Neue methode zur regiospezifischen substitution einiger reaktionsträcer N-heteroaromatischer ringsysteme

Heterobiaryl synthesis by contractive C–C coupling via P(V) intermediates

“…Heteroaryl-heteroaryl coupling has previously been observed at phosphorus centers, but an inability to transform a generic set of pyridines and diazine precursors into the required bis-azaarene phosphonium salts has restricted these processes to specialized cases (25)(26)(27)(28)(29). In our test system, stage A combined the first heterocycle, 2-phenylpyridine, with Tf 2 O at low temperature to form an intermediate pyridinium triflyl salt (not shown); adding fragmentable phosphine 1 (prepared on large scale from diphenyl phosphine and methyl acrylate) (30) results in a para-selective reaction to form dearomatized intermediate Int-I (31)(32)(33)(34)(35)(36)(37). Two equivalents of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) eliminate first the triflyl anion to form phosphonium ion Int-II, and then methyl acrylate to form heteroaryl phosphine 2a in good yield.…”

Selective Functionalization of Pyridines via Heterocyclic Phosphonium Salts

“… The identity of the nucleophile is critical as it must be installed in high efficiency and selectivity while also serving as a versatile functional group. Alongside our investigations, we were inspired by a report from Anders in which pyridine could be transformed into a heterocyclic phosphonium salt through sequential addition of Tf 2 O, PPh 3 , and NEt 3 at low temperature . After initially forming a triflyl salt, attack of PPh 3 results in a dearomatized intermediate (eq 3, I ).…”

“…Thiolates result in C–S bonds such as in nicotine derivative 16 . Reaction with sodium azide forms iminophosphoranes after an in situ Staudinger reaction; , deprotection under neutral conditions gives heteroaryl aniline ( 17 ). Finally, C–C bonds can be formed by adding lithiated heterocycles as in heterobiaryls 18 and 19 ; LCMS analysis indicates intermediate phosphoranes are present during these reactions.…”

Four‐Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides

“…This criterion precludes N-Tf and N-Ts activation as pyridylphosphonium salts will form in the presence of a base. [10] Third, the activating group must tolerate 2-substituted pyridines (Scheme 1 B). Common N-activating groups, such as acyl and alkyl groups, do not function well on this class of pyridines and often require forcing conditions, resulting in low yields of pyridinium salts.…”