2.2 Metal-Promoted DEL-Compatible C—C Bond Forming Reactions

Abstract

DNA-encoded library (DEL) technology relies on the availability of robust and DNA-compatible chemical transformations. Metal-promoted C—C bond forming reactions are widely applied for the synthesis of fine chemicals such as pharmaceuticals. However, their application in DEL technology represents a challenge due to the use of metal catalysts, high temperatures, and organic solvents. In this chapter, we report tailored conditions for the on-DNA application of the Suzuki, Sonogashira, Heck, and Giese reactions. The conditions presented in this chapter have been systematically explored across different DEL designs and structurally-diverse building blocks. By providing a comprehensive insight into the practical implementation of these metal-promoted C—C bond cross-coupling reactions, this review aims at expanding and promoting the application of these transformations in DEL construction.

Key words

DNA-encoded libraries - C—C bond formation - cross-coupling reactions - DEL synthesis - DNA-compatible reactions - Giese reaction - Heck reaction - Sonogashira coupling - Suzuki coupling - metal-catalyzed reactions

• 1 Favalli N, Bassi G, Pellegrino C, Millul J, De Luca R, Cazzamalli S, Yang S, Trenner A, Mozaffari NL, Myburgh R, Moroglu M, Conway SJ, Sartori AA, Manz MG, Lerner RA, Vogt PK, Scheuermann J, Neri D. Nat. Chem. 2021; 13: 540

• 2 Litovchick A, Dumelin CE, Habeshian S, Gikunju D, Guié M.-A, Centrella P, Zhang Y, Sigel EA, Cuozzo JW, Keefe AD, Clark MA. Sci. Rep. 2015; 5: 10916

• 3 Satz AL, Brunschweiger A, Flanagan ME, Gloger A, Hansen NJV, Kuai L, Kunig VBK, Lu X, Madsen D, Marcaurelle LA, Mulrooney C, OʼDonovan G, Sakata S, Scheuermann J. Nat. Rev. Methods Primers 2022; 2: 3

• 4 Yang H, Medeiros PF, Raha K, Elkins P, Lind KE, Lehr R, Adams ND, Burgess JL, Schmidt SJ, Knight SD, Auger KR, Schaber MD, Franklin GJ, Ding Y, DeLorey JL, Centrella PA, Mataruse S, Skinner SR, Clark MA, Cuozzo JW, Evindar G. ACS Med. Chem. Lett. 2015; 6: 531

• 5 Goodnow RA, Dumelin CE, Keefe AD. Nat. Rev. Drug Discovery 2017; 16: 131

• 6 Satz AL, Cai J, Chen Y, Goodnow R, Gruber F, Kowalczyk A, Petersen A, Naderi-Oboodi G, Orzechowski L, Strebel Q. Bioconjugate Chem. 2015; 26: 1623

• 7 Malone ML, Paegel BM. ACS Comb. Sci. 2016; 18: 182

• 8 Ratnayake AS, Flanagan ME, Foley TL, Smith JD, Johnson JG, Bellenger J, Montgomery JI, Paegel BM. ACS Comb. Sci. 2019; 21: 650

• 9 Li J.-Y, Huang H. Bioconjugate Chem. 2018; 29: 3841

• 10 Adamik R, Buchholcz B, Darvas F, Sipos G, Novák Z. Chem.–Eur. J. 2022; 28: e202 103 967

• 11 Ding Y, Clark MA. ACS Comb. Sci. 2015; 17: 1

• 12 Ding Y, DeLorey JL, Clark MA. Bioconjugate Chem. 2016; 27: 2597

• 13 Favalli N, Bassi G, Bianchi D, Scheuermann J, Neri D. Bioorg. Med. Chem. 2021; 41: 116206

• 14 Favalli N, Bassi G, Zanetti T, Scheuermann J, Neri D. Helv. Chim. Acta 2019; 102 e1900033

• 15 Wang X, Sun H, Liu J, Zhong W, Zhang M, Zhou H, Dai D, Lu X. Org. Lett. 2019; 21: 719

• 16 Wang J, Lundberg H, Asai S, Martín-Acosta P, Chen JS, Brown S, Farrell W, Dushin RG, OʼDonnell CJ, Ratnayake AS, Richardson P, Liu Z, Qin T, Blackmond DG, Baran PS. Proc. Natl. Acad. Sci. U. S. A. 2018; 115: e6404

• 17 Xu H, Ma F, Wang N, Hou W, Xiong H, Lu F, Li J, Wang S, Ma P, Yang G, Lerner RA. Adv. Sci. (Weinheim, Ger.) 2019; 6: 1901 551

• 18 DʼAlterio MC, Casals-Cruañas È, Tzouras NV, Talarico G, Nolan SP, Poater A. Chem.–Eur. J. 2021; 27: 13481

• 19 Schäfer P, Palacin T, Sidera M, Fletcher SP. Nat. Commun. 2018; 9: 16216

• 20 Sonogashira K. J. Organomet. Chem. 2002; 653: 46

• 21 Budarin VL, Shuttleworth PS, Clark JH, Luque R. Curr. Org. Synth. 2010; 7: 614

• 22 Bleicher LS, Cosford NDP, Herbaut A, McCallum JS, McDonald IA. J. Org. Chem. 1998; 63: 1109

• 23 Heck RF. J. Am. Chem. Soc. 1969; 91: 6707

• 24 Flick AC, Ding HX, Leverett CA, Kyne RE, Liu KK.-C, Fink SJ, OʼDonnell CJ. J. Med. Chem. 2017; 60: 6480

• 25 Gartner ZJ, Kanan MW, Liu DR. Angew. Chem. Int. Ed. 2002; 41: 1796

• 26 Giese B. Angew. Chem. Int. Ed. Engl. 1983; 22: 753