen b,c,⇑, Wen-Xiang Hu a,⇑ a
Capital Normal University, Beijing 100048, PR China Department of Chemistry, Renmin University of China, Beijing 100872, PR China c Beijing National Laboratory of Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China b
a r t i c l e
i n f o
Article history: Received 26 January 2011 Revised 21 March 2011 Accepted 30 March 2011 Available online 5 April 2011
a b s t r a c t An efficient and environmentally benign method was developed to synthesize the benzocycles from phenyl substituted allylic acetates through gold catalyzed Friedel–Crafts type carbocyclization reaction. Different substitution patterns were investigated, which gave a series of benzocyclohexane derivatives in moderate to excellent yields. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Gold catalyzed reaction Benzocycle Friedel–Crafts reaction Allylic acetate
Utilizing gold complexes in homogeneous organic catalysis has achieved great progress in recent years. In this regard, most of the reported reactions started from the activation of the substrate’s C– C multiple bonds via forming auric p-complexes, and focused on the transformations involving alkyne-, allene-, or olefin-containing derivatives.1 In the process, the gold complex was usually used as the p-acid catalyst. Allylic esters are important building blocks in organic synthesis. These substrates have been widely utilized in transition metal (especially later transition metal, such as: Ni, Pd, Ir, Rh etc.) catalyzed allyl coupling reactions to provide alkene-containing products of variable structural characteristics and diversities.2 However, the study of employing gold complexes in the reaction of allylic esters, to our knowledge, is very limited.34 This is very notable as compared with the extensive research of propargylic esters in gold chemistry.5 We have recently investigated the gold catalyzed reactions of the allylic acetates.6 In our previous results, it was found that gold catalyzed intramolecular nucleophilic addition of the esters onto the allylic acetates would give c-vinyl butyrolactones with high diastereoselectivities (Scheme 1, Eq. 1).6a As an extension of this reaction, carbocyclization of the dienyl acetates via gold catalysis provided 3-vinyl cyclohexanols and their bicyclic derivatives (Scheme 1, Eq. 2).6c And then, we reported the inter-molecular ⇑ Corresponding authors. Fax: +86 10 62516660 (Z.L.C.); fax: +8610 68904750 (W.-X.H.). E-mail addresses: [email protected] (Z.L. Chen), [email protected] (W.-X. Hu). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.03.142
reaction of the allylic acetates with propargylic alcohols to give multifunctionalized oxygen hetereocycles (Scheme 1, Eq. 3).6b It was proposed that an allylic cation intermediate was formed as the key intermediate from allylic acetate in the condition of gold catalyst, which was then trapped by the intra- or intermolecular nucleophiles to give the desired products. We envisioned that the
O RO
Au(I) or
O
Au(III)
ROOC
O
OAc
(Eq. 1)
RO O
O OAc X
Ph
Au(I) or
R1
RO2C RO2C
O Ph
Au(III) X R1, R2=H or OH
X=NTs or C(COOMe)2
OAc R2 R3
R1 R2
R5 +
R4 OH
OAc Gold catalyst
Au(I)
or MeOOC
(Eq. 2) Ph
Oxygen Hetereocycles
(Eq. 3)
CO2R CO2R
Scheme 1. Gold catalyzed reactions of the allylic acetate derivatives.
2991
H. Liu et al. / Tetrahedron Letters 52 (2011) 2990–2993 Table 1 Carbocyclization of 1a to provide benzocycle 2aa
E E OAc
Solvent
E=CO2Et 1a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
CO2Et CO2Et
catalyst
2a
Catalyst (loading %)
Solvent
Time (h)
Yieldb (%)
AuPPh3Cl/AgOTf (5) AuPPh3Cl/AgBF4(5) AuPPh3Cl/AgPF6(5) AuPPh3Cl/AgSbF6(5) AuPPh3Cl/AgSbF6(2) AuPPh3Cl/AgSbF6(1) AuPPh3Cl/AgSbF6(2) AuPPh3Cl/AgSbF6(2) AuPPh3Cl AgSbF6 AuCl AuCl3 AlCl3 FeCl3 Cu(OTf)2 BF3Et2O TsOH AuPPh3Cl/AgSbF6(2) 1 equiv K2CO3
DCM DCM DCM DCM DCM DCM DCE CH3CN DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM
6 6 6 6 12 12 12 12 6 6 6 3 4 4 4 3 4 24
0 0 32 99 95 72 91 0 0 0 0 93 31 0 0 67 Trace 61
a Unless noted, all reactions were carried out at 0.5 mmol scale in solvent (1 mL) at room temperature. b Isolated yields.
