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. 2015 Oct 28;1(7):394-9.
doi: 10.1021/acscentsci.5b00312. Epub 2015 Oct 16.

Remote Meta-C-H Activation Using a Pyridine-Based Template: Achieving Site-Selectivity via the Recognition of Distance and Geometry

Ling Chu  1 , Ming Shang  1 , Keita Tanaka  1 , Qinghao Chen  2 , Natalya Pissarnitski  2 , Eric Streckfuss  2 , Jin-Quan Yu  1
Affiliations

Remote Meta-C-H Activation Using a Pyridine-Based Template: Achieving Site-Selectivity via the Recognition of Distance and Geometry

Ling Chu et al. ACS Cent Sci. .

Erratum in

Abstract

The pyridyl group has been extensively employed to direct transition-metal-catalyzed C-H activation reactions in the past half-century. The typical cyclic transition states involved in these cyclometalation processes have only enabled the activation of ortho-C-H bonds. Here, we report that pyridine is adapted to direct meta-C-H activation of benzyl and phenyl ethyl alcohols through engineering the distance and geometry of a directing template. This template takes advantage of a stronger σ-coordinating pyridine to recruit Pd catalysts to the desired site for functionalization. The U-shaped structure accommodates the otherwise highly strained cyclophane-like transition state. This development illustrates the potential of achieving site selectivity in C-H activation via the recognition of distal and geometric relationship between existing functional groups and multiple C-H bonds in organic molecules.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Design of new template for meta-C–H activation. (a) Pyridyl group directs ortho-C–H activation via cyclic intermediate. (b) Pyridyl group directs meta-C–H activation via cyclophane-like intermediate. (c) Structurally related drug molecules (brand names in parentheses). (d) Key features in the newly designed template.
Figure 2
Figure 2
Tuning of pyridine-based template.
Figure 3
Figure 3
Removal of the directing template.
See this image and copyright information in PMC

References

    1. Katsuki T.; Sharpless K. The first practical method for asymmetric epoxidation. J. Am. Chem. Soc. 1980, 102, 5974–5976. 10.1021/ja00538a077. - DOI
    1. Brown J. M. Selectivity and Mechanism in Catalytic Asymmetric Synthesis. Chem. Soc. Rev. 1993, 22, 25–41. 10.1039/cs9932200025. - DOI
    1. Li S.; Zhu S. F.; Xie J. H.; Song S.; Zhang C. M.; Zhou Q. L. Enantioselective hydrogenation of α-aryloxy and α-alkoxy α,β-unsaturated carboxylic acids catalyzed by chiral spiro Iridium/phosphino-oxazoline complexes. J. Am. Chem. Soc. 2010, 132, 1172–1179. 10.1021/ja909810k. - DOI - PubMed
    1. Jun C.; Lee H.; Hong J. Chelation-assisted intermolecular hydroacylation: direct synthesis of ketone from aldehyde and 1-alkene. J. Org. Chem. 1997, 62, 1200–1201. 10.1021/jo961887d. - DOI
    1. Zhang X.; Cao B.; Yu S.; Zhang X. Rhodium-catalyzed asymmetric hydroformylation of N-allylamides: highly enantioselective approach to β2-amino aldehydes. Angew. Chem., Int. Ed. 2010, 49, 4047–4050. 10.1002/anie.201000955. - DOI - PubMed