Pd-Catalyzed Remote δ-C(sp²)–H Functionalization in Phenylalaninol: Expanding the Library of Phenylalaninols

Abstract

We report the Pd(II)-catalyzed, picolinamide-directed δ-C(sp²)–H (ortho) functionalization of phenylalaninol scaffolds. Assembling of (ortho) δ-C–H arylated, alkylated, benzylated, alkenylated, brominated, and iodinated phenylalaninol scaffolds was accomplished. The δ-C(sp²)–H arylation reaction of phenylalaninol occurred under neat conditions. Hydrolysis of the picolinamide moiety and synthetic utility of the δ-C(sp²)–H arylated substrates were explored. We have also shown the preparation of some modified Matijin–Su (aurantiamide) derivatives using the bis δ-C–H (ortho) arylated phenylalaninol compounds obtained from the δ-C(sp²)–H arylation reaction (Matijin–Su is an anti-HBV agent possessing the phenylalaninol unit). Considering the importance of phenylalaninols, this work contributes to expanding the phenylalaninol library and demonstrates the substrate scope development in remote δ-C(sp²)–H functionalization reactions.

Key words

amino alcohols - biaryls - C–H activation - δ-C(sp²)–H functionalization - palladium - phenylalaninol - terphenyl

Publication History

Received: 26 June 2023

Accepted after revision: 02 August 2023

Accepted Manuscript online:
02 August 2023

Article published online:
25 September 2023

• References


For reviews on C–H functionalization, see:
• 1a Kakiuchi F, Murai S. Acc. Chem. Res. 2002; 35: 826
• 1b Arockiam PA, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879
• 1c Besset T, Poisson T, Pannecoucke X. Chem. Eur. J. 2014; 20: 16830
• 1d Rej S, Das A, Chatani N. Coord. Chem. Rev. 2021; 431: 213683
• 1e Miura M, Satoh T, Hirano K. Bull. Chem. Soc. Jpn. 2014; 87: 751
• 1f He J, Wasa M, Chan KS. L, Shao Q, Yu J.-Y. Chem. Rev. 2017; 117: 8754
• 1g Gandeepan P, Müller T, Zell D, Cera G, Warratz S, Ackermann L. Chem. Rev. 2019; 119: 2192
• 1h Yoshino T, Matsunaga S. Adv. Synth. Catal. 2017; 359: 1245
• 1i Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
• 1j Banerjee A, Sarkar S, Patel BK. Org. Biomol. Chem. 2017; 15: 505
• 1k Jazzar R, Hitce J, Renaudat A, Sofack-Kreutzer J, Baudoin O. Chem. Eur. J. 2010; 16: 2654
• 1l Sinha SK, Guin S, Maiti S, Biswas JP, Porey S, Maiti D. Chem. Rev. 2022; 122: 5682

For reviews on C–H functionalization, see:
• 2a Lu M.-Z, Goh J, Maraswami M, Jia Z, Tian J.-S, Loh T.-P. Chem. Rev. 2022; 122: 17479
• 2b Chen Z, Wang B, Zhang J, Yu W, Liu Z, Zhang Y. Org. Chem. Front. 2015; 2: 1107
• 2c Yanagi T, Nogi K, Yorimitsu H. Tetrahedron Lett. 2018; 59: 2951
• 2d Manoharan R, Jeganmohan M. Asian J. Org. Chem. 2019; 8: 1949
• 2e Higham JI, Bull JA. Org. Biomol. Chem. 2020; 18: 7291

For reviews on bidentate-directing-group-aided C–H functionalization, see:
• 3a Rej S, Ano Y, Chatani N. Chem. Rev. 2020; 120: 1788
• 3b Daugulis O, Roane J, Tran LD. Acc. Chem. Res. 2015; 48: 1053
• 3c Sambiagio C, Schönbauer D, Blieck R, Dao-Huy T, Pototschnig G, Schaaf P, Wiesinger T, Zia MF, Wencel-Delord J, Besset T, Maes BU. W, Schnürch M. Chem. Soc. Rev. 2018; 47: 6603
• 3d Liu B, Romine AM, Rubel CZ, Engle KM, Shi B.-F. Chem. Rev. 2021; 121: 14957
• 3e Rit RK, Yadav MR, Ghosh K, Sahoo AK. Tetrahedron 2015; 71: 4450
• 3f He G, Wang B, Nack WA, Chen G. Acc. Chem. Res. 2016; 49: 635
• 3g Yang X, Shan G, Wang L, Rao Y. Tetrahedron Lett. 2016; 57: 819
• 3h Babu SA, Aggarwal Y, Patel P, Tomar R. Chem. Commun. 2022; 58: 2612
• 3i Correa A. Eur. J. Inorg. Chem. 2021; 2928

