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. 2021 May 12;143(18):6817-6822.
doi: 10.1021/jacs.1c03257. Epub 2021 Apr 28.

Azine Activation via Silylium Catalysis

Carla Obradors  1 , Benjamin List  1
Affiliations

Azine Activation via Silylium Catalysis

Carla Obradors et al. J Am Chem Soc. .

Abstract

Practical, efficient, and general methods for the diversification of N-heterocycles have been a recurrent goal in chemical synthesis due to the ubiquitous influence of these motifs within bioactive frameworks. Here, we describe a direct, catalytic, and selective functionalization of azines via silylium activation. Our catalyst design enables mild conditions and a remarkable functional group tolerance in a one-pot setup.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Traditional approach for the functionalization of N-heterocycles with nucleophiles. (B) Silylium-based Lewis acid catalysis. (C) This work: direct, efficient and general diversification of azines by means of silylium catalyst design.
Figure 2
Figure 2
(A) Proof of concept and effects of the pyridine substitution. (B) Assessment of the catalyst acidity (pKa’s determined in MeCN). (C) Developing highly acidic and chemoselective PADI catalysts. (D) Practical and direct oxidation toward the functionalized product.
Figure 3
Figure 3
Application to a vast variety of N-heterocycles (isolated yields after in situ oxidation and addition step determined by 1H NMR in brackets). General conditions: reaction of 1 equiv of substrate with 2 equiv of SKA in MeCN using 1 mol % of PhPADI at 25 °C followed by DDQ (see SI for all the details). aReaction at 0 °C. bReaction at −20 °C. cUse of CF3PADI. dNeat conditions. eAddition before oxidation after 7 days. fOxidation with PIFA. gReaction in DCM. hOxidation with DIAD. iOxidation with KMnO4. jOxidation with Pd/C 10 mol %.
Figure 4
Figure 4
(A) Mechanistic proposal. (B) Synthesis of dihydropyridine derivatives.
See this image and copyright information in PMC

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