Transition-Metal-Catalyzed Enantioselective Synthesis of Indoles from 2-Alkynylanilines

Abstract

Optically active indole derivatives are ubiquitous in natural products and are widely recognized as privileged components in pharmacologically relevant compounds. Therefore, developing catalytic asymmetric approaches for constructing indole derivatives is highly desirable. In this short review, we summarize methods for the transition-metal-catalyzed enantioselective synthesis of indoles from 2-alkynyl­anilines.

1 Introduction

2 Aminometalation-Triggered Asymmetric Cross-Coupling Reactions/Insertion

2.1 Asymmetric Cross-Coupling Reactions

2.2 Asymmetric Insertion of C=O, C=C and C≡N Bonds

3 Asymmetric Relay Catalysis

4 Conclusion

Key words

indoles - 2-alkynylanilines - aminometalation - cross-coupling - insertion - relay catalysis - axial chirality

Publication History

Received: 19 November 2021

Accepted after revision: 03 January 2022

Accepted Manuscript online:
03 January 2022

Article published online:
22 February 2022

• References

• 1a Taylor WI. Indole Alkaloids . Pergamon Press; Oxford: 1966
• 1b Pritchett BP, Stoltz BM. Nat. Prod. Rep. 2018; 35: 559
• 1c Wang J.-J, Shen Y.-K, Hu W.-P, Hsieh M.-C, Lin F.-L, Hsu M.-K, Hsu M.-H. J. Med. Chem. 2006; 49: 1442
• 1d Yamamoto Y, Kurazono M. Bioorg. Med. Chem. Lett. 2007; 17: 1626
• 1e Gurkan-Alp AS, Mumcuoglu M, Andac CA, Dayanc E, Cetin-Atalay R, Buyukbingol E. Eur. J. Med. Chem. 2012; 58: 346
• 1f Zhuang S.-H, Lin Y.-C, Chou L.-C, Hsu M.-H, Lin H.-Y, Huang C.-H, Lien J.-C, Kuo S.-C, Huang L.-J. Eur. J. Med. Chem. 2013; 66: 466
• 1g Hwang D.-J, Wang J, Li W, Miller DD. ACS Med. Chem. Lett. 2015; 6: 993
• 1h Sherer C, Snape TJ. Eur. J. Med. Chem. 2015; 97: 552
• 1i Zhang M.-Z, Jia C.-Y, Gu Y.-C, Mulholland N, Turner S, Beattie D, Zhang W.-H, Yang G.-F, Clough J. Eur. J. Med. Chem. 2017; 126: 669
• 2 Chen J, Chen J.-J, Yao X, Gao K. Org. Biomol. Chem. 2011; 9: 5334
• 3a Saxton JE. In The Alkaloids, Vol. 51, Chap. 1. Cordell GA. Academic Press; New York: 1998
• 3b Blair LM, Calvert MB, Gaich T, Lindel T, Phaffenbach M, Sperry J. In The Alkaloids: Chemistry and Biology, Vol. 77. Knölker H.-J. Academic Press; Cambridge: 2017
• 4 Zhao N, Li L, Liu J.-H, Zhuang P.-Y, Yu S.-S, Ma S.-G, Qu J, Chen N.-H, Wu L.-J. Tetrahedron 2012; 68: 3288
• 5 Meng D, Li H, Yang M, Ruiz MD. L, Dewnani SV, Jian T, Parker DL. J, Zhang T, Campeau L.-C, Harper B, Wood HB, Xu J, Berger R, Wu JY, Orr RK, Walsh SP. WO2016133793A1, 2016
• 6 Mihalic JT, Chen X.-Q, Fan P.-C, Chen X, Fu Y, Liang L.-L, Reed M, Tang L, Chen J.-L, Jaen J, Li L, Dai K. Bioorg. Med. Chem. Lett. 2011; 21: 7001
• 7 Norton RS, Wells RJ. J. Am. Chem. Soc. 1982; 104: 3628
• 8 Baumann T, Brückner R. Angew. Chem. Int. Ed. 2019; 58: 4714
• 9a Kondo Y, Kojima S, Sakamoto T. J. Org. Chem. 1997; 62: 6507
• 9b Ma C, Liu X, Li X, Flippen-Anderson J, Yu S, Cook JM. J. Org. Chem. 2001; 66: 4525
• 9c Kamijo S, Sasaki Y, Yamamoto Y. Tetrahedron Lett. 2004; 45: 35
• 10a Krüger K, Tillack A, Beller M. Adv. Synth. Catal. 2008; 350: 2153
• 10b Li J.-X, Yang S.-R, Wu W.-Q, Jiang H.-F. Chem. Asian J. 2019; 14: 4114
• 10c Platon M, Amardeil R, Djakovitch L, Hierso J.-C. Chem. Soc. Rev. 2012; 41: 3929
• 10d Sebastião J, Neto S, Zeni G. Org. Chem. Front. 2020; 7: 155
• 10e Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
• 10f Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
• 11 Taylor EC, Katz AH, Salgado-Zamora H, McKillop A. Tetrahedron Lett. 1985; 26: 5963
• 12 Sakamoto T, Kondo Y, Iwashita S, Nagano T, Yamanaka H. Chem. Pharm. Bull. 1988; 36: 1305
• 13 Kondo Y, Shiga F, Murata N, Sakamoto T, Yamanaka H. Tetrahedron 1994; 50: 11803
• 14a Arcadia A, Cacchi S, Marinelli F. Tetrahedron Lett. 1992; 33: 3915
• 14b Cacchi S, Fabrizi G, Goggiamani A. Adv. Synth. Catal. 2006; 348: 1301
• 15 Trost B, McClory A. Angew. Chem. Int. Ed. 2007; 46: 2074
• 16 Li X.-W, Chianese AR, Vogel T, Crabtree RH. Org. Lett. 2005; 7: 5437
• 17 Iritani K, Matsubara S, Utimoto K. Tetrahedron Lett. 1988; 29: 1799
• 18 Rodriguez AL, Koradin C, Dohle W, Knochel P. Angew. Chem. Int. Ed. 2000; 39: 2488
• 19a Cui Y.-M, Lin Y, Xu L.-W. Coord. Chem. Rev. 2017; 330: 37
• 19b Kumarasamy E, Raghunathan R, Sibi MP, Sivaguru J. Chem. Rev. 2015; 115: 11239
• 19c Smyth JE, Butler NM, Keller PA. Nat. Prod. Rep. 2015; 32: 1562
• 19d Privileged Chiral Ligands and Catalysts . Zhou Q.-L. Wiley-VCH; Weinheim: 2011
• 19e Toenjes ST, Gustafson JL. Future Med. Chem. 2018; 10: 409

