Reduction of N,N‐Dimethylcarboxamides to Aldehydes by Sodium Hydride–Iodide Composite

Abstract

A new and concise protocol for selective reduction of N,N‐dimethylamides into aldehydes was established using sodium hydride (NaH) in the presence of sodium iodide (NaI) under mild reaction conditions. The present protocol with the NaH‐NaI composite allows for reduction of not only aromatic and heteroaromatic but also aliphatic N,N‐dimethylamides with wide substituent compatibility. Retention of α‐chirality in the reduction of α‐enantioriched amides was accomplished. Use of sodium deuteride (NaD) offers a new step‐economical alternative to prepare deuterated aldehydes with high deuterium incorporation rate. The NaH‐NaI composite exhibits unique chemoselectivity for reduction of N,N‐dimethylamides over ketones.

Mechanistic Insights on Reduction of Carboxamides by Diisobutylaluminum Hydride and Sodium Hydride−Iodide Composite

“…of NaH and 1 equiv. of NaI afforded 2‐napthaldehyde ( 2a ) in 93 % yield as a sole product ( Scheme ,b ) . Exactly the same trend was observed in the reduction of aliphatic amide 1b ( Scheme ).…”

“…On the other hand, our group recently disclosed that sodium hydride (NaH) could act as a hydride donor in the presence of NaI or LiI in THF, capable of performing controlled reduction of tertiary carboxamides into aldehydes ( Scheme ) . This unique controlled feature could be observed even if the reactions are performed at higher reaction temperature ( i. e ., reflux in THF), implying that the resulting anionic carbinol amine intermediate II is kept extremely stable under the reaction conditions.…”

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. [15] Stimulated by these findings,o ur attention is directed to use of NaH for generation of new metal hydrides of interest through counter ion metathesis with the corresponding metal halides and exploration of their reactivities.…”

Semicarbazide: A Transient Directing Group for C(sp3)−H Arylation of 2‐Methylbenzaldehydes

“…Benzylbenzaldehydes are critical building blocks in the construction of a variety of fused rings, [11] natural products, [12] and biologically active compounds. [13] Numerous synthetic protocols have been successfully demonstrated for 2-benzylbenzaldehydes, including the traditional oxidation of 2-benzylbenzyl alcohols, [14] the reduction of N,N-dimethylcarboxamides, [15] and the rearrangement of aromatic alcohols. [16] While these methods achieved satisfactory yield for 2-benzylbenzaldehydes, their cost-efficiency was hampered by the expensive and not easily available starting materials.…”

“…Compared with Pd(OAc) 2 , Pd (PPh 3 ) 2 Cl 2 as a catalyst could increase the yield of 3 a to 61% while PdCl 2 , Pd(TFA) 2 , and Pd(dppf)Cl 2 achieved inferior performance (entries [10][11][12][13]. The other transition metal catalysts, such as Cu(OAc) 2 , FeCl 2 and Ni(OAc) 2 , were also checked but no catalytic effect on the reaction (entries [14][15][16]. Elevated temperature (120°C) could slightly increase the yield of 3 a to 64% (entry 17).…”