Cristau, PierreVors, Jean-PierreZhu, Jieping2010-11-252010-11-252010-11-25200310.1016/j.tet.2003.08.031https://infoscience.epfl.ch/handle/20.500.14299/58496A two-step sequence involving an Ugi four-component reaction and an intramol. nucleophilic arom. substitution (SNAr) has been developed for the rapid access to biaryl-ether contg. macrocycles. For example, reacting heptanal with butylamine, (3-hydroxyphenyl)acetic acid, and isonitrile I in dry toluene in the presence of NH4Cl gave dipeptide II. II was then cyclized using an intramol. SNAr sequence to give cyclic ether III as a mixt. of 4 diastereomers. In the course of this study, we documented that ammonium chloride can promote the Ugi-4CR in non-polar aprotic solvent (toluene) without the interference of an alternative Passerini reaction. Solid phase synthesis of macrocycles by this two-step sequence was also developed using polymer (Wang resin) supported alpha -(4'-fluoro-3'-nitro)phenethyl isocyanoacetate as one of the inputs. [on SciFinder (R)]Addition reaction (Ugi; prepn. of natural-product like biaryl ether macrocycles by soln. and solid-phase Ugi reaction-intramol. nucleophilic arom. substitution); Substitution reaction (arom.intramol.; prepn. of natural-product like biaryl ether macrocycles by soln. and solid-phase Ugi reaction-intramol. nucleophilic arom. substitution); Ethers Role: SPN (Synthetic preparation)PREP (Preparation) (cyclicmacrocyclic; prepn. of natural-product like biaryl ether macrocycles by soln. and solid-phase Ugi reaction-intramol. nucleophilic arom. substitution); Solid phase synthesis (prepn. of natural-product like biaryl ether macrocycles by soln. and solid-phase Ugi reaction-intramol. nucleophilic arom. substitution)biaryl ether macrocycle soln solid phase prepn; Ugi reaction macrocycle soln solid phase prepn; nucleophilic arom substitution Ugi reaction biaryl ether macrocycle prepntext::journal::journal article::research article