Enantioselective Synthesis of N-Alkylated Indoles Enabled by Nickel-Catalyzed C(sp3)–C(sp3) Coupling

Xin Kui; Jingjie Zhou; Huijie Peng; Deyun Qian

doi:10.1055/a-2515-0296

Synthesis, Table of Contents

Synthesis
DOI: 10.1055/a-2515-0296

feature

Enantioselective Synthesis of N-Alkylated Indoles Enabled by Nickel-Catalyzed C(sp³ )–C(sp³ ) Coupling

Xin Kui‡

^aKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products; School of Pharmacy, Yunnan University, Kunming 650500, P. R. China

^bSchool of Chemical Science and Technology, Yunnan University, Kunming 650500, P. R. China

,

Jingjie Zhou‡

^aKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products; School of Pharmacy, Yunnan University, Kunming 650500, P. R. China

^bSchool of Chemical Science and Technology, Yunnan University, Kunming 650500, P. R. China

,

Huijie Peng

^aKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products; School of Pharmacy, Yunnan University, Kunming 650500, P. R. China

^bSchool of Chemical Science and Technology, Yunnan University, Kunming 650500, P. R. China

,

Deyun Qian ∗

^aKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products; School of Pharmacy, Yunnan University, Kunming 650500, P. R. China

^bSchool of Chemical Science and Technology, Yunnan University, Kunming 650500, P. R. China

› Author Affiliations

Abstract

All articles of this category

Abstract

Although considerable efforts have been made to construct chiral functionalized indoles, catalytic and efficient methods to access a diverse range of chiral N-alkylated indoles bearing a stereocenter with two minimally different alkyl groups at the N-1 position from readily accessible substrates remain limited. Here, we describe a modular Ni-catalyzed C(sp³ )–C(sp³ ) cross-coupling strategy that couples an array of N-indolyl-substituted alkenes with alkyl iodides to yield chiral α,α-dialkyl indoles in single regioisomeric form, in up to 90% yield and 99% ee.

Key words

asymmetric catalysis - nickel catalysis - C(sp³ )–C(sp³ ) cross-coupling - indole - alkylation

Full Text

References

References

1a McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Iii AD. P, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, Brandt M, Miller WH, Dhanak D, Verma SK, Tummino PJ, Creasy CL. Nature 2012; 492: 108
1b Bradley WD, Arora S, Busby J, Balasubramanian S, Gehling VS, Nasveschuk CG, Vaswani RG, Yuan C.-C, Hatton C, Zhao F, Williamson KE, Iyer P, Méndez J, Campbell R, Cantone N, Garapaty-Rao S, Audia JE, Cook AS, Dakin LA, Albrecht BK, Harmange J.-C, Daniels DL, Cummings RT, Bryant BM, Normant E, Trojer P. Chem. Biol. 2014; 21: 1463
1c Gehling VS, Vaswani RG, Nasveschuk CG, Duplessis M, Iyer P, Balasubramanian S, Zhao F, Good AC, Campbell R, Lee C, Dakin LA, Cook AS, Gagnon A, Harmange J.-C, Audia JE, Cummings RT, Normant E, Trojer P, Albrecht BK. Bioorg. Med. Chem. Lett. 2015; 25: 3644
1d Vaswani RG, Gehling VS, Dakin LA, Cook AS, Nasveschuk CG, Duplessis M, Iyer P, Balasubramanian S, Zhao F, Good AC, Campbell R, Lee C, Cantone N, Cummings RT, Normant E, Bellon SF, Albrecht BK, Harmange J.-C, Trojer P, Audia JE, Zhang Y, Justin N, Chen S, Wilson JR, Gamblin SJ. J. Med. Chem. 2016; 59: 9928

2a Bandini M, Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
2b Dalpozzo R. Chem. Soc. Rev. 2015; 44: 742
2c Chen J.-B, Jia Y.-X. Org. Biomol. Chem. 2017; 15: 3550
2d Trubitsõn D, Kanger T. Symmetry 2020; 12: 1184

