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Organic & Biomolecular Chemistry COMMUNICATION Iron-catalyzed arylation of α-aryl-α-diazoesters Published on 05 January 2016. Downloaded by North Dakota State University on 10/01/2016 19:15:26.
Ji-Min Yang,a Yan Cai,a Shou-Fei Zhu*a,b and Qi-Lin Zhoua,b Received 00th January 20xx, Accepted 00th January 20xx DOI: 10.1039/x0xx00000x www.rsc.org/
An iron-catalyzed arylation of α-aryl-α-diazoesters with electronrich benzenes was developed, which provides an efficient method for the preparation of 1,1-diarylacetates with high yields and excellent chemo- and regioselectivities.
iron-catalyzed arylation of α-aryl-α-diazoacetates with N,Ndialkylanilines and other electron-rich benzenes, producing α,αdiarylacetates with high yield and excellent chemo- and regioselectivity.
Catalytic direct carbon-hydrogen bond (C–H) functionalization is the focus of research in organic synthesis.1 Because the benzene ring is a ubiquitous substructure in organic compounds, the functionalization of C–H bonds of benzene ring attracts tremendous attention nowadays. The Friedel-Crafts type arylation of diazo compounds provides an efficient method for functionalizing benzene ring, and achieved a remarkable progress in the past decades.2 Traditionally, the dirhodium(II) complexes are widely used catalysts for this transformation. 3 Recently, the Cu catalysts,4 Au catalysts,5 and Brønsted acids6 were also applied for the arylation of diazo compounds. Iron, given its low price, ready availability, and environmentally friendly character, is an ideal alternative to the precious metal catalysts.7 However, only one iron-catalyzed arylation of diazo compounds was reported using iron(III)-porphyrin as catalyst,8 which has C(sp3)–H insertion, ylide rearrangement, Büchner reaction and other side-reactions. As a part of our lasting interests in the development of iron-catalyzed reactions,9 we investigated the non-porphyrin iron-catalyzed arylation of αaryl-α-diazoacetates and found that the complex generated from FeCl3, 1,10-phenanthroline (phen), and NaBArF 10 is an efficient catalyst. The iron-catalyzed arylation reaction is particularly efficient for the N,N-dialkylanilines, which are challenging substrates in the reported catalysts for arylation reactions.3-5 As the dialkylamino group can be converted to versatile functional groups,11 the arylation with N,Ndialkylanilines is of synthetic importance. Herein we report the
Table 1 Iron-catalyzed arylation of methyl 2-diazo-2-phenylacetates with N,Ndimethylaniline: optimization of the reaction conditions a
a. State
Key Laboratory and Institute of Elemento-Organic Chemistry Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China. Email: [email protected] Electronic Supplementary Information (ESI) available: Detailed experimental procedures, and the analysis data of new compounds. See DOI: 10.1039/x0xx00000x b. Collaborative
Entry
[M]
Ligand
x
Time (h)
Yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16c
FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3.6H2O FeCl2 Fe(OTf)2 FeBr3 CoCl2 NiCl2 CuCl2 FeCl3
----Phen TMEDA PPh3 Dppe Phen Phen Phen Phen Phen Phen Phen Phen
0 5 10 15 15 15 15 15 15 15 15 15 15 15 15 3
24 12 8 8 8 10 24 24 8 20 8 7 6 18 8 8
15 63 74 86 93 87 28 46 90 50 75 79 58 56 74 81
a
Reaction conditions: [M]/ligand/NaBArF/1a/2a = 0.01:0.012:0.03:0.2:0.3 (mmol), in 4 mL of DCE at 70 oC. b Isolated yield. c Using 1 mol% of catalyst.
