Synthetic Organic Reactions Mediated by Sodium Hydride

Abstract

In synthetic organic chemistry, sodium hydride (NaH) has been utilized almost exclusively as a routine Brønsted base, while NaH has not been considered to work as a hydride donor. Recently, our group has serendipitously found that NaH can function as a unique hydride donor by its solvothermal treatment with sodium iodide (NaI) or lithium iodide (LiI) in tetrahydrofuran (THF) as a solvent. This discovery led to the development of unprecedented reductive molecular transformations such as hydrodecyanation of α quaternary benzyl cyanides, controlled reduction of amides into aldehydes, dearylation of arylphopsphine oxides, and hydrodehalogenation of haloarenes. Moreover, this concise protocol allows for the use of NaH as enhanced Lewis acid and Brønsted base, enabling directed aromatic C H sodiation, nucleophilic amination of methoxy arenes, and C2 amination of pyridines (the Chichibabin amination). Scheme 2. Molecular alkali metal hydrides.

Molecular Main Group Metal Hydrides

“…There is long-standing interest in the use of Group 1 hydrides as simple reducing agents. ,− Their intractability, however, militates against their more widespread uptake as reagents of broad utility. Despite such issues, the last two decades have seen significant progress in the use of Group 1 species in homogeneous catalysis and a number of systems, which invoke molecular hydride intermediates have also been described. − …”

Partial reductions of carboxylic acids and their derivatives to aldehydes

“…Sodium hydride (NaH), usually used as a strong base, is surprisingly capable of reducing amides to aldehydes (Scheme 31). As reported by Chiba and coworkers, [86][87][88] treating structurally diverse N,N-dimethyl amides 116 with 3 equiv. of NaH and 1 equiv.…”

Controlled Reduction of Nitriles by Sodium Hydride and Zinc Chloride

“…Our group recently disclosed a simple and concise protocol to utilize sodium hydride (NaH) as an unprecedented hydride donor to organic polar -electrophiles in the presence of sodium or lithium iodide (NaI or LiI). 9,10 For example, hydrodecyanation of -quaternary benzyl cyanides could be performed under the NaH-LiI system (Scheme 1B). 10c,g The process is triggered by hydride reduction of the cyano group by activated NaH to afford an iminyl sodium intermediate, that subsequently undergoes concerted C-C bond cleavage and 1,2-proton shift to deliver an alkane product with elimination of a cyanide ion.…”