Asymmetric Transfer Hydrogenation of Heterocyclic Compounds in Continuous Flow Using an Immobilized Chiral Phosphoric Acid as the Catalyst

This manuscript is dedicated to Professor David A. Evans.

Abstract

This manuscript describes transfer hydrogenation of bicyclic nitrogen-containing heterocyclic compounds using the immobilized chiral phosphoric acid catalyst (R)-PS-AdTRIP in batch and continuous flow. A significant improvement in enantioselectivities is achieved in continuous flow with a fluidized bed reactor packed with (R)-PS-AdTRIP when the flow rate is increased from 0.2 mL/min to 2.0–2.5 mL/min. The optimized continuous flow conditions consistently provide 4–6% ee higher selectivity than transfer hydrogenation in batch with 2 mol% of (R)-PS-AdTRIP, and are used to generate multiple chiral products with the same fluidized bed reactor.

Key words

transfer hydrogenation - chiral phosphoric acid - continuous flow - enantioselectivity - heterocycles

Publication History

Received: 11 March 2023

Accepted after revision: 03 May 2023

Accepted Manuscript online:
03 May 2023

Article published online:
29 June 2023

• References



• 1a Taylor AP, Robinson RP, Fobian YM, Blakemore DC, Jones LH, Fadeyi O. Org. Biomol. Chem. 2016; 14: 6611
• 1b Heravi MM, Zadsirjan V. RSC Adv. 2020; 10: 44247
• 1c Vitaku E, Smith DT, Njardarson J. J. Med. Chem. 2014; 57: 10257
• 1d Kerru N, Gummidi L, Maddila S, Gangu KK, Jonnalagadda SB. Molecules 2020; 25: 1909
• 2a Flick AC, Leverett CA, Ding HX, McInturff EL, Fink SJ, Mahapatra S, Carney DW, Lindsey EA, DeForest JC, France SP, Berritt S, Bigi-Botterill SV, Gibson TS, Watson RB, Liu Y, O’Donnell CJ. J. Med. Chem. 2022; 65: 9607
• 2b Flick AC, Leverett CA, Ding HX, McInturff EL, Fink SJ, Mahapatra S, Carney DW, Lindsey EA, DeForest JC, France SP, Berritt S, Bigi-Botterill SV, Gibson TS, Liu Y, O’Donnell CJ. J. Med. Chem. 2021; 64: 3607
• 3a Yu J, Zhou Y, Chen DF, Gong LZ. Pure Appl. Chem. 2014; 86: 1217
• 3b Vinogradov MG, Turova OV, Zlotin SG. Org. Biomol. Chem. 2019; 17: 3670
• 3c Zhang Y.-C, Jiang F, Shi F. Acc. Chem. Res. 2020; 53: 425
• 3d Magriotis PA. RSC Med. Chem. 2020; 11: 745
• 4a Rueping M, Theissmann T, Antonchick AP. Synlett 2006; 1071
• 4b Rueping M, Antonchick AP, Theissmann T. Angew. Chem. Int. Ed. 2006; 45: 3683
• 4c Rueping M, Tato F, Schoepke FR. Chem. Eur. J. 2010; 16: 2688
• 4d Rueping M, Merino E, Koenigs RM. Adv. Synth. Catal. 2010; 352: 2629
• 5a Pálvölgyi ÁM, Scharinger F, Schnürch M, Bica-Schröder K. Eur. J. Org. Chem. 2021; 5367
• 5b Parmar D, Sugiono E, Raja S, Rueping M. Chem. Rev. 2014; 114: 9047
