Application of α-Aminoalkyl Radicals as Reaction Activators

Abstract

α-Aminoalkyl radicals are easily accessible through multiple pathways from various precursors. Apart from their utilization as nitrogen-containing building blocks, they have recently been used as halogen atom abstraction reagents or single-electron reductants to transform organic halides or sulfonium salts into their corresponding highly reactive radical species. Benefiting from the richness of various halides and the diverse reactivity of radical intermediates, new transformations of halides and sulfonium salts have been developed. This short review summarizes this emerging chemistry that uses α-aminoalkyl radicals as the reaction activators.

1 Introduction

2 Activation of Halides as Halogen-Atom Transfer Agents

2.1 Addition to Unsaturated Bonds

2.1.1 Addition to C=C Bonds

2.1.2 Addition to C=O Bonds

2.2 Substitution Reactions

2.2.1 Deuteration

2.2.2 Olefination

2.2.3 Allylation

2.2.4 Aromatic Substitution

2.2.5 Amination

3 Activation of Sulfonium Salts as Single-Electron Reductants

4 Conclusion and Outlook

Key words

α-aminoalkyl radicals - halides - halogen-atom transfer - hydrogen-atom transfer - radical addition - radical substitution - sulfonium salts

Publication History

Received: 28 September 2021

Accepted after revision: 03 November 2021

Accepted Manuscript online:
03 November 2021

Article published online:
15 December 2021

• References

• 1a Free Radicals: Dynamics of Elementary Processes, Vol. 1. Kochi JK. Wiley-Interscience; New York: 1973
• 1b Curran DP. Synthesis 1988; 417
• 1c Curran DP. Synthesis 1988; 489
• 1d Jasperse CP, Curran DP, Fevig TL. Chem. Rev. 1991; 91: 1237
• 1e Radicals in Organic Synthesis, 1st ed. Renaud P, Sibi M. Wiley-VCH; Weinheim: 2001
• 1f Togo H. Advanced Free Radical Reactions for Organic Synthesis. Elsevier; Amsterdam: 2003
• 1g Zard SZ. Radical Reactions in Organic Synthesis . Oxford University Press; Oxford: 2003
• 1h Yan M, Lo JC, Edwards JT, Baran PS. J. Am. Chem. Soc. 2016; 138: 12692
• 1i Studer A, Curran DP. Angew. Chem. Int. Ed. 2016; 55: 58
• 1j Crespi S, Fagnoni M. Chem. Rev. 2020; 120: 9790
• 1k Proctor RS. J, Colgan AC, Phipps RJ. Nat. Chem. 2020; 12: 990
• 1l Parsaee F, Senarathna MC, Kannangara PB, Alexander SN, Arche PD. E, Welin ER. Nat. Rev. Chem. 2021; 5: 486
• 2a Gomberg M. J. Am. Chem. Soc. 1900; 22: 757
• 2b Gomberg M. J. Am. Chem. Soc. 1901; 23: 496
• 2c Gomberg M. J. Am. Chem. Soc. 1902; 24: 597
• 3a Narayanam JM. R, Stephenson CR. J. Chem. Soc. Rev. 2011; 40: 102
