Reduction of N-Allylamides by LiAlH₄: Unexpected Attack of the Double Bond with Mechanistic Studies of Product and Byproduct Formation

Abstract

The reduction of secondary allyl amides with LiAlH4 can lead to a concomitant reduction of the double bond. Previously, an excess of LiAlH4 in hazardous solvents was used for the reduction. This work discusses optimized reaction conditions in tBuOMe as a safe solvent, with only a 1.5-fold excess of LiAlH4, without reduction of the double bond in most cases. (1)H and (2)D NMR spectroscopic studies give evidence for the mechanism of the reduction of the amide as well as the double bond: Amide reduction generally precedes double bond reduction. Sterically hindered allylamides are an exception. They are reduced considerably more slowly at higher temperatures, and double bond reduction is observed before amide reduction has gone to completion.

Phase-Controlled Colloidal Syntheses of Iron Sulfide Nanocrystals via Sulfur Precursor Reactivity and Direct Pyrite Precipitation

“…48 This isomer is particularly prone to nucleophilic attack at the α-CH 2 position (Scheme 2a). 49 The expected product of a single N-based substitution, N-allyl-octylamine was not observed (by comparison with the product from a known reaction 50 ). However, N-allyl-octylamine is more nucleophilic than octylamine.…”

N-Heterocycle-Forming Amino/Carboperfluoroalkylations of Aminoalkenes by Using Perfluoro Acid Anhydrides: Mechanistic Studies and Applications Directed Toward Perfluoroalkylated Compound Libraries

“…Anhydrous dichloromethane was purchased from Kanto. The known alkenes 1a – e , 1f , 1g , 1h , 1i , 1j , 1k , 1l , 1m – n , 1o – p , and 1q – r were prepared according to the literature.…”

Nickel(0)‐Catalyzed N‐Allylation of Amides and p‐Toluenesulfonamide with Allylic Alcohols under Neat and Neutral Conditions

“…N ‐Allylbenzamide (8a): The general procedure B was applied to amide 7a (393 mg, 3.25 mmol, 1 equiv.) and allyl alcohol (663 µL, 9.75 mmol, 3 equiv.).…”