Gold/Iridium Catalyzed Alkynylamide Cyclization/Asymmetric Allylic Benzylation Cascade Reaction★

doi:10.6023/A23030103

Abstract

Asymmetric allylic substitution reactions involving benzyl nucleophilic reagents can rapidly construct chiral molecules containing benzyl fragments, which has attracted widespread attention from organic chemists. Formal asymmetric allylic benzylation reactions have been achieved by utilizing methylene oxazole as an equivalent of benzyl nucleophile. However, the development of highly efficient asymmetric allylic benzylation reactions remains a great challenge mainly due to the poor stability and synthetic difficulty of methylene oxazole. In this work, we have developed gold- and iridium- catalyzed alkynylamide cyclization/asymmetric allylic benzylation cascade reactions. In the presence of gold-carbene complex (Au1) and the combination of [Ir(cod)Cl]₂and (S_a)-Carreira ligand, a wide range of enantioenriched oxazole derivatives, bearing a benzylic stereogenic center, were obtained in 49%~87% yields with 98%~>99% ee. A general procedure is described as the following: To a dried Schlenk tube were added [Ir(cod)Cl]₂ (5.4 mg, 0.008 mmol, 4 mol%), (S_a)-L1 (16.2 mg, 0.032 mmol, 16 mol%) and 1,2-dichloroethane (1 mL) under argon atmosphere. The mixture was stirred at room temperature for 15 minutes to give a chiral iridium complex solution. Under an argon atmosphere, alkynylamide (0.2 mmol, 1.0 equiv.), allyl alcohol (0.4 mmol, 2.0 equiv.), Au1 (0.02 mmol, 12.4 mg, 10 mol%), Fe(OTf)₂ (0.2 mmol, 70.6 mg, 1.0 equiv.) and 3 Å molecular sieves (80.0 mg) were added to another dry Schlenk tube, and then the above-prepared iridium catalyst was added. The reaction mixture was stirred at 40 ℃ until the starting materials were consumed (monitored by thin layer chromatography, TLC). The mixture was quenched with water (5 mL), and extracted with dichloromethane (5 mL×3). The combined organic layers were dried over anhydrous Na₂SO₄, filtered, and then concentrated in vacuo to afford the crude product. The residue was purified by column chromatography (V(petroleum ether)/V(ethyl acetate)=15/1 or 10/1) to afford product 3.

Key words: asymmetric catalysis, allylic benzylation, alkynylamide cyclization, cascade reaction, gold, iridium

Cite this article

Rui-Xiang Wang, Qing-Ru Zhao, Qing Gu, Shu-Li You. Gold/Iridium Catalyzed Alkynylamide Cyclization/Asymmetric Allylic Benzylation Cascade Reaction^★[J]. Acta Chimica Sinica, 2023, 81(5): 431-434.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 4

