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. 2017 Jul 21;2(7):3806-3815.
doi: 10.1021/acsomega.7b00717. eCollection 2017 Jul 31.

Palladium-Catalyzed Decarboxylative Ortho-Acylation of Tertiary Benzamides with Arylglyoxylic Acids

Joydev K Laha  1 , Ketul V Patel  1 , Sheetal Sharma  1
Affiliations

Palladium-Catalyzed Decarboxylative Ortho-Acylation of Tertiary Benzamides with Arylglyoxylic Acids

Joydev K Laha et al. ACS Omega. .

Abstract

A palladium-catalyzed ortho-acylation of tertiary benzamides using arylglyoxylic acids has been described. Unlike the palladium insertion reported to occur in the distorted N-C(O) amide bond of tertiary benzamides, the current study unveils ortho C-H palladation in acylic or cyclic N,N-dialkylbenzamides affording ortho-acylated tertiary benzamides in good to excellent yields. Our experimental study on the mechanism provides information on the tendency of the amide nitrogen toward weak coordination with palladium as opposed to oxygen. However, density functional theory calculations suggest coordination of amide oxygen to palladium, which makes the mechanism especially interesting. A Pd(II)/Pd(III) catalytic cycle and nucleophilic attack by the acyl radical rather than arylglyoxylate anion are supported by mechanistic studies.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Use of Tertiary Benzamides in Acylation Chemistry
Scheme 2
Scheme 2. Scope of Arylglyoxylic Acids
Scheme 3
Scheme 3. Scope of Tertiary Benzamides
Scheme 4
Scheme 4. Control Experiments
Figure 1
Figure 1
DFT Calculation of Palladium Intermediate I and Intermediate II.
Scheme 5
Scheme 5. Plausible Mechanism
See this image and copyright information in PMC