presence of the allylic cation intermediate might also promote the intramolecular C–C bond formation between phenyl group and allylic acetates to provide the benzocycle derivatives (Scheme 1). Benzocycles appear frequently as common structural units in natural and unnatural products with biological potentials.7 The
classical routes to prepare these compounds have recourse to the cyclic radical addition and carbopalladation of the 2-alkenyl/alkynyl aryl halides, in which, the tedious preparation of the aryl halide reactants was needed.8a In 2002, Ma and Zhang reported the acid catalyzed cyclic Friedel–Crafts reaction of 6-acetoxy-4-alkenyl arenes to construct the benzocycle derivatives.8 However, the synthetic utility of this reaction was dwarfed by the high reaction temperature and the use of the acidic solvent (TFA/HOAc = 3:1). In this Letter, we will report an efficient and environmentally benign method to synthesize these important structural entities via gold catalyzed carbocyclization of the phenyl substituted allylic acetates. In this reaction, gold complex was used as the strong lewis acid catalyst. The readily available 4-acetoxy-2-isopentene substituted benzylmalonate 1a was chosen as the model system for our initial investigation. When compound 1a was treated with 5% mol equiv of AuPPh3Cl/AgOTf or AuPPh3Cl/AgBF4 in DCM at rt, no product was obtained (Table 1, entries 1 and 2). To enhance the catalyst’s lewis acidity, the silver source was changed from AgOTf and AgBF4 to AgPF6 and AgSbF6. To our delight, the reaction occurred when 5% mol equiv of AuPPh3Cl/AgPF6 was employed, giving product 2a in 32% yield (Table 1, entry 3), while combination of AuPPh3Cl/AgSbF6 (5% mol equiv) afforded the desired product in nearly quantitative yield (Table 1, entry 4). The effect of the catalyst loading on the reaction yield was then tested. 2% mol equiv of catalyst also gave a high reaction yield, though with a long reaction time (Table 1, entry 5). However, further reducing the gold catalyst amount to 1% led to a much less yield (Table 1, entry 6). In solvent screening experiments, no reaction occurred in CH3CN. The effect of dichloroethane (DCE) was similar to DCM (Table 1, entries 7 and 8). AuPPh3Cl or AgSbF6 alone failed to catalyze the reaction at all. (Table 1, entries 9 and 10). Among the non-phosphine-ligated gold catalysts, AuCl3 had the highest catalytic activity (Table 1, entry 12). Lewis acids such as BF3Et2O, Cu(OTf)2, AlCl3, FeCl3 were also examined. BF3Et2O, and
Table 2 Gold catalyzed carbocyclization of phenyl substituted allylic acetates 1 to synthesize benzocycle derivatives 2a
E E
R2
R3 OAc
catalyst
R1
CO2Et CO2Et
Solvent R2
E=CO2Et or CO2Me R1 Entry
Substrate
1
EtO2C EtO2C
1
2 % Cat.
Time (h)
R3
CO2Et CO2Et
OAc
2
12
95
1a
2 3
4
2a OAc
MeO2C MeO2C
R
1b, R= tBu 1c, R= F
2 5
E
2 6 R
87 23
CO2Me CO2Me
2
4
95 2d
1d Ph MeO2C MeO2C
E 2b, R= tBu 2c, R= F E=CO2Me
OAc
MeO2C MeO2C
5 6
Yield (%)b
Product
OAc 1e, R = H 1f, R = tBu R
2 2
4 2
99 97
E E 2e, R = H 2f, R = tBu E=CO2Me
R
Ph
(continued on next page)
2992
H. Liu et al. / Tetrahedron Letters 52 (2011) 2990–2993
Table 2 (continued) Entry
Substrate
% Cat.
Time (h)
Yield (%)b
Product
Ph
7
CO2Me CO2Me
OAc
MeO2C MeO2C
2
0.5
99 2g Ph
1g Ph
8
OAc
MeO2C MeO2C
2
1
1h
Ph
E E
2h
MeO2C CO2Me
9
OAc E=CO2Me
2
2
75
1i E E
2i CO2Me CO2Me
OAc
10
91
CO2Me CO2Me
1j
E=CO2Me
MeO2C MeO2C
2
4
2
24
65
2j anti/syn = 1/1
OAc EE NTs
OAc
11
TsN
72 2k
1k a b
Unless noted, all reactions were carried out at 0.5 mmol scale in 1 mL DCM at room temperature with the addition of 2% mol equiv of Ph3PAuCl/AgSbF6. Isolated yields.