References 11

[1]	(a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921. doi: 10.1021/cr020027w
	(b) Lu, Z.; Ma, S. Angew. Chem. Int. Ed. 2008, 47, 258.
	(c) Weaver, J. D.; Recio, A., III; Grenning, A. J.; Tunge, J. A. Chem. Rev. 2011, 111, 1846. doi: 10.1021/cr1002744
	For a book, see:
	(d) Transition Metal Catalyzed Enantioselective Allylic Substitution: Organic Synthesis, Ed.: Kazmaier, U., Springer,eidelberg, 2012.
[2]	(a) Heterocycles in Natural Product Synthesis, Eds.: Majumdar, K. C.; Chattopadhyay, S. K., Wiley-VCH,Weinheim, 2011. pmid: 25255204
	(b) Metalation of Azoles and Related Five-Membered Ring Heterocycles: Topics in Heterocyclic Chemistry, Vol. 29, Ed.: Gribble, G. W., Springer, Heidelberg, 2012. pmid: 25255204
	(c) Heteroocyclic Chemistry in Drug Discovery, Ed.: Li, J.-J., Wiley, Hoboken, 2013. pmid: 25255204
	(d) Roughley, S. D.; Jordan, A. M. J. Med. Chem. 2011, 54, 3451. doi: 10.1021/jm200187y pmid: 25255204
	(e) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257. doi: 10.1021/jm501100b pmid: 25255204
[3]	(a) Trost, B. M.; Thaisrivongs, D. A. J. Am. Chem. Soc. 2008, 130, 14092. doi: 10.1021/ja806781u
	(b) Trost, B. M.; Thaisrivongs, D. A. J. Am. Chem. Soc. 2009, 131, 12056. doi: 10.1021/ja904441a
	(c) Trost, B. M.; Thaisrivongs, D. A.; Hartwig, J. J. Am. Chem. Soc. 2011, 133, 12439. doi: 10.1021/ja205523e
[4]	(a) Sha, S.-C.; Jiang, H.; Mao, J.; Bellomo, A.; Jeong, S. A.; Walsh, P. J. Angew. Chem. Int. Ed. 2016, 55, 1070. doi: 10.1002/anie.v55.3
	(b) Mao, J.; Zhang, J.; Jiang, H.; Bellomo, A.; Zhang, M.; Gao, Z.; Dreher, S. D.; Walsh, P. J. Angew. Chem. Int. Ed. 2016, 55, 2526. doi: 10.1002/anie.v55.7
[5]	(a) Mosrin, M.; Knochel, P. Org. Lett. 2009, 11, 1837. doi: 10.1021/ol900342a pmid: 19317432
	(b) Duez, S.; Steib, A. K.; Manolikakes, S. M.; Knochel, P. Angew. Chem. Int. Ed. 2011, 50, 7686. doi: 10.1002/anie.201103074 pmid: 19317432
	(c) Haas, D.; Hammann, J. M.; Greiner, R.; Knochel, P. ACS Catal. 2016, 6, 1540. doi: 10.1021/acscatal.5b02718 pmid: 19317432
[6]	(a) Liu, X.-J.; You, S.-L. Angew. Chem. Int. Ed. 2017, 56, 4002. doi: 10.1002/anie.201700433
	(b) Liu, X.-J.; Zhang, W.-Y.; Zheng, C.; You, S.-L. Angew. Chem. Int. Ed. 2022, e202200164.
[7]	For selected reviews on Ir-catalyzed asymmetric allylic substitution reactions, see: a Hartwig, J. F.; Stanley, L. M. Acc. Chem. Res. 2010, 43, 1461. pmid: 28649462
	(b) Liu, W.-B.; Xia, J.-B.; You, S.-L. Top. Organomet. Chem. 2012, 38, 155. pmid: 28649462
	(c) Zhuo, C.-X.; Zheng, C.; You, S.-L. Acc. Chem. Res. 2014, 47, 2558. doi: 10.1021/ar500167f pmid: 28649462
	(d) Hethcox, J. C.; Shockley, S. E.; Stoltz, B. M. ACS Catal. 2016, 6, 6207. doi: 10.1021/acscatal.6b01886 pmid: 28649462
