Letter Cite This: Org. Lett. 2017, 19, 6708−6711
pubs.acs.org/OrgLett
Bismuth Triflate-Catalyzed Vinylogous Nucleophilic 1,6-Conjugate Addition of para-Quinone Methides with 3‑Propenyl-2silyloxyindoles Kai-Xue Xie, Zhi-Pei Zhang, and Xin Li* State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, P. R. China S Supporting Information *
ABSTRACT: A highly diastereoselective vinylogous nucleophilic 1,6-conjugate addition reaction of para-quinone methides with 3-propenyl-2-silyloxyindoles by a bismuth triflate catalyst has been developed. A number of diphenylmethane type compounds functionalized with oxindole motifs was obtained with excellent yields (up to 99%) and very good diastereoselectivities (up to Z/ E > 99:1).
V
additions, Mannich reactions, AAA reactions, aldolcyclization cascade reactions, and Michael−Michael cascade reaction, in which 3-alkylidene-2-oxindoles were used as nucleophiles, have been reported as successful (Scheme 1).7 However, 3alkylidene-2-oxindoles have never been studied as nucleophiles in an 1,6-addition reaction. On the other hand, para-quinone methides (p-QMs), which are widely occurring motifs in
inylogous reaction represents a powerful chemical tool for the preparation of structurally complex molecules in organic synthesis. Inspired by the success of asymmetric vinylogous Mukaiyama additions,1 a number of vinylogous reactions, including the vinylogous Mannich reaction, vinylogous aldol reaction, and vinylogous Diels−Alder cycloaddition reactions,2 has been widely studied and found useful for the construction of multifunctional molecules. In particular, the vinylogous Michael reaction, due to its practical property, has received great attention in the past few years. Despite the progress that has been made in the synthesis of vinylogous Michael 1,4-addition reactions,3 vinylogous Michael 1,6addition reactions are very rare. To date, only two examples were reported. In 2013, Jørgensen reported the vinylogous Michael 1,6-addition of methyl-substituted olefinic azlactones and butyrolactones to aromatic and aliphatic 2,4-dienal.4a In 2015, Ye and Dixon developed an asymmetric doubly vinylogous Michael addition of α,β-unsaturated γ-butyrolactams to sterically congested β-substituted cyclic dienones by a L-tertleucine derivative catalyst.4b Therefore, the development of new strategies of the vinylogous Michael 1,6-addition is highly desirable. Over the past decades, a number of nucleophiles, such as silyl dienolates, butyrolactones, lactams, enones, and α,α-dicyanoalkenes, had been extensively explored as Michael donors in the vinylogous Michael addition reaction.5 Recently, 3-alkylidene-2oxindoles, which are privileged scaffolds present as fascinating heterocycles in many natural products and bioactive molecules,6 have attracted more and more attention as vinylogous nucleophiles. As a result, vinylogous Michael 1,4© 2017 American Chemical Society
Scheme 1. Vinylogous 1,6-Addition Reaction of p-QMs with 3-Propenyl-2-silyloxyindoles
Received: November 4, 2017 Published: November 28, 2017 6708
DOI: 10.1021/acs.orglett.7b03433 Org. Lett. 2017, 19, 6708−6711
Letter
Organic Letters
Scheme 2. Substrate Scope with Respect to the p-QMsa−c
various natural products and pharmaceuticals,8−10 have shown great potential as 1,6-Michael acceptors for their intrinsic electrophilic nature (Scheme 1).11,12,13b,i,j In the past few years, a large number of 1,6-conjugation addition reactions of p-QMs was reported.13 Herein, we report the vinylogous nucleophilic 1,6-conjugate addition reaction of p-QMs with 3-propenyl-2silyloxyindoles (Scheme 1), which displays very wide substrate scopes and affords the corresponding substituted α-alkylideneδ-diaryl-2-oxindole products with complete γ-site and Zselectivity in excellent yields. We initiated our investigations using p-QMs (1a) and NBoc-protected 3-(2-propenyl)-2-tert-butyldimethyl-silyloxyindole (2a) in the presence of InBr3 as Lewis acid catalyst in dichloromethane at −78 °C. Although the vinylogous 1,6addition product 3a can be obtained with good 96:4 dr, the yield is poor (Table 1, entry 1). We then examined a series of Table 1. Optimization of the Reaction Conditionsa
entry
Lewis acid
solvent
time (h)
yield (%)b
dr (Z/E)c
1 2 3 4 5 6 7 8 9 10 11 12d
InBr3 Sc(OTf)3 La(OTf)3 Y(OTf)3 Bi(OTf)3 BiCl3 Bi(OAc)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 THF Et2O MTBE toluene CH2Cl2
12 12 12 12 12 12 12 12 12 12 12 24
39 44 trace trace 92 35 trace 11 49 trace 74 85
96:4 95:5 nde nde 98:2 99:1 nde 99:1 98:2 nde 99:1 98:2
a
Unless noted otherwise, reactions were performed under argon with 0.1 mmol of 1 and 0.12 mmol of 2a in 0.5 mL of solvent with 0.01 mmol of Lewis acid at −78 °C for 12 h. bIsolated products. c Determined by 1H NMR analysis of the crude reaction mixture. dThe reaction time is 36 h.
