Palladium-Catalyzed ortho-Alkylation of Iodoarenes Enabled by a Cooperative Cycloolefin Ligand and a Bulky Trialkylphosphine

Xiao-Xia Wang; Lei Jiao

doi:10.1055/a-2504-3732

Synlett, Table of Contents

Synlett 2025; 36(08): 956-962
DOI: 10.1055/a-2504-3732

synpacts

Palladium-Catalyzed ortho-Alkylation of Iodoarenes Enabled by a Cooperative Cycloolefin Ligand and a Bulky Trialkylphosphine

Authors

Xiao-Xia Wang
Lei Jiao∗

Abstract

All articles of this category

Abstract

We recently achieved ortho-alkylation of iodoarenes utilizing a dual-ligand catalytic system that effectively combines palladium/olefin ligand cooperative catalysis with reversible C(sp²)–I reductive elimination enabled by a bulky trialkylphosphine ligand. Through careful mechanistic investigations, we confirmed the compatibility of the crucial steps involved in this process by isolating key organometallic intermediates and studying the stoichiometry of their transformations. By utilizing this protocol, we successfully achieved the ortho-alkylation of a variety of iodoarene substrates, thereby expanding the scope of applications for Catellani-type reactions. This study showcases the synthetic potential of the Pd/olefin ligand cooperative system as an innovative complement to established Pd/norbornene catalysis. In this Synpacts article, we present the conceptual framework underpinning this reaction and detail the key aspects of its development.

1 Introduction

2 Research Background

2.1 The Catellani Reaction: Pd/Norbornene Catalysis

2.2 Cooperative Cycloolefin Ligands for the Catellani-Type Reactions

2.3 C–X Reductive Elimination on Pd Center

3 Development of the Reaction

3.1 Proof-of-Concept by Stoichiometric Reactions

3.2 Substrate Scope and Synthetic Applications

4 Conclusion

Key words

ortho-alkylation - iodoarene - reductive elimination - cooperative olefin ligand - palladium catalysis - Catellani reaction

Full Text

References

References

1a Corbet J.-P, Mignani G. Chem. Rev. 2006; 106: 2651
1b Magano J, Dunetz JR. Chem. Rev. 2011; 111: 2177
1c Beletskaya IP, Ananikov VP. Chem. Rev. 2011; 111: 1596

2a Hodgson HH. Chem. Rev. 1947; 40: 251
2b Evano G, Nitelet A, Thilmany P, Dewez DF. Front. Chem. 2018; 6: 114

3 Botla V, Fontana M, Voronov A, Maggi R, Motti E, Maestri G, Della Ca’ N. Angew. Chem. Int. Ed. 2023; 62: e202218928
4 Wang X.-X, Jiao L. J. Am. Chem. Soc. 2024; 146: 25552
5 Catellani M, Frignani F, Rangoni A. Angew. Chem. Int. Ed. Engl. 1997; 36: 119

6a Lautens M, Piguel S. Angew. Chem. Int. Ed. 2000; 39: 1045
6b Bressy C, Alberico D, Lautens M. J. Am. Chem. Soc. 2005; 127: 13148
6c Candito DA, Lautens M. Angew. Chem. Int. Ed. 2009; 48: 6713
6d Liu H, El-Salfiti M, Lautens M. Angew. Chem. Int. Ed. 2012; 51: 9846

For representative reviews of the Catellani reaction, see:

7a Catellani M. Top. Organomet. Chem. 2005; 14: 21
7b Catellani M, Motti E, Della Ca’ N. Acc. Chem. Res. 2008; 41: 1512
7c Martins A, Mariampillai B, Lautens M. Top. Curr. Chem. 2009; 292: 1
7d Ye J, Lautens M. Nat. Chem. 2015; 7: 863
7e Della Ca’ N, Fontana M, Motti E, Catellani M. Acc. Chem. Res. 2016; 49: 1389
7f Liu Z.-S, Gao Q, Cheng H.-G, Zhou Q. Chem. Eur. J. 2018; 24: 15461
7g Wegmann M, Henkel M, Bach T. Org. Biomol. Chem. 2018; 16: 5376
7h Wang J, Dong G. Chem. Rev. 2019; 119: 7478
7i Dong S, Luan X. Chin. J. Chem. 2021; 39: 1690
7j Chen Z, Zhang F. Tetrahedron 2023; 134: 133307