The reaction of methyl 2-diazo-2-phenylacetate (1a) and N,Ndimethylaniline (2a) was performed in the presence of 5 mol% iron catalyst in 1,2-dichloroethane (DCE) at 70 °C. The simple iron salt FeCl3 gave a very low yield; however, the yield was significantly improved by adding NaBArF (Table 1, entries 1–4). The NaBArF is considered to enhance the Lewis acidity of the iron catalyst by exchanging anion to a bulky and non-
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coordinating BArF-. The effect of ligands on the reaction was then estimated. Bidentate nitrogen ligands such as phen and N,N,N',N'-tetramethylethylenediamine (TMEDA) slightly increased the yield (entries 5 and 6), whereas the phosphine ligands PPh3 and 1,2-bis(diphenylphosphino)ethane (dppe), markedly decreased the yield and reaction rate (entries 7 and 8). The FeCl3.6H2O could also be used as a suitable catalyst precursor of the arylation reaction without O–H insertion product of water been detected (entry 9). When other iron salts, such as FeCl2, Fe(OTf)2, FeBr3 were used as the precursor of catalysts, the yield dropped (entries 10–12). The CoCl2, NiCl2, and CuCl2 were also compared with FeCl3 and found to be less efficient under the standard reaction conditions (entries 13–15). The Brønsted acids, such as TfOH6 cannot catalyze the arylation of N,N-dimethylaniline, which might partially attribute to the formation of a salt between the aniline and the acid. The reaction has an excellent chemo- and regioselectivity. Several potential side reactions such as C(sp3)–H insertion of N-methyl, the ylide rearrangement of amino group, and the alkylation at ortho position of amino group,2 were not detected in the reaction. Only trace amount of dimers of diazoesters and corresponding carbenes were detected as by-product.2 Satisfactory yield was obtained even when the catalyst loading was reduced to 1 mol% (entry 16).
A variety of α-aryl-α-diazoacetates were investigated inOnline the View Article DOI: 10.1039/C5OB02418H arylation with N,N-dimethylaniline (2a) under the optimal reaction conditions. As shown in Table 2, all the reactions proceeded smoothly, affording the desired products with high yields. Generally, the α-aryl-α-diazoacetates having meta or para electron-withdrawing groups exhibited slower reaction rates, but still afforded the corresponding products in high yields (entries 3–5). The diazo compounds having fused rings (1k and 1l) or heteroaromatic rings (1m and 1n) also exhibited excellent outcomes (entries 11–14). Table 3 Iron-catalyzed arylation of methyl 2-diazo-2-phenylacetates.a
Table 2 Iron-catalyzed arylation of α-aryl-α-diazoacetates with N,N-dimethylanilinea
a
The reaction conditions and analysis are similar with those of Table 1, entry 5. The spots in the substrates are reaction position.
Entry
Ar
Product
Time (h)
Yield (%)
1 2 3 4 5 6 7 8 9 10 11 12
C6H5 (1a) 2-ClC6H4 (1b) 3-ClC6H4 (1c) 4-ClC6H4 (1d) 3-BrC6H4 (1e) 2-MeC6H4 (1f) 4-MeC6H4 (1g) 2-MeOC6H4 (1h) 3-MeOC6H4 (1i) 4-MeOC6H4 (1j) 2-naphthyl (1k)
3aa 3ba 3ca 3da 3ea 3fa 3ga 3ha 3ia 3ja 3ka 3la
8 7 24 12 24 8 6 5 6 5 8 5
93 83 86 94 87 85 88 79 80 82 86 80
3ma
6
92
3na
7
88
(1l) 13 (1m) 14
(1n) a
The reaction conditions and analysis are similar with those of Table 1, entry 5.
