1,5-Diaza-3,7-diphosphacyclooctanes (P₂N₂): An Underappreciated Ligand Class for Nickel- and Palladium-Catalyzed Heck-Type Cross-Couplings

Abstract

1,5-Diaza-3,7-diphosphacyclooctane (P₂N₂) scaffolds represent a readily accessible, tunable ligand class for transition metals. However, despite their prevalence in areas such as electrocatalysis and coordination chemistry, P₂N₂ ligands have been rarely used to make catalysts for organic synthesis. Research into Mizoroki–Heck-type aldehyde, alcohol, and alkene arylation reactions has revealed that the P₂N₂ family outperforms many commonly used phosphines. This Synpacts article summarizes our work and provides a broad overview on the preparation and application of P₂N₂ ligands in organic synthesis. It also serves to highlight how a simple, modular class of ligands can solve contemporary challenges with transition-metal catalysis, including novel reactivity and exceptional regioselectivity.

Key words

transition-metal catalysis - Mizoroki–Heck coupling - ligand design - regioselectivity - reductive cross-coupling

Publication History

Received: 22 July 2024

Accepted: 12 August 2024

Article published online:
25 September 2024

• References

• 1 Märkl VG, Jin GY, Schoerner C. Tetrahedron Lett. 1980; 21: 1409
• 2 Galan BR, Schöffel J, Linehan JC, Seu C, Appel AM, Roberts JA. S, Helm ML, Kilgore UJ, Yang JY, DuBois DL, Kubiak CP. J. Am. Chem. Soc. 2011; 133: 12767
• 3 Moiseev DV, James BR. Phosphorus, Sulfur Silicon Relat. Elem. 2022; 197: 327
• 4a Fraze K, Wilson AD, Appel AM, Rakowski DuBois M, DuBois DL. Organometallics 2007; 26: 3918
• 4b Kilgore UJ, Stewart MP, Helm ML, Dougherty WG, Kassel WS, Rakowski DuBois M, DuBois DL, Bullock RM. Inorg. Chem. 2011; 50: 10908
• 4c Brunner FM, Neville ML, Kubiak CP. Inorg. Chem. 2020; 59: 16872
• 4d Thomas GT, Isbrandt ES, Newman SG. Org. Synth. 2024; 101: 1

Vanadium:
• 5a Egbert JD, Labios LA, Darmon JM, Piro NA, Kassel WS, Mock MT. Eur. J. Inorg. Chem. 2016; 1293

Chromium:
• 5b Mock MT, Chen S, Rousseau R, O’Hagan MJ, Dougherty WG, Kassel WS, DuBois DL, Bullock RM. Chem. Commun. 2011; 47: 12212

Manganese:
• 5c Welch KD, Dougherty WG, Kassel WS, Dubois DL, Bullock RM. Organometallics 2010; 29: 4532

Iron:
• 5d Liu T, Chen S, O’Hagan MJ, Rakowski DuBois M, Bullock RM, DuBois DL. J. Am. Chem. Soc. 2012; 134: 6257

Cobalt:
• 5e Wiedner ES, Yang JY, Dougherty WG, Kassel WS, Bullock RM, Rakowski DuBois M, DuBois DL. Organometallics 2010; 29: 5390

Nickel:
• 5f Appel AM, Pool DH, O’Hagan M, Shaw WJ, Yang JY, Rakowski DuBois M, DuBois DL, Bullock MR. ACS Catal. 2011; 1: 777

Copper:
• 5g Strelnik ID, Dayanova IR, Krivolapov DB, Litvinov IA, Musina EI, Karasik AA, Sinyashin OG. Polyhedron 2018; 139: 1

Molybdenum:
• 5h Kane JC, Wong EH, Yap GP, Rheingold AL. Polyhedron 1999; 18: 1183

Ruthenium:
• 5i Stubbs JM, Chapple DE, Boyle PD, Blacquiere JM. ChemCatChem 2018; 10: 4001

Rhodium:
• 5j Lilio AM, Reineke MH, Moore CE, Rheingold AL, Takase MK, Kubiak CP. J. Am. Chem. Soc. 2015; 137: 8251