For selected recent researches on novel electrophiles in the Catellani reaction, see:

8a Dong Z, Dong G. J. Am. Chem. Soc. 2013; 135: 18350
8b Zhou P.-X, Ye Y.-Y, Liu C, Zhao L.-B, Hou J.-Y, Chen D.-Q, Tang Q, Wang A.-Q, Zhang J.-Y, Huang Q.-X, Xu P.-F, Liang Y.-M. ACS Catal. 2015; 5: 4927
8c Wang J, Zhang L, Dong Z, Dong G. Chem 2016; 1: 581
8d Sun F.-G, Li M, He C, Wang B, Li B, Sui X, Gu Z. J. Am. Chem. Soc. 2016; 138: 7456
8e Bai L, Liu J, Hu W, Li K, Wang Y, Luan X. Angew. Chem. Int. Ed. 2018; 57: 5151
8f Cai W, Gu Z. Org. Lett. 2019; 21: 3204
8g Lv W, Chen Y, Wen S, Ba D, Cheng G. J. Am. Chem. Soc. 2020; 142: 14864
8h Zhang Z, Chen X, Li X.-S, Wang C.-T, Niu Z.-J, Zhang B.-S, Liu X.-Y, Liang Y.-M. Org. Lett. 2022; 24: 6897
8i Liu X, Fu Y, Chen Z, Liu P, Dong G. Nat. Chem. 2023; 15: 1391

For selected recent research on novel termination reagents in the Catellani reaction, see:

9a Motti E, Della Ca’ N, Xu D, Piersimoni A, Bedogni E, Zhou Z.-M, Catellani M. Org. Lett. 2012; 14: 5792
9b Zhou P.-X, Ye Y.-Y, Ma J.-W, Zheng L, Tang Q, Qiu Y.-F, Song B, Qiu Z.-H, Xu P.-F, Liang Y.-M. J. Org. Chem. 2014; 79: 6627
9c Shi H, Babinski DJ, Ritter T. J. Am. Chem. Soc. 2015; 137: 3775
9d Sun F, Li M, He C, Wang B, Li B, Sui X, Gu Z. J. Am. Chem. Soc. 2016; 138: 7456
9e Li R, Dong G. Angew. Chem. Int. Ed. 2018; 57: 1697
9f Zhang B.-S, Li Y, An Y, Zhang Z, Liu C, Wang X.-G, Liang Y.-M. ACS Catal. 2018; 8: 11827
9g Bai L, Liu J, Hu W, Li K, Wang Y, Luan X. Angew. Chem. Int. Ed. 2018; 57: 5151

For selected recent research on Pd(II)-initiated Catellani reaction, see:

10a Jiao L, Bach T. J. Am. Chem. Soc. 2011; 133: 12990
10b Jiao L, Herdtweck E, Bach T. J. Am. Chem. Soc. 2012; 134: 14563
10c Wang X.-C, Gong W, Fang L.-Z, Zhu R.-Y, Li SH, Engle KM, Yu J.-Q. Nature 2015; 519: 334
10d Dong Z, Wang J, Dong G. J. Am. Chem. Soc. 2015; 137: 5887
10e Shi G, Shao C, Ma X, Gu Y, Zhang Y. ACS Catal. 2018; 8: 3775
10f Chen S, Liu Z.-S, Yang T, Hua Y, Zhou Z, Cheng H.-G, Zhou Q. Angew. Chem. Int. Ed. 2018; 57: 7161
10g Li R, Liu F, Dong G. Chem 2019; 5: 929
10h Sukowski V, van Borselen M, Mathew S, Fernández-Ibánez MA. Angew. Chem. Int. Ed. 2022; 61: e202201750