a
Unless noted otherwise, reactions were performed under argon with 0.1 mmol of 1a and 0.12 mmol of 2a in 0.5 mL of solvent with 0.01 mmol of Lewis acid at −78 °C. bIsolated products. cDetermined by 1H NMR analysis of the crude reaction mixture. d5 mol % catalyst was used. eNot determined.
on the ortho-position of the phenyl ring were quite amenable to the studied vinylogous 1,6-addition process and offered the corresponding products 3a−3g with very good results (77− 98% yields and 94:6 to 99:1 Z/E). To our surprise, when pQMs bearing o-CF3 group were used as electrophile, only 55% yield of 3h was obtained. Further examination of the substrate scope indicated that the p-QMs with either electron-withdrawing or electron-donating substituents on the para- and meta-positions of the phenyl ring all worked well in the vinylogous 1,6-addition strategy, in which adducts 3i−3q were obtained in excellent yields (84−99%) and high diastereoselectivities (Z/E > 99:1). The doubly substituted and naphthylsubstituted p-QMs were also well tolerated (3r−3v, 88−99% yields and 95:5 to >99:1 Z/E). Replacing the phenyl group with a heteroaromatic thiophene ring afforded 3w in 99% yield and >99:1 Z/E. Furthermore, nonsymmetric p-QMs could also be more easily processed to give products 3x and 3y with very good yields and Z/E values. Next, the scope of 3-alkenyl-2-silyloxyindoles was surveyed to react with p-QMs 1a (Scheme 3). When 5-position substituted indoles with electron-withdrawing groups were used as substrates, the reactions proceeded smoothly and afforded the corresponding products 4a and 4b in good yields with high diastereoselectivities. This protocol could be
Lewis acid catalysts (Table 1, entries 1 to 7).14 When using Sc(OTf)3 as catalyst, the yield was enhanced slightly (Table 1, entry 2) and only a trace of the product was observed by using La(OTf)3 or Y(OTf)3 as catalyst (Table 1, entries 3 and 4). Remarkably, Bi(OTf)3 was found to afford the adduct 3a with 92% yield and 98:2 Z/E ratio (Table 1, entry 5). Other bismuth-type catalysts, such as BiCl3 and Bi(OAc)3, were also examined, in which the yields of 3a dropped greatly (Table 1, entries 6 and 7).15 The reaction was then optimized by screening solvent in the presence of Bi(OTf)3 (Table 1, entries 5 and 8−11). As a result, the initial used CH2Cl2 gave the best result. Lowering the catalyst loading can lead to a decrease in yield (Table 1, entry 12). With the optimized conditions in hand, the scope of p-QMs was briefly investigated (Scheme 2). Most of the p-QMs employed in the reaction delivered the corresponding products in good yields and excellent diastereoselectivities. We first examined p-QMs bearing various substituents on the phenyl ring. As a result, the p-QMs with electron-donating substituents 6709
DOI: 10.1021/acs.orglett.7b03433 Org. Lett. 2017, 19, 6708−6711
Letter
Organic Letters Scheme 3. Substrate Scope with Respect to the 3-Alkenyl-2silyloxyindolesa−c
Scheme 4. Gram-Scale Experiment and Transformation of the Product
In conclusion, we have developed a method of bismuth triflate-catalyzed highly diastereoselective vinylogous 1,6conjugate addition of para-quinone methides with 3-propenyl-2-silyloxyindoles. This protocol works well for a wide range of p-QMs and 3-propenyl-2-silyloxyindoles and affords the vinylogous 1,6-addition products with good yields (up to 99%) and high diastereoselectivities (up to >99:1 Z/E).
a
Unless noted otherwise, reactions were performed under argon with 0.1 mmol of 1a and 0.12 mmol of 2 in 0.5 mL of solvent with 0.01 mmol of Lewis acid at −78 °C. bIsolated products. cDetermined by 1H NMR analysis of the crude reaction mixture.