For examples, see:
• 20a Ito C, Thoyama Y, Omura M, Kajiura I, Furukawa H. Chem. Pharm. Bull. 1993; 41: 2096
• 20b Bringmann G, Tasler S, Endress H, Kraus J, Messer K, Wohlfarth M, Lobin W. J. Am. Chem. Soc. 2001; 123: 2703
• 20c Bringmann G, Tasler S. Tetrahedron 2001; 57: 331
• 20d Berens U, Brown JM, Long J, Selke R. Tetrahedron: Asymmetry 1996; 7: 285
• 20e Anilkumar GN, Lesburg CA, Selyutin O, Rosenblum SB, Zeng Q, Jiang Y, Chan T.-Y, Pu H, Vaccaro H, Wang L, Bennett F, Chen KX, Duca J, Gavalas S, Huang Y, Pinto P, Sannigrahi M, Velazquez F, Venkatraman S, Vibulbhan B, Agrawal S, Butkiewicz N, Feld B, Ferrari E, He Z, Jiang C.-k, Palermo RE, Mcmonagle P, Huang H.-C, Shih N.-Y, Njoroge G, Kozlowski JA. Bioorg. Med. Chem. Lett. 2011; 21: 5336
• 20f Luz JG, Carson MW, Condon B, Clawson D, Pustilnik A, Kohlman DT, Barr RJ, Bean JS, Dill MJ, Sindelar DK, Maletic M, Coghlan MJ. J. Med. Chem. 2015; 58: 6607
• 20g Mino T, Komatsu S, Wakui K, Yamada H, Saotome H, Sakamoto M, Fujita T. Tetrahedron: Asymmetry 2010; 21: 711
• 21a Ototake N, Morimoto Y, Mokuya A, Fukaya H, Shida Y, Kitagawa O. Chem. Eur. J. 2010; 16: 6752
• 21b Morimoto Y, Shimizu S, Mokuya A, Ototake N, Saito A, Kitagawa O. Tetrahedron 2016; 72: 5221
• 22a Zhang Y.-C, Jiang F, Shi F. Acc. Chem. Res. 2020; 53: 425
• 22b Li T.-Z, Liu S.-J, Tan W, Shi F. Chem. Eur. J. 2020; 26: 15779
• 22c Kitagawa O. Acc. Chem. Res. 2021; 54: 719
• 22d Cheng JK, Xiang S.-H, Li S, Ye L, Tan B. Chem. Rev. 2021; 121: 4805
• 22e Corti V, Bertuzzi G. Synthesis 2020; 52: 2450

