Mechanistic studies of biomimetic oxygenation reactions in aqueous solution

Abstract

Part I The mechanism of the O-O bond cleavage of tert-alkyl hydroperoxide by iron (III) porphyrin complexes has been studied using 2-methyl-l-phenylpropan-2-yl hydroperoxide (MPPH). MPPH has been shown to be an excellent mechanistic probe capable of distinguishing between free alkoxyl radical chemistry and radical-free (enzyme mimetic) chemistry in non-porphyrin iron(III) complex catalyzed oxidations of hydrocarbons by tent-alkyl hydroperoxides. When the O-O bond of MPPH is cleaved homolytically by the iron complexes, PhCHO and PhCH20H are generated. In contrast, heterolytic reduction of MPPH by the iron complexes yields an alcohol (MPPOH). High valent iron(IV) oxo porphyrin cation radical formed via heterolysis affords a stereospecific epoxide product. Therefore, the mechanism of the O-O bond cleavage of tent-alkyl hydroperoxides can be determined by analyzing the products derived from the decomposition of MPPH and the epoxide product formed by iron complexes. Product studies obtained in the cis-stilbene epoxidation by Fe(TDFPPS)^3- and MPPH at various pHs in aqueous solutions showed that the yields of cis-stilbene oxide and MPPOH formed were higher at low pH values. As the pH of the reaction solution increased, the yields of cis-stilbene oxide and MPPOH products decreased and the amounts of PhCHO and PhCH₂OH increased. In addition to the pH effect on hydroperoxide O-O bond cleavage, I found that the O-O bond cleavage was significantly affected by porphyrin ligands bound to iron and the general trend appeared to be that more electronegatively-substituted iron porphyrins gave a high percentage of heterolysis, whereas homolysis prevailed in the reactions with less electronegatively-substituted iron porphyrins. Another factor that affects hydroperoxide O-O bond cleavage is the presence of imidazoles. Imidazoles such as 5-chloro-l-methylimidazole and 1-phenylimidazole increased the yields of cis-stilbene oxide and MPPOH products, whereas 1-methylimidazole and 1,2-dimethylimidazole did not alter the ratio of heterolysis to homolysis significantly. Oxidant effect on hydroperoxide O-O bond cleavage is also under investigation. Result from the isotopically labeled water, H₂^18 O, experiments indicated that the high valent iron(IV) oxo porphyrin cation radical is reactive intermediate in the epoxidation of olefin in aqueous solutions. Little incorporation of ^18O into CBZ oxide from H₂^18O in buffered water-methanol-acetonitrile solutions indicates that oxygen atom transfer from high valent iron(IV) oxo porphyrin cation radical to substrate is via "oxo-hydroxo tautomerism" mechanism proposed by Meunier et al In summary, the O-O bond of alkyl hydroperoxides is cleaved both heterolytically and homolytically and partitioning between the two pathways significantly depends on the reaction conditions such as the pH of the reaction solutions and the nature of porphyrin and axial ligands. Part II Competitive epoxidations of cis-stilbene and traps-stilbene by various oxidants such as MCPBA, oxone, H₂O₂, and PhIO in the presence of iron(III) porphyrin complexes were examined. The ratios of cis- to traps-stilbene oxides formed varied with the pH of the reaction solutions. In the case of Fe(TDFPPS)^3-, the ratios of cis- to traps-stilbene oxides were about 1.0 at low pH values. As the pH of the reaction solutions increased, the yield of cis-stilbene oxide