• 5c Phillips AM. F, Pombeiro AJ. L. Catalysts 2023; 13: 419
• 5d Zheng C, You SL. Chem. Soc. Rev. 2012; 41: 2498
• 6 Rueping M, Sugiono E, Steck A, Theissmann T. Adv. Synth. Catal. 2010; 352: 281
• 7 Bartoszek M, Beller M, Deutsch J, Klawonn M, Kockritz A, Nemati N, Pews-Davtyan A. Tetrahedron 2008; 64: 1316
• 8a Bleschke C, Schmidt J, Kundu DS, Blechert S, Thomas A. Adv. Synth. Catal. 2011; 353: 3101
• 8b Kundu DS, Schmidt J, Bleschke C, Thomas A, Blechert S. Angew. Chem. Int. Ed. 2012; 51: 5456
• 9a Osorio-Planes L, Rodriguez-Escrih C, Pericas MA. Chem. Eur. J. 2014; 20: 2367
• 9b Clot-Almenara L, Rodriguez-Escrich C, Osorio-Planes L, Pericas MA. ACS Catal. 2016; 6: 7642
• 9c Lai J, Fianchini M, Pericas MA. ACS Catal. 2020; 10: 14971
• 9d Chaudhari MB, Gupta P, Llanes P, Pericas MA. Adv. Synth. Cat. 2023; 365: 527
• 10 Li S, Zhang J, Chen S, Ma X. J. Catal. 2022; 416: 139
• 11a Chen X, Jiang H, Li X, Hou B, Gong W, Wu X, Han X, Zheng F, Liu Y, Jiang J, Cui Y. Angew. Chem. Int. Ed. 2019; 58: 14748
• 11b Chen X, Qiao Z, Hou B, Jiang H, Gong W, Dong J, Li H.-Y, Cui Y, Liu Y. Nano Res. 2021; 14: 466
• 12a Rodriguez-Escrich C, Pericas MA. Eur. J. Org. Chem. 2015; 6: 1173
• 12b Rodriguez-Escrich C, Pericas MA. Chem. Rec. 2018; 19: 1872
• 13 Wang S, Zhelavskyi O, Lee J, Argüelles AJ, Khomutnyk YY, Mensah E, Guo H, Hourani R, Zimmerman PM, Nagorny P. J. Am. Chem. Soc. 2021; 143: 18592
• 14a Hoffmann S, Seayad AM, List B. Angew. Chem. Int. Ed. 2005; 44: 7424
• 14b Adair G, Mukherjee S, List B. Aldrichimica Acta 2008; 41: 31
• 15a Jiao P, Nakashima D, Yamamoto H. Angew. Chem. Int. Ed. 2008; 47: 2411
• 15b Mensah E, Camasso N, Kaplan W, Nagorny P. Angew. Chem. Int. Ed. 2013; 52: 13939
• 16a Ouellet SG, Tuttle JB, MacMillan DW. C. J. Am. Chem. Soc. 2005; 127: 32
• 16b Ouellet SG, Walji AM, MacMillan DW. C. Acc. Chem. Res. 2007; 40: 1327
• 17 Zhu C, Akiyama T. Org. Lett. 2009; 11: 4180
• 18 Gao B, Meng W, Feng X, Du H. Org. Lett. 2022; 24: 3955
• 19a Chen Q.-A, Wang D.-S, Zhou Y.-G, Duan Y, Fan H.-J, Yang Y, Zhang Z. J. Am. Chem. Soc. 2011; 133: 6126
• 19b Saito K, Shibata Y, Yamanaka M, Akiyama T. J. Am. Chem. Soc. 2013; 135: 11740
• 20 Chen Q, Gao K, Duan Y, Ye Z, Shi L, Yang Y, Zhou Y. J. Am. Chem. Soc. 2012; 134: 2442
• 21 Sun S, Nagorny P. Chem. Commun. 2020; 56: 8432
• 22 Saito K, Miyashita H, Akiyama T. Chem. Commun. 2015; 51: 16648
• 23 Han ZY, Xiao H, Chen XH, Gong LZ. J. Am. Chem. Soc. 2009; 131: 9182
• 24 Zhao ZB, Wang J, Zhu ZH, Chen MW, Zhou YG. Org. Lett. 2021; 23: 9112
• 25 Qin J, Chen F, He YM, Fan QH. Org. Chem. Front. 2014; 1: 952