For selected reviews on the transition-metal-catalyzed formation of heterocyclic compounds, see:
• 23a Alonso F, Beletskaya IP, Yus M. Chem. Rev. 2004; 104: 3079
• 23b Hartwig JF. Organotransition Metal Chemistry: From Bonding to Catalysis . University Science Books; Mill Valley (CA, USA): 2010
• 23c Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals, 2nd ed. Beller M, Bolm C. Wiley-VCH; Weinheim: 2004
• 23d Tsuji J. Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis. John Wiley & Sons; New York: 2000
• 24 He Y.-P, Wu H, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2020; 59: 2105
• 25a Djafri A, Roussel C, Sandström J. J. Chem. Soc., Perkin Trans. 2 1985; 273
• 25b Zhang S, Yao Q.-J, Liao G, Li X, Li H, Chen H.-M, Hong X, Shi B.-F. ACS Catal. 2019; 9: 1956
• 26 Tian M, Bai D, Zheng G, Chang J, Li X. J. Am. Chem. Soc. 2019; 141: 9527
• 27 Li X, Zhao L, Qi Z, Li X. Org. Lett. 2021; 23: 5901
• 28 Wang C.-S, Wei L, Fu C, Wang X.-H, Wang C.-J. Org. Lett. 2021; 23: 7401
• 29 Yang W.-C, Chen X.-B, Song K.-L, Wu B, Gan W.-E, Zheng Z.-J, Cao J, Xu L.-W. Org. Lett. 2021; 23: 1309
• 30 Sun Y.-L, Wang X.-B, Sun F.-N, Chen Q.-Q, Cao J, Xu Z, Xu L.-W. Angew. Chem. Int. Ed. 2019; 58: 6747
• 31a Liu Y.-L, Lin X.-Y. Adv. Synth. Catal. 2019; 361: 876
• 31b Manabu H, Takashi M, Kazuaki I. Curr. Org. Chem. 2007; 11: 127
• 31c Pu L, Yu H.-B. Chem. Rev. 2001; 101: 757
• 31d Gbubele JD, Olszewski TK. Org. Biomol. Chem. 2021; 19: 2823
• 32 Chen J, Han X, Lu X. J. Org. Chem. 2017; 82: 1977
• 33 Chen J, Han X, Lu X. Org. Lett. 2018; 20: 7470

For selected developed drugs with a hydropyrano[3,4-b]indole skeleton, see:
• 34a Demerson CA, Abraham NA, Schilling G, Martel RR, Asciak CJ. J. Med. Chem. 1983; 26: 1778
• 34b LaPorte MG, Draper TL, Miller LE. Bioorg Med. Chem. Lett. 2010; 20: 2968
• 34c Schunk S, Linz K, Frormann S, Hinze C, Oberbörsch S, Sundermann B, Zemolka S, Englberger W, Germann T, Christoph T, Kögel B.-Y, Schröder W, Harlfinger S, Saunders D, Kless A, Schick H, Sonnenschein H. ACS Med. Chem. Lett. 2014; 5: 851
• 35a Larghi EL, Kaufman TS. Eur. J. Org. Chem. 2011; 27: 5195
• 35b Lombardo VM, Thomas CD, Scheidt KA. Angew. Chem. Int. Ed. 2013; 52: 12910
• 35c Ascic E, Ohm RG, Petersen R, Hansen MR, Hansen CL, Madsen D, Tanner D, Nielsen TE. Chem. Eur. J. 2014; 20: 3297
• 35d Zhao C, Chen SB, Seidel D. J. Am. Chem. Soc. 2016; 138: 9053
• 36 Chen J, Han X, Lu X. Angew. Chem. Int. Ed. 2017; 56: 14698