Different dialkylaminobenzenes were examined in the ironcatalyzed arylation of methyl 2-diazo-2-phenylacetate. All dialkylaminobenzenes including those with an electrondonating group such as methyl (2e) and methoxyl (2f) gave arylation product at para position in high yields (Table 3). However, the dimethylaminobenzene 2g having an electronwithdrawing chlorine atom showed a very low yield (17%). The amide 2h is totally inactive under the standard reaction conditions. These results demonstrate that the present iron catalysts are efficient for the dialkylaminobenzene substrates and are complementary with the gold catalysts, which prefer working with amidobenzenes instead of aminobenzenes. 5b,c In addition to dialkylaminobenzenes, 1,3-dimethoxybenzene (2i) and 1,3,5-trimethoxybenzene (2j) also underwent the arylation reaction with methyl 2-diazo-2-phenylacetate in good yield. It is worth mentioning that the iron catalyst exhibited excellent chemo- and regio-selectivity for all these substrates, and usual side reactions, such as C(sp3)–H insertion, ylide rearrangement, Büchner reaction didn’t observed in all these cases. Unlike our previousely reported system,9b the iron catalyst in this study exhibited less efficiency for the insertion of N-methyl indole: giving desired C-H functional product in moderate yield (57%) with several unidentified by-products.
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Notes and references 1
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Scheme 1 Gram-scale experiment
The iron-catalyzed arylation reaction could be easily scale up to gram-scale with retaining excellent yield (1.5 g of product, 93% yield, Scheme 1), which indicates its potential applications in organic synthesis. The N,N-dimethylamino group of the arylation products has many potential transformations. Scheme 2 illustrated the reactions we carried out with 3aa. The oxidation of 3aa with PhIO/TMSN3, followed by hydrolysis released free amino group (4). The deamination of 3aa by reaction with methyl iodide and the reduction of the resulting quaternary ammonium salt afforded diphenylacetate 5. This transformation enables dialkylaniline to be utilized as benzene surrogate. By activation with trifluoromethanesulfonate, the dialkylamino group of compound 3aa can serve as a leaving group for Suzuki coupling (6). In addition, the ester group of the arylation products were easily converted to amino and other functional groups by corresponding reactions (see Supporting Information).
Scheme 2 Transformations of 3aa. [IMes.HCl = 1,3-bis(2,4,6trimethylphenyl)imidazolium chloride; DEAD = diethyl azodicarboxylate; DPPA = diphenylphosphoryl azide]
In summary, we developed an efficient iron-catalyzed arylation of α-aryl-α-diazoesters with electron-rich benzenes. The reaction proceeds under mild conditions with high yields and excellent chemo- and regio-selectivity. From the arylation products, versatile α,α-diarylacetates, α,α-diarylmethylamines and other useful compounds were obtained.
Conclusions We thank the National Natural Science Foundation of China, the National Basic Research Program of China (2012CB821600), the “111” project (B06005) of the Ministry of Education of China, and the National Program for Support of Top-notch Young Professionals for financial support.
