One-Pot Reductive Allylation of Amides by Using a Combination of Titanium Hydride and an Allylzinc Reagent: Application to a Total Synthesis of (–)-Castoramine

Abstract

A one-pot direct reductive allylation protocol has been developed for the synthesis of secondary amines by using titanium ­hydride and an allylzinc reagent. This protocol is applicable to a broad range of substrates, including acyclic amides, benzamides, α,β-unsaturated amides, and lactams. The stereochemical outcome obtained from the reaction with crotylzinc reagent suggested that the allylation reaction proceeds through a six-membered cyclic transition state. A total synthesis of (–)-castoramine was accomplished by following this protocol for the highly stereoselective construction of contiguous stereo­centers.

Mild Divergent Semireductive Transformations of Secondary and Tertiary Amides via Zirconocene Hydride Catalysis

“…The hydrozirconation of amides utilizing Schwartz’s reagent (Cp 2 ZrHCl) has proven to be a useful synthetic strategy for the direct conversion of amides to the corresponding imines or aldehydes via amidato zirconocene or zirconocene hemiaminal complexes (Figure a). , Despite the redox efficiency of this chemistry, its application on scale is economically and environmentally untenable due to the stoichiometric use of an air- and moisture-sensitive metal hydride. Herein, we report a mild approach for the divergent partial reduction of both secondary and tertiary amides using 5 mol % of zirconocene dichloride ( 1 ) for the express preparation of structurally diverse imines and derivatives thereof.…”