Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Ligand-Controlled Inversion of Diastereo- and Enantioselectivity in Silver-Catalyzed Azomethine Ylide−Imine Cycloaddition of Glycine Aldimino Esters with Imines Bo Yu,† Ke-Fang Yang,† Xing-Feng Bai,†,‡ Jian Cao,† Zhan-Jiang Zheng,† Yu-Ming Cui,† Zheng Xu,† Li Li,† and Li-Wen Xu*,†,‡ †
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 311121, P. R. China ‡ Suzhou Research Institute and State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Suzhou, Jiangsu 215123, P. R. China S Supporting Information *
ABSTRACT: A highly diastereo- and enantioselective silver-catalyzed azomethine ylide−imine (AYI) cycloaddition reaction of glycine aldimino esters with imines was developed in which the Xing-Phos-controlled syn-selective or DTBM-Segphos-induced anti-selective AYI cycloaddition reaction could be applied to the synthesis of a variety of stereodivergent 1-alkyl-2,5-substituted imidazolidines with high yields and excellent enantioselectivities (up to 99% ee) as well as good diastereoselectivities (up to 99:1 dr) under mild reaction conditions.
T
Scheme 1. Synthesis of Chiral Imidazolidines from Various Starting Materials and Our Strategy Based on the Potential Stereoselectivity of P-Ligands for the 1,3-Dipolar Cycloaddition with General Imines
he silver-catalyzed 1,3-dipolar cycloaddition of glycine aldimino esters with structurally diverse electrophiles is a powerful strategy for the construction of N-heterocycles, and in the past decade, it has drawn considerable attention from synthetic chemists.1 In this context, the design and synthesis of novel chiral P-ligands is crucial for the enantioselective 1,3dipolar cycloaddition and becomes an important topic in developing enantioselective silver-catalyzed cycloaddition reactions, which makes the construction of numerous fivemembered N-heterocyclic core-containing natural products and molecular scaffolds by catalytic 1,3-dipolar cycloaddition of glycine iminoesters with activated alkenes more and more simple.1−3 Meanwhile, although continuous efforts toward atom-economic [3 + 2] cycloaddition enable the catalytic synthesis of imidazolidines in a minimal number of synthetic steps with the aid of organocatalysis, transition-metal catalysis, visible-light irradiation, Lewis acid, or high temperature,4 there are few reports on the enantioselective azomethine ylide−imine (AYI) cycloaddition of glycine-derived azomethine ylides with imines that could be applied to the synthesis of chiral imidazolidines.5 In this regard, chiral Brønsted acid5a,c,e and CuBF4/(S,Rp)-PPFOMe5b as well as palladium catalyst with a chiral ammonium−phosphine hybrid ligand5d were proven to be effective catalysts in the cycloaddition reaction of highly activated imines (Scheme 1) such as 2-aminomalonate-5a,c or isatin-derived imines,5e fluorinated imines,5b and N-sulfonyl © XXXX American Chemical Society
Received: March 1, 2018
A
DOI: 10.1021/acs.orglett.8b00702 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters imines.5d Very recently, Guo6a and our group6b independently reported dimerization-type homo-1,3-dipolar [3 + 2] cycloaddition reaction that provided good to excellent enantioselectivity in the one-pot construction of chiral imidazolidines and its polymeric derivatives, respectively. However, the catalytic asymmetric AYI cycloaddition of azomethine ylides with general alkyl/aryl imines has been less investigated,6 and to the best of our knowledge, there is no report describing the asymmetric synthesis of chiral 1-alkyl-2,5-substituted imidazolidines via AYI cycloaddition of glycine iminoesters with a range of readily available simple imines, but not self-dimerization. Herein, we report the first example of highly enantioselective and diastereoselective AYI cycloaddition enabled by two different P-ligands (Figure 1), wherein both syn- and anti-
Table 1. Optimization for the AYI Cycloaddition of Glycine Aldimino Ester 1a with imine 2aa
entry
variation from the conditions A
1 2
no DTBM-Segphos instead of XingPhos toluene instead of EtOAc THF instead of EtOAc Et2O instead of EtOAc Cu(OAc)2 instead of AgOAce AgOTf instead of AgOAce no basee Et3N instead of K2CO3e
3 4 5 6 7 8 9
Figure 1. X-ray structures of chiral products 3ag and 3aj.