For reviews on remote C–H functionalization, see:
• 4a Martinez-Mingo M, Rodríguez N, Arryás RG. Carretero J. C. Chem. Commun. 2022; 58: 2034
• 4b Zhang Q, Shi B.-F. Chem. Sci. 2021; 12: 841
• 4c Das J, Guin S, Maiti D. Chem. Sci. 2020; 11: 10887
• 4d Mingo MM, Rodríguez N, Arryás RG, Carretero JC. Org. Chem. Front. 2021; 8: 4914
• 4e Ni S.-F, Huang G, Chen Y, Wright JS, Li M, Dang L. Coord. Chem. Rev. 2022; 455: 214255
• 4f Li B, Elsaid M, Ge H. Chem 2022; 8: 1254
• 4g Talukdar K, Shah TA, Sarkar T, Roy S, Maharana PK, Punniyamurthy T. Chem. Commun. 2021; 57: 13221

For DG-aided β-C–H functionalization of carboxylic acids, see:
• 5a Shabashov D, Daugulis O. J. Am. Chem. Soc. 2010; 132: 3965
• 5b Aihara Y, Chatani N. J. Am. Chem. Soc. 2013; 135: 5308
• 5c Wu X, Zhao Y, Ge H. J. Am. Chem. Soc. 2015; 137: 4924
• 5d Kanyiva KS, Kuninobu Y, Kanai M. Org. Lett. 2014; 16: 1968
• 5e Reddy MD, Blanton AN, Watkins EB. J. Org. Chem. 2017; 82: 5080
• 5f Hoshiya N, Takenaka K, Shuto S, Uenishi J. Org. Lett. 2016; 18: 48
• 5g Shang R, Ilies L, Nakamura E. J. Am. Chem. Soc. 2015; 137: 7660
• 5h Cera G, Haven T, Ackermann L. Angew. Chem. Int. Ed. 2016; 55: 1484
• 5i Zhang S.-Y, Li Q, He G, Nack WA, Chen G. J. Am. Chem. Soc. 2015; 137: 531
• 5j Padmavathi R, Sankar R, Gopalakrishnan B, Parella R, Babu SA. Eur. J. Org. Chem. 2015; 3727
• 5k Kaur R, Banga S, Babu SA. Org. Biomol. Chem. 2022; 20: 4391
• 5l Dalal A, Babu SA. Synthesis 2021; 53: 3307
• 5m Parella R, Babu SA. J. Org. Chem. 2015; 80: 12379
• 5n Hao X.-Q, Du C, Zhu X, Li P.-X, Zhang J.-H, Niu J.-L, Song M.-P. Org. Lett. 2016; 18: 3610
• 5o Reddy C, Bisht N, Parella R, Babu SA. J. Org. Chem. 2016; 81: 12143

For DG-aided γ-C(sp²)–H functionalization of amines, see:
• 6a Zeng W, Nukeyeva M, Wang Q, Jiang C. Org. Biomol. Chem. 2018; 16: 598
• 6b Zhao Y, Chen G. Org. Lett. 2011; 13: 4850
• 6c Aggarwal Y, Padmavathi R, Singh P, Babu SA. Asian J. Org. Chem. 2022; 11: e202200327
• 6d Bisht N, Singh P, Babu SA. Synthesis 2022; 54: 4059
• 6e Singh P, Dalal A, Babu SA. Asian J. Org. Chem. 2019; 8: 877
• 6f Rej S, Chatani N. ACS Catal. 2018; 8: 6699
• 6g Bolsakova J, Lukasevics L, Grigorjeva L. J. Org. Chem. 2020; 85: 4482
• 6h Landge VG, Parveen A, Nandakumar A, Balaraman E. Chem. Commun. 2018; 54: 7483
• 6i de Leon DA.-P, Sánchez-Chávez AC, Polindara-García LA. J. Org. Chem. 2019; 84: 12809
• 6j Parella R, Babu SA. J. Org. Chem. 2017; 82: 6550
• 6k Pasunooti KK, Banerjee B, Yap T, Jiang Y, Liu C.-F. Org. Lett. 2015; 17: 6094
• 6l Seki A, Takahashi Y. Tetrahedron Lett. 2021; 74: 153130
• 6m He G, Chen G. Angew. Chem. Int. Ed. 2011; 50: 5192
• 6n Narang U, Singh P, Babu SA. Eur. J. Org. Chem. 2023; 26: e202300463

