Nucleophilic reaction of 1,8-diazabicyclo[5.4.0]undec-7-ene and 1,5-diazabicyclo[4.3.0]non-5-ene with methyl pheophorbide a. Unexpected products

Trialkylsilyl triflates promote the direct nucleophilic reaction of non·nucleophilic DBU and DBN with methyl pheophorbide a (1) to give substituted chi orin e6 amides 3 and 4. where the bicyclic bases have undergone ring opening. The reaction most likely results from coordination of trialkylsilyl triflates to the ~. ketoester in I, forming an ion'pair intermediate 6. The adduct 6 is so strongly electron-deficient that it can electrophilically attack the nonbonding nitrogen electron pairs in DBU and DBN. Trialkylsilyl triflates l such as tert-butyldimethylsilyl triflate (TBDMSOTf) and trimethylsilyl triflate (TMSOTf) are powerful silylating agents and a wide range of active hydrogen containing compounds are silylated in the presence of amines.2 Combination of these triflates with the hindered amidine 1.8-diaza­ bicyclo(5.4.0)undec· 7-ene (DBU)3 has also been used in the selective ring-opening reactions of oxiranes.1 Due to the highly electron-withdrawing triflate moiety the silicon in trialkylsilyl triflates is strongly electron-deficient and can directly attack the heteroatoms in carbonyl and analogous systems,4 and many reports have shown that they can act as catalysts to accelerate a variety of nucleophilic reactions in aprotic media.s We report here that a degradation of chlorophyll a, methyl pheophorbide a (1) which alone does not electrophilically react with DBU or DBN, has reacted, through catalytic activation by TMSOTf and TBDMSOTf, with nucleophilic DBU and DBN. The isocyclic ring (ring V) of methyl pheophorbide a (1) is a substituted ~-ketoester and enolization occurs readily in polar solvents. However, attempts to isolate it as an enol ester or a silyl enol ether led to very unstable products. 6 In 1979, Hynninen et aO reported that the enol ate could be trapped by using tetrapropylammonium fluoride in combination with trimethylsilyl chloride (TMSCl). We repeated the reported procedure but found the yield of silyl enol ether was quite low «10%). Due to the low stability of the trimethylsilyl enol ether we attempted to replace TMSCI with the more stable tert-butyldimethylsilyl chloride (TBDMSCI). Using DBU to enolize the ~·ketoester function of methyl pheophorbide a (1) and subsequently treatment with TBDMSCI, to trap the enolate, surprisingly gave none of the desired silyl enol ether. Instead, a less mobile 3 (-5% yield) was separated from the unchanged starting material 1. Subsequently we found that the green product 3 could be obtained in good yield