diastereomeric isomers of chiral 1-alkyl-2,5-substituted imidazolidines could be obtained, respectively, with good to excellent stereoselectivities and yields by ligand-controlled silver catalysis. As our syn-(R,Rs)-Xing-Phos is a very good P-ligand in the [3 + 2] cycloaddition of glycine aldimino esters and activated alkenes with completely stereochemistry,7 we envisioned that the intermolecular cycloaddition of glycine aldimino ester 1a with imine 2a could be promoted smoothly by a silver catalyst and Xing-Phos under mild reactions conditions. Gratifyingly, a series of investigation on chiral ligands, transition-metal salts, basic additives, and solvents (see Scheme S1 and Table S1) revealed that the AYI cycloaddition proceeds smoothly in the presence of a AgOAc/Xing-Phos catalyst system. The choice of metal catalyst, silver salt, and chiral ligand is crucial for this transformation and stereoselectivity. Moreover, other reaction parameters were also non-negligible (entries 3−9). As shown in Table 1, we confirmed that the presence of 10 mol % of K2CO3 was necessary to obtain the desired imidazolidine 3aa with good yield (70%), high diastereoselectivity (anti/syn = 75:25), and excellent ee value (93% ee) in EtOAc and at −20 °C (Table 1, entry 1). Unexpectedly, in this model reaction, the results with (R)-DTBM-Segphos were far superior to those with syn-(R,Rs)-Xing-Phos, a significant reverse of diastereoselectivity (anti/syn = 99:1), and excellent enantioselectvity (99% ee) was achieved (see entry 2). These results indicate that there is an obvious match/mismatch scenario between Ag/L catalyst and substrate and reinforce the point that it is a ligandcontrolled inversion of diastereo- and enantioselectivity in this reaction. We also examined various metal sources and additives as well as solvents in the presence of DTBM-Segphos (Tables S4−S6) and identified the Na2CO3 as the best basic additive in EtOAc. Under the optimized reaction conditions summarized in Table 1, various glycine aldimino esters 1a−k with general imines 2a−k (Scheme 2) were surveyed in the two versions of this AYI cycloaddition reactions for stereoselective construction of two diastereomeric isomers with high ee values. As shown in Scheme 3, the AYI cycloaddition tolerates a broad of substitutions at the aromatic ring of glycine aldimino esters or aromatic imines. In most cases, the corresponding
yieldb (%)
dr (anti/syn)c
eed (%)
70 79
25/75 99/1
93 99
64 55 33 42 34 61 51
26/74 21/79 28/72 20/80 21/79 30/70 2/98
91 90 89 71 69 88 50
a
Reaction conditions and more experimental results: see Tables S1− S6 and Scheme S1. bIsolated and total yield of 3aa. cDetermined by 1 H NMR. dThe ee value of the major isomer is determined by chiral HPLC. eThe solvent is toluene.