increased relatively and the ratios were over 15.0 at pH 11.5 indicating that another distinct intermediate besides high valent iron(IV) oxo porphyrin cation radical capable of epoxidizing olefins was present. In the cis-stilbene epoxidation, cis-stilbene oxide was formed predominantly with only a trace amount of traps-stilbene oxide formation. Major product in the epoxidation of traps-stilbene was also stereoretentive traps-stilbene oxide. Therefore, the involvement of peroxyl radical (ROO) and oxo iron(IV) porphyrin as epoxidizing agents was excluded since these species should oxidize olefins nonstereospecifically. Another plausible intermediate at high pH values is Fe^III-OOR which prefers cis-stilbene to transstilbene due to steric hindrance. In addition to the pH effect on the ratios of cis- to traps-stilbene oxides, the ratios of the oxide products were affected by central metal ion of porphyrin complexes. In the competitive epoxidations of cis-stilbene and traps-stilbene by manganase(III) porphyrin complexes, the ratios of cis- to traps-stilbene oxides were little changed with pHs of the reaction solutions. They were also affected by porphyrin ligands bound to iron. Moreover, in the case of several iron porphyrins, the ratios of the oxide products depended on the oxidants used and this oxidant effect is under investigation. In summary, reactive intermediate at low pH values is high valent iron(IV) oxo porphyrin cation radical and plausible intermediate at high pH values is Fe^III-OOR. cis-trans Selectivities depend on the electronic nature and steric effect of porphyrin ligands and central metal ion of porphyrin complexes. ; 수용성 용액에서 철(III) 포르피린 착물에 의해 산화제로부터 기질로 산소 원자가 전달되는 메커니즘을 살펴보았다. 특히, 철(Ill) 포르피린 착물과 tert-alkyl hydroperoxide가 반응하여 생기는 (Porp)Fe^IlI-OOR 종의 O-O 결합이 끊어지는 메커니즘에 초점을 두었고, 산소 원자의 source로는 2-methyl-l-phenylpropan-2-yl hydroperoxide (MPPH)를 사용하였다. MPPH는 mechanistic probe로서 alkyl hydroperoxide의 O-O 결합 분해에 대한 많은 정보를 제공하는데, MPPH의 O-O 결합이 균등하게 끊어 지면 PhCHO (benzaldehyde)와 PhCH₂OH (benzyl alcohol)이 생성되고, 불균등하게 끊어지면 알코올인 MPPOH가 생성된다. 또한 (Porp)Fe^IlI-OOR 종의 O-O 결합이 불균등하게 분리되면 활성 중간체로 알려져 있는 고산화가 철(IV) 옥소 포르피린 양이온 라디칼 착물 [(Porp)^+·Fe^IV=O]]이 생기므로 에폭사이드 생성물도 얻을 수 있다. 그러므로 반응의 결과로 생긴 여러 생성물을 분석하고 확인함으로써 역으로 반응 메커니즘을 추정할 수 있는 것이다. 다양한 pH의 수용성 용액에서 Fe(TDFPPS)^3-와 MPPH를 사용한 cis-stilbene의 에폭시화 반응을 수행한 결과, 낮은 pH에서 많은 에폭사이드 생성물이 생겼으며 pH가 증가할수록 그 양이 감소하였다. 그리고 benzyl alcohol과 benzaldehyde의 양은 반응 용액의 pH가 높아질수록 증가함을 알 수 있었다. 반응 용액의 pH가 같을지라도 철(Ill) 포르피린 착물의 리간드에 따라 반응성이 달라짐을 확인하였는데, Fe(TDFPPS)^3- 외에 Fe(TDCPPs)^3-, Fe(TMPyP)^5+, Fe(TTMDSP)^7- 촉매로 실험을 한 결과, 배위된 리간드의 전기음성도가 클수록 cis-stilbene oxide의 수측률이 높았다. Hydroperoxide의 O-O 결합이 끊어지는 메커니즘에 영향을 미치는, 따라서 에폭시화 반응의 반응성에 변화를 줄 수 있는 또다른 인자로는 이미다졸의 존재 여부를 들 수 있다. 이미다졸이 반응 용액에서 철 포르피린 촉매의 axial 위치에 배위되어 전자를 끌어당기거나 밀게 되면, 철의 전자밀도에 변화가 일어나게 되므로 불균등 분해와 균등 분해의 정도가 변할 수 있는 것이다. 5-Chloro-l-methylimidazole이나 I-phenylimidazole과 같은 전자를 덜 주는 이미다졸이 존재할 경우 에폭사이드 생성물은 증가하였고, 반대로 전자를 밀어주는 l-methylimidazole이나 l,2-dimethylimidazole이 존재하는 경우에는 에폭사이드 수득률에 큰 변화가 없거나 조금 감소하는 경향을 보였다. 산화제에 따라서도 에폭시화 반응의 경향은 달라지는데, 이 부분에 대한 연구는 현재 진행 중이다. H₂^(18)O 실험을 통해 에폭시화 반응의 활성 중간체는 고산화가 철(IV) 옥소 포르피린 양이온 라디칼 착물 [(Porp)^+·Fe^(IV)=O]]임을 확인하였고, 혼합 용매에서는 ^(18)O이 함입되지 않는 것으로 보아 Meunier가 제안한 ‘oxo-hydroxo tautomerism 을 통한 산소 원자 전달 과정도 확인할 수 있었다. 이처럼 에폭시화 반응을 일으키는 중간체는 고산화가 철(IV) 옥소 포르피린 양이온 라디칼 착물이며, hydroperoxide의 O-O 결합이 분해되는 메커니즘은 pH나 포르피린 리간드의 전기적 성질, 배위된 axial ligand의 성질, 그리고 산화제의 종류와 같은 다양한 반응 조건에 의해서 정해진다고 추정할 수 있다.