The Direct Pd-Catalyzed β-C(sp³)–H Activation of Carboxylic Acids

Abstract

The carboxylic acid moiety is one of the most versatile and abundant functional groups. However, despite of tremendous progress in the field of C–H functionalization reactions its use as a directing group for C(sp³)–H activation has remained limited. In this Synpact article we present the challenges associated with the carboxylic acid moiety as a native directing group and report on the newest developments in this field, including our recent study in which we developed a generally applicable protocol for the direct palladium catalyzed β-C(sp³)–H arylation of propionic acid and related α-branched aliphatic acids giving access to hydrocinnamic acids derivatives in a highly straightforward manner.

1 Introduction

2 Challenges in the C(sp³)–H Bond Activation of Carboxylic Acids

3 History/State of the Art

4 Studies towards a General β-C(sp³)–H Functionalization of ­Aliphatic Acids

5 Conclusion

Key words

C–H activation - carboxylic acids - arylation - palladium ­catalysis - propionic acid

• References

• 1 Falbe J. Bauer W. Büchel KH. Houben J. Weyl T. Carboxylic Acids and Carboxylic Acid Derivatives . Thieme; Stuttgart: 1985

For selected reviews on the synthetic utility of C–H activation processes, see:
• 2a Jazzar R. Hitce J. Renaudat A. Sofack-Kreutzer J. Baudoin O. Chem. Eur. J. 2010; 16: 2654
• 2b Wencel-Delord J. Dröge T. Liu F. Glorius F. Chem. Soc. Rev. 2011; 40: 4740
• 2c McMurray L. O'Hara F. Gaunt MJ. Chem. Soc. Rev. 2011; 40: 1885
• 2d Yamaguchi J. Yamaguchi AD. Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
• 2e Wencel-Delord J. Glorius F. Nat. Chem. 2013; 5: 369
• 2f Hartwig JF. J Am Chem. Soc. 2016; 138: 2
• 2g Gensch T. Hopkinson MN. Glorius F. Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
• 2h He J. Wasa M. Chan KS. L. Shao Q. Yu J.-Q. Chem. Rev. 2017; 117: 8754
• 3 Pichette Drapeau M. Gooßen LJ. Chem. Eur. J. 2016; 22: 18654
• 4 For reviews highlighting this situation, see ref. 2a,b,f–h and: Arndtsen BA. Bergman RG. Mobley TA. Peterson TA. Acc. Chem. Res. 1995; 28: 154

It is well-known that Pd carboxylates exist in complex equilibria between monomeric, dimeric, and trimeric species in solution, which depend on various parameters. The problems associated with the desired C–H activation processes are presented based on the monomeric complexes for simplicity. For representative discussions of this matter, see:
• 5a Bianchini C. Meli A. Oberhauser W. Organometallics 2003; 22: 4281
• 5b Bakhmutov V. Berry JF. Cotton FA. Ibragimov S. Murillo CA. Dalton Trans. 2005; 1989
• 6a Gross KM. Beak P. J. Am. Chem. Soc. 2001; 123: 315
• 6b Whisler MC. MacNeil S. Snieckus V. Beak P. Angew. Chem. Int. Ed. 2004; 43: 2206
• 7a Stephenson TA. Morehouse SM. Powell AR. Heffer JP. Wilkinson G. J. Chem. Soc. 1965; 3632
• 7b Hermans A. Wenkin M. Devillers M. J. Mol. Catal. A: Chem. 2001; 136: 59
• 7c Chen X. Engle KM. Wang D.-H. Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094
• 7d Engle KM. Mei T.-S. Wasa M. Yu J.-Q. Acc. Chem. Res. 2012; 45: 788
• 8a Beesley RM. Ingold CK. Thorpe JF. J. Chem. Soc., Trans. 1915; 107: 1080
• 8b Jung ME. Piizzi G. Chem. Rev. 2005; 105: 1735
• 9a Giri R. Maugel N. Li J.-J. Wang D.-H. Breazzano SP. Saunders LB. Yu J.-Q. J. Am. Chem. Soc. 2007; 129: 3510