■
extended to the benzylideneoxindole (R2 = Ar) in which the desired products 4c−4g were obtained with good yields (up to 97%) and excellent diastereoselectivities (up to >99:1 E/Z). Moreover, the substrates with substituents on the phenyl ring at the Cβ-position could also tolerate the current studied vinylogous 1,6-addition strategy, affording the desired products 4h−4k with very good yields (up to 98%) and excellent E/Z values (up to >99:1). The geometry of the double bond of the adduct was determined by single-crystal X-ray diffraction analysis. To probe the efficiency of the current vinylogous nucleophilic 1,6-conjugate addition strategy in preparative synthesis, the viability of reducing the catalyst loading and increasing the reaction scale was examined (Scheme 4). To our delight, corresponding product 3m was obtained without any loss of the yield (91%) with 5 mol % bismuth triflate catalyst under the standard reaction conditions. The synthetic applicability of this protocol was also investigated by the transformation of 3m (Scheme 4). N-Boc deprotection of 3m was conducted smoothly by TFA in which 5 was easily obtained in 99% yield without any loss of the diastereoselectivity. When 3m was treated with AlCl3, both de-tertbutylation and N-Boc deprotection happened and delivered product 6 in excellent yield and diastereoselectivity. Reduction of the 3m with NaBH4 in methanol afforded the diastereomeric mixture of N,O-acetals, which was dehydrated rapidly with Bi(OTf)3 to give corresponding product 7 in 63% yield with 3:1 dr.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b03433. Experimental procedures and characterization data(PDF) Accession Codes
CCDC 1579053 and 1579477 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
■
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Xin Li: 0000-0001-6020-9170 Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS We are grateful to the NNSFC (Grant Nos. 21390400 and 21421062) and Nankai University for financial support. 6710
DOI: 10.1021/acs.orglett.7b03433 Org. Lett. 2017, 19, 6708−6711
Letter
Organic Letters
■
R.; Lopes, L. M. X. Phytochemistry 2009, 70, 590. (c) Dehn, R.; Katsuyama, Y.; Weber, A.; Gerth, K.; Jansen, R.; Steinmetz, H.; Höfle, G.; Müller, R.; Kirschning, A. Angew. Chem., Int. Ed. 2011, 50, 3882. (d) Sridar, C.; D’Agostino, J.; Hollenberg, P. F. Drug Metab. Dispos. 2012, 40, 2280. (11) Baeyer, A.; Villiger, V. Ber. Dtsch. Chem. Ges. 1903, 36, 2774. (12) (a) Parra, A.; Tortosa, M. ChemCatChem 2015, 7, 1524. (b) Caruana, L.; Fochi, M.; Bernardi, L. Molecules 2015, 20, 11733. (c) Chauhan, P.; Kaya, U.; Enders, D. Adv. Synth. Catal. 2017, 359, 888. (d) Liao, J.-Y.; Ni, Q.; Zhao, Y. Org. Lett. 2017, 19, 4074. (e) Roiser, L.; Waser, M. Org. Lett. 2017, 19, 2338. (f) Molleti, N.; Kang, J.-Y. Org. Lett. 2017, 19, 958. (g) Huang, B.; Shen, Y.; Mao, Z.J.; Liu, Y.; Cui, S.-L. Org. Lett. 2016, 18, 4888. (h) Yuan, Z.-B.; Wei, W.; Lin, A.-J.; Yao, H.-Q. Org. Lett. 2016, 18, 3370. (i) Ramanjaneyulu, B. T.; Mahesh, S.; Anand, R. V. Org. Lett. 2015, 17, 3952. (j) Yuan, Z.B.; Liu, L.; Pan, P.; Yao, H.