For DG-aided remote γ-C–H functionalization of carboxylic acids, see:
• 7a Li Y, Zhang P, Liu Y.-J, Yu Z.-X, Shi BF. ACS Catal. 2020; 10: 8212
• 7b Bisht N, Babu SA, Tomar R. Asian J. Org. Chem. 2020; 9: 1225
• 7c Bisht N, Babu SA. Tetrahedron 2016; 72: 5886
• 7d Liu Y, Huang B, Cao X, Wan J.-P. ChemCatChem 2016; 8: 1470
• 7e Liu M, Yang P, Karunananda MK, Wang Y, Liu P, Engle KM. J. Am. Chem. Soc. 2018; 140: 5805
• 7f Liu M, Dutta A, Jeganmohan M. J. Org. Chem. 2022; 87: 13154

For DG-aided remote δ-C(sp²)–H functionalization of carboxylic acids, see:
• 8a Guan M, Pang Y, Zhang J, Zhao Y. Chem. Commun. 2016; 52: 7043
• 8b Li G, Li P, Zhang J, Shi D.-Q, Zhao Y. Org. Chem. Front. 2017; 4: 1931
• 8c Padmavathi R, Babu SA. Asian J. Org. Chem. 2019; 8: 899
• 8d Tomar R, Kumar A, Dalal A, Bhattacharya D, Singh P, Babu SA. Asian J. Org. Chem. 2022; 11: e202200311

For intermolecular δ-C(sp²)–H functionalization of simple phenethylamines, see:
• 9a Nadres ET, Santos GI. F, Shabashov D, Daugulis O. J. Org. Chem. 2013; 78: 9689
• 9b Chen C, Guan M, Zhang J, Wen Z, Zhao Y. Org. Lett. 2015; 17: 3646
• 9c Liu P, Han J, Wang Q, Huang Z, Shi D, Zeng R, Zhao YS. RSC Adv. 2015; 5: 60646
• 9d Ye X, Shi X. Org. Lett. 2014; 16: 4448
• 9e Han J, Wang N, Huang Z.-B, Zhao Y, Shi D.-Q. Org. Biomol. Chem. 2017; 15: 5112
• 9f Dai C, Huang Z.-B, Liu L, Han Y, Shi D.-Q, Zhao Y. Eur. J. Org. Chem. 2020; 826
• 9g Martínez AM, Echavarren J, Alonso I, Rodríguez N, Arryás RG, Carretero JC. Chem. Sci. 2015; 6: 5802
• 9h Li S, Ji H, Cai L, Li G. Chem. Sci. 2015; 6: 5595
• 9i Guan M, Chen C, Zhang J, Zeng R, Zhao Y. Chem. Commun. 2015; 51: 12103
• 9j Ye X, He Z, Ahmed T, Weise K, Akhmedov NG, Petersen JL, Shi X. Chem. Sci. 2013; 4: 3712
• 9k Rajkumar V, Naveen Babu SA. ChemistrySelect 2016; 1: 1207
• 9l Barluenga J, Álvarez-Gutierrez JM, Ballesteros A, González JM. Angew. Chem. Int. Ed. 2007; 46: 12181

For intramolecular δ-C(sp²)–H amination of phenethylamines, see:
• 10a Wang C, Chen C, Zhang J, Han J, Wang Q, Guo K, Liu P, Guan M, Yao Y, Zhao Y. Angew. Chem. Int. Ed. 2014; 53: 9884
• 10b Takamatsu K, Hirano K, Satoh T, Miura M. J. Org. Chem. 2015; 80: 3242
• 10c Nadres ET, Daugulis O. J. Am. Chem. Soc. 2012; 134: 7
• 10d He G, Zhao Y, Zhang S, Lu C, Chen G. J. Am. Chem. Soc. 2012; 134: 3
• 11 For intramolecular δ-C(sp²)–H carbonylative cyclization of phenethylamine, see: Zhang L, Wang C, Han J, Huang Z.-B, Zhao Y. J. Org. Chem. 2016; 81: 5256