	(e) Qu, J.; Helmchen, G. Acc. Chem. Res. 2017, 50, 2539. doi: 10.1021/acs.accounts.7b00300 pmid: 28649462
	(f) Rössler, S. L.; Petrone, D. A.; Carreira, E. M. Acc. Chem. Res. 2019, 52, 2657. doi: 10.1021/acs.accounts.9b00209 pmid: 28649462
	(g) Cheng, Q.; Tu, H.-F.; Zheng, C.; Qu, J.-P.; Helmchen, G.; You, S.-L. Chem. Rev. 2019, 119, 1855. doi: 10.1021/acs.chemrev.8b00506 pmid: 28649462
[8]	(a) Singha, S.; Serrano, E.; Mondal, S.; Daniliuc, C. G.; Glorius, F. Nat. Catal. 2020, 3, 48. doi: 10.1038/s41929-019-0387-3 pmid: 35476460
	(b) Butcher, T. W.; Yang, J. L.; Amberg, W. M.; Watkins, N. B.; Wilkinson, N. D.; Hartwig, J. F. Nature 2020, 583, 548. doi: 10.1038/s41586-020-2399-1 pmid: 35476460
	(c) Chen, P.; Li, Y.; Chen, Z.-C.; Du, W.; Chen, Y.-C. Angew. Chem. Int. Ed. 2020, 59, 7083. doi: 10.1002/anie.v59.18 pmid: 35476460
	(d) Han, M.; Yang, M.; Wu, R.; Li, Y.; Jia, T.; Gao, Y.; Ni, H.-L.; Hu, P.; Wang, B.-Q.; Cao, P. J. Am. Chem. Soc. 2020, 142, 13398. doi: 10.1021/jacs.0c01766 pmid: 35476460
	(e) Tu, H.-F.; Yang, P.; Lin, Z.; Zheng, C.; You, S.-L. Nat. Chem. 2020, 12, 838. doi: 10.1038/s41557-020-0489-1 pmid: 35476460
	(f) Rossi-Ashton, J. A.; Clarke, A. K.; Donald, J. R.; Zheng, C.; Taylor, R. J. K.; Unsworth, W. P.; You, S.-L. Angew. Chem. Int. Ed. 2020, 59, 7598. doi: 10.1002/anie.202001956 pmid: 35476460
	(g) Wang, J.; Qi, X.; Min, X.-L.; Yi, W.; Liu, P.; He, Y. J. Am. Chem. Soc. 2021, 143, 10686. doi: 10.1021/jacs.1c04400 pmid: 35476460
	(h) Davis, C. R.; Luvaga, I. K.; Ready, J. M.; J. Am. Chem. Soc. 2021, 143, 4921. doi: 10.1021/jacs.1c01242 pmid: 35476460
	(i) Jiang, R.; Ding, L.; Zheng, C.; You, S.-L. Science 2021, 371, 380. doi: 10.1126/science.abd6095 pmid: 35476460
	(j) Crisenza, G. E. M.; Faraone, A.; Gandolfo, E.; Mazzarella, D.; Melchiorre, P. Nat. Chem. 2021, 13, 575. doi: 10.1038/s41557-021-00683-5 pmid: 35476460
	(k) Xiao, L.; Wei, L.; Wang, C.-J. Angew. Chem. Int. Ed. 2021, 60, 24930. doi: 10.1002/anie.v60.47 pmid: 35476460
	(l) Peng, Y.; Huo, X.; Luo, Y.; Wu, L.; Zhang, W. Angew. Chem. Int. Ed. 2021, 60, 24941. doi: 10.1002/anie.v60.47 pmid: 35476460
	(m) Zhang, M.-M.; Chen, P.; Xiong, W.; Hui, X.-S.; Lu, L.-Q.; Xiao, W.-J. CCS Chem. 2021, 3, 3383. pmid: 35476460
	(n) Deng, Y.; Liang, X.; Wei, K.; Yang, Y.-R. J. Am. Chem. Soc. 2021, 143, 20622. doi: 10.1021/jacs.1c11265 pmid: 35476460
	(o) Zhao, Q.-R.; Jiang, R.; You, S.-L. Acta Chim. Sinica 2021, 79, 1107. (in Chinese) doi: 10.6023/A21070320 pmid: 35476460
	(赵庆如, 蒋茹, 游书力, 化学学报, 2021, 79, 1107.) doi: 10.6023/A21070320 pmid: 35476460
