(2H‐Azirin‐2‐yl)methyl]phosphonate: Darstellung aus allylischen α‐ und γ‐Hydroxyphosphonaten und Anwendung zur diastereoselektiven Synthese von substituirten [(Aziridin‐2‐yl)methyl]phosphonsäureestern

Abstract

[(2H‐Azirin‐2‐yl)methyl]phosphonates: Synthesis from Allylic α‐ and γ‐Hydroxyphosphonates and Application to Diastereoselective Formation of Substituted [(Aziriden‐2‐yl)methyl]phosphonatesVarious substituted (3‐azido‐1‐alkenyl)phosphonates 3 (R3 = alkyl) or their equilibrium mixtures with the regioisomeric α‐azidophosphonates 4 (R3 = Ph) have been synthesized from allylic α‐ or γ‐hydroxyphosphonates 2 or 1 by Mitsunobu reaction with TPP/DEAD/HN3, and converted into the new [(2H‐azirin‐2yl)methyl]phosphonates 6 upon heating in toluene with DBU catalysis. The transformation 3/4→6 proceeds via base‐catalyzed rearrangement to the (3‐azido‐2‐alkenyl)‐phosphonates 5 and subsequent thermolysis. Reduction of the 2H‐azirines 6 with NaBH4 in methanol at 5°C results in the predominant formation of the disubstituted aziridines cis‐7. Addition of trimethylsilyl cyanide to compounds 6 yields stereoselectively the highly functionalized aziridines trans‐8, while NaOCH3‐catalyzed addition of dimethyl phosphite proceeds with even higher selectivity to yield the bisphosphonates trans‐9 with excellent yields.