13950-56-6Relevant articles and documents
Mechanistic Investigation of Biocatalytic Heme Carbenoid Si?H Insertions
Khade, Rahul L.,Chandgude, Ajay L.,Fasan, Rudi,Zhang, Yong
, p. 3101 - 3108 (2019)
Recent studies reported the development of biocatalytic heme carbenoid Si?H insertions for the selective formation of carbon-silicon bonds, but many mechanistic questions remain unaddressed. To this end, a DFT mechanistic investigation was performed which reveals an FeII-based concerted hydride transfer mechanism with early transition state feature. The results from these computational analyses are consistent with experimental data of radical trapping, kinetic isotope effects, and structure-reactivity data using engineered variants of hemoproteins. Detailed geometric and electronic profiles along the heme catalyzed Si?H insertion pathways were provided to help understand the origin of experimental reactivity trends. Quantitative relationships between reaction barriers and some properties such as charge transfer from substrate to heme carbene and Si?H bond length change from reactant to transition state were found. Results suggest catalyst modifications to facilitate the charge transfer from the silane substrate to the carbene, which was determined to be a major electronic driving force of this reaction, should enable the development of improved biocatalysts for Si?H carbene insertion reactions.
Highly syn-selective elimination of peterson anti-adducts to give Z-α,β-unsaturated esters
Murai, Yutaka,Nakagawa, Akira,Kojima, Satoshi
, p. 228 - 231 (2017)
Peterson adducts have been known to stereospecifically give syn-elimination products upon treatment with base except when the product olefin is in conjugation with an electron-withdrawing group. The missing piece has been put in place by using a catalytic amount of DBU, by which syn-elimination could be effected to provide the thermally less stable Z-olefin from the anti-adduct with high selectivity.
Chemoselective Cyclopropanation over Carbene Y-H Insertion Catalyzed by an Engineered Carbene Transferase
Moore, Eric J.,Steck, Viktoria,Bajaj, Priyanka,Fasan, Rudi
, p. 7480 - 7490 (2018/06/25)
Hemoproteins have recently emerged as promising biocatalysts for promoting a variety of carbene transfer reactions including cyclopropanation and Y-H insertion (Y = N, S, Si, B). For these and synthetic carbene transfer catalysts alike, achieving high chemoselectivity toward cyclopropanation in olefin substrates bearing unprotected Y-H groups has proven remarkably challenging due to competition from the more facile carbene Y-H insertion reaction. In this report, we describe the development of a novel artificial metalloenzyme based on an engineered myoglobin incorporating a serine-ligated Co-porphyrin cofactor that is capable of offering high selectivity toward olefin cyclopropanation over N-H and Si-H insertion. Intramolecular competition experiments revealed a distinct and dramatically altered chemoselectivity of the Mb(H64V,V68A,H93S)[Co(ppIX)] variant in carbene transfer reactions compared to myoglobin-based variants containing the native histidine-ligated heme cofactor or other metal/proximal ligand substitutions. These studies highlight the functional plasticity of myoglobin as a "carbene transferase" and illustrate how modulation of the cofactor environment within this metalloprotein scaffold represents a valuable strategy for accessing carbene transfer reactivity not exhibited by naturally occurring hemoproteins or transition metal catalysts.