	(p) Yang, P.-S.; Liu, C.-X.; Zhang, W.-W.; You, S.-L. Acta Chim. Sinica 2021, 79, 742. (in Chinese) doi: 10.6023/A21050198 pmid: 35476460
	(杨普苏, 刘晨旭, 张文文, 游书力, 化学学报, 2021, 79, 742.) doi: 10.6023/A21050198 pmid: 35476460
	(q) Ding, L.; Song, H.; Zheng, C.; You, S.-L. J. Am. Chem. Soc. 2022, 144, 4770. doi: 10.1021/jacs.2c01103 pmid: 35476460
	(r) Liu, X.-J.; Zhang, W.-Y.; Zheng, C.; You, S.-L. Angew. Chem. Int. Ed. 2022, 61, e2022001. pmid: 35476460
	(s) Moghadam, F. A.; Hicks, E. F.; Sercel, Z. P.; Cusumano, A. Q.; Bartberger, M. D.; Stoltz, B. M. J. Am. Chem. Soc. 2022, 144, 7983. doi: 10.1021/jacs.2c02960 pmid: 35476460
	(t) Yang, P.; Wang, R.-X.; Cheng, Y.-Z.; Zheng, C.; You, S.-L. Angew. Chem. Int. Ed. 2022, 61, e202213520. pmid: 35476460
	(u) Yang, W.-L.; Shang, X.-Y.; Luo, X.; Deng, W.-P. Angew. Chem. Int. Ed. 2022, 61, e202203661. pmid: 35476460
	(v) Jiang, R.; Zhao, Q.-R.; Zheng, C.; You, S.-L. Nat. Catal. 2022, 5, 1089. doi: 10.1038/s41929-022-00879-z pmid: 35476460
	(w) Zhang, J.; Yang, W.-L.; Zheng, H.; Wang, Y.; Deng, W.-P. Angew. Chem. Int. Ed. 2022, 61, e202117079. pmid: 35476460
	(x) Wu, Z.-H.; Wang, H.-Y.; Yang, H.-L.; Wei, L.-H.; Hayashi, T.; Duan, W.-L. Angew. Chem. Int. Ed. 2022, 61, e202213904. pmid: 35476460
	(y) Yang, W.-L.; Shang, X.-Y.; Ni, T.; Yan, H.; Luo, X.; Zhen, H.; Li, Z.; Deng, W.-P. Angew. Chem. Int. Ed. 2022, 61, e202210207. pmid: 35476460
	(z) Fu, C.; Xiong, Q.; Xiao, L.; He, L.; Bai, T.; Zhang, Z.; Dong, X.-Q.; Wang, C.-J. Chin. J. Chem. 2022, 40, 1059. doi: 10.1002/cjoc.v40.9 pmid: 35476460
	(aa) Tang, X.; Su, Z.; Lin, Q.; Lin, L.; Dong, S.; Feng, X. Chin. J. Chem. 2022, 40, 1793. doi: 10.1002/cjoc.v40.15 pmid: 35476460
	(ab) Jia, S.-H.; Chen, S.-Y.; Liu, Z.-S.; Cheng, H.-G.; Zhou, Q.-H. Chin. J. Org. Chem. 2022, 42, 3373. (in Chinese) doi: 10.6023/cjoc202209002 pmid: 35476460
	(贾仕虎, 陈思元, 刘泽水, 程鸿刚, 周强辉, 有机化学, 2022, 42, 3373.) doi: 10.6023/cjoc202209002 pmid: 35476460
	(ac) Xie, J.-H.; Hou, Y.-M.; Feng, Z.; You, S.-L. Angew. Chem. Int. Ed. 2023, 63, e202216396. pmid: 35476460
[9]	Liu, X.-J.; Zheng, C.; Yang, Y.-H.; Jin, S.; You, S.-L. Angew. Chem. Int. Ed. 2019, 58, 10493. doi: 10.1002/anie.v58.31
[10]	(a) Seppanen, O.; Aikonen, S.; Muuronen, M.; Alamillo-Ferrer, C.; Bures, J.; Helaja, J. Chem. Commun. 2020, 56, 14697. doi: 10.1039/D0CC05999D
	(b) Yang, G.; Ke, Y.-M.; Zhao., Y. Angew. Chem. Int. Ed. 2021, 60, 12775. doi: 10.1002/anie.v60.23
	(c) Ma, Y.; Ali, H. S.; Hussein, A. A. Catal. Sci. Technol. 2022, 12, 674. doi: 10.1039/D1CY01617B
[11]	(a) Kim, U. B.; Jung, D. J.; Jeon, H. J.; Rathwell, K.; Lee, S. Chem. Rev. 2020, 120, 13382. doi: 10.1021/acs.chemrev.0c00245
	(b) Wei, L.; Wang, C.-J. Chem Catal. 2023, 3, 100455.