Scheme 2. Substrates of AYI Cycloaddition Reactions in This Work
imidazolidines 3 were isolated with moderate to good yields and diastereoselectivities (up to 98:2 dr) as well as good to excellent enantioselectivities (for major isomer, syn-3 products, with up to 99% ee). The procedure was also applied to aliphatic imines 2b−d with promising diastereocontrol and good yields (corresponding imidazolidine products syn-3ab, syn-3ac, and syn-3ad, in 50−70% yields, dr from 81:19 to 89:11), albeit with varied enantiocontrol from 58 to 97% ee’s. In particular for aliphatic imine 2c with a branched i-Pr group, higher yield (70%) and better enantioselectivity (97% ee) than that for linear aliphatic imines were observed. This result supported the magic effect of the multiple stereogenic substituents on syn-(R, Rs)-Xing-Phos7,8 in the silver-mediated AYI cycloaddition reactions under conditions A. Notably, the stereochemical and configuration assignment of syn-3ag was determined by Xray analysis (Figure 1) in which the structure of syn-products 3 was further confirmed with good syn-selectivity in this XingPhos-controlled AYI cycloaddition reaction. To further study the scope of AYI cycloaddition reactions that were controlled by an Ag/(R)-DTBM-Segphos catalyst system, the effect of the substituents at two types of imines on B
DOI: 10.1021/acs.orglett.8b00702 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 3. Scope of the Catalytic Asymmetric AYI Cycloaddition Reactions: Syn-Selectivity Controlled by Ag/ Xing-Phos Catalyst System
Scheme 4. Scope of the Catalytic Asymmetric AYI Cycloaddition Reactions: Anti-Selectivity Controlled by Ag/ (R)-DTBM-Segphos Catalyst System
reactivity and stereoselectivity was also investigated in detail. As shown in Scheme 4, a series of simple and representative glycine aldimino esters 1a−j derived from aromatic or heterocyclic aldehydes bearing electron-rich, -neutral, or -deficient groups on the aromatic ring reacted smoothly with general imines 2a−j to afford the desired imidazolidines 3 in good yields, almost complete diastereoselectivity (up to 99:1 dr), and excellent enanatioselectivities (93−99% ee). It appears that the linear aliphatic imines were well tolerated in the Ag/ (R)-DTBM-Segphos-controlled AYI cycloaddition reactions that proceeded with excellent diastereoselectivity (98:2 dr) providing high yields and enantioselectivity (for anti-3ab and anti-3ac, 95% ee and 99% ee, respectively). Similarly, the longchain aliphatic imine 2e is also a suitable substrate in this reaction because a high level of diastereoselectivity and enantioselectivity was reserved under conditions B (anti-3ae, 98:2 dr and 96% ee). It should be noted that hetereoatomsubstituted glycine aldimino ester or general imine was also a type of exceptional substrate, leading to the corresponding imidazolidines exclusively in good yields and excellent diastereoselectivity (99:1 dr for anti-3ja and anti-3aj) as well as excellent enantioselectivities (anti-3ja, 99% ee and anti-3aj, 94% ee, respectively). In addition, The X-ray crystal structures of anti-3aj confirmed that the stereochemistry of the corresponding imidazolidines 3 was different from that of the Ag/Xing-Phos catalyst system (Figure 1). These results demonstrate the feasibility of chiral P-ligand-controlled the syn- or anti- selective construction of imidazolidines, allowing stereochemical diverse one-pot C−C and C−N bond installations during the course of the AYI cycloaddition reaction. On the basis of the experimental results, we proposed the catalytic cycle of chiral ligand-controlled silver-catalyzed AYI cycloaddition of glycine aldimino ester with general imines