AlCl3 gave 2a in moderate yields, together with a mixture of elimination products (Table 1, entries 13 and 16). In the control experiments, TsOH afforded trace amount of 2a. Treating 1a in the basic condition gave 2a in 61% yield after a prolonged reaction time (Table 1, entry 18). By using the condition from entry 5 in Table 1, the scope and limitations of this reaction were then explored.9 A number of cyclic and linear substrates with different substitution patterns at the phenyl group as well as at the allylic acetate moiety were prepared from the simple starting materials by utilizing –C(COOMe) or TsN– as the linker group. Table 2 showed some representative examples for the preparation of the benzocycle derivatives 2 using a variety of differently substituted substrates 1a–1k. The influence of the substituent R1 on the phenyl group (Table 2’s Scheme) was first studied by using terminal 4-acetoxy-2-isopentene as the electrophile. It was found that substrates 1b and 1d, bearing an electrorich phenyl group (Table 2, entries 2 and 4), worked better than their electro-deficient analogue 1c. Compound 2c was obtained only in 23% yield, even in the condition of 5% mol equiv of gold catalyst. Compound 2d was formed as the para-selective product, without formation of the ortho isomer. The substituents at the double bond and at the ally carbon also affected the reaction yield. As compared with the results of 2a, 2b, and 2d, product 2e, 2f, and 2g can be obtained in slightly higher reaction yields (Table 2, entries 5–7). In the reaction of naphthyl containing substrate 1h, only ortho-selective product 2h was separated in 91% yield (Table 2, entry 8). This means the electric effect is more favored. The cyclic substrate 1i can be transformed into tricyclic product 2i, with a slightly lower yield (75%, Table 2, entry 9). Substrate 1j, which contained two allylic acetate units, was also investigated. It provided the corresponding tricyclic product 2j in 65% yield with a ratio of anti/syn = 1:1 (Table 2, entry 10). Substrate with –NTs as the linker group was then studied. As compared with the result obtained from 1a, TsN– containing substrate 1k gave the desired products in relative low yield (72%, Table 2, entry 11).
To determine the effect of the substrate’s stereochemistry on the reaction yield, we turned to investigate the reactions of compound 3 (regioisomer of 1e) and trans-1h. Treating 3 with Ph3PAuCl/AgSbF6 in DCM gave 2e in 97% yield (Scheme 2, Eq. 4), while the reaction of trans-1h afforded 2h in 79% yield (Scheme 2, Eq. 5). These results were similar to those of 1e, 1h (Table 2, entry 5, 9). Nevertheless, when the alcoholic analogue 4 underwent the same transformation in the condition of gold catalyst, the corresponding product 2e was obtained only in 56% yield, which is considerably lower than that of 1e. A plausible mechanism started from the formation of an allylic cation intermediate, which was then trapped by the intramolecular electrophilic substitution reaction to give the desired product. This conforms to the similar reactivities exhibited by compound 3 (regioisomer of 1e) and trans-1h. Ph OAc
MeO2C MeO2C
CO2Me CO2Me
Ph3PAuCl/ AgSbF6 (2%)
(Eq. 4)
DCM, rt
3
2e, 97%
MeO2C CO2Me
Ph3PAuCl/ AgSbF6 (2%) OAc
Ph
MeO2C CO2Me (Eq. 5)
DCM, rt
Trans-1h
2h, 79%
MeO2C CO2Me Ph OH
CO2Me CO2Me (Eq. 6)
Ph3PAuCl/ AgSbF6 (2%) DCM, rt
4
2e, 56%
Ph
Scheme 2. Investigation of the reaction of compound 3, trans-1h, and compound 4.
H. Liu et al. / Tetrahedron Letters 52 (2011) 2990–2993
Eq. 6’s result means that the presence of the acetate would favor the formation of the allylic cation intermediate. In summary, we herein have developed an efficient and environmentally benign new method for the preparation of the benzocycles via a gold catalyzed carbocyclization. Different substitution patterns were investigated, which gave a series of benzocyclohexane derivatives in moderate to excellent yields. The reaction proceeded via a Friedel–Crafts type carbocyclization process, in which, the gold catalyst exhibited high lewis acidity.
3.
4.
5.
Acknowledgment
6.
Support of this work by the grant from the National Sciences Foundation of China (Nos. 20872176 and Nos. 21072224) is gratefully acknowledged.
7.
Supplementary data 8.
Supplementary data (a brief experimental details and the spectra data for all the products) associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.03.142. References and notes 1. For recent general reviews, see: (a) Krause, N.; Winter, C. Chem. Rev. 2011, 111, 1994; (b) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49, 5232; (c) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Soc. Rev. 2009, 38, 3208; (d) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395; (e) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239; (f) Arcadi, A. Chem. Rev. 2008, 108, 3266; (g) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395; (h) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180; (i) Fürstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410; (j) Skouta, R.; Li, C.-J. Tetrahedron 2008, 64, 4917. 2. (a) Trost, B. M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford, 1982; pp 799– 938. Vol. 8; (b) Godelski, S. A. In Comprehensive Organic Synthesis; Trost, B. M.,
9.
