Chiral Lithium Amides: Tuning Asymmetric Synthesis on the Basis of Structural Parameters

Abstract

An overview on the structural arrangements adopted by Chiral Lithium Amides (CLAs), alone or in mixed complexes, is presented. These species are important reagents for asymmetric synthesis and understanding their organization is essential to improve their design and the reaction conditions.

Enantioselective Synthesis of the 1,3‐Dienyl‐5‐Alkyl‐6‐Oxy Motif: Method Development and Total Synthesis

“…Later on, for corresponding enantioselective method we sought to chiral lithium amides. According to the seminal work of Shioiri, Koga, and Zakarian, [10] chiral lithium amides have already been successfully applied as noncovalent stereodirecting auxiliaries in the enantioselective α-alkylation of a series of carboxylic acids. However, to the best of our knowledge, there is no literature precedents using conjugated polyenoic acids, presumably due to the dramatically lower reactivity upon initial deprotonation of much less acidic Hɛ compared to very acidic Hα previously reported.…”

“…[13] Accordingly, an enantioinduction model (Figure S1) was proposed to rationalize the absolute configuration of alkylation products obtained in our experimental results, following Collum & Zakarian stereoinduction model which has been widely used in enantioselective α-alkylation of carboxylic acids. [10] With enantioselective method in hand, now we proceeded to total synthesis of a series of natural products, by using our enantioenriched α-adducts as the key 1,3-dienyl-5alkyl-6-oxy intermediate. We commenced our synthesis by focusing on two polyketides all bearing the 1,3-dienyl-5-…”

“…Isolated from various Streptomyces species, Streptimidone (10) belongs to glutarimide antibiotics and has been shown to have strong antimicrobial activity against eukaryotic cells. [14] Therefore, Streptimidone (10) has been recognized as promising antimicrobial candidate.…”

“…Isolated from various Streptomyces species, Streptimidone (10) belongs to glutarimide antibiotics and has been shown to have strong antimicrobial activity against eukaryotic cells. [14] Therefore, Streptimidone (10) has been recognized as promising antimicrobial candidate. In 2000, Kiyota group achieved the 11-step enantioselective total synthesis of four stereoisomers of 10, starting from commercially available methyl (S)-3-hydroxy-2-methylpropanoate.…”

Lithium Amide Protected against Hydrolysis by Aggregated Lithium Halides: An MS + DFT Investigation

“…Their chiral congeners are also powerful species largely employed in asymmetric synthesis for diastereoselective and enantioselective processes. Actually, these reagents can be used directly as chiral bases, but they can also behave as chiral nucleophiles or be associated with another lithiated reagent and be regarded as chiral ligands …”