(Scheme 5). Because of the large differences in chemical structure for such two P-ligands, syn-(R,Rs)-Xing-Phos and (R)DTBM-Segphos, the syn-selective approach of cycloaddition controlled by the silver/ syn-(R,Rs)-Xing-Phos catalyst system, and the anti-selectivity dominated by Ag/(R)-DTBM-Segphos Scheme 5. Proposed Pathway Showing the Stereoselective and Facial Coordination of the Silver Atom with the Substrates
C
DOI: 10.1021/acs.orglett.8b00702 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
(2) (a) Nájera, C.; Sansano, J. M. Chem. Rec. 2016, 16, 2430. (b) Liu, H. C.; Tao, H. Y.; Cong, H. J.; Wang, C. J. J. Org. Chem. 2016, 81, 3752. (c) Ponce, A.; Alonso, I.; Adrio, J.; Carretero, J. C. Chem. - Eur. J. 2016, 22, 4952. (d) Cheng, H. G.; Zhang, R. M.; Yang, S. W.; Wang, M.; Zeng, X. F.; Xie, L. J.; Xie, C. S.; Wu, J.; Zhong, G. F. Adv. Synth. Catal. 2016, 358, 970 and references cited therein. (3) For recent examples on the use of glycine imino esters as a family of building blocks in the enantioselective synthesis of functionalized heterocycles, see: (a) Sugita, S.; Takeda, N.; Tohnai, N.; Miyata, M.; Miyata, O.; Ueda, M. Angew. Chem., Int. Ed. 2017, 56, 2469. (b) Chen, S. M.; Bacauanu, V.; Knecht, T.; Mercado, B. Q.; Bergman, R. G.; Ellman, A. J. Am. Chem. Soc. 2016, 138, 12664. (c) Swain, S. P.; Shih, Y. C.; Tsay, S. C.; Jacob, J.; Lin, C. C.; Hwang, K. C.; Horng, J. C.; Hwu, J. R. Angew. Chem., Int. Ed. 2015, 54, 9926. (d) Zhang, L.; Liu, H. L.; Qiao, G. Y.; Hou, Z. F.; Liu, Y.; Xiao, Y. M.; Guo, H. C. J. Am. Chem. Soc. 2015, 137, 4316. (e) Li, Q. H.; Wei, L.; Wang, C. J. J. Am. Chem. Soc. 2014, 136, 8685. (f) Notably, the first example of catalytic asymmetric 1,3-dipolar cycloaddition of iminoesters and alkenes was only reported in 2002; see: Longmire, J. M.; Wang, B.; Zhang, X. M. J. Am. Chem. Soc. 2002, 124, 13400. (4) (a) Orcel, U.; Waser, J. Angew. Chem., Int. Ed. 2016, 55, 12881. (b) Xia, P. J.; Sun, Y. H.; Xiao, J. A.; Zhou, Z. F.; Wen, S. S.; Xiong, Y.; Ou, G. C.; Chen, X. Q.; Yang, H. J. Org. Chem. 2015, 80, 11573. (c) Sun, Y. H.; Xiong, Y.; Peng, C. Q.; Li, W.; Xiao, J. A.; Yang, H. Org. Biomol. Chem. 2015, 13, 7907. (d) Suárez-Pantiga, S.; Colas, K.; Johansson, M. J.; Mendoza, A. Angew. Chem., Int. Ed. 2015, 54, 14094. (e) Mancebo-Aracil, J.; Muñoz-Guillena, M. J.; Such-Basáñez, I.; Sansano-Gil, J. M. ChemPlusChem 2012, 77, 770. (f) Saima, Y.; Khamarui, S.; Gayen, K. S.; Pandit, P.; Maiti, D. K. Chem. Commun. 2012, 48, 6601. (g) Erkizia, E.; Aldaba, E.; Vara, Y.; Arrieta, A.; Gornitzka, H.; CossI ó , F. P. ARKIVOC 2004, 2005, 189. (h) Amornraksa, K.; Barr, D.; Donegan, G.; Grigg, R.; Ratananukul, P.; Sridharan, V. Tetrahedron 1989, 45, 4649. (5) (a) Liu, W. J.; Chen, X. H.; Gong, L. Z. Org. Lett. 2008, 10, 5357. (b) Li, Q. H.; Wei, L.; Chen, X.; Wang, C. J. Chem. Commun. 2013, 49, 6277. (c) Zhu, R. Y.; Wang, C. S.; Jiang, F.; Shi, F.; Tu, S. J. Tetrahedron: Asymmetry 2014, 25, 617. (d) Ohmatsu, K.; Kawai, S.; Imagawa; Ooi, T. ACS Catal. 2014, 4, 4304−4306. (e) Wang, Y. M.; Zhang, H. H.; Li, C.; Fan, T.; Shi, F. Chem. Commun. 2016, 52, 1804− 1807. (6) (a) Jia, H.; Liu, H.; Guo, Z.; Huang, J.; Guo, H. Org. Lett. 2017, 19, 5236. (b) Yu, B.; Bai, X. F.; Lv, J. Y.; Yuan, Y.; Cao, J.; Zheng, Z. J.; Xu, Z.; Cui, Y. M.; Yang, K. F.; Xu, L. W. Adv. Synth. Catal. 2017, 359, 3577. (7) (a) Bai, X. F.; Song, T.; Xu, Z.; Xia, C. G.; Huang, W. S.; Xu, L. W. Angew. Chem., Int. Ed. 2015, 54, 5255. (b) Bai, X. F.; Xu, Z.; Xia, C. G.; Zheng, Z. J.; Xu, L. W. ACS Catal. 