For selected recent research on structurally modified NBEs for fine-tuning of the Catellani reaction, see:

11a Shen P.-X, Wang X.-C, Wang P, Zhu R.-Y, Yu J.-Q. J. Am. Chem. Soc. 2015; 137: 11574
11b Wang J, Li R, Dong Z, Liu P, Dong G. Nat. Chem. 2018; 10: 866
11c Li R, Dong G. J. Am. Chem. Soc. 2020; 142: 17859
11d Liu X, Wang J, Dong G. J. Am. Chem. Soc. 2021; 143: 9991

For selected recent research on structurally modified NBEs to achieve asymmetric reactions, see:

12a Liu Z.-S, Hua Y, Gao Q, Ma Y, Tang H, Shang Y, Cheng H.-G, Zhou Q. Nat. Catal. 2020; 3: 727
12b Gao Q, Wu C, Deng S, Li L, Liu Z.-S, Hua Y, Ye J, Liu C, Cheng H.-G, Cong H, Jiao Y, Zhou Q. J. Am. Chem. Soc. 2021; 143: 7253
12c Liu Z.-S, Xie P.-P, Hua Y, Wu C, Ma Y, Chen J, Cheng H.-G, Hong X, Zhou Q. Chem 2021; 7: 1917
12d Hua Y, Liu Z.-S, Xie PP, Ding B, Cheng H.-G, Hong X, Zhou Q. Angew. Chem. Int. Ed. 2021; 60: 12824
12e Bai M, Jia S, Zhang J, Cheng H.-G, Cong H, Liu S, Huang Z, Huang Y, Chen X, Zhou Q. Angew. Chem. Int. Ed. 2022; 61: e202205245
12f Zhou L, Cheng H.-G, Li L, Wu K, Hou J, Jiao C, Deng S, Liu Z, Yu J.-Q, Zhou Q. Nat. Chem. 2023; 15: 815

13 Zheng Y.-X, Jiao L. Nat. Synth. 2022; 1: 180
14 Wang F.-Y, Li Y.-X, Jiao L. J. Am. Chem. Soc. 2023; 145: 4871

15a Roy AH, Hartwig JF. J. Am. Chem. Soc. 2001; 123: 1232
15b Stambuli JP, Bühl M, Hartwig JF. J. Am. Chem. Soc. 2002; 124: 9346
15c Roy AH, Hartwig JF. J. Am. Chem. Soc. 2003; 125: 13944
15d Roy AH, Hartwig JF. Organometallics 2004; 23: 1533

16 Le CM, Menzies PJ. C, Petrone DA, Lautens M. Angew. Chem. Int. Ed. 2015; 54: 254

17a Quesnel JS, Arndtsen BA. J. Am. Chem. Soc. 2013; 135: 16841
17b Fang X, Cacherat B, Morandi B. Nat. Chem. 2017; 9: 1105
17c Lee YH, Morandi B. Nat. Chem. 2018; 10: 1016
17d De La Higuera Macias M, Arndtsen BA. J. Am. Chem. Soc. 2018; 140: 10140

18a Newman SG, Lautens M. J. Am. Chem. Soc. 2010; 132: 11416
18b Nareddy P, Mantilli L, Guénée L, Mazet C. Angew. Chem. Int. Ed. 2012; 51: 3826
18c Zeidan N, Bognar S, Lee S, Lautens M. Org. Lett. 2017; 19: 5058

19a Allen DV, Venkataraman D. J. Org. Chem. 2003; 68: 4590
19b Bielawski M, Zhu M, Olofsson B. Adv. Synth. Catal. 2007; 349: 2610