-Q.; Lin, A.-J. J. Org. Chem. 2017, 82, 8743. (k) Yang, C.; Gao, S.; Yao, H.-Q.; Lin, A.-J. J. Org. Chem. 2016, 81, 11956. (13) For selected examples: (a) Chu, W.-D.; Zhang, L.-F.; Bao, X.; Zhao, X.-H.; Zeng, C.; Du, J.-Y.; Zhang, G.-B.; Wang, F.-X.; Ma, X.-Y.; Fan, C.-A. Angew. Chem., Int. Ed. 2013, 52, 9229. (b) Caruana, L.; Kniep, F.; Johansen, T. K.; Poulsen, P. H.; JØrgensen, K. A. J. Am. Chem. Soc. 2014, 136, 15929. (c) Lou, Y.; Cao, P.; Jia, T.; Zhang, Y.; Wang, M.; Liao, J. Angew. Chem., Int. Ed. 2015, 54, 12134. (d) Yuan, Z.; Fang, X.; Li, X.; Wu, J.; Yao, H.; Lin, A. J. Org. Chem. 2015, 80, 11123. (e) Wang, Z.; Wong, Y. F.; Sun, J. Angew. Chem., Int. Ed. 2015, 54, 13711. (f) He, F.-S.; Jin, J.-H.; Yang, Z.-T.; Yu, X.; Fossey, J. S.; Deng, W.-P. ACS Catal. 2016, 6, 652. (g) Zhao, K.; Zhi, Y.; Wang, A.; Enders, D. ACS Catal. 2016, 6, 657. (h) Deng, Y.-H.; Zhang, X.-Z.; Yu, K.-Y.; Yan, X.; Du, J.-Y.; Huang, H.; Fan, C.-A. Chem. Commun. 2016, 52, 4183. (i) Li, X.; Xu, X.; Wei, W.; Lin, A.; Yao, H. Org. Lett. 2016, 18, 428. (j) Shen, Y.; Qi, J.; Mao, Z.; Cui, S. Org. Lett. 2016, 18, 2722. (k) Dong, N.; Zhang, Z.-P.; Xue, X.-S.; Li, X.; Cheng, J.-P. Angew. Chem., Int. Ed. 2016, 55, 1460. (l) Zhang, Z.-P.; Dong, N.; Li, X. Chem. Commun. 2017, 53, 1301. (m) Zhang, X.-Z.; Gan, K.-J.; Liu, X.-X.; Deng, Y.-H.; Wang, F.-X.; Yu, K.-Y.; Zhang, J.; Fan, C.-A. Org. Lett. 2017, 19, 3207. (14) The Lewis acids cause reaction to occur by coordination at the oxygen, activating the carbonyl group to nucleophilic attack, and help the TBS group to leave, forming enol negative ions to attack p-QMs. (15) It is indicated that the anion of Lewis acid played an important role in this reaction. However, the mechanism is still unknown.
REFERENCES
(1) (a) Carswell, E. L.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2006, 45, 7230. (b) Mandai, H.; Mandai, K.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 17961. (c) Wieland, L. C.; Vieira, E. M.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 570. (d) Curti, C.; Battistini, L.; Ranieri, B.; Pelosi, G.; Rassu, G.; Casiraghi, G.; Zanardi, F. J. Org. Chem. 2011, 76, 2248. (e) Li, J.; Huang, R.; Xing, Y.-K.; Qiu, G.; Tao, H.-Y.; Wang, C.-J. J. Am. Chem. Soc. 2015, 137, 10124. (2) (a) Verkade, J. M. M.; van Hemert, L. J. C.; Quaedflieg, P. J. L. M.; Rutjes, F. P. J. T. Chem. Soc. Rev. 2008, 37, 29. (b) Casiraghi, G.; Zanardi, F.; Appendino, G.; Rassu, G. Chem. Rev. 2000, 100, 1929. (c) Casiraghi, G.; Battistini, L.; Curti, C.; Rassu, G.; Zanardi, F. Chem. Rev. 2011, 111, 3076. (d) Kalesse, M. Top. Curr. Chem. 2005, 244, 43. (e) Mondal, S.; Mukherjee, S.; Yetra, S. R.; Gonnade, R. G.; Biju, A. T. Org. Lett. 2017, 19, 4367. (f) Tian, X.; Hofmann, N.; Melchiorre, P. Angew. Chem., Int. Ed. 2014, 53, 2997. (g) Jadhav, A. P.; Ali, A.; Singh, R. P. Adv. Synth. Catal. 2017, 359, 1508. (3) (a) Brown, S. P.; Goodwin, N. C.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 1192. (b) Qin, T.; Johnson, R. P.; Porco, J. A., Jr J. Am. Chem. Soc. 2011, 133, 1714. (c) Li, X.; Lu, M.; Dong, Y.; Wu, W.; Qian, Q.; Ye, J.; Dixon, D. J. Nat. Commun. 