HETEROGENEOUS IRON CATALYZED CYCLOPROPANATION REACTION
Creators: name: SARKAR, ABHIJNAN
Publisher: name: Universit� degli Studi di Milano
Year: 2020

description: Until now, NGR (nitrogen-enriched graphene) catalysts have mostly been employed for hydrogenation/oxidation reactions. In this piece of work, we expand the field of applicability of an iron NGR catalyst to cyclopropanation reactions. In this work, a heterogeneous Fe-based nitrogen-doped carbon supported catalyst has been successfully employed for the cyclopropanation reaction of alkenes. According to best of our knowledge, this is the first example of a heterogeneous Fe-catalyzed cyclopropanation reaction in today's date. These kinds of materials, generally employed for reduction or oxidation reaction, are now indeed effective catalyst also for carbene transfer reactions. The activity of Fe/Phen@C-800in the reaction was initially explored by using ethyl diazoacetate and ?-methylstyrene as substrates as the model transformation. Various parameters such as solvent, temperature, time and catalyst support etc. were changed. The nature of the solvent has a minimal influence both on the reaction yield and diasteroselectivity making this reaction versatile from the media profile. The variation of the reaction temperature furnished the product in slightly lower yield. When a 5-fold amount of the olefin with respect to the diazo compound was used, homocoupling products (diethyl fumarate and diethyl maleate) deriving from EDA were detected in very low amount (&lt;5 %). Even when the amount of olefin was decreased (1.5 eq) homocoupling side products increased, although a very good yield of the cyclopropane was maintained, demonstrating the applicability of the procedure even to more expensive olefins. Interestingly, the catalyst is water tolerant and only a slight decreased yield was obtained using a ?wet? solvent. A change in the catalyst support from carbon to inorganic oxides (MgO or SiO2) does not significantly affect the yield and the diastero selectivity. Furthermore control experiments effected by employing catalysts prepared by the same procedure employed for Fe/Phen@C-800, but omitting either Fe(OAc)2 or Phen, resulted in no detectable formation of cyclopropane. Fe/Phen@C-800-catalysts showed good results in dimethoxyethane at 60 �C for 4 h, affording high yields of the desired cyclopropanes (mixture of cis and trans isomers) and only &lt;5 % ethyl maleate and fumarate. The model reaction has been successfully scaled-up to 15-fold without significant variations of yield and diasteroisomeric ratio. The developed protocol allows obtaining several cyclopropanes from aromatic and aliphatic olefins and different diazocompounds. High to excellent yields were obtained for terminal olefins, including geminally substituted ones. Aliphatic olefins require longer reaction times. A moderate trans diastereoselectivity was observed in all cases. The catalysts do not show any activity towards internal olefins and can be used to selectively cyclopropanate a terminal olefin in a substrate containing both internal and terminal olefinic groups. The selectivity for the terminal double bond can be explained by the lack of activity of the catalyst in the case of internal olefins, most likely due to a hindered approach of the substrate to the carbene formed on the surface of the catalyst. Mono substituted diazo compounds (ester or ketone) afforded the corresponding cyclopropanes in excellent yields. More sterically demanding diazocompounds such as t-BDA has a dramatic effect on the diasteroselection, furnishing the cis- isomer only in traces. Disubstituted diazomethanes proved to be more challenging. Mono substituted diazo compounds such as diphenyldiazomethane failed to afford corresponding cyclopropanes under standard conditions, although it yielded the product in moderate yield at a higher temperature and longer reaction time (100 �C for 8h in toluene), while the more stable diazomalonate did not react even under these conditions. The catalysts was recycled several times, but a gradual deactivation is immediately observed since the first recycle. In principle, the loss of activity can be attributed either to metal leaching or to deactivation of the catalyst. After the first recycle, ICP analysis of the solution showed that only 0.1% of the initial iron had been lost in solution. This result indicates that the loss of recycling ability is not due to metal leaching. In order to make the whole process both efficient and effective, two routes of reactivation were explored. Attempted reactivation of the catalyst at 300 �C seems to have a slightly positive effect but that at 400 �C is not effective. The initial catalyst activity was effectively restored using an oxidative reactivation protocol under mild conditions (H2O2, 3 v/v% aqueous solution), which may be of more general use even for other reactions if olefins or other polymerizable compounds are employed as substrates. Oxidative regeneration is typical for catalyst that suffer of physicochemical deactivation (e.g. fouling or poisoning). Indeed, we verified that complete deactivation of the catalyst occurs even by treating the material only with styrene under the reaction conditions and the activity is restored by oxidative treatment. This result indicates the polymerization of the olefin on the catalytic surface as a possible cause for the deactivation rather than a mechanical or thermal modification of the catalyst.