For δ-C(sp²)–H alkenylation of phenylalanines, see:
• 12a Bai Z, Cai C, Yu Z, Wang H. Angew. Chem. Int. Ed. 2018; 27: 13912
• 12b Zheng Y, Song W. Org. Lett. 2019; 21: 3257
• 12c Terrey MJ, Peery CC, Cross WB. Org. Lett. 2019; 21: 104
• 12d Cai C, Wang F, Xiao X, Sheng W, Liu S, Chen J, Zheng J, Xie R, Bai Z, Wang H. Chem. Commun. 2022; 58: 4861
• 12e García-Rubia A, Laga E, Cativiela C, Urriolabeitia EP, Gómez-Arrayás R, Carretero JC. J. Org. Chem. 2015; 80: 3321
• 12f Zhao F, Jia X, Zhao J, Fei C, Liu L, Liu G, Wang D, Chen F. RSC Adv. 2017; 7: 25031
• 12g Ge Y, Chen X, Dong Y, Wang H.-N, Li Y, Chen G. Org. Biomol. Chem. 2021; 19: 7141

For δ-C(sp²)–H functionalization of phenylalanines/tyrosines, see:
• 13a Zhang S.-Y, He G, Nack WA, Zhao Y, Li Q, Chen G. J. Am. Chem. Soc. 2013; 135: 2124
• 13b Segundo MS, Correa A. Chem. Sci. 2019; 10: 8872
• 13c Li J.-J, Mei T.-S, Yu J.-Q. Angew. Chem. Int. Ed. 2008; 120: 6552
• 13d Wang X, Niu S, Xu L, Zhang C, Meng L, Zhang X, Ma D. Org. Lett. 2017; 19: 246
• 13e Zhang L.-S, Chen G, Wang X, Guo Q.-Y, Zhang X.-S, Pan F, Chen K, Shi Z.-J. Angew. Chem. Int. Ed. 2014; 53: 3899
• 13f Andrade-Sampedro P, Matxain JM, Correa A. Chem. Eur. J. 2021; 27: 5782
• 13g Singh P, Babu SA. Eur. J. Org. Chem. 2023; 26: e202300440

For intramolecular δ-C(sp²)–H amination of phenylalanines, see:
• 14a Yang M, Jiang X, Shi Z.-J. Org. Chem. Front. 2015; 2: 51
• 14b Zheng Y, Song W, Zhu Y, Wei B, Xuan L. Org. Biomol. Chem. 2018; 16: 2402
• 14c He Y.-P, Zhang C, Fan M, Wu Z, Ma D. Org. Lett. 2015; 17: 496
• 14d Vickers CJ, Mei T.-S, Yu J.-Q. Org. Lett. 2010; 12: 2511
• 14e Mei T.-S, Leow D, Xiao H, Laforteza BN, Yu J.-Q. Org. Lett. 2013; 15: 3058
• 14f Han B, Li B, Qi L, Yang P, He G, Chen G. Org. Lett. 2020; 22: 6879
• 15 For intramolecular δ-C(sp²)–H carbonylative cyclization of phenylalanine, see: Lukasevics L, Cizikovs A, Grigorjeva L. Org. Lett. 2021; 23: 2748
• 16 For an available example of picolinamide-DG-aided remote δ-C(sp²)–H functionalization of phenylalaninol, see: He G, Lu C, Zhao Y, Nack WA, Chen G. Org. Lett. 2012; 14: 2944

For available examples of remote δ-C(sp²)–H carbonylation of phenylalaninol, see:
• 17a López B, Rodriguez A, Santos D, Albert J, Ariza X, Garcia J, Granell J. Chem. Commun. 2011; 47: 1054
• 17b Albert J, Ariza X, Calvet T, Font-Bardia M, Garcia J, Granell J, Lamela A, Lopez B, Martinez M, Ortega L, Rodriguez A, Santos D. Organometallics 2013; 32: 649
• 17c Taneda H, Inamoto K, Kondo Y. Org. Lett. 2016; 18: 2712

