Pd-catalyzed monoselective ortho -C-H alkylation of N -quinolyl benzamides

Evidence for stereoretentive coupling of secondary alkyl iodides

Shu Yu Zhang, Qiong Li, Gang He, William A. Nack, Gong Chen

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

We report a method for the monoselective alkylation of ortho-C-H bonds of N-quinolyl benzamides with both primary and secondary alkyl halides under palladium catalysis. With promotion by NaHCO3 and (BnO)2PO2H or (PhO)2PO2H, symmetric benzamide substrates can be selectively ortho-alkylated to give either mono- or dialkylated products by simply adjusting the amount of NaHCO3 applied. The use of phosphate notably improves the alkylation yield, although it may not be directly involved in C-H palladation or the subsequent functionalization step. Kinetic isotope effect studies indicate that C-H palladation is not the rate-limiting step. Examination of the reactions of an isolated palladacycle intermediate with both cis- and trans-4-methylcyclohexyl iodides revealed surprising stereoretentive couplings of these alkyl iodides. This evidence strongly suggests that the functionalization of the palladacycle with secondary alkyl iodides proceeds via a rarely precedented concerted oxidative addition pathway.

Original languageEnglish (US)
Pages (from-to)531-539
Number of pages9
JournalJournal of the American Chemical Society
Volume137
Issue number1
DOIs
StatePublished - Jan 14 2015

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Benzamides
Alkylation
Iodides
Palladium
Catalysis
Isotopes
Phosphates
Kinetics
Substrates

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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title = "Pd-catalyzed monoselective ortho -C-H alkylation of N -quinolyl benzamides: Evidence for stereoretentive coupling of secondary alkyl iodides",
abstract = "We report a method for the monoselective alkylation of ortho-C-H bonds of N-quinolyl benzamides with both primary and secondary alkyl halides under palladium catalysis. With promotion by NaHCO3 and (BnO)2PO2H or (PhO)2PO2H, symmetric benzamide substrates can be selectively ortho-alkylated to give either mono- or dialkylated products by simply adjusting the amount of NaHCO3 applied. The use of phosphate notably improves the alkylation yield, although it may not be directly involved in C-H palladation or the subsequent functionalization step. Kinetic isotope effect studies indicate that C-H palladation is not the rate-limiting step. Examination of the reactions of an isolated palladacycle intermediate with both cis- and trans-4-methylcyclohexyl iodides revealed surprising stereoretentive couplings of these alkyl iodides. This evidence strongly suggests that the functionalization of the palladacycle with secondary alkyl iodides proceeds via a rarely precedented concerted oxidative addition pathway.",
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Pd-catalyzed monoselective ortho -C-H alkylation of N -quinolyl benzamides : Evidence for stereoretentive coupling of secondary alkyl iodides. / Zhang, Shu Yu; Li, Qiong; He, Gang; Nack, William A.; Chen, Gong.

In: Journal of the American Chemical Society, Vol. 137, No. 1, 14.01.2015, p. 531-539.

Research output: Contribution to journalArticle

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