2014, 5, 4479. (d) Zhang, M.-J.; Li, R.; He, Y.-H.; Guan, Z. Catal. Commun. 2017, 98, 85. (e) Chen, X.-Y.; Liu, Q.; Chauhan, P.; Li, S.; Peuronen, A.; Rissanen, K.; Jafari, E.; Enders, D. Angew. Chem., Int. Ed. 2017, 56, 6241. (f) Zhan, G.; Shi, M.-L.; Lin, W.-J.; Ouyang, Q.; Du, W.; Chen, Y.-C. Chem. - Eur. J. 2017, 23, 6286. (g) Arlt, A.; Toyama, H.; Takada, K.; Hashimoto, T.; Maruoka, K. Chem. Commun. 2017, 53, 4779. (h) Jia, Z.-L.; Wang, Y.; Zhao, C.-G.; Zhang, X.-H.; Xu, P.-F. Org. Lett. 2017, 19, 2130. (4) (a) Dell’Amico, L.; Albrecht, L.; Naicker, T.; Poulsen, P. H.; JØrgensen, K. A. J. Am. Chem. Soc. 2013, 135, 8063. (b) Gu, X.; Guo, T.; Dai, Y.; Franchino, A.; Fei, J.; Zou, C.; Dixon, D. J.; Ye, J. Angew. Chem., Int. Ed. 2015, 54, 10249. (5) (a) Rout, S.; Ray, S. K.; Unhale, R. A.; Singh, V. K. Org. Lett. 2014, 16, 5568. (b) DiIorio, N.; Righi, P.; Mazzanti, A.; Mancinelli, M.; Ciogli, A.; Bencivenni, G. J. Am. Chem. Soc. 2014, 136, 10250. (c) Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.; Sartori, A.; Pelosi, G.; Casiraghi, G.; Zanardi, F. Adv. Synth. Catal. 2014, 356, 2330. (d) Gu, Y.; Wang, Y.; Yu, T.-Y.; Liang, Y.-M.; Xu, P.-F. Angew. Chem., Int. Ed. 2014, 53, 14128. (e) Uraguchi, D.; Yoshioka, K.; Ueki, Y.; Ooi, T. J. Am. Chem. Soc. 2012, 134, 19370. (f) Zhang, W.; Tan, D.; Lee, R.; Tong, G.; Chen, W.; Qi, B.; Huang, K.-W.; Tan, C.-H.; Jiang, Z. Angew. Chem., Int. Ed. 2012, 51, 10069. (g) Manna, M. S.; Kumar, V.; Mukherjee, S. Chem. Commun. 2012, 48, 5193. (h) Choudhury, A. R.; Mukherjee, S. Org. Biomol. Chem. 2012, 10, 7313. (i) Manna, M. S.; Mukherjee, S. Chem. - Eur. J. 2012, 18, 15277. (6) (a) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2003, 2209. (b) Galliford, C. V.; Scheidt, K. A. Angew. Chem., Int. Ed. 2007, 46, 8748. (7) (a) Feng, J.; Li, X.; Cheng, J.-P. J. Org. Chem. 2017, 82, 1412. (b) Curti, C.; Rassu, G.; Zambrano, V.; Pinna, L.; Pelosi, G.; Sartori, A.; Battistini, L.; Zanardi, F.; Casiraghi, G. Angew. Chem., Int. Ed. 2012, 51, 6200. (c) Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.; Sartori, A.; Pelosi, G.; Zanardi, F.; Casiraghi, G. Adv. Synth. Catal. 2013, 355, 1881. (8) (a) Peter, M. G. Angew. Chem., Int. Ed. Engl. 1989, 28, 555. (b) Itoh, T. Prog. Polym. Sci. 2001, 26, 1019. (c) Toteva, M. M.; Richard, J. P. Adv. Phys. Org. Chem. 2011, 45, 39. (9) (a) Takao, K.-I.; Sasaki, T.; Kozaki, T.; Yanagisawa, Y.; Tadano, K.-I.; Kawashima, A.; Shinonaga, H. Org. Lett. 2001, 3, 4291. (b) Barragán-Huerta, B. E.; Peralta-Cruz, J.; González-Laredo, R. F.; Karchesy, J. Phytochemistry 2004, 65, 925. (c) Martin, H. J.; Magauer, T.; Mulzer, J. Angew. Chem., Int. Ed. 2010, 49, 5614. (d) Jansen, R.; Gerth, K.; Steinmetz, H.; Reinecke, S.; Kessler, W.; Kirschning, A.; Müller, R. Chem. - Eur. J. 2011, 17, 7739. (10) (a) Hamels, D.; Dansette, P. M.; Hillard, E. A.; Top, S.; Vessières, A.; Herson, P.; Jaouen, G.; Mansuy, D. Angew. Chem., Int. Ed. 2009, 48, 9124. (b) Messiano, G. B.; da Silva, T.; Nascimento, I. 6711
DOI: 10.1021/acs.orglett.7b03433 Org. Lett. 2017, 19, 6708−6711