3a Stanley LM, Hartwig JF. Angew. Chem. Int. Ed. 2009; 48: 7841
3b Trost BM, Osipov M, Dong G. J. Am. Chem. Soc. 2010; 132: 15800
3c Chen L.-Y, Yu X.-Y, Chen J.-R, Feng B, Zhang H, Qi Y.-H, Xiao W.-J. Org. Lett. 2015; 17: 1381
3d Ye K.-Y, Cheng Q, Zhuo C.-X, Dai L.-X, You S.-L. Angew. Chem. Int. Ed. 2016; 55: 8113
3e Jang SH, Kim HW, Jeong W, Moon D, Rhee YH. Org. Lett. 2018; 20: 1248
3f Kim SW, Schempp TT, Zbieg JR, Stivala CE, Krische MJ. Angew. Chem. Int. Ed. 2019; 58: 7762
3g Sun M, Liu M, Li C. Chem. Eur. J. 2021; 27: 3457

4a Sevov CS, Zhou J, Hartwig JF. J. Am. Chem. Soc. 2014; 136: 3200
4b Ye Y, Kim S.-T, Jeong J, Baik M.-H, Buchwald SL. J. Am. Chem. Soc. 2019; 141: 3901
4c Allen JR, Bahamonde A, Furukawa Y, Sigman MS. J. Am. Chem. Soc. 2019; 141: 8670

5a Kainz QM, Matier CD, Bartoszewicz A, Zultanski SL, Peters JC, Fu GC. Science 2016; 351: 681
5b Bartoszewicz A, Matier CD, Fu GC. J. Am. Chem. Soc. 2019; 141: 14864

6a Arredondo V, Hiew SC, Gutman ES, Premachandra ID. U. A, Van Vranken DL. Angew. Chem. Int. Ed. 2017; 56: 4156
6b Peng Q, Huang M, Xu G, Zhu Y, Shao Y, Tang S, Zhang X, Sun J. Angew. Chem. Int. Ed. 2023; 62: e202313091

7a Bandini M, Eichholzer A, Tragni M, Umani-Ronchi A. Angew. Chem. Int. Ed. 2008; 47: 3238
7b Cui H.-L, Feng X, Peng J, Lei J, Jiang K, Chen Y.-C. Angew. Chem. Int. Ed. 2009; 48: 5737
7c Cai Q, Zheng C, You S.-L. Angew. Chem. Int. Ed. 2010; 49: 8666
7d Hong L, Sun W, Liu C, Wang L, Wang R. Chem. Eur. J. 2010; 16: 440
7e Xie Y, Zhao Y, Qian B, Yang L, Xia C, Huang H. Angew. Chem. Int. Ed. 2011; 50: 5682
7f Chen M, Sun J. Angew. Chem. Int. Ed. 2017; 56: 4583
7g Cai Y, Gu Q, You S.-L. Org. Biomol. Chem. 2018; 16: 6146
7h Mukherjee S, Shee S, Poisson T, Besset T, Biju AT. Org. Lett. 2018; 20: 6998
7i Yang X, Luo G, Zhou L, Liu B, Zhang X, Gao H, Jin Z, Chi YR. ACS Catal. 2019; 9: 10971
7j Zi Y, Lange M, Schultz C, Vilotijevic I. Angew. Chem. Int. Ed. 2019; 58: 10727
7k Wang Y, Wang S, Shan W, Shao Z. Nat. Commun. 2020; 11: 226

8a Morley AD, Pugliese A, Birchall K, Bower J, Brennan P, Brown N, Chapman T, Drysdale M, Gilbert IH, Hoelder S, Jordan A, Ley SV, Merritt A, Miller D, Swarbrick ME, Wyatt PG. Drug Discovery Today 2013; 18: 1221
8b Choi J, Fu GC. Science 2017; 356: eaaf7230

9a Lipp A, Badir SO, Molander GA. Angew. Chem. Int. Ed. 2021; 60: 1714
9b Lu F.-D, Chen J, Jiang X, Chen J.-R, Lu L.-Q, Xiao W.-J. Chem. Soc. Rev. 2021; 50: 12808