References

    1. Kettner C. A.; Jagannathan S.; Forsyth T. P. PCT Int. Appl. 2001002424, 11 Jan 2001;
    2. Bae I. H.; Choi J. K.; Chough C.; Keum S. J.; Kim S.; Jang S. K.; Kim B. M. ACS Med. Chem. Lett. 2014, 5, 255–258. 10.1021/ml4003293. - DOI - PMC - PubMed
    3. Boatman D. P.; Adams J. W.; Moody J. V.; Babych E. D.; Schrader T. O. PCT Int. Appl. 2005063745, 14 Jul 2005;
    4. Seno K.; Okuno T.; Nishi K.; Murakami Y.; Yamada K.; Nakamoto S.; Ono T. Bioorg. Med. Chem. Lett. 2001, 11, 587–590. 10.1016/S0960-894X(01)00003-8. - DOI - PubMed
    1. Laufer R. S.; Dmitrienko G. I. J. Am. Chem. Soc. 2002, 124, 1854–1855. 10.1021/ja0167809. - DOI - PubMed
    2. Horton D. A.; Bourne G. T.; Smythe M. L. Chem. Rev. 2003, 103, 893–930. 10.1021/cr020033s. - DOI - PubMed
    3. Khanolkar A. D.; Lu D.; Ibrahim M.; Duclos R. I. Jr.; Thakur G. A.; Malan T. P. Jr.; Porreca F.; Veerappan V.; Tian X.; George C.; Parrish D. A.; Papahatjis D. P.; Makriyannis A. J. Med. Chem. 2007, 50, 6493–6500. 10.1021/jm070441u. - DOI - PubMed
    4. Khanolkar A. D.; Lu D.; Ibrahim M.; Duclos R. I. Jr.; Thakur G. A.; Malan T. P. Jr.; Porreca F.; Veerappan V.; Tian X.; George C.; Parrish D. A.; Papahatjis D. P.; Makriyannis A. J. Med. Chem. 2007, 50, 6493–6500. 10.1021/jm070441u. - DOI - PubMed
    5. James L. I.; Korboukh V. K.; Krichevsky L.; Baughman B. M.; Herold J. M.; Norris J. L.; Jin J.; Kireev D. B.; Janzen W. P.; Arrowsmith C. H.; Frye S. V. J. Med. Chem. 2013, 56, 7358–7371. 10.1021/jm400919p. - DOI - PMC - PubMed
    1. Jørgensen K. B.; Rantanen T.; Dörfler T.; Snieckus V. J. Org. Chem. 2015, 80, 9410–9424. 10.1021/acs.joc.5b01300. - DOI - PubMed
    2. Nüllen M. P.; Göttlich R. Synthesis 2011, 2011, 1249–1254. 10.1055/s-0030-1259968. - DOI
    3. Gosselin F.; Lau S.; Nadeau C.; Trinh T.; O’Shea P. D.; Davies I. W. J. Org. Chem. 2009, 74, 7790–7797. 10.1021/jo901798d. - DOI - PubMed
    4. Naka H.; Uchiyama M.; Matsumoto Y.; Wheatley A. E. H.; McPartlin M.; Morey J. V.; Kondo Y. J. Am. Chem. Soc. 2007, 129, 1921–1930. 10.1021/ja064601n. - DOI - PubMed
    5. Wunderlich S. H.; Knochel P. Chem. - Eur. J. 2010, 16, 3304–3307. 10.1002/chem.200903157. - DOI - PubMed
    6. Snieckus V. Chem. Rev. 1990, 90, 879–933. 10.1021/cr00104a001. - DOI
    7. Whisler M. C.; MacNeil S.; Snieckus V.; Beak P. Angew. Chem., Int. Ed. 2004, 43, 2206–2225. 10.1002/anie.200300590. - DOI - PubMed
    8. Board J. C.; Cosman J. L.; Rantanen T.; Singh S. P.; Snieckus V. Platinum Met. Rev. 2013, 57, 234–258. 10.1595/147106713X672311. - DOI
    1. Fang P.; Li M.; Ge H. J. Am. Chem. Soc. 2010, 132, 11898–11899. 10.1021/ja105245f. - DOI - PubMed
    2. Li M.; Ge H. Org. Lett. 2010, 12, 3464–3467. 10.1021/ol1012857. - DOI - PubMed
    3. Li C.; Li W. P.; Zhou W.; et al. Chem. - Eur. J. 2011, 17, 10208–10212. 10.1002/chem.201101192. - DOI - PubMed
    4. Wang H.; Guo L. N.; Duan X. H. Org. Lett. 2012, 14, 4358–4361. 10.1021/ol301801r. - DOI - PubMed
    5. Zhou W.; Li H.; Wang L. Org. Lett. 2012, 14, 4594–4597. 10.1021/ol3020557. - DOI - PubMed
    6. Miao J.; Ge H. Org. Lett. 2013, 15, 2930–2933. 10.1021/ol400919u. - DOI - PubMed
    7. Li H.; Li P.; Zhao Q.; Wang L. Chem. Commun. 2013, 49, 9170–9172. 10.1039/c3cc45492d. - DOI - PubMed
    8. Park J.; Kim M.; Sharma S.; Park E.; Kim A.; Lee S. H.; Kwak J. H.; Jung Y. H.; Kim I. S. Chem. Commun. 2013, 49, 1654–1656. 10.1039/c3cc38764j. - DOI - PubMed
    9. Vanjari R.; Nand Singh K. Chem. Soc. Rev. 2015, 44, 8062–8096. 10.1039/C5CS00003C. - DOI - PubMed
    10. Wu Y.; Sun L.; Chen Y.; Zhou Q.; Huang J. W.; Miao H.; Luo H. B. J. Org. Chem. 2016, 81, 1244–1250. 10.1021/acs.joc.5b02535. - DOI - PubMed
    11. Lee P. Y.; Liang P.; Yu W. Y. Org. Lett. 2017, 19, 2082–2085. 10.1021/acs.orglett.7b00677. - DOI - PubMed
    1. Gooßen L. J.; Rudolphi F.; Oppel C.; Rodrguez N. Angew. Chem. 2008, 120, 3085–5088. 10.1002/ange.200705127. - DOI - PubMed
    2. Angew. Chem., Int. Ed. 2008, 47, 3043 - 3045.10.1002/anie.200705127 - PubMed
    3. Liu J.; Liu Q.; Yi H.; Qin C.; Bai R.; Qi X.; Lan Y.; Lei A. Angew. Chem., Int. Ed. 2014, 53, 502–506. 10.1002/anie.201308614. - DOI - PubMed