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. 2010 Mar 24;132(11):3965-72.
doi: 10.1021/ja910900p.

Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds

Dmitry Shabashov  1 , Olafs Daugulis
Affiliations

Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds

Dmitry Shabashov et al. J Am Chem Soc. .

Abstract

We have developed a method for auxiliary-directed, palladium-catalyzed beta-arylation and alkylation of sp(3) and sp(2) C-H bonds in carboxylic acid derivatives. The method employs a carboxylic acid 2-methylthioaniline- or 8-aminoquinoline amide substrate, aryl or alkyl iodide coupling partner, palladium acetate catalyst, and an inorganic base. By employing 2-methylthioaniline auxiliary, selective monoarylation of primary sp(3) C-H bonds can be achieved. If arylation of secondary sp(3) C-H bonds is desired, 8-aminoquinoline auxiliary may be used. For alkylation of sp(3) and sp(2) C-H bonds, 8-aminoquinoline auxiliary affords the best results. Some functional group tolerance is observed and amino- and hydroxy-acid derivatives can be functionalized. Preliminary mechanistic studies have been performed. A palladacycle intermediate has been isolated, characterized by X-ray crystallography, and its reactions have been studied.

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Figures

Scheme 1
Scheme 1
Auxiliaries for sp3 C-H Bond Arylation
Scheme 2
Scheme 2
Synthesis of Nitrile and Isonitrile Complexes
Figure 1
Figure 1
ORTEP view of 13. Selected interatomic distances (Å) and angles (deg): Pd(1)-N(2) = 1.969(4), Pd(1)-C(12) = 2.012(6), Pd(1)-N(3) = 2.013(5), Pd(1)-N(1) = 2.124(5), N(2)-Pd(1)-C(12)-C(11) = 18.3(5), N(2)-Pd(1)-C(12) = 83.3(2).
Figure 2
Figure 2
ORTEP view of 16. Selected interatomic distances (Å) and angles (deg): Pd-N(2) = 1.981(3), Pd-C(15) = 1.993(4), Pd-C(12) = 2.072(3), Pd-N(1) = 2.171(3), Pd-Br(1) = 2.4411(5), Pd-Br(2) = 2.4690(5), N(1)- Pd-N(2)-C(8) = 2.0(2), Pd-N(2)-C(10)-C(11) = -5.5(4).
Scheme 3
Scheme 3
H/D Exchange Studies.
Scheme 4
Scheme 4
Arylation and Alkylation of Palladated Intermediates
Scheme 5
Scheme 5
Reaction Mechanism
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