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. 2020 Sep 29;11(42):11554-11561.
doi: 10.1039/d0sc04808a.

Organoborohydride-catalyzed Chichibabin-type C4-position alkylation of pyridines with alkenes assisted by organoboranes

Ying Wang  1 , Runhan Li  2 , Wei Guan  2 , Yanfei Li  1 , Xiaohong Li  1 , Jianjun Yin  1 , Ge Zhang  1 , Qian Zhang  1 , Tao Xiong  1 , Qian Zhang  1   3
Affiliations

Organoborohydride-catalyzed Chichibabin-type C4-position alkylation of pyridines with alkenes assisted by organoboranes

Ying Wang et al. Chem Sci. .

Abstract

The first NaBEt3H-catalyzed intermolecular Chichibabin-type alkylation of pyridine and its derivatives with alkenes as the latent nucleophiles is presented with the assistance of BEt3, and a series of branched C4-alkylation pyridines, even highly congested all-carbon quaternary center-containing triarylmethanes can be obtained in a regiospecific manner. Therefore, the conventional reliance on high cost and low availability transition metal catalysts, prior formation of N-activated pyridines, organometallic reagents, and extra oxidation operation for the construction of a C-C bond at the C4-position of the pyridines in previous methods are not required. The corresponding mechanism and the key roles of the organoborane were elaborated by the combination of H/D scrambling experiments, 11B NMR studies, intermediate trapping experiments and computational studies. This straightforward and mechanistically distinct organocatalytic technology not only opens a new door for the classical but still far less well-developed Chichibabin-type reaction, but also sets up a new platform for the development of novel C-C bond-forming methods.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Direct C4-position C–C bond-forming of pyridines and Chichibabin-type transformations.
Scheme 2
Scheme 2. Substrate scope of alkenes and pyridines.a,b aReaction conditions for (A) styrenes (0.75 mmol, 1.5 equiv.), pyridines (0.5 mmol), NaBEt3H (0.2 mmol), BEt3 (1.0 mmol) in dry THF (1.0 mL) at 100 °C for 12 hours under a N2 atmosphere; yield was determined by 1H NMR spectroscopy of the crude mixture, using CH2Br2 as the internal standard. bReaction conditions for (B) 1,1-diaryl alkenes (0.75 mmol, 1.5 equiv.), pyridine (0.5 mmol), NaBEt3H (0.15 mmol), BEt3 (1.0 mmol) in dry THF (1.0 mL) at 70 °C for 12 hours under a N2 atmosphere; isolated yields. cUsing NaH instead of NaBEt3H. d24% alkene was recovered. e57% alkene was recovered. fThese reactions were carried out at 140 °C. g50% alkene was recovered.
Scheme 3
Scheme 3. H/D scrambling experiments.
Fig. 1
Fig. 1. Intermediate investigation experiments.
Fig. 2
Fig. 2. Calculated energy profiles of the NaBEt3H-catalyzed alkylation reaction of pyridine with the alkene. (A) Calculated energy profile of pyridine with BEt3. (B) DFT-computed reaction pathway for NaBEt3H-catalysed alkylation of styrene with pyridine. (C) The relative Gibbs energies and structures of different C–B interactions between styrene and 1,1-diphenylethene. (D) DFT-computed reaction pathway for NaBEt3H-catalysed alkylation of diphenylethene with pyridine.
Scheme 4
Scheme 4. Plausible mechanism.
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