[(2H-AZIRIN-2-YL)METHYL]PHOSPHONATES - SYNTHESIS FROM ALLYLIC ALPHA-HYDROXYPHOSPHONATE AND GAMMA-HYDROXYPHOSPHONATE AND APPLICATION TO DIASTEREOSELECTIVE FORMATION OF SUBSTITUTED [(AZIRIDIN-2-YL)METHYL]PHOSPHONATES

Various substituted (3-azido-1-alkenyl)phosphonates 3 (R(3) = alkyl) or their equilibrium mixtures with the regioisomeric alpha-azidophosphonates 4 (R(3) = Ph) have been synthesized from allylic alpha- or gamma-hydroxyphosphonates 2 or 1 by Mitsunobu reaction with TPP/DEAD/HN3, and converted into the new [2H-azirin-2-yl)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 degrees 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.