• 3b Schultz DM, Yoon TP. Science 2014; 343: 1239176
• 3c Shaw MH, Twilton J, MacMillan DW. C. J. Org. Chem. 2016; 81: 6898
• 3d Romero NA, Nicewicz DA. Chem. Rev. 2016; 116: 10075
• 4a Hu J, Wang J, Nguyen TH, Zheng N. Beilstein J. Org. Chem. 2013; 9: 1977
• 4b Nakajima K, Miyake Y, Nishibayashi Y. Acc. Chem. Res. 2016; 49: 1946
• 4c Leitch JA, Rossolini T, Rogova T, Maitland JA. P, Dixon DJ. ACS Catal. 2020; 10: 2009
• 4d Wu X, Ren J, Shao Z, Yang X, Qian D. ACS Catal. 2021; 11: 6560
• 5a Zuo Z, MacMillan DW. C. J. Am. Chem. Soc. 2014; 136: 5257
• 5b Zuo Z, Ahneman DT, Chu L, Terrett JA, Doyle AG, MacMillan DW. C. Science 2014; 345: 437
• 5c Zuo Z, Cong H, Li W, Choi J, Fu GC, MacMillan DW. C. J. Am. Chem. Soc. 2016; 138: 1832
• 5d Noble A, MacMillan DW. C. J. Am. Chem. Soc. 2014; 136: 11602
• 6a Beatty JW, Stephenson CR. J. Acc. Chem. Res. 2015; 48: 1474
• 6b McManus JB, Onuska NP. R, Nicewicz DA. J. Am. Chem. Soc. 2018; 140: 9056
• 6c Prier CK, MacMillan DW. C. Chem. Sci. 2014; 5: 4173
• 7a Pratsch G, Lackner GL, Overman LE. J. Org. Chem. 2015; 80: 6025
• 7b Qin T, Cornella J, Li C, Malins LR, Edwards JT, Kawamura S, Maxwell BD, Eastgate MD, Baran PS. Science 2016; 352: 801
• 7c Qin T, Malins LR, Edwards JT, Merchant RR, Novak AJ. E, Zhong JZ, Mills RB, Yan M, Yuan C, Eastgate MD, Baran PS. Angew. Chem. Int. Ed. 2017; 56: 260
• 7d Proctor RS. J, Davis HJ, Phipps RJ. Science 2018; 360: 419
• 7e Fu M.-C, Shang R, Zhao B, Wang B, Fu Y. Science 2019; 363: 1429
• 7f Ni S, Padial NM, Kingston C, Vantourout JC, Schmitt DC, Edwards JT, Kruszyk MM, Merchant RR, Mykhailiuk PV, Sanchez BB, Yang S, Perry MA, Gallego GM, Mousseau JJ, Collins MR, Cherney RJ, Lebed PS, Chen JS, Qin T, Baran PS. J. Am. Chem. Soc. 2019; 141: 6726
• 8a Cuesta-Galisteo S, Schörgenhumer J, Wei X, Merino E, Nevado C. Angew. Chem. Int. Ed. 2021; 60: 1605
• 8b He Y, Song H, Chen J, Zhu S. Nat. Commun. 2021; 12: 638
• 8c Qian D, Bera S, Hu X. J. Am. Chem. Soc. 2021; 143: 1959
• 8d Wang J.-W, Li Y, Nie W, Chang Z, Yu Z.-A, Zhao Y.-F, Lu X, Fu Y. Nat. Commun. 2021; 12: 1313
• 8e Wang S, Zhang T.-Y, Zhang J.-X, Meng H, Chen B.-H, Shu W. Nat. Commun. 2021; 12: 2771
• 9a Jeffrey JL, Petronijevic FR, MacMillan DW. C. J. Am. Chem. Soc. 2015; 137: 8404
• 9b Nakajima M, Fava E, Loescher S, Jiang Z, Rueping M. Angew. Chem. Int. Ed. 2015; 54: 8828
• 9c Uraguchi D, Kinoshita N, Kizu T, Ooi T. J. Am. Chem. Soc. 2015; 137: 13768
• 10a Yoon UC, Mariano PS. Acc. Chem. Res. 1992; 25: 233
• 10b Cho DW, Yoon UC, Mariano PS. Acc. Chem. Res. 2011; 44: 204
