Facile access to a heterocyclic, sp³-rich chemical scaffold via a tandem condensation/intramolecular nitrone–alkene [3+2] cycloaddition strategy

Abstract

A heterocyclic, sp(3)-rich chemical scaffold was synthesised in just 6 steps via a highly regio- and diastereo-selective tandem nitrone formation/intramolecular nitrone-alkene [3+2] cycloaddition reaction. A library of 543 lead-like compounds based on the scaffold core has been produced.

PdII‐Mediated Oxidative Amination for Access to a 9‐Azabicyclo[4.2.1]nonane Compound Library and Anatoxin‐a

“…As part of our studies into the synthesis of chemical scaffolds for drug discovery, we set out to develop a catalytic and selective protocol for the heterocyclisation of aminocyclooct‐4‐enes. It was envisaged that a regioselective and high‐yielding protocol would expediate entry to series of 9‐azabicyclo[4.2.1]nonane derived chemical scaffolds that could be further derivatised to generate a lead‐like compound library.…”

Enantioselective Synthesis of a Tricyclic, sp3‐Rich Diazatetradecanedione: an Amino Acid‐Based Natural Product‐Like Scaffold

“…Furopyrane A was synthesized from a d ‐ribose derivative by an intramolecular hetero Diels–Alder reaction . The key step for the construction of spiro lactam B consists of a domino nitrone formation/intramolecular [3+2] cycloaddition and phenol C was built by a domino Petasis/intramolecular hetero Diels–Alder reaction …”

“…[4] Representative examples for heterocyclic,s p 3 -rich scaffolds are shown in Scheme1.Furopyrane A was synthesized from a d-ribose derivativeb ya ni ntramolecular hetero Diels-Alder reaction. [5] Thek ey step for the construction of spiro lactam B consists of ad ominonitronef ormation/intramolecular [3+ +2] cycloaddition [6] and phenol C was built by ad omino Petasis/intramolecular hetero Diels-Alder reaction. [7] All three examples have in commont hat the complexitygenerating step consists of am ulticomponent reaction, ac ycloaddition or ac ombination of both.…”

“…Retrosynthetic analysiso f1,b ased on an intramolecular epoxide openinga nd two amide bond formations, leads to epoxide 2,w hich in turn is accessible from advanced vinyl iodide buildingb lock 3 and d-iodinated amino acid derivative 4 by a Negishic oupling (Scheme 2). 3 can be derived from d-aspartic acid (5), whereas 4 can be derived from l-pyroglutamic acid (6). The synthesis of 3 wasa ccomplished in 7steps (Scheme 3).…”

Synthesis of Structurally Diverse N‐Substituted Quaternary‐Carbon‐Containing Small Molecules from α,α‐Disubstituted Propargyl Amino Esters

“…[23] Moreover,w ithin af ragment-based drug discovery context,t here have been recent calls for the design and synthesis of novel compounds that feature multiple 3D growth vectors whilst incorporating polar functionality form olecular recognition. [24] In response to this, notable examples of efficient syntheses of diverse sp 3 -rich libraries have been recently published, [25][26][27][28][29][30][31][32] however there is stilla no utstanding need for diversel ibraries featuring this key N-containing quaternary stereocenter motif.…”