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For selected reviews, see: (a) D. Alberico, M. E. Scott and M. Lautens, Chem. Rev., 2007, 107, 174; (b) H. M. L. Davies and J. R. Manning, Nature, 2008, 451, 417; (c) R. Giri, B.-F. Shi, K. M. Engle, N. Maugel and J.-Q. Yu, Chem. Soc. Rev., 2009, 38, 3242; (d) C.-J. Li, Acc. Chem. Res., 2009, 42, 335; (e) T. W. Lyons and M. S. Sanford, Chem. Rev., 2010, 110, 1147; (f) T. Newhouse and P. S. Baran, Angew. Chem. Int. Ed., 2011, 50, 3362; (g) K. M. Engle, T.-S. Mei, M. Wasa and J.-Q. Yu, Acc. Chem. Res., 2012, 45, 788; (h) J. Yamaguchi, A. D. Yamaguchi and K. Itami, Angew. Chem. Int. Ed., 2012, 51, 8960. 2 For reviews, see: (a) M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds; chapter 6.3, p325, Wiley: New York, 1998; (b) Z. Zhang and J. Wang, Tetrahedron, 2008, 64, 6577; (c) S.-F. Zhu and Q.-L. Zhou, Nat. Sci. Rev., 2014, 1, 580; (d) A. Ford, H. Miel, A. Ring, C. N. Slattery, A. R. Maguire, M. A. McKervey, Chem. Rev. 2015, 115, 9981. 3 (a) D. F. Taber and R. E. Ruckle, Jr. J. Am. Chem. Soc., 1986, 108, 7686; (b) M. Hrytsak and T. Durst, J. Chem. Soc., Chem. Commun., 1987, 1150; (c) M. P. Doyle, M. S. Shanklin, H. Q. Pho and S. N. Mahapatro, J. Org. Chem., 1988, 53, 1017; (d) A. Padwa, D. J. Austin, A. T. Price, M. A. Semones, M. P. Doyle, M. N. Protopopova, W. R. Winchester and A. Tran, J. Am. Chem. Soc., 1993, 115, 8669; (e) H. M. L. Davies and Q. Jin, Org. Lett., 2004, 6, 1769; (f) C. P. Park, A. Nagle, C. H. Yoon, C. Chen and K. W. Jung, J. Org. Chem., 2009, 74, 6231; (g) J. Kim, Y. Ohk, S. H. Park, Y. Jung and S. Chang, Chem. Asian J., 2011, 6, 2040; (h) W.-W. Chan, S.-F. Lo, Z. Zhou and W.-Y. Yu, J. Am. Chem. Soc., 2012, 134, 13565; (i) B. Xu, M.-L. Li, X.-D. Zuo, S.-F. Zhu, Q.-L. Zhou, J. Am. Chem. Soc. 2015, 137, 8700. 4 (a) E. Tayama, T. Yanaki, H. Iwamoto and E. Hasegawa, Eur. J. Org. Chem., 2010, 6719; (b) E. Tayama, M. Ishikawa, H. Iwamoto and E. Hasegawa, Tetrahedron Lett., 2012, 53, 5159. 5 (a) I. Rivilla, B. P. Gómez-Emeterio, M. R. Fructos, M. M. DíazRequejo and P. J. Pérez, Organometallics, 2011, 30, 2855; (b) Z. Yu, B. Ma, M. Chen, H.-H. Wu, L. Liu and J. Zhang, J. Am. Chem. Soc., 2014, 136, 6904; (c) Y. Xi, Y. Su, Z. Yu, B. Dong, E. J. McClain, Y. Lan and X. Shi, Angew. Chem. Int. Ed., 2014, 53, 9817. 6 C. Zhai, D. Xing, C. Jing, J. Zhou, C. Wang, D. Wang and W. Hu, Org. Lett., 2014, 16, 2934. See also ref. 3c and 4b. 7 (a) C. Bolm, J. Legros, J. Le Paih and L. Zani, Chem. Rev., 2004, 104, 6217; (b) S. Enthaler, K. Junge and M. Beller, Angew. Chem., Int. Ed., 2008, 47, 3317; (c) B. D. Sherry and A. Fürstner, Acc. Chem. Res., 2008, 41, 1500; (d) C.-L. Sun, B.-J. Li and Z.-J. Shi, Chem. Rev., 2011, 111, 1293; (e) K. Gopalaiah, Chem. Rev., 2013, 113, 3248; (f) I. Bauer and H.-J. Knölker, Chem. Rev., 2015, 115, 3170. 8 H. M. Mbuvi and L. K. Woo, Organometallics, 2008, 27, 637. 9 (a) S.-F. Zhu, Y. Cai, H.-X. Mao, J.-H. Xie and Q.-L. Zhou, Nature Chem., 2010, 2, 546; (b) Y. Cai, S.-F. Zhu, G.-P. Wang and Q.-L. Zhou, Adv. Synth. Catal., 2011, 353, 2939; (c) J.-J. Shen, S.-F. Zhu, Y. Cai, H. Xu, X.-L. Xie and Q.-L. Zhou, Angew. Chem. Int. Ed., 2014, 53, 13188; (d) N. Guo, M.-Y. Hu, Y. Feng and S.-F. Zhu, Org. Chem. Front., 2015, 2, 692. 10 Sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, which could be prepared at hundreds gram scale starting from easily accessible 1-bromo-3,5-bis(trifluoromethyl)benzene in one port with 60–70% yield following the slightly modified literature procedures: (a) Brookhart, M.; Grant, B.; Volpe, A. F. Organometallics 1992, 11, 3920. (b) Nishida, H.; Takada, N.; Yoshimura, M.; Sonoda, T.; Kobayashi, H. Bull. Chem. Soc. Jpn. 1984, 57, 2600. 11 (a) N. A. Paras and D. W. C. MacMillan, J. Am. Chem. Soc., 2002, 124, 7894; (b) Z. Li and C.-J. Li, J. Am. Chem. Soc., 2004, 126, 11810; (c) A. J. Catino, J. M. Nichols, B. J. Nettles and M. P.
