Access to Chiral Seven-Member Cyclic Amines via Rh-Catalyzed

Jul 3, 2017 - Access to Chiral Seven-Member Cyclic Amines via Rh-Catalyzed Asymmetric ... Gang LiuZhengyu HanXiu-Qin DongXumu Zhang. Organic ...
0 downloads 0 Views 1001KB Size
Download PDF
Letter pubs.acs.org/OrgLett

Access to Chiral Seven-Member Cyclic Amines via Rh-Catalyzed Asymmetric Hydrogenation Pan Li,†,‡ Yi Huang,‡ Xinquan Hu,*,† Xiu-Qin Dong,*,‡ and Xumu Zhang*,§,‡ †

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. China § Department of Chemistry, South University of Science and Technology of China, Shenzhen, 518000, P. R. China ‡

S Supporting Information *

ABSTRACT: A highly efficient asymmetric hydrogenation of azepine/oxazepine-type seven-member cyclic imine hydrochlorides was successfully developed using Rh/bisphosphine-thiourea ligand ZhaoPhos, affording various chiral seven-member cyclic amines with full conversions, high yields, and excellent enantioselectivities (up to 96% yield, >99% ee). Additionally, this asymmetric hydrogenation can proceed well on gram scale with excellent ee value. Moreover, control experimental results displayed that the anion-bonding interaction between the chloride ion of the substrate and thiourea motif of the ZhaoPhos played an important role to obtain excellent enantioselectivity.

C

derivatives for the construction of chiral seven-member cyclic amine 2,3-dihydro-1H-benzo[b]azepines with excellent enantioselectivities.6b In 2011, Tian reported an asymmetric Pictet− Spengler-type reaction of 4-(2-aminoaryl)indoles with imines catalyzed by chiral phosphoric acid to afford various structurally diverse indolo[3,4-cd][1]benzazepines.6c In 2014, Nguyen and co-workers developed a Rh-catalyzed sequential allylic amination−olefin hydroacylation reaction to access chiral sevenmember cyclic amines.6d The catalytic asymmetric hydrogenation of cyclic imines emerged as one of the most straightforward synthetic methodologies to prepare corresponding chiral cyclic amines.7 Recently, Zhou and co-workers successfully realized Ir/C3*-TunePhos-catalyzed asymmetric hydrogenation of fused benzodiazepinones and benzodiazepines to provide seven-member cyclic amines.7f Despite the great advances that have been achieved, it is still highly desirable to develop effective synthetic methods to construct valuable chiral seven-member cyclic amines. Recently, we developed chiral bifunctional bisphosphine-thiourea ligands (ZhaoPhos) based on the synergistic activation strategy via cooperating transition metal catalysis and organocatalysis.8 Some challenging asymmetric hydrogenation reactions were accomplished smoothly by the activation modes of hydrogenbonding catalysis8a,c−f,h and anion-binding catalysis.8b,g Herein, we believed that the asymmetric hydrogenation of 11Hdibenzo[b,e]azepine/oxazepine hydrochlorides can be success-

hiral macrocyclic amines and derivatives have attracted much attention due to their wide application in the synthesis of numerous natural products and medicinal compounds.1 Among these chiral macrocyclic amines, chiral seven-member cyclic amines are important and powerful motifs of biologically active molecules and pharmaceuticals.2 For example, Cephalotaxine possessed excellent anticancer activity,3 Stemonine displayed potent antibechic effect on clinical evaluation,4 and (R)-Mianserin acted as a kind of antiulcer drug and antidepressant5 (Figure 1).

Figure 1. Examples of biologically active compounds and pharmaceuticals with chiral seven-member cyclic amine motifs.

