Borane-Catalyzed Reduction of Pyridines via a Hydroboration/Hydrogenation Cascade

Abstract

We have developed a method for a B(C 6 F 5 ) 3 -catalyzed hydroboration/hydrogenation cascade reduction of pyridines. The method was particularly effective for 2,3-disubstituted pyridines, which generated piperidines in high yields with high cis selectivity. Mechanistic studies indicated that the pyridine substrates and the piperidine products sequentially acted as bases in cooperation with B(C 6 F 5 ) 3 to split H 2 . The broad functional group tolerance of the method allowed its use for the synthesis of some biologically active molecules.

Direct synthesis of sila-benzoazoles through hydrosilylation and rearrangement cascade reaction of benzoazoles and silanes

“…7b and 7c and DFT results 11,44 . The concerted activation of the Si-H bond in Ph 2 SiH 2 by B(C 6 F 5 ) 3 and 1a is similar to that in hydrosilylation/hydroboration reactions catalyzed by B(C 6 F 5 ) 3 reported previously [45][46][47][48][49][50] .…”

Borane-Catalyzed C3-Alkylation of Pyridines with Imines, Aldehydes, or Ketones as Electrophiles

“…The emergence of frustrated Lewis pair chemistry , in which, because of steric hindrance, the activity of a Lewis acid is not quenched by a coexisting Lewis basehas enabled borane-catalyzed 1,4-hydroboration and 1,4-hydrosilylation of pyridines. , By utilizing the resulting 1,4-dihydropyridines (1,4-DHPs), we recently accomplished pyridine reduction by means of borane-catalyzed cascade reactions − involving 1,4-hydroboration and subsequent transfer hydrogenation (Scheme c). Because 1,4-DHPs are nucleophilic, we hypothesized that C3-selective pyridine functionalization could be achieved via tandem reactions involving borane-catalyzed 1,4-hydroboration, nucleophilic addition of the resulting 1,4-DHPs to external electrophiles, and subsequent oxidative aromatization (Scheme d).…”

“…Although the proposed strategy looks straightforward, several competing reaction pathwaysincluding reduction of the electrophiles by hydroboranes or 1,4-DHPs and cascade reduction − are possible, which may explain why no examples of such reactions with external electrophiles have been reported. Nevertheless, we were encouraged by a report of ruthenium-catalyzed cascade hydrosilylation reactions that generate C3-silylated pyridines and by recently developed interrupted pyridine reduction reactions. , Herein, we report that despite the potential challenges of our proposed strategy, we successfully used it for reactions of pyridines with imine and carbonyl electrophiles, thus forming carbon–carbon bonds with exclusive regioselectivity for C3.…”

Regioselective Rhodium‐Catalyzed 1,2‐Hydroboration of Pyridines and Quinolines Enabled by the Tris(8‐quinolinyl)phosphite Ligand**

“…Examples of magnesium-catalyzed hydroboration of pyridine derivatives, either yielding a mixture of 1,2-and 1,4-DHP compounds, [30,41] or the 1,2-isomer selectively (Figure 1), [31] have also been reported in the literature. 1,4-hydroborated products can be selectively obtained using metal catalysts based on K, [32] Ni (Figure 1), [33] Zn, [22] Ge, [40] Zr, [34] Ru (Fig-ure 1), [35] or Ce [36] compounds, cooperative Cu/Feheterobimetallic [42] or Ni/Al-heterotrimetallic scaffold [43] or Hfbased metal-organic frameworks, [34] organocatalytic protocols involving either organoboranes [44][45][46][47][48] or organophosphanes, [49,50] or even under basic, catalyst-free conditions. [51,52] By contrast, the 1,2-regioselective reduction of N-heteroaromatic compounds is a much more challenging task (Figure 1).…”