Stereoselective P‐Cyclisation and ­Diastereoisomeric Purification of 5‐Phenyl‐3‐(pyridin‐2‐yl)‐1,3,2‐oxazaphospholidine Formed from a Thermolabile Protecting Group

Abstract

A one‐pot, two‐step synthesis of 5‐phenyl‐3‐(pyridin‐2‐yl)‐1,3,2‐oxazaphospholidine from linear precursor bis(diisopropylamino){2‐[(pyridin‐2‐yl)amino]‐1‐phenylethoxy}phosphine is achieved using a stereoselective intramolecular cyclisation. Application of a pure enantiomer {1‐phenyl‐2‐[(pyridin‐2‐yl)amino]ethanol} enabled partial diastereopurification by crystallisation. For all four diastereoisomers, the absolute configuration of the P‐centre was determined using X‐ray crystallography and correlative 31P NMR data. Stereochemically pure 5a was then used in nucleoside phosphitylation reactions with partial loss of stereopurity by retention of configuration on the phosphorus centre.

Facile Installation of β-Hydroxyarylethylamino Motifs at the C2-Position of Quinoline Moiety via Copper-Catalyzed [3+3]-Cycloaddition Reaction of N-Oxide with N-Ts Aziridine

“…Likewise, the 2-bromo pyridine was reacted with β-hydroxyarylethylamine to form the aminated product via the nucleophilic aromatic substitution (S N Ar) reaction. 6d e Though these protocols were apparently straightforward, the use of strong basic conditions and the requirement of a prefunctionalized 2-amino or 2-bromo compound had its own shortages like poor regioselectivity. Further, to our knowledge, there is no report on the synthesis of β-hydroxyarylethylamino-functionalized benzofused pyridine the so-called quinoline derivatives.…”

Fluorescent 2-(Pyridin-2-yl)vinyl Pyridine Dyes and Their Thermocontrolled Release

“…Therefore, we decided to develop the methodology for “switchable” probes with a better control of their thermocyclization . Recently, it has been demonstrated that thermolabile protecting groups (TPGs) are effective systems in the protection of hydroxyl, − amine, phosphate, − and carboxyl functions . Among these, N -pyridin-2-yl derivatives were developed as devices in heat-drive “chemical switch” and “click-clack” approaches.…”

Experimental and computational studies on a protonated 2-pyridinyl moiety and its switchable effect for the design of thermolytic devices

“…N 2 from the aminoethanol substituent or N4 from the 4-amino group, should not be neglected. Nitrogen N 2 is involved in the cyclization of the 2PyTPG group and, together with the participation of the phosphate center, forms an oxazaphospholidine ring [ 18 ] Furthermore, N 2 serves an important role in the oxidation of the H-phosphonate diester by an iodinated intermediate [ 15 ].…”