Owing to the remarkable importance of chiral seven-member cyclic amines, great efforts have been made to develop asymmetric catalytic synthetic methods to construct these compounds.6 In 2002, Hoveyda and co-workers described Mocatalyzed asymmetric ring-closing metathesis to synthesize chiral seven-member cyclic amines.6a In 2010, You and coworkers developed an Ir/phosphoramidite-catalyzed asymmetric tandem allylic vinylation and amination reaction of (E)-but2-ene-1,4-diyl dimethyl dicarbonate with ortho-amino styrene © 2017 American Chemical Society

Received: June 7, 2017 Published: July 3, 2017 3855

DOI: 10.1021/acs.orglett.7b01726 Org. Lett. 2017, 19, 3855−3858

Letter

Organic Letters

enantioselectivity (94% ee, Table 1, entry 6). And the ligand L2 without a thiourea motif provided a very poor ee value (27% ee, Table 1, entry 7). The reaction results displayed that the thiourea motif of our ligand ZhaoPhos can activate the substrate 6-methyl-11H-dibenzo[b,e]azepine hydrochloride 1a through anion-bonding interaction. Subsequently, we investigated the solvent effect in the asymmetric hydrogenation of 6-methyl-11H-dibenzo[b,e]azepine hydrochloride 1a with the ZhaoPhos as the ligand. High reactivities and excellent enantioselectivities can be achieved in DCM, ethanol, isopropanol, 1,4-dioxane, and tetrahydrofuran (THF) (>99% conversions, 94%−96% ee, Table 2, entries 1−3, 6−7). Poor to moderate enantioselectiv-

fully achieved by Rh/ZhaoPhos with high reactivity and excellent enantioselectivity through forming anion-bonding interaction (Scheme 1). Scheme 1. Synthesis of Chiral Seven-Member Cyclic Amines

Table 2. Screening Solvents for Asymmetric Hydrogenation of 6-Methyl-11H-dibenzo[b,e]azepine Hydrochloride (1a)a Initially, we began our investigation by evaluating chiral diphosphine ligands for the asymmetric hydrogenation of model substrate 6-methyl-11H-dibenzo[b,e]azepine hydrochloride 1a9 with the catalyst generated in situ by mixing [Rh(COD)Cl]2 with ligand at room temperature. As shown in Table 1, several diphosphine ligands, such as (RC, SP)-DuanPTable 1. Screening Ligands for Asymmetric Hydrogenation of 6-Methyl-11H-dibenzo[b,e]azepine Hydrochloride (1a)a

entry

ligand

conv (%)b

ee (%)c

1 2 3 4 5 6 7

(Rc,Sp)-DuanPhos Josiphos Binapine (S)-SegPhos ZhaoPhos L1 L2

>99 >99 >99 >99 >99 >99 >99

35 60 37 40 96 94 27

entry

solvent

conv (%)b

ee (%)c

1 2 3 4 5 6 7 8d 9e 10f

DCM EtOH i PrOH MeOH CF3CH2OH 1,4-dioxane THF DCM DCM DCM

>99 >99 >99 >99 >99 >99 >99 >99 >99 >99

96 94 96 83 27 96 96 96 95 93

a

Unless otherwise noted, all reations were carried out with a Rh/ ZhaoPhos/1a (0.1 mmol) ratio of 6/6.6/100 in solvent under 5 MPa of H2. bConversion was determined by 1H NMR analysis. cEe was determined by chiral HPLC analysis. dThe catalyst loading is 1.0 mol %. eThe reaction was carried out with a Rh/ZhaoPhos/1a (0.1 mmol)/tetrabutylammonium bromide ratio of 6/6.6/100/100. fThe reaction was carried out with a Rh/ZhaoPhos/1a (0.1 mmol)/ tetrabutylammonium iodide ratio of 6/6.6/100/100.

a

Unless otherwise noted, all reations were carried out with a Rh/ ZhaoPhos/1a (0.1 mmol) ratio of 6/6.6/100 in DCM under 5 MPa of H2. bConversion was determined by 1H NMR analysis. cEe was determined by chiral HPLC analysis.