For excellent reviews on the Heck reaction, see:
• 37a Heck RF. Acc. Chem. Res. 1979; 12: 146
• 37b Beletskaya IP, Cheprakov AV. Chem. Rev. 2000; 100: 3009
• 37c Negishi E, Copéret C, Ma S, Liou S.-Y, Liu F. Chem. Rev. 1996; 96: 3650
• 38a Wu X.-F, Anbarasan P, Neumann H, Beller M. Angew. Chem. Int. Ed. 2010; 49: 9047
• 38b Negishi E. Angew. Chem. Int. Ed. 2011; 50: 6738
• 38c Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6722
• 39 Wang G, Li J.-C, Zhou Y.-G, Ye Z.-S. Org. Lett. 2021; 23: 802
• 40 He Y.-P, Cao J, Wu H, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2021; 60: 7093
• 41 Cao J, Wu H, Wang Q, Zhu J. Nat. Chem. 2021; 13: 671
• 42 Yuan K, Liu L, Chen J, Guo S, Yao H, Lin A. Org. Lett. 2018; 20: 3477
• 43 Whyte A, Bajohr J, Arora R, Torelli A, Lautens M. Angew. Chem. Int. Ed. 2021; 60: 20231
• 44a Littell R, Greenblatt EN, Allen GR. J. Med. Chem. 1972; 15: 875
• 44b Kam TS, Subramaniam G, Chen W. Phytochemistry 1999; 51: 159
• 44c Zeng T, Wu X.-Y, Yang S.-X, Lai W.-C, Shi S.-D, Zou Q, Liu Y, Li L.-M. J. Nat. Prod. 2017; 80: 864
• 44d Yap W.-S, Gan C.-Y, Sim K.-S, Lim S.-H, Low Y.-Y, Kam T.-S. J. Nat. Prod. 2016; 79: 230
• 44e Li Y, Li J, Ding H, Li A. Natl. Sci. Rev. 2017; 4: 397
• 44f Li L, Chen Z, Zhang X, Jia Y. Chem. Rev. 2018; 118: 3752
• 44g Usman M, Hu X.-D, Liu W.-B. Chin. J. Chem. 2020; 38: 737
• 44h Wang N, Jiang X. Chem. Rec. 2021; 21: 295
• 45 Hu X.-D, Chen Z.-H, Zhao J, Sun R.-Z, Zhang H, Qi X, Liu W.-B. J. Am. Chem. Soc. 2021; 143: 3734
• 46a Tietze LF. Chem. Rev. 1996; 96: 115
• 46b Lee JM, Na Y, Han H, Chang S. Chem. Soc. Rev. 2004; 33: 302
• 46c Wasilke JC, Obrey SJ, Baker RT, Bazan GC. Chem. Rev. 2005; 105: 1001
• 46d Ambrosini LM, Lambert TH. ChemCatChem 2010; 2: 1373
• 46e Ramachary DB, Jain S. Org. Biomol. Chem. 2011; 9: 1277
• 46f Lohr TL, Marks TJ. Nat. Chem. 2015; 7: 477
• 46g Wang P.-S, Chen D.-F, Gong L.-Z. Top. Curr. Chem. 2020; 378: 9
• 46h Wang P.-S, Li K.-N, Zhou X.-L, Wu X, Han Z.-Y, Guo R, Gong L.-Z. Chem. Eur. J. 2013; 19: 6234
• 47 Zhao F, Li N, Zhu Y.-F, Han Z.-Y. Org. Lett. 2016; 18: 1506
• 48 Yang G, Pan J, Ke Y.-M, Liu Y, Zhao Y. Angew. Chem. Int. Ed. 2021; 60: 20689