Palladium:
• 5k Seu CS, Ung D, Doud MD, Moore CE, Rheingold AL, Kubiak CK. Organometallics 2013; 32: 4556

Tungsten and Platinum:
• 5l Musina EI, Khrizanforova VV, Strelnik ID, Valitov MI, Spiridonova YS, Krivolapov DB, Litvinov IA, Kadirov MK, Lönnecke P, Hey-Hawkins E, Budnikova YH, Karasik AA, Sinyashin OG. Chem. Eur. J. 2014; 20: 3169

Rhenium:
• 5m Karasik AA, Naumov RN, Sinyashin OG, Belov GP, Novikova HV, Lönnecke P, Hey-Hawkins E. Dalton Trans. 2003; 2209

Gold:
• 5n Spiridonova YS, Strelnik ID, Musina EI, Hey-Hawkins E, Litvinov IA, Karasik AA. Russ. J. Coord. Chem. (Engl. Transl.) 2020; 46: 477
• 6 Hulley EB, Helm ML, Bullock RM. Chem. Sci. 2014; 5: 4729
• 7 Chapple DE, Boyle PD, Blacquiere JM. ChemCatChem 2021; 13: 3789
• 8 Karasik AA, Musina EI, Strelnik ID, Dayanova IR, Elistratova JG, Mustafina AR, Sinyashin OG. Pure Appl. Chem. 2019; 91: 839
• 9a Wilson AD, Newell RH, McNevin MJ, Muckerman JT, Rakowski DuBois M, DuBois DL. J. Am. Chem. Soc. 2006; 128: 358
• 9b Yang JY, Bullock RM, Shaw WJ, Twamley B, Fraze K, Rakowski DuBois M, DuBois DL. J. Am. Chem. Soc. 2009; 131: 5935
• 10 Morra S. Front. Microbiol. 2022; 13: 853626
• 11 Wiedner ES, Appel AM, Raugei S, Shaw WJ, Bullock RM. Chem. Rev. 2022; 122: 12427
• 12 Galan BR, Reback ML, Jain A, Appel AM, Shaw WJ. Eur. J. Inorg. Chem. 2013; 5366
• 13 Roy S, Sharma B, Pecaut J, Simon P, Fontecave M, Tran PD, Derat E, Artero V. J. Am. Chem. Soc. 2017; 139: 3685
• 14 Yang JY, Bullock RM, Dougherty WG, Kassel WS, Twamley B, DuBois DL, Rakowski DuBois M. Dalton Trans. 2010; 39: 3001
• 15 Clevenger AL, Stolley RM, Aderibigbe J, Louie J. Chem. Rev. 2020; 120: 6124
• 16 Fihri A, Luart D, Len C, Solhy A, Chevrin C, Polshettiwar V. Dalton Trans. 2011; 40: 3116
• 17 Del Zotto A, Amoroso F, Baratta W, Rigo P. Eur. J. Org. Chem. 2009; 110
• 18 Karasik AA, Naumov RN, Balueva AS, Spiridonova YS, Golodkov ON, Novikova HV, Belov GP, Katsyuba SA, Vandyukova EE, Lönnecke P, Hey-Hawkins E, Sinyashin OG. Heteroat. Chem. 2006; 17: 499
• 19 Weiss CJ, Das P, Miller DL, Helm ML, Appel AM. ACS Catal. 2014; 4: 2951
• 20a Bow J.-PP, Boyle PD, Blacquiere JM. Eur. J. Inorg. Chem. 2015; 4162
• 20b Stubbs JM, Bow J.-PJ, Hazlehurst RJ, Blacquiere JM. Dalton Trans. 2016; 45: 17100
• 20c Stubbs JM, Bridge BJ, Blacquiere JM. Dalton Trans. 2019; 48: 7928
• 20d Bridge BJ, Boyle PD, Blacquiere JM. Organometallics 2020; 39: 2570
• 20e Chapple DE, Hoffer MA, Boyle PD, Blacquiere JM. Organometallics 2022; 41: 1532
• 21a Vandavasi JK, Hua X.-Y, Ben Halima H, Newman SG. Angew. Chem. Int. Ed. 2017; 56: 15441
• 21b Vandavasi JK, Newman SG. Synlett 2018; 29: 2081
• 22a Okude Y, Hirano S, Hiyama T, Nozaki H. J. Am. Chem. Soc. 1977; 99: 3179
• 22b Jin H, Uenishi J, Christ WJ, Kishi Y. J. Am. Chem. Soc. 1986; 108: 5644
• 22c Fürstner A. Chem. Rev. 1999; 99: 991
• 23a Majumdar KK, Cheng C.-H. Org. Lett. 2000; 2: 2295
• 23b Garcia KJ, Gilbert MM, Weix DJ. J. Am. Chem. Soc. 2019; 141: 1823
• 23c Ishida S, Suzuki H, Uchida S, Yamaguchi E, Itoh A. Eur. J. Org. Chem. 2019; 7483
• 24 Swyka RA, Zhang W, Richardson J, Ruble JC, Krische MJ. J. Am. Chem. Soc. 2019; 141: 1828
• 25 Isbrandt ES, Nasim A, Zhao K, Newman SG. J. Am. Chem. Soc. 2021; 143: 14646
• 26 Verheyen T, van Turnhout L, Vandavasi JK, Isbrandt ES, De Borggraeve WM, Newman SG. J. Am. Chem. Soc. 2019; 141: 6869
• 27a Twilton J, Christensen M, DiRocco DA, Ruck RT, Davies IW, MacMillan DW. C. Angew. Chem. Int. Ed. 2018; 57: 5369
• 27b Zhang S, Li L, Li J, Shi J, Xu K, Gao W, Zong L, Li G, Findlater M. Angew. Chem. Int. Ed. 2021; 60: 7275
• 28 MacQueen PM, Tassone JP, Diaz C, Stradiotto M. J. Am. Chem. Soc. 2018; 140: 5023
• 29 Nasim A, Thomas GT, Ovens JS, Newman SG. Org. Lett. 2022; 24: 7232