• 11a Kohls P, Jadhav D, Pandey G, Reiser O. Org. Lett. 2012; 14: 672
• 11b Miyake Y, Nakajima K, Nishibayashi Y. J. Am. Chem. Soc. 2012; 134: 3338
• 11c Zhu S, Das A, Bui L, Zhou H, Curran DP, Rueping M. J. Am. Chem. Soc. 2013; 135: 1823
• 11d Mizoguchi H, Oikawa H, Oguri H. Nat. Chem. 2014; 6: 57
• 11e Zhang P, Xiao T, Xiong S, Dong X, Zhou L. Org. Lett. 2014; 16: 3264
• 11f Lee KN, Lei Z, Ngai M.-Y. J. Am. Chem. Soc. 2017; 139: 5003
• 12a Miyake Y, Nakajima K, Nishibayashi Y. Chem. Eur. J. 2012; 18: 16473
• 12b Zhou H, Lu P, Gu X, Li P. Org. Lett. 2013; 15: 5646
• 12c Fava E, Millet A, Nakajima M, Loescher S, Rueping M. Angew. Chem. Int. Ed. 2016; 55: 6776
• 12d Wang C, Qin J, Shen X, Riedel R, Harms K, Meggers E. Angew. Chem. Int. Ed. 2016; 55: 685
• 12e Kizu T, Uraguchi D, Ooi T. J. Org. Chem. 2016; 81: 6953
• 13a McNally A, Prier CK, MacMillan DW. C. Science 2011; 334: 1114
• 13b El Khatib M, Serafim RA. M, Molander GA. Angew. Chem. Int. Ed. 2016; 55: 254
• 14a Noble A, McCarver SJ, MacMillan DW. C. J. Am. Chem. Soc. 2015; 137: 624
• 14b Dai X, Cheng D, Guan B, Mao W, Xu X, Li X. J. Org. Chem. 2014; 79: 7212
• 14c Xuan J, Zeng T.-T, Feng Z.-J, Deng Q.-H, Chen J.-R, Lu L.-Q, Xiao W.-J, Alper H. Angew. Chem. Int. Ed. 2015; 54: 1625
• 14d Xie J, Shi S, Zhang T, Mehrkens N, Rudolph M, Hashmi AS. K. Angew. Chem. Int. Ed. 2015; 54: 6046
• 14e Qi L, Chen Y. Angew. Chem. Int. Ed. 2016; 55: 13312
• 14f Fuentes de Arriba AL, Urbitsch F, Dixon DJ. Chem. Commun. 2016; 52: 14434
• 15a Hager D, MacMillan DW. C. J. Am. Chem. Soc. 2014; 136: 16986
• 15b Patel NR, Kelly CB, Siegenfeld AP, Molander GA. ACS Catal. 2017; 7: 1766
• 16a Rand AW, Yin H, Xu L, Giacoboni J, Martin-Montero R, Romano C, Montgomery J, Martin R. ACS Catal. 2020; 10: 4671
• 16b Shu X, Huan L, Huang Q, Huo H. J. Am. Chem. Soc. 2020; 142: 19058
• 16c Gu J.-W, Min Q.-Q, Yu L.-C, Zhang X. Angew. Chem. Int. Ed. 2016; 55: 12270
• 16d Wei X, Shu W, García-Domínguez A, Merino E, Nevado C. J. Am. Chem. Soc. 2020; 142: 13515
• 16e Zhang G, Zhou S, Fu L, Chen P, Li Y, Zou J, Liu G. Angew. Chem. Int. Ed. 2020; 59: 20439
• 17a Schubert S, Renaud P, Carrupt PA, Schenk K. Helv. Chim. Acta 1993; 76: 2473
• 17b Armstrong DA, Rauk A, Yu D. J. Am. Chem. Soc. 1993; 115: 666
• 17c Wayner DD. M, Clark KB, Rauk A, Yu D, Armstrong DA. J. Am. Chem. Soc. 1997; 119: 8925
• 17d Jansen TL, Trabjerg I, Rettrup S, Pagsberg P, Sillesen A. Acta Chem. Scand. 1999; 53: 1054
• 17e Mayer PM, Glukhovtsev MN, Gauld JW, Radom L. J. Am. Chem. Soc. 1997; 119: 12889
• 17f Aurrecoechea JM, Suero R. ARKIVOC 2004; (xiv): 10