Entry	[Au] (x mol%)	L	Solvent	Yield of 3a^b	ee of 3a^c
1^e	Au1	(S_a)-L1	DCE	60%	>99%
2	Au1	(S_a)-L1	DCE	95% (87%^d)	>99%
3^f	Au1	(S_a)-L1	DCE	94%	>99%
4	AuCl₃	(S_a)-L1	DCE	68%	>99%
5	Ph₃PAuCl	(S_a)-L1	DCE	50%	>99%
6	Me₂SAuCl	(S_a)-L1	DCE	75%	49%
7^g	Ph₃PAuMe	(S_a)-L1	DCE	trace	N.D.^h
8	Au1	(S_a)-L2	DCE	36%	52%
9	Au1	(S_a)-L3	DCE	66%	96%
10	Au1	(S_a)-L1	dioxane	54%	>99%
11	Au1	(S_a)-L1	THF	20%	N.D. ^h
12	Au1	(S_a)-L1	toluene	52%	>99%
13	Au1	(S_a)-L1	MeCN	trace	N.D. ^h
14	Au1	(S_a)-L1	CHCl₃	70%	>99%

Entry	[Au] (x mol%)	L	Solvent	Yield of 3a^b	ee of 3a^c
1^e	Au1	(S_a)-L1	DCE	60%	>99%
2	Au1	(S_a)-L1	DCE	95% (87%^d)	>99%
3^f	Au1	(S_a)-L1	DCE	94%	>99%
4	AuCl₃	(S_a)-L1	DCE	68%	>99%
5	Ph₃PAuCl	(S_a)-L1	DCE	50%	>99%
6	Me₂SAuCl	(S_a)-L1	DCE	75%	49%
7^g	Ph₃PAuMe	(S_a)-L1	DCE	trace	N.D.^h
8	Au1	(S_a)-L2	DCE	36%	52%
9	Au1	(S_a)-L3	DCE	66%	96%
10	Au1	(S_a)-L1	dioxane	54%	>99%
11	Au1	(S_a)-L1	THF	20%	N.D. ^h
12	Au1	(S_a)-L1	toluene	52%	>99%
13	Au1	(S_a)-L1	MeCN	trace	N.D. ^h
14	Au1	(S_a)-L1	CHCl₃	70%	>99%

