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    Engineered myoglobins and other hemoproteins have recently emerged as promising catalysts for asymmetric olefin cyclopropanation reactions via carbene transfer chemistry. Despite this progress, the transformation of electron-poor alkenes has proven very challenging using these systems. Here, we describe the design of a myoglobin-based carbene transferase incorporating a non-native iron-porphyrin cofactor and axial ligand, as an efficient catalyst for the asymmetric cyclopropanation of electron-deficient alkenes. Using this metalloenzyme, a broad range of both electron-rich and electron-deficient alkenes are cyclopropanated with high efficiency and high diastereo- and enantioselectivity (up to >99% de and ee). Mechanistic studies revealed that the expanded reaction scope of this carbene transferase is dependent upon the acquisition of metallocarbene radical reactivity as a result of the reconfigured coordination environment around the metal center. The radical-based reactivity of this system diverges from the electrophilic reactivity of myoglobin and most of known organometallic carbene transfer catalysts. This work showcases the value of cofactor redesign toward tuning and expanding the reactivity of metalloproteins in abiological reactions and it provides a biocatalytic solution to the asymmetric cyclopropanation of electrodeficient alkenes. The metallocarbene radical reactivity exhibited by this biocatalyst is anticipated to prove useful in the context of a variety of other synthetic transformations.
    Reactivity
    Transferase
    Citations (103)
    Asymmetric intermolecular cyclopropanations are well documented; however, highly enantioselective intramolecular examples are less common. This report describes a method for intramolecular cyclopropanation using a carbenoid precursor flanked on both sides by electron-withdrawing groups. Yields and enantioselectivities vary widely and demonstrate the difficulty of this reaction. Interestingly, vinyl halides are tolerated and allow for the enantioselective synthesis of halocyclopropanes.
    Carbenoid
    Citations (0)
    We have developed gold(I)-catalyzed oxidative cyclopropanation of 1,6-enynes derived from propiolamides employing diphenyl sulfoxide as an oxidant. 1,6-Enynes having a terminal alkyne and a propiolamide tether efficiently transformed into cyclopropane carboxaldehyde derivatives.
    Cyclopropane
    Sulfoxide
    Alkyne
    Citations (39)
    The inside cover picture, provided by Haixu Wang, Cong-Ying Zhou, and Chi-Ming Che, illustrates the cobalt-catalyzed conversion of N-tosylhydrazones to cycloheptatriene fused pyrrolidines and cyclopropane fused pyrrolidines. With Co(II)-porphyrin as catalyst, alkyl diazomethanes generated in situ from N-tosylhydrazones underwent intramolecular Buchner reaction and arene cyclopropanation in highly chemo- and regio-selective manner. The obtained cyclopropane fused pyrrolidines can be readily converted to other nitrogen heterocycles with potential synthetic and biological interests. Details of this work can be found in the communication on pages 2253–2258 (H. Wang, C.-Y. Zhou, C.-M. Che, Adv. Synth. Catal. 2017, 359, 2253–2258; DOI: 10.1002/adsc.201700205).
    Cyclopropane
    Cycloheptatriene
    Citations (0)
    This first synthesis of a vinyldiazo­lactone lead to the discovery of its successful utility in rhodium-catalyzed asymmetric C-H insertion and cyclopropanation. Rh2(S,R-MenthAZ)4, a carboxamidate chiral rhodium catalyst, provided the highest ee and selectivity for C-H insertion using 1,4-cyclohexadiene. In contrast, vinylarenes undergo an efficient cyclopropanation under the same catalytic system with high yields and good diastereoselectivities. Reduction of the lactone and subsequent divinyl cyclopropane Cope rearrangement gives rapid access to hydroazulenes, seven-membered carbocycles that are present in many natural products.
    Cyclopropane
    Citations (0)
    Abstract An efficient dirhodium(II)‐catalyzed macrocyclization reaction of alkyne‐containing diazoacetates through intramolecular metal carbene cyclopropanation is described. This method provides a variety of 12‐ to 22‐membered macrocyclic alkynes, which incorporate ortho ‐aryl, cyclopropane, and cyclopropene units, in good to excellent yields under mild reaction conditions. magnified image
    Cyclopropene
    Cyclopropane
    Alkyne
    Citations (1)
    Abstract The transition‐metal‐catalyzed cyclopropanation of alkenes by the decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes, but is tempered by the potentially explosive nature of diazo substrates. Herein we report the Mo‐catalyzed regiospecific deoxygenative cyclopropanation of readily available and bench‐stable 1,2‐dicarbonyl compounds, in which one of the two carbonyl groups acts as a carbene equivalent upon deoxygenation and engages in the subsequent cyclopropanation process. The use of a commercially available Mo catalyst afforded an array of valuable cyclopropanes with exclusive regioselectivity in up to 90 % yield. The synthetic utility of this method was further demonstrated by gram‐scale syntheses, late‐stage functionalization, and the cyclopropanation of a simple monocarbonyl compound. Preliminary mechanistic studies suggest that phosphine (or silane) acts as both a mild reductant and a good oxygen acceptor that efficiently regenerates the catalytically active Mo catalyst through reduction of the Mo‐oxo complexes.
    Deoxygenation
    Citations (30)
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    Citations (1)
    Key words cobalt catalysis - asymmetric radical reaction - cyclopropanation - diazo reagents
    Citations (0)