• 18a Kuo JL, Lorenc C, Abuyuan JM, Norton JR. J. Am. Chem. Soc. 2018; 140: 4512
• 18b Nocera G, Young A, Palumbo F, Emery KJ, Coulthard G, McGuire T, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2018; 140: 9751
• 18c Wang X, Dai Y, Gong H. Top. Curr. Chem. 2016; 374: 43
• 18d Ye S, Xiang T, Li X, Wu J. Org. Chem. Front. 2019; 6: 2183
• 18e Novaes LF. T, Liu J, Shen Y, Lu L, Meinhardt JM, Lin S. Chem. Soc. Rev. 2021; 50: 7941
• 19a Neumann WP. Synthesis 1987; 665
• 20a Chatgilialoglu C, Ferreri C, Landais Y, Timokhin VI. Chem. Rev. 2018; 118: 6516
• 20b Yorimitsu H, Oshima K. In Radicals in Organic Synthesis . Renaud P, Sibi MP. Wiley-VCH; Weinheim: 2008: 11-27
• 20c Le C, Chen TQ, Liang T, Zhang P, MacMillan DW. C. Science 2018; 360: 1010
• 20d Zhang P, Le CC, MacMillan DW. C. J. Am. Chem. Soc. 2016; 138: 8084
• 21a Kharasch MS, Jensen EV, Urry WH. Science 1945; 102: 128
• 21b Iqbal J, Bhatia B, Nayyar NK. Chem. Rev. 1994; 94: 519
• 21c Lu MZ, Loh TP. Org. Lett. 2014; 16: 4698
• 21d Li X, Xu J, Gao Y, Fang H, Tang G, Zhao Y. J. Org. Chem. 2015; 80: 2621
• 21e Liu Y, Zhang J.-L, Song R.-J, Li J.-H. Org. Chem. Front. 2014; 1: 1289
• 21f Tian Y, Liu Z.-Q. RSC Adv. 2014; 4: 64855
• 22a Lan X.-W, Wang N.-X, Xing Y. Eur. J. Org. Chem. 2017; 5821
• 22b Wang F, Chen P, Liu G. Acc. Chem. Res. 2018; 51: 2036
• 22c Ouyang XH, Song RJ, Li JH. Chem. Asian J. 2018; 13: 2316
• 22d Lin J, Song R.-J, Hu M, Li J.-H. Chem. Rec. 2019; 19: 440
• 22e Bao X, Li J, Jiang W, Huo C. Synthesis 2019; 51: 4507
• 22f Li Z.-L, Fang G.-C, Gu Q.-S, Liu X.-Y. Chem. Soc. Rev. 2020; 49: 32
• 22g Wu X, Zhu C. Acc. Chem. Res. 2020; 53: 1620
• 23 Neff RK, Su Y.-L, Liu S, Rosado M, Zhang X, Doyle MP. J. Am. Chem. Soc. 2019; 141: 16643
• 24 Su YL, De Angelis L, Tram L, Yu Y, Doyle MP. J. Org. Chem. 2020; 85: 3728
• 25 Su Y.-L, Tram L, Wherritt D, Arman H, Griffith WP, Doyle MP. ACS Catal. 2020; 10: 13682
• 26 Bonnett R, Guy RG, Lanigan D. Tetrahedron 1976; 32: 2439
• 27 Liu S, Su Y.-L, Sun T.-Y, Doyle MP, Wu Y.-D, Zhang X. J. Am. Chem. Soc. 2021; 143: 13195
• 28 Roberts BP, Steel AJ. J. Chem. Soc., Perkin Trans. 2 1994; 2411
• 29 Constantin T, Zanini M, Regni A, Sheikh NS, Juliá F, Leonori D. Science 2020; 367: 1021
• 30 Caiger L, Sinton C, Constantin T, Douglas JJ, Sheikh NS, Juliá F, Leonori D. Chem. Sci. 2021; 12: 10448
• 31a Gupta V, Kahne D. Tetrahedron Lett. 1993; 34: 591
• 31b Oyama M. J. Org. Chem. 1965; 30: 2429
• 32a Harbeson SL, Tung RD. MedChem News 2014; 2: 8
• 32b Gant TG. J. Med. Chem. 2014; 57: 3595