ities were obtained when the hydrogenations were performed in methanol and trifluoroethanol (>99% conversions, 27%− 83% ee, Table 2, entries 4−5). We finally selected DCM as the best choice, because the substrate 1a exhibited better solubility in DCM, and it is much cheaper and more easily available than other solvents. When the catalyst loading was reduced to 1.0 mol %, the same reaction result was attained (>99% conversion, 96% ee, Table 2, entry 8). Different counterions were also investigated. The addition of bromide counterion from tetrabutylammonium bromide (TBAB) and iodide counterion from tetrabutylammonium iodide (TBAI) provided slightly lower enantioselectivities. With the optimized reaction conditions in hand, we focused on the substrate scope of the asymmetric hydrogenation of seven-member cyclic imine hydrochlorides 11H-dibenzo[b,e]azepine hydrochlorides 1. As summarized in Scheme 2, a series of chiral seven-member cyclic amines were obtained in high yields and excellent enantioselectivities. Whether R1 is an electron-withdrawing group (1b−1c) or R2 is an electrondonating group (1d−1e), 92%−98% ee and 94%−96% yields were obtained. In addition, the substrate bearing naphthyl ring 1f was hydrogenated well with 92% yield and 98% ee. When the

hos, JosiPhos, (S)-Segphos, and Binapine, displayed poor enantioselectivities (35−60% ee, > 99% conversions, Table 1, entries 1−4). The bisphosphine-thiourea ligand ZhaoPhos can provide full conversion and excellent enantioselectivity (96% ee, >99% conversion, Table 1, entry 5). Another chiral bisphosphine-thiourea ligand L1 afforded slightly lower 3856

DOI: 10.1021/acs.orglett.7b01726 Org. Lett. 2017, 19, 3855−3858

Letter

Organic Letters

dibenzo[b,e]azepine 3 as the substrate into this asymmetric hydrogenation. Much lower enantioselectivity was observed (Scheme 4). This result implied that the chloride ion of the 6-

Scheme 2. Substrate Scope Study for Asymmetric Hydrogenation of 11H-Dibenzo[b,e]azepine/oxazepine Hydrochlorides (1)a

Scheme 4. Control Experiment

methyl-11H-dibenzo[b,e]azepine hydrochloride 1a played an important role to achieve excellent enantioselectivity in this catalytic system. In summary, we successfully developed a highly efficient asymmetric hydrogenation of azepine/oxazepine-type sevenmember cyclic imine hydrochlorides catalyzed by Rh/bisphosphine-thiourea ligand ZhaoPhos. A series of chiral seven-member cyclic amines were obtained with excellent results (up to 96% yield, >99% ee). In addition, this asymmetric hydrogenation of 6-methyl-11H-dibenzo[b,e]azepine hydrochloride 1a proceeded well on gram scale with excellent enantioselectivity. Moreover, control experiments were conducted and the results demonstrated that the anion-bonding interaction between the chloride ion of the substrate and thiourea motif of the ZhaoPhos played an important role in obtaining excellent enantioselectivity in this asymmetric hydrogenation.

a

1 (0.1 mmol) and a Rh/ZhaoPhos/1 ratio of 1/1.1/100 in DCM under 5 atm of H2; conversion was determined by 1H NMR analysis; yield of isolated product; ee was determined by chiral HPLC analysis. The configuration of 2 was determined as (S) by comparing the optical rotation data with those reported by the literature.7b,9