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Doyle, J. Am. Chem. Soc., 2006, 128, 5648; (d) E. E. Parent, C. S. Dence, C. Jenks, T. L. Sharp, M. J. Welch and J. A. Katzenellenbogen, J. Med. Chem., 2007, 50, 1028; (e) J. T. Reeves, D. R. Fandrick, Z. Tan, J. J. Song, H. Lee, N. K. Yee and C. H. Senanayake, Org. Lett., 2010, 12, 4388; (f) S. S. Bhojgude, T. Kaicharla and A. T. Biju, Org. Lett., 2013, 15, 5452.
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Organic & Biomolecular Chemistry COMMUNICATION Iron-catalyzed arylation of α-aryl-α-diazoesters Published on 05 January 2016. Downloaded by North Dakota State University on 10/01/2016 19:15:26.
Ji-Min Yang,a Yan Cai,a Shou-Fei Zhu*a,b and Qi-Lin Zhoua,b Received 00th January 20xx, Accepted 00th January 20xx DOI: 10.1039/x0xx00000x www.rsc.org/
An iron-catalyzed arylation of α-aryl-α-diazoesters with electronrich benzenes was developed, which provides an efficient method for the preparation of 1,1-diarylacetates with high yields and excellent chemo- and regioselectivities.
iron-catalyzed arylation of α-aryl-α-diazoacetates with N,Ndialkylanilines and other electron-rich benzenes, producing α,αdiarylacetates with high yield and excellent chemo- and regioselectivity.
Catalytic direct carbon-hydrogen bond (C–H) functionalization is the focus of research in organic synthesis.1 Because the benzene ring is a ubiquitous substructure in organic compounds, the functionalization of C–H bonds of benzene ring attracts tremendous attention nowadays. The Friedel-Crafts type arylation of diazo compounds provides an efficient method for functionalizing benzene ring, and achieved a remarkable progress in the past decades.2 Traditionally, the dirhodium(II) complexes are widely used catalysts for this transformation. 3 Recently, the Cu catalysts,4 Au catalysts,5 and Brønsted acids6 were also applied for the arylation of diazo compounds. Iron, given its low price, ready availability, and environmentally friendly character, is an ideal alternative to the precious metal catalysts.7 However, only one iron-catalyzed arylation of diazo compounds was reported using iron(III)-porphyrin as catalyst,8 which has C(sp3)–H insertion, ylide rearrangement, Büchner reaction and other side-reactions. As a part of our lasting interests in the development of iron-catalyzed reactions,9 we investigated the non-porphyrin iron-catalyzed arylation of αaryl-α-diazoacetates and found that the complex generated from FeCl3, 1,10-phenanthroline (phen), and NaBArF 10 is an efficient catalyst. The iron-catalyzed arylation reaction is particularly efficient for the N,N-dialkylanilines, which are challenging substrates in the reported catalysts for arylation reactions.3-5 As the dialkylamino group can be converted to versatile functional groups,11 the arylation with N,Ndialkylanilines is of synthetic importance. Herein we report the
Table 1 Iron-catalyzed arylation of methyl 2-diazo-2-phenylacetates with N,Ndimethylaniline: optimization of the reaction conditions a
a. State
Key Laboratory and Institute of Elemento-Organic Chemistry Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China. Email: [email protected] Electronic Supplementary Information (ESI) available: Detailed experimental procedures, and the analysis data of new compounds. See DOI: 10.1039/x0xx00000x b. Collaborative
Entry
[M]
Ligand
x
Time (h)
Yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16c
FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3.6H2O FeCl2 Fe(OTf)2 FeBr3 CoCl2 NiCl2 CuCl2 FeCl3
----Phen TMEDA PPh3 Dppe Phen Phen Phen Phen Phen Phen Phen Phen
0 5 10 15 15 15 15 15 15 15 15 15 15 15 15 3
24 12 8 8 8 10 24 24 8 20 8 7 6 18 8 8
15 63 74 86 93 87 28 46 90 50 75 79 58 56 74 81
a
Reaction conditions: [M]/ligand/NaBArF/1a/2a = 0.01:0.012:0.03:0.2:0.3 (mmol), in 4 mL of DCE at 70 oC. b Isolated yield. c Using 1 mol% of catalyst.
