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. 2008 Mar 19;130(11):3645-51.
doi: 10.1021/ja7104784. Epub 2008 Feb 27.

Synthesis of dihydropyridines and pyridines from imines and alkynes via C-H activation

Denise A Colby  1 , Robert G Bergman, Jonathan A Ellman
Affiliations

Synthesis of dihydropyridines and pyridines from imines and alkynes via C-H activation

Denise A Colby et al. J Am Chem Soc. .

Abstract

A convenient one-pot C-H alkenylation/electrocyclization/aromatization sequence has been developed for the synthesis of highly substituted pyridine derivatives from alkynes and alpha,beta-unsaturated N-benzyl aldimines and ketimines that proceeds through dihydropyridine intermediates. A new class of ligands for C-H activation was developed, providing broader scope for the alkenylation step than could be achieved with previously reported ligands. Substantial information was obtained about the mechanism of the reaction. This included the isolation of a C-H activated complex and its structure determination by X-ray analysis; in addition, kinetic simulations using the Copasi software were employed to determine rate constants for this transformation, implicating facile C-H oxidative addition and slow reductive elimination steps.

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Figures

Figure 1
Figure 1
Ligands for C-H activation.
Figure 2
Figure 2
X-ray crystal structure (ORTEP diagram) of 17 with thermal ellipsoids drawn at the 50% probability level. Hydrogen atoms distant from the metal center have been omitted for clarity.
Figure 3
Figure 3
Experimental and simulated timecourses for the reaction of 1 with 5 equivalents of 3-hexyne using 2.5 mol% [RhCl(coe)2]2 and 5 mol% 6b at 25 ± 0.5 °C. A: experimental timecourse for Scheme 1. For plots B – D, the experimental and simulated data for Scheme 2 are overlaid, with experimental data designated using dashed lines and the corresponding simulated data using solid lines. Starting concentrations of 1: B; 0.10 M, C; 0.025 M, D; 0.50 M. The error in the values for the experimental data were <10%. See the Supporting Information for further details. Simulated data were obtained using the appropriate starting concentrations of reactants A, B and D, and using the following rate constants: k1 = 250 M−1h−1; k2 = 50 M−1h−1; k3 = 8 h−1; k4 = 0.6 h−1; k5 = 0.03 h−1.
Scheme 1
Scheme 1
Proposed Mechanistic Pathway
Scheme 2
Scheme 2
Simplified system for modeling in Copasi and the values obtained for k1 – k5.
See this image and copyright information in PMC

References

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