2015, 5, 6016. (8) (a) Bai, X. F.; Zhang, J.; Xia, C. G.; Xu, J. X.; Xu, L. W. Tetrahedron 2016, 72, 2690. (b) Bai, X. F.; Li, L.; Xu, Z.; Zheng, Z. J.; Xia, C. G.; Cui, Y. M.; Xu, L. W. Chem. - Eur. J. 2016, 22, 10399. (c) Zhao, Q.; Vuong, M. H.; Bai, X. F.; Pannecoucke, X.; Xu, L. W.; Bouillon, J. P.; Jubault, P. Chem. - Eur. J. 2018, DOI: 10.1002/ chem.201706167. (9) (a) Cabrera, S.; Arrayás, R. G.; Martín-Matute, B.; Cossío, F. P.; Carretero, J. C. Tetrahedron 2007, 63, 6587. (b) Zeng, W.; Chen, G.Y.; Zhou, Y.-G.; Li, Y.-X. J. Am. Chem. Soc. 2007, 129, 750. (c) Nájera, C.; de Gracia Retamosa, M.; Sansano, J. M.; Cózar, A. D.; Cossío, F. P. Tetrahedron: Asymmetry 2008, 19, 2913. (d) Kim, H. Y.; Shih, H.-J.; Knabe, W. E.; Oh, K. Angew. Chem., Int. Ed. 2009, 48, 7420. (e) Nájera, C.; de Gracia Retamosa, M.; Martin-Rodriguez, M.; Sansano, J. M.; de Cozar, A.; Cossío, F. P. Eur. J. Org. Chem. 2009, 2009, 5622. (f) Yamashita, Y.; Imaizumi, T.; Guo, X. X.; Kobayashi, S. Chem. - Asian J. 2011, 6, 2550. (g) Castello, L. M.; Nájera, C.; Sansano, J. M.; Larranaga, O.; de Cozar, A.; Cossío, F. P. Adv. Synth. Catal. 2014, 356, 3861.
system might be aroused predominately from steric repulsion (DTBM-Segphos) or possibly weak hydrogen-bonding interactions (Xing-Phos) between the P-ligand and in situ formed azomethine ylide that is coordinated to the silver center (Scheme 5), in which the tetracoordinated transition state I-a or II-a favored the formation of the corresponding intermediate I-b or II-b, respectively,9 followed by intramolecular N-addition to imine to give the desired syn- or anti-imidazolidines 3. In summary, we have described the first example of P-ligandcontrolled diastereoselective AYI cycloaddition of glycine aldimino esters with general imines. It was found that both Xing-Phos and DTBM-Segphos were critically effective Pligands in the silver-catalyzed AYI cycloaddition reaction, in which a variety of chiral imidazolidines displayed high levels of enantio- and diastereoselectivity. More interestingly, the discovery of this two-ligand-varied catalyst system by tuning the steric repulsion and electronic effect that give controllable access to both diastereomeric products of a catalytic enantioselective transformation from a common starting material provided a synthetic strategy with switchable stereoselectivity.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00702. Spectra for all new compounds 3, detailed experimental procedures, and crystallographic data (PDF) Accession Codes
CCDC 1590229 and 1816519 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.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Jian Cao: 0000-0002-7782-0299 Li-Wen Xu: 0000-0001-5705-0015 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This project was supported by the National Natural Science Foundation of China (Nos. 21472031, 21703051, 21702211, and 21773051) and the Zhejiang Provincial Natural Science Foundation of China (LZ18B020001, LY16E030009, LY17B030005, and LY17E030003). We also thank Dr. Z. R. Qu, Dr. K. Z. Jiang, Dr. C. Q. Sheng, and Dr. Q. H. Pan (all at HZNU) for their technical and analytical support.
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REFERENCES
(1) For representative reviews, see: (a) Pellissier, H. Chem. Rev. 2016, 116, 14868. (b) Hashimoto, T.; Maruoka, K. Chem. Rev. 2015, 115, 5366. (c) Nájera, C.; Sansano, J. M. J. Organomet. Chem. 2014, 771, 78 and references cited therein. D
DOI: 10.1021/acs.orglett.8b00702 Org. Lett. XXXX, XXX, XXX−XXX