10 Pezzetta C, Bonifazi D, Davidson RW. M. Org. Lett. 2019; 21: 8957
11 Gandolfo E, Tang X, Raha Roy S, Melchiorre P. Angew. Chem. Int. Ed. 2019; 58: 16854
12 Lacker CR, DeLano TJ, Chen EP, Kong J, Belyk KM, Piou T, Reisman SE. J. Am. Chem. Soc. 2022; 144: 20190
13 Li L, Ren J, Zhou J, Wu X, Shao Z, Yang X, Qian D. Nat. Commun. 2022; 13: 6861

For selected reviews:

14a Wang X.-X, Lu X, Li Y, Wang J.-W, Fu Y. Sci. China Chem. 2020; 63: 1586
14b He Y, Chen J, Jiang X, Zhu S. Chin. J. Chem. 2022; 40: 651
14c Wang Y, He Y, Zhu S. Acc. Chem. Res. 2022; 55: 3519
14d Zhang Z, Bera S, Fan C, Hu X. J. Am. Chem. Soc. 2022; 144: 7015
14e Yang P.-F, Shu W. Chem Catal. 2023; 3: 100508

For selected recent examples:

14f Wang Z, Yin H, Fu GC. Nature 2018; 563: 379
14g Zhou F, Zhang Y, Xu X, Zhu S. Angew. Chem. Int. Ed. 2019; 58: 1754
14h He S.-J, Wang J.-W, Li Y, Xu Z.-Y, Wang X.-X, Lu X, Fu Y. J. Am. Chem. Soc. 2020; 142: 214
14i Bera S, Mao R, Hu X. Nat. Chem. 2021; 13: 270
14j Wang J.-W, Liu D.-G, Chang Z, Li Z, Fu Y, Lu X. Angew. Chem. Int. Ed. 2022; 61: e202205537
14k Zhao L, Zhu Y, Liu M, Xie L, Liang J, Shi H, Meng X, Chen Z, Han J, Wang C. Angew. Chem. Int. Ed. 2022; 61: e202204716
14l Wang X, Xue J, Rong Z.-Q. J. Am. Chem. Soc. 2023; 145: 15456
14m Chen C, Guo W, Qiao D, Zhou J, Wang Y, Zhu S. CCS Chem. 2024; 6: 898
14n Liu M, Shi H, Meng X, He R, Huang J, Wang J, Lv J, Wang C. CCS Chem. 2024; 6: 1929
14o Yang P.-F, Zhao H.-T, Chen X.-Y, Shu W. Nat. Synth. 2024; 3: 1360
14p He H.-D, Chitrakar R, Cao Z.-W, Wang D.-M, She L.-Q, Zhao P.-G, Wu Y, Xu Y.-Q, Cao Z.-Y, Wang P. Angew. Chem. Int. Ed. 2024; 63: e202313336
14q Zhou J, He Y, Liu Z, Wang Y, Zhu S. Adv. Sci. 2024; 11: 2306447

15 Ren J, Sun Z, Zhao S, Huang J, Wang Y, Zhang C, Huang J, Zhang C, Zhang R, Zhang Z, Ji X, Shao Z. Nat. Commun. 2024; 15: 3783

16a Qian D, Bera S, Hu X. J. Am. Chem. Soc. 2021; 143: 1959
16b Wu X, Ren J, Shao Z, Yang X, Qian D. ACS Catal. 2021; 11: 6560
16c Liu C, Kui X, Lu Q, Liu H, Qian D. Chem Catal. 2024; 4: 100798
16d Wu X, Li S, Chen L, Ma S, Ma B, Song L, Qian D. J. Am. Chem. Soc. 2024; 146: 22413
16e Wu X, Yan X, Qian D. Synthesis 2025;

Supplementary Material

Supporting Information

Enantioselective Synthesis of N-Alkylated Indoles Enabled by Nickel-Catalyzed C(sp3 )–C(sp3 ) Coupling

Enantioselective Synthesis of N-Alkylated Indoles Enabled by Nickel-Catalyzed C(sp³ )–C(sp³ ) Coupling