For DG-aided remote δ-C(sp³)–H functionalization of aliphatic amines and amino acids, see:
• 18a Zhan B.-B, Li Y, Xu J.-W, Nie X.-L, Fan J, Jin L, Shi B.-F. Angew. Chem. Int. Ed. 2018; 57: 5858
• 18b Martínez-Mingo M, García-Viada A, Alonso I, Rodríguez N, Arryás RG, Carretero JC. ACS Catal. 2021; 11: 5310
• 18c Guin S, Dolui P, Zhang X, Paul S, Singh VK, Pradhan S, Chandrashekar HB, Anjana SS, Paton RS, Maiti D. Angew. Chem. Int. Ed. 2019; 58: 5633
• 18d Xu J.-W, Zhang Z.-Z, Rao W.-H, Shi B.-F. J. Am. Chem. Soc. 2016; 138: 10750
• 18e Cui W, Chen S, Wu J.-Q, Zhao X, Hu W, Wang H. Org. Lett. 2014; 16: 4288

For remote δ-C–H functionalization of amines using native/transient DGs, see:
• 19a Chandrashekar HB, Dolui P, Li B, Mandal A, Liu H, Guin S, Ge H, Maiti D. Angew. Chem. Int. Ed. 2021; 60: 18194
• 19b Lin H, Pan X, Barsamian AI, Kamenecka TM, Bannister TD. ACS Catal. 2019; 9: 4887
• 19c Chen Y.-Q, Wang Z, Wu Y, Wisniewski SR, Qiao JX, Ewing WR, Eastgate MD, Yu J.-Q. J. Am. Chem. Soc. 2018; 140: 17884

For DG-aided remote ε-C(sp²)–H functionalization of amine substrates, see:
• 20a Naveen Rajkumar V, Babu SA, Gopalakrishnan B. J. Org. Chem. 2016; 81: 12197
• 20b Nack WA, He G, Zhang S.-Y, Lu C, Chen G. Org. Lett. 2013; 15: 3440
• 20c See ref. 10a.

For selected papers dealing with applications of phenylalaninol derivatives, see:
• 21a Meyers AI, Brengel GP. Chem. Commun. 1997; 1
• 21b Lee C.-J, Kim TH, Kim JN, Lee U. Tetrahedron: Asymmetry 2002; 13: 9
• 21c Liu X, Hu L, Jiang L, Jia J, Zhang D, Chen X. Eur. J. Org. Chem. 2015; 2291
• 21d Amat M, Santos MM. M, Bassas O, Llor N, Escolano C, Gómez-Esqué A, Molins E, Allin SM, McKee V, Bosch J. J. Org. Chem. 2007; 72: 5193
• 21e Meissner Z, Chrzanowska M. Tetrahedron: Asymmetry 2015; 26: 225
• 21f Mao P, Yang L, Xiao Y, Yuan J, Mai W, Gao J, Zhang X. Chin. J. Org. Chem. 2019; 39: 443
• 21g Ferrer-Gago FJ, Koh LQ, Lane DP. Chem. Eur. J. 2020; 26: 379
• 21h Jia J, Chen R, Liu H, Li X, Jia Y, Chen X. Org. Biomol. Chem. 2016; 14: 7334
• 21i Corrado ML, Knaus T, Schwaneberg U, Mutti FG. Org. Process Res. Dev. 2022; 26: 2085

For selected papers dealing with bioactive phenylalaninol derivatives, see:
• 22a Hashizume H, Miyamae T, Morikawa T, Hagiwara M. Chem. Pharm. Bull. 1992; 40: 3113
• 22b Hodge CN, Aldrich PE, Bacheler LT, Chang C.-H, Eyermann CJ, Garber S, Grubb M, Jackson DA, Jadhav PK, Korant B, Lam PY. S, Maurin MB, Meek JL, Otto MJ, Rayner MR, Reid C, Sharpe TR, Shum L, Winslow DL, Erickson-Viitanen S. Chem. Biol. 1996; 3: 301
• 22c Çiçek İ, Tunç T, Ogutcu H, Adurrahmanoglu S, Günel A, Damirel N. ChemistrySelect 2020; 5: 4650
• 22d Scholz D, Billich A, Charpiot B, Ettmayer P, Lehr P, Rosenwirth B, Schreiner E, Gstach H. J. Med. Chem. 1994; 37: 3079
• 22e Ankersen M, Johansen NL, Madsen K, Hansen BS, Raun K, Nielsen KK, Thøgersen H, Hansen TK, Peschke B, Lau J, Lundt BF, Andersen PH. J. Med. Chem. 1998; 41: 3699