For a general overview of the Mizoroki–Heck cross-coupling, see:
• 30a Heck RF. Org. React. (Hoboken, NJ U. S.) 1982; 27: 345
• 30b Davies GD. Jr, Hallberg A. Chem. Rev. 1989; 89: 1433
• 30c de Meijere A, Meyer FE. Angew. Chem. Int. Ed. 1995; 33: 2379
• 30d Beletskaya IP, Cheprakov AV. Chem. Rev. 2000; 100: 3009
• 30e The Mizoroki-Heck Reaction . Oestreich M., Wiley; Oxford: 2009
• 30f Bhakta S, Ghosh T. Adv. Synth. Catal. 2020; 362: 5257

For discussions on the mechanisms of Ni- and Pd-catalyzed Mizoroki–Heck couplings, see:
• 31a Crisp GT. Chem. Soc. Rev. 1998; 27: 427
• 31b Lin B.-L, Liu L, Fu Y, Luo S.-W, Chen Q, Guo Q.-X. Organometallics 2004; 23: 2114
• 31c Surawatanawong P, Hall MB. Organometallics 2008; 27: 6222
• 31d Menezes da Silva VH, Braga AA. C, Cundari TR. Organometallics 2016; 35: 3170
• 31e Chernyshev VM, Ananikov VP. ACS Catal. 2022; 12: 1180
• 32a de Vries JG. Can. J. Chem. 2001; 79: 1086
• 32b Ree N, Göller AH, Jensen JH. ACS Omega 2022; 7: 45617
• 33 Mizoroki T, Mori K, Ozaki A. Bull. Chem. Soc. Jpn. 1971; 44: 581
• 34 Heck RF. Pure Appl. Chem. 1978; 50: 691
• 35a Cabri W, Candiani I, Bedeschi A. J. Org. Chem. 1992; 57: 3558
• 35b Cabri W, Candiani I, Bedeschi A, Santi R. J. Org. Chem. 1993; 58: 7421
• 36 Zou Y, Qin L, Ren X, Lu Y, Li Y, Zhou J. Chem. Eur. J. 2013; 19: 3504
• 37 For a single example of a linear selective Mizoroki–Heck coupling between an aryl triflate and a styrene, see: Zhou JS, Huang S, Teng S, Chi YR. Chem. Commun. 2021; 57: 3933