• 32c Atzrodt J, Derdau V, Fey T, Zimmermann J. Angew. Chem. Int. Ed. 2007; 46: 7744
• 32d Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 1758
• 32e Pirali T, Serafini M, Cargnin S, Genazzani AA. J. Med. Chem. 2019; 62: 5276
• 33a Soulard V, Villa G, Vollmar DP, Renaud P. J. Am. Chem. Soc. 2018; 140: 155
• 33b Liu C, Chen Z, Su C, Zhao X, Gao Q, Ning GH, Zhu H, Tang W, Leng K, Fu W, Tian B, Peng X, Li J, Xu QH, Zhou W, Loh KP. Nat. Commun. 2018; 9: 80
• 33c Yang X, Ben H, Ragauskas AJ. Asian J. Org. Chem. 2021; 10: 2473
• 34a Heck RF. Palladium-Catalyzed Vinylation of Organic Halides. In Organic Reactions, Vol. 27. Dauben WG. John Wiley & Sons; Hoboken: 1982: 345
• 34b Beletskaya IP, Cheprakov AV. Chem. Rev. 2000; 100: 3009
• 34c Littke AF, Fu GC. Angew. Chem. Int. Ed. 2002; 41: 4176
• 34d Knowles JP, Whiting A. Org. Biomol. Chem. 2007; 5: 31
• 34e Doucet H, Lemhadri M, Battace A, Berthiol F, Zair T, Santelli M. Synthesis 2008; 1142
• 35a Netherton MR, Fu GC. In Palladium in Organic Synthesis . Tsuji J. Springer-Verlag; Berlin: 2005: 85
• 35b Wang G.-Z, Shang R, Cheng W.-M, Fu Y. J. Am. Chem. Soc. 2017; 139: 18307
• 35c Kurandina D, Parasram M, Gevorgyan V. Angew. Chem. Int. Ed. 2017; 56: 14212
• 36a Tsuji J. Pure Appl. Chem. 1999; 71: 1539
• 36b Tsuji J. In Handbook of Organopalladium Chemistry for Organic Synthesis, Vol. 2. Negishi E.-i. John Wiley & Sons; New York: 2002: 1669
• 36c Marshall JA. Chem Rev. 2000; 100: 3163
• 36d Cheng Q, Tu H.-F, Zheng C, Qu J.-P, Helmchen G. Chem. Rev. 2019; 119: 1855
• 37a Jørgensen KA. Synthesis 2003; 1117
• 37b Bandini M, Melloni A, Umani-Ronchi A. Angew. Chem. Int. Ed. 2004; 43: 550
• 37c Kakiuchi F, Murai S. Acc. Chem. Res. 2002; 35: 826
• 37d Li B.-J, Yang S.-D, Shi Z.-J. Synlett 2008; 949
• 37e Messaoudi S, Brion J.-D, Alami M. Eur. J. Org. Chem. 2010; 6495
• 38 Constantin T, Juliá F, Sheikh NS, Leonori D. Chem. Sci. 2020; 11: 12822
• 39 Górski B, Barthelemy A.-L, Douglas JJ, Juliá F, Leonori D. Nat. Catal. 2021; 4: 623
• 40 Alvarez EM, Karl T, Berger F, Torkowski L, Ritter T. Angew. Chem. Int. Ed. 2021; 60: 13609
• 41a Shao Z, Zhang H. Chem. Soc. Rev. 2009; 38: 2745
• 41b Zhong C, Shi X. Eur. J. Org. Chem. 2010; 2999
• 41c Zhou J. Chem. Asian J. 2010; 5: 422
• 41d Allen AE, MacMillan DW. C. Chem. Sci. 2012; 3: 633
• 41e Du Z, Shao Z. Chem. Soc. Rev. 2013; 42: 1337
• 41f Chen DF, Han ZY, Zhou XL, Gong LZ. Acc. Chem. Res. 2014; 47: 2365
• 41g Inamdar SM, Shinde VS, Patil NT. Org. Biomol. Chem. 2015; 13: 8116
• 41h Afewerki S, Córdova A. Chem. Rev. 2016; 116: 13512