For selected papers dealing with bioactive Matijin–Su aurantiamide derivatives comprising of phenylalaninol motifs, see:
• 23a Isshiki K, Asai Y, Tanaka S, Nishio M, Uchida T, Okuda T, Komatsubara S, Sakurai N. Biosci., Biotechnol., Biochem. 2001; 65: 1195
• 23b Yang Y, Zhang L.-h, Yang B.-x, Tian J.-k, Zhang L. J. Cell. Mol. Med. 2015; 19: 1055
• 23c Xu B, Wang N, Pan W, Qiu J, Cao P, Zhu M, Feng Y, Liang G. Bioorg. Chem. 2014; 56: 34
• 23d Jia J.-M, Tao H.-H, Feng B.-M. Chem. Pharm. Bull. 2009; 57: 99
• 23e Qiu J, Xu B, Huang Z, Pan W, Cao P, Liu C, Hao X, Song B, Liang G. Bioorg. Med. Chem. 2011; 19: 5352
• 23f Xu B, Huang Z, Liu C, Cai Z, Pan W, Cao P, Hao X, Liang G. Bioorg. Med. Chem. 2009; 17: 3118
• 23g Hu Z.-X, Zhang Y.-G, An Q, Xu B.-X, Pan W.-D, Cao P.-X, Liu C.-X, Huang Z.-M, Xia W, Qiu J.-Y, Liang G.-Y. Tetrahedron 2014; 70: 9592
• 23h Yen C.-T, Hwang T.-L, Hwang Y, Wu Y.-C, Hsieh P.-W. Eur. J. Med. Chem. 2009; 44: 1933
• 23i Yen C.-T, Wu C.-C, Lee J.-C, Chen S.-L, Morris-Natschke SL, Hsieh P.-W, Wu Y.-C. Eur. J. Med. Chem. 2010; 45: 2494
• 23j Xu G, Liu Q, Yuan J, Hu Z, Ma F, Liang G, Xu B. Chin. J. Org. Chem. 2016; 36: 1617
• 23k Yang Y, Dai J.-H, Shi C.-Y, Tao L, He S.-L, Tian Y, Sheng J. Mater. Express 2020; 10: 2056
• 23l Mastromarino M, Kirpotina LN, Schepetkin IA, Quinn MT, Lacivita E, Leopoldo M. Med. Chem. Commun. 2019; 10: 2078
• 24 O’Donovan DH, Fusco CD, Spring DR. Tetrahedron Lett. 2016; 57: 2962
• 25 CCDC 2234266 [(RS)-6g] contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures

For selected reviews dealing with biaryls, see:
• 26a Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6722
• 26b de Meijere A, Bräse S, Oestreich M. Metal-Catalyzed Cross-Coupling Reactions and More. Wiley-VCH; Weinheim: 2014
• 26c Feliu L, Planas M. Int. J. Pept. Res. Ther. 2005; 11: 53
• 26d Willemse T, Schepens W, van Vlijmen HW, Maes BU. W, Ballet S. Catalysts 2017; 7: 74
• 27a Ameen D, Snape TJ. Med. Chem. Commun. 2013; 4: 893
• 27b Nair V, Thomas S, Mathew SC, Abhlash KG. Tetrahedron 2006; 62: 6731
• 28 There can be two scenarios with regard to the functionalization of δ-C–H bonds in substrates. In the first case, a substrate that has no γ-C–H bond but has a δ-C–H bond and is subjected to δ-C–H functionalization. In the second case, a substrate that has a γ-C–H bond and a δ-C–H bond and is subjected to regioselective δ-C–H functionalization. In general, both scenarios comprising of functionalization of δ-C–H bonds are challenging. Nonetheless, the second case comprising selective functionalization of the δ-C–H bond in a substrate which also has a γ-C–H bond is an arduous task. The current work deals with the functionalization of the δ-C–H bond in a substrate which does not possess a γ-C–H bond.
• 29 For selected references dealing with functionalization of a δ-C–H bond in a substrate which does not possess a γ-C–H bond, see refs. 6a, 9–17, and 19a.
• 30 For a selected reference dealing with selective functionalization of the δ-C–H bond in a substrate that also has a γ-C–H bond, see ref. 18a.