The reaction of methyl 2-diazo-2-phenylacetate (1a) and N,Ndimethylaniline (2a) was performed in the presence of 5 mol% iron catalyst in 1,2-dichloroethane (DCE) at 70 °C. The simple iron salt FeCl3 gave a very low yield; however, the yield was significantly improved by adding NaBArF (Table 1, entries 1–4). The NaBArF is considered to enhance the Lewis acidity of the iron catalyst by exchanging anion to a bulky and non-
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coordinating BArF-. The effect of ligands on the reaction was then estimated. Bidentate nitrogen ligands such as phen and N,N,N',N'-tetramethylethylenediamine (TMEDA) slightly increased the yield (entries 5 and 6), whereas the phosphine ligands PPh3 and 1,2-bis(diphenylphosphino)ethane (dppe), markedly decreased the yield and reaction rate (entries 7 and 8). The FeCl3.6H2O could also be used as a suitable catalyst precursor of the arylation reaction without O–H insertion product of water been detected (entry 9). When other iron salts, such as FeCl2, Fe(OTf)2, FeBr3 were used as the precursor of catalysts, the yield dropped (entries 10–12). The CoCl2, NiCl2, and CuCl2 were also compared with FeCl3 and found to be less efficient under the standard reaction conditions (entries 13–15). The Brønsted acids, such as TfOH6 cannot catalyze the arylation of N,N-dimethylaniline, which might partially attribute to the formation of a salt between the aniline and the acid. The reaction has an excellent chemo- and regioselectivity. Several potential side reactions such as C(sp3)–H insertion of N-methyl, the ylide rearrangement of amino group, and the alkylation at ortho position of amino group,2 were not detected in the reaction. Only trace amount of dimers of diazoesters and corresponding carbenes were detected as by-product.2 Satisfactory yield was obtained even when the catalyst loading was reduced to 1 mol% (entry 16).
A variety of α-aryl-α-diazoacetates were investigated inOnline the View Article DOI: 10.1039/C5OB02418H arylation with N,N-dimethylaniline (2a) under the optimal reaction conditions. As shown in Table 2, all the reactions proceeded smoothly, affording the desired products with high yields. Generally, the α-aryl-α-diazoacetates having meta or para electron-withdrawing groups exhibited slower reaction rates, but still afforded the corresponding products in high yields (entries 3–5). The diazo compounds having fused rings (1k and 1l) or heteroaromatic rings (1m and 1n) also exhibited excellent outcomes (entries 11–14). Table 3 Iron-catalyzed arylation of methyl 2-diazo-2-phenylacetates.a
Table 2 Iron-catalyzed arylation of α-aryl-α-diazoacetates with N,N-dimethylanilinea
a
The reaction conditions and analysis are similar with those of Table 1, entry 5. The spots in the substrates are reaction position.