[1]	Chengjun Wang, Yueliang Wang, Huiqiao Wang, Zhaoxiang Deng. Unveiling the Chemical Incompatibility of Au-Ag Heteronanoassembly [J]. Acta Chimica Sinica, 2024, 82(7): 763-771.
[2]	Haoning Zheng, Jinyu Liu. Research Progress on Organocatalytic Functionalization of Indole in the Carbocyclic Ring [J]. Acta Chimica Sinica, 2024, 82(6): 641-657.
[3]	Peng Tao, Xiaokang Zheng, Guoliang Wang, Xinghao Sheng, He Jiang, Wentao Li, Jibiao Jin, Sui-Hung Wong, Yanqin Miao, Hua Wang, Wai-Yeung Wong. Novel Bipolar Orange Emissive Iridium(III) Complexes: Design, Synthesis, and Electroluminescence^★ [J]. Acta Chimica Sinica, 2023, 81(8): 891-897.
[4]	Jianghao Luo, Haowen Ma, Jiehao Zhang, Wei Zhou, Qian Cai. Synthesis of Pyrrolo[3,2-d]pyrimidin-4-ones via Cascade Alkyne−isocyanide [3＋2] Cycloaddition/Boulton-Katritzky Rearrangement/Ring Expansion Process^★ [J]. Acta Chimica Sinica, 2023, 81(8): 898-904.
[5]	Xinpu Fu, Xiuling Wang, Weiwei Wang, Rui Si, Chunjiang Jia. Fabrication and Mechanism Study of Clustered Au/CeO₂ Catalyst for the CO Oxidation Reaction^★ [J]. Acta Chimica Sinica, 2023, 81(8): 874-883.
[6]	Zhanglong Yu, Zhongliang Li, Changjiang Yang, Qiangshuai Gu, Xinyuan Liu. Research Progress on Copper-Catalyzed Enantioselective Desymmetrization of Diols^★ [J]. Acta Chimica Sinica, 2023, 81(8): 955-966.
[7]	Shuang Yang, Ningyi Wang, Qingqing Hang, Yuchen Zhang, Feng Shi. Advances in Catalytic Asymmetric Reactions Involving o-Hydroxyphenyl Substituted p-Quinone Methides^★ [J]. Acta Chimica Sinica, 2023, 81(7): 793-808.
[8]	Qingduan Meng, Jiahong Han, Yixiao Pan, Wei Hao, Qing-Hua Fan. Asymmetric Synthesis of C₁-Symmetric Chiral N-Heterocyclic Carbene (NHC) Ligands and Their Applications in Asymmetric Catalysis^★ [J]. Acta Chimica Sinica, 2023, 81(10): 1271-1279.
[9]	Lai Zhang, Jian Xiao, Yawen Wang, Yu Peng. Recent Advances on the Construction of Chiral Dihydrobenzofurans by Asymmetric [3+2] Cyclization Reactions of Phenols (Quinones) and Alkenes [J]. Acta Chimica Sinica, 2022, 80(8): 1152-1164.
[10]	Jinyue Ma, Lufei Huang, Baowen Zhou, Lin Yao. Construction and Catalysis Advances of Inorganic Chiral Nanostructures [J]. Acta Chimica Sinica, 2022, 80(11): 1507-1523.
[11]	Qing-Ru Zhao, Ru Jiang, Shu-Li You. Ir-catalyzed Sequential Asymmetric Allylic Substitution/Olefin Isomerization for the Synthesis of Axially Chiral Compounds [J]. Acta Chimica Sinica, 2021, 79(9): 1107-1112.
[12]	Pusu Yang, Chen-Xu Liu, Wen-Wen Zhang, Shu-Li You. Ir-Catalyzed Enantioselective Friedel-Crafts Type Allylic Substitution of Indolizines [J]. Acta Chimica Sinica, 2021, 79(6): 742-746.
[13]	Bo-Shuai Mu, Zhi-Hao Zhang, Wen-Biao Wu, Jin-Sheng Yu, Jian Zhou. Recent Advances in Synthesis of Chiral 1,2-Dihydropyridines [J]. Acta Chimica Sinica, 2021, 79(6): 685-693.
[14]	Yijun Guo, Bing Wei, Xiang Zhou, Dongbao Yao, Haojun Liang. DNA Walker-Programmed Nanoparticle Superlattice [J]. Acta Chimica Sinica, 2021, 79(2): 192-199.
[15]	Yi Li, Ming-Hua Xu. Applications of Asymmetric Petasis Reaction in the Synthesis of Chiral Amines [J]. Acta Chimica Sinica, 2021, 79(11): 1345-1359.

金/铱接力催化炔基酰胺环化/不对称烯丙基苄基化串联反应^★