A protocol for the anti-Markovnikov hydrofunctionalization of alkenes has been developed by the use of a benzyl group as a traceless redox-active hydrogen donor. Under copper catalysis and in the presence of CF - or N -containing hypervalent iodine reagents, a series of homoallylic alcohol derivatives were hydrofunctionalized regioselectivity. A similar principle was also applied to the hydrofunctionalization of alkenols.

A simple protocol for hydrodebromination and -deiodination of halo(hetero)arenes was enabled by sodium hydride (NaH) in the presence of lithium iodide (LiI). Mechanistic studies showed that an unusual concerted nucleophilic aromatic substitution operates in the present process.

ZuschriftenScheme 2. Substrate scope.[a] The reactions were conducted using 0.5 mmol of the amides 1.Y ields of the isolated alcohols 2 and amines 3 are given.[b] The reaction was conducted using 5equiv of NaH, 2equiv of ZnI 2 and 2equiv of NaI.[c] The reaction was conducted using 7equiv of NaH and 3.5 equiv of ZnCl 2 .[d] 1aj > 98 %ee; 2aj > 97 %ee; 3aj > 98 % ee as measured by the Mosher method (see the Supporting Information).[e] Amine 3ak was formed in 35 %yield. [f]Amine 3al was formed in 31 %yield. Bn = benzyl, Ph = phenyl, TIPS = triisopropylsilyl.Scheme 5. DFT calculations for model reactions of benzamide with (ZnH 2 ) 2 or (ZnHCl) 2 species. Energy changes and bond lengths at the wB97XD/SDD&6-31 + G* (scrf = smd, THF) level of theory are shown in kcal mol À1 and ,respectively.

A new method for the synthesis of a-branched amines by reductive functionalization of tertiary carboxamides and lactams is described. The process relies on the efficient and controlled reduction of tertiary amides by a sodium hydride/ sodium iodide composite, in situ treatment of the resulting anionic hemiaminal with trimethylsilyl chloride and subsequent coupling with nucleophilic reagents including Grignard reagents and tetrabutylammonium cyanide. The new method exhibits broad functional-group compatibility, operates under transition-metal-free reaction conditions, and is suitable for various synthetic applications on both sub-millimole and on multigram scales. Recently, the Chiba group disclosed a controlled hydride reduction of tertiary carboxamides for the synthesis of aldehydes using a combination of NaH and NaI in THF. [15] Key to the success of this chemistry was the stability (prior to aqueous work-up) of the anionic hemiaminal intermediates formed through single hydride transfer from the activated NaH to the carboxamides. [16] Building on this discovery, we Scheme 1. Selected a-branched amines currently used in the clinic.

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.