Premium
A Substrate‐Based Folding Process Incorporating Chemodifferentiating ABB′ Three‐Component Reactions of Terminal Alkynoates and 1,2‐Dicarbonyl Compounds: A Skeletal‐Diversity‐Oriented Synthetic Manifold
Author(s) -
Tejedor David,
SántosExpósito Alicia,
GarcíaTellado Fernando
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200600749
Subject(s) - electrophile , nucleophile , folding (dsp implementation) , chemistry , combinatorial chemistry , substrate (aquarium) , component (thermodynamics) , process (computing) , catalysis , organic chemistry , computer science , oceanography , physics , geology , electrical engineering , thermodynamics , engineering , operating system
A novel three‐component reaction (3CR)‐based folding process that is able to generate complexity and skeletal diversity is described. The process utilizes chemodifferentiating organocatalyzed ABB′ 3CRs of a terminal conjugated alkynoate (building block) with α‐dicarbonyl compounds (diversity‐generating blocks) to generate an array of different molecular topologies (γ‐lactones, linear propargylic enol ethers, or 1,3‐dioxolane rings). Amides and esters behave as efficient reactivity‐encoding elements (σ) of the attached keto functionality. Three chemical properties govern the chemical outcome of this folding process: acidity, nucleophilicity (of the catalyst), and carbonyl electrophilicity. Overall, this substrate‐based folding process generates three different molecular architectures from the same modular functionalities (ketones) and under the same reaction conditions (methyl propiolate and tertiary amine). In addition, and very importantly for combinatorial applications, all of the products share a common reactive functionality that allows them to be collective substrates for a subsequent diversity‐generating process.