Identification and optimization of novel pyrimido-isoxazolidine and oxazine as selective hydride donors

Two novel carbon skeletons (3S,3a′R)-6′-(methylthio)-5′,7a′-dihydro-1′H-spiro[indoline-3,3′-isoxazolo[3,4-d]pyrimidine]-2,4′(3a′H)-dione (11a) and 3-(methylthio)-4a,5,7,11c-tetrahydropyrimido[4′,5′:3,4][1,2]oxazino[6,5-b]indol-1(2H)-one (12a) are characterized as hydride donors. The generation of these hydride sources during the spiroannulation reaction between isatin (4) and pyrimidine (5) through the free radical mechanism, was confirmed by (i) the increase in the stoichiometric yields of 11 and 12 when the same reaction was carried out in the presence of free radical initiators (e.g., mCPBA) and (ii) the formation of oxazepine (14) when AIBN was used as free radical initiator. The PKIE [KH/KD] values 4.5 and 4.9 obtained when deuterated 11a (d) was used in the presence of TFA and TFA-d, respectively, suggest the hydride transfer step to be the rate determining step. These hydrides donors selectively reduce aldehyde in the presence of other reducible groups.