For examples of intramolecular reactions, see:
• 9b Kao L.-C. Sen A. J. Chem. Soc., Chem. Commun. 1991; 1242
• 9c Dangel BD. Johnson JA. Sames D. J. Am. Chem. Soc. 2001; 123: 8149
• 9d Fraunhoffer KJ. Prabagaran N. Sirois LE. White MC. J. Am. Chem. Soc. 2006; 128: 9032
• 9e Lee JM. Chang S. Tetrahedron Lett. 2006; 47: 1375
• 9f Novák P. Correa A. Gallardo-Donaire J. Martin R. Angew. Chem. Int. Ed. 2011; 50: 12236
• 10 Zaitsev LV. G. Shabashov D. Daugulis O. J. Am. Chem. Soc. 2005; 127: 13154
• 11a Wang D.-H. Wasa M. Giri R. Yu J.-Q. J. Am. Chem. Soc. 2008; 130: 7190
• 11b Zhu R.-Y. Farmer ME. Chen Y.-Q. Yu J.-Q. Angew. Chem. Int. Ed. 2016; 55: 10578
• 12 Wasa M. Engle KM. Yu J.-Q. J. Am. Chem. Soc. 2009; 131: 9886
• 13a Lyons TW. Sanford MS. Chem. Rev. 2010; 110: 1147
• 13b Rouquet G. Chatani N. Angew. Chem. Int. Ed. 2013; 52: 11726
• 13c Chen Z. Wang B. Zhang J. Yu W. Liu Z. Zhang Y. Org. Chem. Front. 2015; 2: 1107
• 13d Daugulis O. Roane J. Tran LD. Acc. Chem. Res. 2015; 48: 1053
• 13e Qiu G. Wu J. Org. Chem. Front. 2015; 2: 169
• 13f Yang X. Shan G. Wang L. Rao Y. Tetrahedron Lett. 2016; 57: 819

The disadvantages associated with the use of directing groups can partially be compensated through the recycling of the respective auxiliaries. For selected examples highlighting this, see:
• 13g Zhu Q. Ji D. Liang T. Wang X. Xu Y. Org. Lett. 2015; 17: 3798
• 13h Mu D. Gao F. Chen G. He G. ACS Catal. 2017; 7: 1880
• 13i Jerhaoui S. Djukic J.-P. Wencel-Delord J. Colbert F. Chem. Eur. J 2017; 23: 15594
• 14a Rousseau G. Breit B. Angew. Chem. Int. Ed. 2011; 50: 2450
• 14b Zhang F.-L. Hong K. Li T.-J. Park H. Yu J.-Q. Science 2016; 351: 252
• 14c Gandeepan P. Ackermann L. Chem. 2018; 4: 199
• 15a Chen G. Zhuang Z. Li G.-C. Saint-Denis TG. Hsiao Y. Joe CL. Yu J.-Q. Angew. Chem. Int. Ed. 2017; 56: 1506
• 15b Zhu Y. Chen X. Yuan C. Li G. Zhang J. Zhao Y. Nat. Commun. 2017; 8: 14904
• 16 Ghosh KK. van Gemmeren M. Chem. Eur. J. 2017; 23: 17697
• 17a Wencel-Delord J. Colober F. Org. Chem. Front. 2016; 3: 394
• 17b Berkessel A. Adrio JA. Hüttenhain D. Neudörfl JM. J. Am. Chem. Soc. 2006; 128: 8421
• 18 Korneev S. Synthesis 2013; 45: 1000
• 19 Yang K. Li Q. Liu Y. Li G. Ge H. J. Am. Chem. Soc. 2016; 138: 12775
• 20a Margolin S. Stephens IR. Spoerlein MT. Makovsky A. Belloff GB. J. Am. Pharm. Assoc. 1953; 42: 476
• 20b Papa D. Ginsberg HF. Lederman I. DeCamp V. J. Am. Chem. Soc. 1953; 75: 1107
• 20c Shapiro R. Man EB. J. Am. Med. Assoc. 1960; 173: 1352
• 20d Hoppe JO. Ackerman JH. Larsen AA. Moss J. J. Med. Chem. 1970; 13: 997
• 20e Ballesteros C. Vicente J. Carrasco-Garcia R. Mateo R. de la Fuente J. Gorttázar C. Eur. J. Wildl. Res. 2011; 57: 749
• 20f Sage M. Fourel I. Lahoreau J. Siat V. Berny P. Rossi S. Environ. Sci. Pollut. Res. 2013; 20: 2893