For a representative selection of electron-rich alkenes in Mizoroki–Heck couplings, see:
• 38a Cabri W, Candiani I. Acc. Chem. Res. 1995; 28: 2
• 38b Hyder Z, Ruan J, Xiao J. Chem. Eur. J. 2008; 14: 5555
• 38c Gøgsig WM, Kleimark J, Nilsonn Lill SO, Korsager S, Lindhardt AT, Norrby P.-O, Skrydstrup T. J. Am. Chem. Soc. 2012; 134: 443
• 38d Domzalska-Piecyzykolan A, Funes-Ardoiz I, Furman B, Bolm C. Angew. Chem. Int. Ed. 2021; 61: e202109801

For representative β-selective Mizoroki–Heck couplings with styrenes, see:
• 39a Heck RF, Nolley JP. Jr. J. Org. Chem. 1972; 37: 2320
• 39b Ehle AR, Zhou Q, Watson MP. Org. Lett. 2012; 14: 1202
• 39c Yu L, Huang Y, Wei Z, Ding Y, Su C, Xu Q. J. Org. Chem. 2015; 80: 8677

For representative α-selective Mizoroki–Heck couplings with styrenes, see:
• 40a Garnes-Portolés F, Greco R, Olivier-Meseguer J, Castellanos-Soriano J, Jiménez MC, López-Haro M, Hernández-Garrido JC, Boronat M, Pérez-Ruiz R, Levya-Pérez A. Nat. Catal. 2021; 4: 293
• 40b Lui K, Leifert D, Studer A. Nat. Synth. 2022; 1: 565

For a representative β-selective Mizoroki–Heck coupling with terminal aliphatic alkenes, see:
• 41a Werner EW, Sigman MS. J. Am. Chem. Soc. 2011; 133: 9692

For a representative α-selective Mizoroki–Heck coupling with terminal aliphatic alkenes, see:
• 41b Tasker SZ, Gutierrez AC, Jamison TF. Angew. Chem. Int. Ed. 2014; 53: 1858

For representative β-selective Mizoroki–Heck couplings with electron-deficient alkenes, see:
• 42a Dieck HA, Heck RF. J. Am. Chem. Soc. 1974; 96: 1133
• 42b Kantchev EA. B, Peh G.-R, Zhang C, Ying JY. Org. Lett. 2008; 10: 3949
• 42c Islam MS, Nahra F, Tzouras NV, Barakat A, Cazin CS. J, Nolan SP, Al-Majid AM. Eur. J. Inorg. Chem. 2019; 4695

For representative α-selective Mizoroki–Heck couplings with electron-deficient alkenes, see:
• 42d Wucher P, Caporaso L, Roesle P, Ragone F, Cavallo L, Mecking S, Göttker-Schnetmann I. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 8955
• 43 Zhang W.-S, Ji D.-W, Li Y, Zhang X.-X, Mei Y.-K, Chen B.-Z, Chen Q.-A. Nat. Commun. 2023; 14: 651
• 44 Duhamel T, Scaringi S, Leforestier B, Poblader-Bahamonde AI, Mazet C. JACS Au 2023; 3: 261
• 45 Roughley SD, Jordan AM. J. Med. Chem. 2011; 54: 3451
• 46a Isbrandt ES, Chapple DE, Tu NP. T, Dimakos V, Beardall AM. M, Boyle PD, Rowley C, Blacquiere JM, Newman SG. J. Am. Chem. Soc. 2024; 146: 5650
• 46b Chen Z, Isbrandt ES, Newman SG. Org. Lett. 2024; 26: 7723
• 47 For an overview of the Open Reaction Database (ORD), see: Kearnes SM, Maser MR, Wleklinski M, Kast A, Doyle AG, Dreher SD, Hawkins JM, Jensen KF, Coley CW. J. Am. Chem. Soc. 2021; 143: 18820
• 48 Bruno NC, Tudge MT, Buchwald SL. Chem. Sci. 2013; 4: 916