Entry
Ar
Product
Time (h)
Yield (%)
1 2 3 4 5 6 7 8 9 10 11 12
C6H5 (1a) 2-ClC6H4 (1b) 3-ClC6H4 (1c) 4-ClC6H4 (1d) 3-BrC6H4 (1e) 2-MeC6H4 (1f) 4-MeC6H4 (1g) 2-MeOC6H4 (1h) 3-MeOC6H4 (1i) 4-MeOC6H4 (1j) 2-naphthyl (1k)
3aa 3ba 3ca 3da 3ea 3fa 3ga 3ha 3ia 3ja 3ka 3la
8 7 24 12 24 8 6 5 6 5 8 5
93 83 86 94 87 85 88 79 80 82 86 80
3ma
6
92
3na
7
88
(1l) 13 (1m) 14
(1n) a
The reaction conditions and analysis are similar with those of Table 1, entry 5.
Different dialkylaminobenzenes were examined in the ironcatalyzed arylation of methyl 2-diazo-2-phenylacetate. All dialkylaminobenzenes including those with an electrondonating group such as methyl (2e) and methoxyl (2f) gave arylation product at para position in high yields (Table 3). However, the dimethylaminobenzene 2g having an electronwithdrawing chlorine atom showed a very low yield (17%). The amide 2h is totally inactive under the standard reaction conditions. These results demonstrate that the present iron catalysts are efficient for the dialkylaminobenzene substrates and are complementary with the gold catalysts, which prefer working with amidobenzenes instead of aminobenzenes. 5b,c In addition to dialkylaminobenzenes, 1,3-dimethoxybenzene (2i) and 1,3,5-trimethoxybenzene (2j) also underwent the arylation reaction with methyl 2-diazo-2-phenylacetate in good yield. It is worth mentioning that the iron catalyst exhibited excellent chemo- and regio-selectivity for all these substrates, and usual side reactions, such as C(sp3)–H insertion, ylide rearrangement, Büchner reaction didn’t observed in all these cases. Unlike our previousely reported system,9b the iron catalyst in this study exhibited less efficiency for the insertion of N-methyl indole: giving desired C-H functional product in moderate yield (57%) with several unidentified by-products.
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Scheme 1 Gram-scale experiment
The iron-catalyzed arylation reaction could be easily scale up to gram-scale with retaining excellent yield (1.5 g of product, 93% yield, Scheme 1), which indicates its potential applications in organic synthesis. The N,N-dimethylamino group of the arylation products has many potential transformations. Scheme 2 illustrated the reactions we carried out with 3aa. The oxidation of 3aa with PhIO/TMSN3, followed by hydrolysis released free amino group (4). The deamination of 3aa by reaction with methyl iodide and the reduction of the resulting quaternary ammonium salt afforded diphenylacetate 5. This transformation enables dialkylaniline to be utilized as benzene surrogate. By activation with trifluoromethanesulfonate, the dialkylamino group of compound 3aa can serve as a leaving group for Suzuki coupling (6). In addition, the ester group of the arylation products were easily converted to amino and other functional groups by corresponding reactions (see Supporting Information).
Scheme 2 Transformations of 3aa. [IMes.HCl = 1,3-bis(2,4,6trimethylphenyl)imidazolium chloride; DEAD = diethyl azodicarboxylate; DPPA = diphenylphosphoryl azide]
In summary, we developed an efficient iron-catalyzed arylation of α-aryl-α-diazoesters with electron-rich benzenes. The reaction proceeds under mild conditions with high yields and excellent chemo- and regio-selectivity. From the arylation products, versatile α,α-diarylacetates, α,α-diarylmethylamines and other useful compounds were obtained.
Conclusions We thank the National Natural Science Foundation of China, the National Basic Research Program of China (2012CB821600), the “111” project (B06005) of the Ministry of Education of China, and the National Program for Support of Top-notch Young Professionals for financial support.
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