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Fleming, I., Eds.; Pergamon: Oxford, 1991; pp 585–661. Vol. 4; (c) Hegedus, L. S. In Organometallics in Synthesis; Schlosser, M., Ed.; Wiley: Chichester, 1994; pp 427–444; (d) Hegedus, L. S. Organische Synthesemit übergangsmetallen; VCH: Weinhein, 1995. (a) Marion, N.; Gealageas, R.; Nolan, S. P. Org. Lett. 2007, 9, 2653; (b) Gourlaouen, C.; Marion, N.; Nolan, S. P.; Maseras, F. Org. Lett. 2009, 11, 81; (c) Porcel, S.; López-Carrillo, V.; Garci9 a-Yebra, C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2008, 47, 1883. The reaction of allenyl carbinol esters or allyl alcohol: (a) Buzas, A. K.; Istrate, F. M.; Gagosz, F. Org. Lett. 2007, 9, 985; (b) Aponick, A.; Li, C.-Y.; Biannic, B. Org. Lett. 2008, 10, 669. For reviews, see: (a) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750; (b) Marco-Contelles, J.; Soriano, E. Chem. Eur. J. 2007, 13, 1350. (a) Wang, Y. H.; Zhu, L. L.; Zhang, Y. X.; Chen, Z. Chem. Commun. 2010, 46, 577; (b) Chen, Z.; Zhang, Y.-X.; Wang, Y.-H.; Zhu, L.-L.; Liu, H.; Li, X.-X.; Guo, L. Org. Lett. 2010, 12, 3468; (c) Zhu, L.-L.; Wang, Y.-H.; Zhang, Y.-X.; Li, X.-X.; Liu, H.; Chen, Z. J. Org. Chem. 2011, 76, 441. (a) Kuramoto, M.; Yamada, K.; Shikano, M.; Yazawa, K.; Arimoto, H.; Okamura, T.; Uemura, D. Chem. Lett. 1997, 885; (b) Buckingham, J., Ed. Dictionary of Natural Products; Chapman & Hall, London, 1994, Vol. 1, pp. 812–813.; (c) Palmer, D. C.; Strauss, M. J. Chem. Rev. 1977, 77, 1–36; (d) Shiotani, S.; Kometani, T.; Mitsuhashi, K.; Nozawa, T.; Kurobe, A.; Futsukaichi, O. J. Med. Chem. 1976, 19, 803. (a) Ma, S.; Zhang, J. Tetrahedron Lett. 2002, 43, 3435. and references therein; (b) Ma, S.; Zhang, J. Tetrahedron 2003, 59, 6273. General Procedure for the gold catalyzed Friedel–Crafts type carbocyclization reaction of allylic acetate: The gold catalyst was generated in a oven-dried schlenk tube containing a magnetic stir bar under N2 by addition of AgSbF6 (0.02 equiv), AuPPh3Cl (0.02 equiv), and 0.5 mL CH2Cl2. After stirring the catalyst mixture at room temperature for 2 min, a solution of substrate 1a (0.5 mmol) in 0.5 mL CH2Cl2 was added. The resulting mixture was allowed to stand at room temperature until complete consumption of starting material monitored by TLC analysis, then the solvent was removed by rotary evaporation, and the residue was purified by column chromatography on silica gel to afford the described compound 2a in 95% yield. The spectral data of diethyl 3,4-dihydro-4-methyl-4vinylnaphthalene-2,2(1H)-dicarboxylate 2a: 1H NMR (400 MHz, CDCl3): d 7.18– 7.15 (m, 4H), 5.85 (dd, J = 17.3,10.5 Hz, 1H), 4.93 (d, J = 10.6 Hz, 1H), 4.63 (d, J = 17.2 Hz, 1H), 4.17 (q, J = 7.1 Hz, 2H), 4.08 (q, J = 7.1 Hz, 2H), 3.33 (d, J = 16.0 Hz, 1H), 3.12 (d, J = 16.1 Hz, 1H), 2.52 (d, J = 14.3 Hz, 1H), 2.38 (d, J = 14.2 Hz, 1H), 1.39 (s, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 171.9, 170.9, 147.0, 139.7, 133.7, 128.8, 127.7, 126.4, 126.1, 112.5, 61.4, 61.1, 52.3, 40.8, 40.5, 35.0, 29.3, 14.0, 13.8.