Hydride Reduction by a Sodium Hydride–Iodide Composite

Abstract

Sodium hydride (NaH) is widely used as aBrønsted base in chemical synthesis and reacts with various Brønsted acids,whereas it rarely behaves as areducing reagent through delivery of the hydride to polar p electrophiles.T his study presents aseries of reduction reactions of nitriles,amides,and imines as enabled by NaH in the presence of LiI or NaI. This remarkably simple protocol endows NaH with unprecedented and unique hydride-donor chemical reactivity.Hydridereductionofpolarp electrophiles,such as carbonyl compounds,c arbonitriles,a nd imines,i so ne of the most fundamental and important molecular transformations in chemical synthesis.[1] In this context, av ariety of covalent hydrides,s uch as borane,a lane,m etal borohydrides,m etal aluminum hydrides,and silanes,have often been employed as the reagents of choice for stereo-, regio-, and chemoselective hydride-transfer processes.Bycontrast, alkali-metal hydrides have rarely been employed as hydride sources;i nstead, they are used almost exclusively as strong Brønsted bases for deprotonation reactions in chemical synthesis. [2,3] Herein, we report that NaH can act as ahydride donor in reactions with nitriles,a mides,a nd imines when it has been subjected to simple solvothermal treatment with LiI or NaI in THF.O f particular interest is the outcome of hydride reduction reactions of nitriles and amides,w hich deliver the corresponding alkanes (through decyanation) and aldehydes, respectively.During the course of our experiments on the a-methylation of diphenylacetonitrile (1)t op repare tertiary carbonitrile 2a,weinvestigated its reaction with NaH (3 equiv) and MeI (1.2 equiv) in THF (85 8 8Ci nas ealed tube;S cheme 1). Although the desired tertiary nitrile 2a was isolated in 74 % yield, we were surprised to observe the formation of 1,1-diphenylethane (3a)i n2 5% yield as aside product. Assuming that 3a was formed by the decyanation of nitrile 2a,w e expected that this decyanation reaction could be generalized to am ore versatile synthetic strategy

N‐Silylation of Amines Mediated by Et3SiH/KOtBu

“…When the reactions were carried out with NaO t Bu as base, no silylated products were produced, while NaH was found to be effective, although in low‐to‐moderate yields (see Table S1 in Supporting Information file). Interestingly, KH was also ineffective in producing silylated products and this point comes up for comment later in this article …”

“…This may initially seem curious, as commercial KH was not effective in promoting the reactions in the laboratory. However, a strong difference in reactivity between a free KH molecule and the commercial solid aggregate is expected …”

“…Interestingly, KH was also ineffective in producing silylated products and this point comes up for comment later in this article. [33][34][35] The conversion of the amines 1-4 to silyl derivatives as a function of time in the presence of KO t Bu (0.2 equiv. ), was monitored by 1 H-NMR.…”

Hydrodehalogenation of Haloarenes by a Sodium Hydride–Iodide Composite

“…[12,13] This unprecedented and unique hydride donor reactivity of sodium hydride-iodide composite stimulated us to further explore development of new reductive transformation with the composite.H erein, we report use of sodium hydrideiodide composite to perform hydrodehalogenation of aw ide range of bromo-and iodoarenes under mild reaction conditions (Scheme 1c). [12,13] This unprecedented and unique hydride donor reactivity of sodium hydride-iodide composite stimulated us to further explore development of new reductive transformation with the composite.H erein, we report use of sodium hydrideiodide composite to perform hydrodehalogenation of aw ide range of bromo-and iodoarenes under mild reaction conditions (Scheme 1c).…”

Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides

“…We have recently uncovered aconcise protocol to activate NaH in the presence of dissolving iodides such as NaI/LiI in tetrahydrofuran (THF) and the composite performs unprecedented reductive transformations such as hydrodecyanation of a-quaternary benzyl cyanides, [11] hydrodehalogenation of haloarenes, [12,13] and controlled reduction of N,N-dimethylcarboxamides to aldehydes. [11,14] In these reactions,i ti s assumed that activated NaH could be generated through counter ion metathesis between polymeric inactive NaH with dissolving NaI/LiI.…”