R3 group was changed from a methyl group (1a) to an ethyl group (1g), moderate enantioselectivity was observed in the asymmetric hydrogenation (71% ee). Encouraged by these excellent results in the asymmetric hydrogenation of 11Hdibenzo[b,e]azepine hydrochlorides, we turned our attention to exploring the asymmetric hydrogenation of various oxazepinetype seven-member cyclic imine hydrochlorides.7a The asymmetric hydrogenation of the substrates with different substituents, such as a methyl group (2i), haloid (2j−2k), and naphthyl group (2l), proceeded smoothly with high yields and excellent enantioselectivities (93%−96% yields, 94%−99% ee). In addition, the asymmetric hydrogenation of 6-methyl-11Hdibenzo[b,e]azepine hydrochloride 1a proceeded efficiently on gram scale under the optimized reaction conditions. And the desired product chiral seven-member cyclicamine (2a) can be obtained with 99% conversion, 94% yield, and 92% ee (Scheme 3). In order to further evaluate the role of anion-bonding interaction between the chloride ion of the substrate and thiourea motif of the ZhaoPhos, we applied 6-methyl-11H-

■

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b01726. General procedure and spectroscopic data (PDF)

■

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. *E-mail: [email protected]. ORCID

Xumu Zhang: 0000-0001-5700-0608 Notes

Scheme 3. Asymmetric Hydrogenation of 6-Methyl-11Hdibenzo[b,e]azepine Hydrochloride 1a on Gram Scale

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We are grateful for financial support of the Important Sci-Tech Innovative Project of Hubei Province (2015ACA058), the National Natural Science Foundation of China (Grant Nos. 21372179, 21432007, 21502145), and Natural Science Foundation of Hubei Province (Grant No. 2016CFB449). 3857

