Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Nov 20;135(46):17508-13.
doi: 10.1021/ja409014v. Epub 2013 Nov 8.

Ligand-accelerated ortho-C-H alkylation of arylcarboxylic acids using alkyl boron reagents

Peter S Thuy-Boun  1 , Giorgio Villa, Devin Dang, Paul Richardson, Shun Su, Jin-Quan Yu
Affiliations

Ligand-accelerated ortho-C-H alkylation of arylcarboxylic acids using alkyl boron reagents

Peter S Thuy-Boun et al. J Am Chem Soc. .

Abstract

A protocol for the Pd(II)-catalyzed ortho-C-H alkylation of phenylacetic and benzoic acids using alkylboron reagents is disclosed. Monoprotected amino acid ligands (MPAA) were found to significantly promote reactivity. Both potassium alkyltrifluoroborates and alkylboronic acids were compatible coupling partners. The possibility of a radical alkyl transfer to Pd(II) was also investigated.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Ligand Effect: Rate Profile for Conversion of 1a to 3a.
Scheme 1
Scheme 1
Development of C(sp2)–H Alkylation
Scheme 2
Scheme 2
(A) Reaction Inhibition by TEMPO (B) Alkyltrifluoroborate Homocoupling (C) Putative Reaction Pathways
Scheme 3
Scheme 3
Selective C–H Methylation of Biaryl 9a Generates 9b, BMS-98947-055-01. Reaction Conditions: aStd-BQ: 1.5 equiv MeBF3K, Ligand = Boc-Thr(tBu)-OH, 110 °C, 2 h; b3 equiv MeBF3K, Ligand = Boc-Phe-OH, 90 °C, 12 h.
See this image and copyright information in PMC

References

    1. Kobayashi J, Ishibashi M. Chem. Rev. 1993;93:1753–1769.
    2. Newman DJ, Cragg GM. J. Nat. Prod. 2004;67:1216–1238. - PubMed
    3. Cragg DJ, Grothaus PG, Newman D. J. Chem. Rev. 2009;109:3012–3043. - PubMed
    1. McGrath NA, Brichacek M, Njardarson JT. J. Chem. Ed. 2010;87:1348–1349.
    2. Carey JS, Laffan D, Thomson C, Williams MT. Org. Biomol. Chem. 2006;4:2337–2347. - PubMed

    1. For selected reviews, see: Kakiuchi F, Chatani N. Adv. Synth. Catal. 2003;345:1077–1101. Pousen TB, Jorgensen KA. Chem Rev. 2008;108:2903–2915. Chopade PR, Louie J. Adv. Synth. Catal. 2006;348:2307–2327. Jana R, Pathak TP, Sigman MS. Chem. Rev. 2011;111:1417–1492.

    1. Littke AF, Fu GC. Angew. Chem. Int. Ed. 1999;38:2411–2413. - PubMed
    2. Littke AF, Dai C, Fu GC. J. Am. Chem. Soc. 2000;122:4020–4028.
    3. Netherton MR, Dai C, Neuschutz K, Fu GC. J. Am. Chem. Soc. 2001;123:10099. - PubMed
    4. Kirchoff JH, Netherton MR, Hills ID, Fu GC. J. Am. Chem. Soc. 2002;124:13662–13663. - PubMed
    5. Everson DA, Shrestha R, Weix DJ. J. Am. Chem. Soc. 2010;132:920–921. - PubMed
    6. Everson DA, Jones BA, Weix DJ. J. Am. Chem. Soc. 2012;134:6146–6159. - PMC - PubMed

    1. For early examples of catalytic pyridine and oxazoline directed C(sp2)–H alkylation, see: Chen X, Goodhue CE, Yu J-Q. J. Am. Chem. Soc. 2006;128:12634–12635. Chen X, Li J-J, Hao X-S, Goodhue CE, Yu J-Q. J. Am. Chem. Soc. 2006;128:78–79. Shi B-F, Maugel N, Zhang Y-H, Yu J-Q. Angew. Chem. Int. Ed. 2008;47:4882–4886.

Publication types