DOI: 10.1021/acs.orglett.7b01726 Org. Lett. 2017, 19, 3855−3858

Letter

Organic Letters

■

REFERENCES

(1) (a) Yang, J.; Wu, H.; Shen, L.; Qin, Y. J. Am. Chem. Soc. 2007, 129, 13794−13795. (b) Williams, D. R.; Shamim, K.; Reddy, J. P.; Amato, G. S.; Shaw, S. M. Org. Lett. 2003, 5, 3361−3364. (c) Cook, G. R.; Shanker, P. S.; Peterson, S. L. Org. Lett. 1999, 1, 615−618. (2) (a) Husain, S. M.; Fröhlich, R.; Schepmann, D.; Wünsch, B. J. Org. Chem. 2009, 74, 2788−2793. (b) Smith, B. M.; Smith, J. M.; Tsai, J. H.; Schultz, J. A.; Gilson, C. A.; Estrada, S. A.; Chen, R. R.; Park, D. M.; Prieto, E. B.; Gallardo, C. S.; Sengupta, D.; Dosa, P. I.; Covel, J. A.; Ren, A.; Webb, R. R.; Beeley, N. R. A.; Martin, M.; Morgan, M.; Espitia, S.; Saldana, H. R.; Bjenning, C.; Whelan, K. T.; Grottick, A. J.; Menzaghi, F.; Thomsen, W. J. J. Med. Chem. 2008, 51, 305−313. (c) Dols, P. P. M. A.; Folmer, B. J. B.; Hamersma, H.; Kuil, C. W.; Lucas, H.; Ollero, L.; Rewinkel, J. B. M.; Hermkens, P. H. H. Bioorg. Med. Chem. Lett. 2008, 18, 1461−1467. (d) Hoyt, S. B.; London, C.; Gorin, D.; Wyvratt, M. J.; Fisher, M. H.; Abbadie, C.; Felix, J. P.; Garcia, M. L.; Li, X.; Lyons, K. A.; McGowan, E.; MacIntyre, D. E.; Martin, W. J.; Priest, B. T.; Ritter, A.; Smith, M. M.; Warren, V. A.; Williams, B. S.; Kaczorowski, G. J.; Parsons, W. H. Bioorg. Med. Chem. Lett. 2007, 17, 4630−4634. (3) Powell, R. G.; Weisleder, D.; Smith, C. R.; Wolff, I. A. Tetrahedron Lett. 1969, 10, 4081−4084. (4) Irie, H.; Harada, H.; Ohno, K.; Mizutani, T.; Uyeo, S. J. Chem. Soc. D 1970, 5, 268−269. (5) Pawłowska, J.; Czarnocki, Z.; Wojtasiewicz, K.; Maurin, J. K. Tetrahedron: Asymmetry 2003, 14, 3335−3342. (6) Selected examples: (a) Dolman, S. J.; Sattely, E. S.; Hoveyda, A. H.; Schrock, R. R. J. Am. Chem. Soc. 2002, 124, 6991−6997. (b) He, H.; Liu, W.-B.; Dai, L.-X.; You, S.-L. Angew. Chem., Int. Ed. 2010, 49, 1496−1499. (c) Cheng, D.-J.; Wu, H.-B.; Tian, S.-K. Org. Lett. 2011, 13, 5636−5639. (d) Arnold, J. S.; Mwenda, E. T.; Nguyen, H. M. Angew. Chem., Int. Ed. 2014, 53, 3688−3692. (7) (a) Shen, H.-Q.; Gao, X.; Liu, C.; Hu, S.-B.; Zhou, Y.-G. Org. Lett. 2016, 18, 5920−5923. (b) Gao, K.; Yu, C.-B.; Li, W.; Zhou, Y.-G.; Zhang, X. Chem. Commun. 2011, 47, 7845−7847. (c) Balakrishna, B.; Bauzá, A.; Frontera, A.; Vidal-Ferran, A. Chem. - Eur. J. 2016, 22, 10607−10613. (d) Yang, Z.; Ding, Z.; Chen, F.; He, Y.-M.; Yang, N.; Fan, Q.-H. Eur. J. Org. Chem. 2017, 2017, 1973−1977. (e) Ding, Z.-Y.; Chen, F.; Qin, J.; He, Y.-M.; Fan, Q.-H. Angew. Chem., Int. Ed. 2012, 51, 5706−5710. (f) Gao, K.; Wu, B.; Yu, C.-B.; Chen, Q.-A.; Ye, Z.-S.; Zhou, Y.-G. Org. Lett. 2012, 14, 3890−3893. (g) Borrmann, R.; Koenigs, R. M.; Zoller, J.; Rueping, M. Synthesis 2016, 49, 310−318. (h) Horiguchi, K.; Yamamoto, E.; Saito, K.; Yamanaka, M.; Akiyama, T. Chem. - Eur. J. 2016, 22, 8078−8083. (8) (a) Han, Z.; Wang, R.; Gu, G.; Dong, X.-Q.; Zhang, X. Chem. Commun. 2017, 53, 4226. (b) Wen, J.; Tan, R.; Liu, S.; Zhao, Q.; Zhang, X. Chem. Sci. 2016, 7, 3047−3051. (c) Wen, J.; Jiang, J.; Zhang, X. Org. Lett. 2016, 18, 4451−4453. (d) Han, Z.; Li, P.; Zhang, Z.; Chen, C.; Wang, Q.; Dong, X.-Q.; Zhang, X. ACS Catal. 2016, 6, 6214−6218. (e) Li, P.; Zhou, M.; Zhao, Q.; Wu, W.; Hu, X.; Dong, X.Q.; Zhang, X. Org. Lett. 2016, 18, 40−43. (f) Li, P.; Hu, X.; Dong, X.Q.; Zhang, X. Chem. Commun. 2016, 52, 11677−11680. (g) Zhao, Q.; Wen, J.; Tan, R.; Huang, K.; Metola, P.; Wang, R.; Anslyn, E. V.; Zhang, X. Angew. Chem. 2014, 126, 8607−8610. (h) Zhao, Q.; Li, S.; Huang, K.; Wang, R.; Zhang, X. Org. Lett. 2013, 15, 4014−4017. (9) Balakrishna, B.; Bauzá, A.; Frontera, A.; Vidal-Ferran, A. Chem. Eur. J. 2016, 22, 10607−10613.

3858

DOI: 10.1021/acs.orglett.7b01726 Org. Lett. 2017, 19, 3855−3858