Highly cis-Selective Rh(I)-Catalyzed Cyclopropanation Reactions

Abstract

The performance of recently reported highly cis-diastereoselective Rh(I) cyclopropanation catalysts has been significantly improved by a systematic study of different reaction parameters (catalyst activation, solvent, temperature, stoichiometry). The catalyst efficiency and diastereoselectivity were enhanced by changing the activating agent from AgOTf to NaBArf. With this new system, the Rh(I) catalyst was shown to be a highly efficient and cis-diastereoselective cyclopropanation catalyst in reactions between α-diazoacetates and a range of different alkenes and substituted derivatives. Particularly noteworthy is the remarkable reactivity and cis-diastereoselectivity displayed in the reactions between ethyl diazoacetate and cyclopentene, 2,5-dihydrofuran, and benzofuran, with yields up to 99% and cis-selectivities greater than 99%.

Designing ‘Totem’ C2‐Symmetrical Iron Porphyrin Catalysts for Stereoselective Cyclopropanations

“…Note that the eco-tolerability of cyclopropanationr eactions can be further enhanced i) by using continuous flow methodologies due to the safe handling of hazardous reagents such as diazo compounds, [17][18][19][20] ii)bya pplying biomimeticc atalysts coupling very good catalytic activity with natural high chemical selectivity, [21][22][23][24][25][26] and iii)bye mploying unconventional catalytic systems such as supramolecular cage catalysts whichs imulate the working operandi of enzymes. [27][28][29][30] Amongst all the metal catalysts, metal porphyrins were very activea nd ruthenium, [31][32][33][34] osmium, [35,36] rhodium, [37][38][39] and iridium [40] porphyrin complexes have been extensively employed to promote cyclopropanationr eactions. In spite of the good catalytic efficiency of the above-mentioned porphyrin catalysts, their high cost and toxicity prompted the study of the more eco-friendly first-row transition metal porphyrins, such as cobalt [41][42][43][44][45][46] and iron [47][48][49][50][51][52][53][54] derivatives.…”

Catalytic Enantioselective Synthesis of Highly Functionalized Difluoromethylated Cyclopropanes

“…Pleasingly,t he para-methyl, para-tert-butyl, and para-methoxy derivatives were readily converted into the corresponding cyclopropanes 3b-d in excellent yields with complete diastereoselectivity in favor of the trans isomer, [20] and excellent enantiomeric excesses.Asimilar reactivity was observed for the metasubstituted aryl derivatives as 3e and 3f were obtained in excellent yields and 99 % ee. [22] Finally,weextended the scope to two other diazo ketones, 1b (R = CN) and 1c(R = CO 2 Me), which were readily converted into the expected cyclopropanes 3m and 3n in good yields, very high diastereoselectivity,and excellent ee values for 3n. [21] Thestereochemical outcome of the reaction is in agreement with the model depicted by Davies and co-workers.…”

Catalytic Enantioselective Synthesis of Highly Functionalized Difluoromethylated Cyclopropanes

“…[19] Moreover,the presence of the benzofuran ring was well tolerated, and the corresponding cyclopropane 3l was isolated in high yield with high d.r.and ee values.Note that no side reaction on the benzofuran ring was observed. [22] Finally,weextended the scope to two other diazo ketones, 1b (R = CN) and 1c(R = CO 2 Me), which were readily converted into the expected cyclopropanes 3m and 3n in good yields, very high diastereoselectivity,and excellent ee values for 3n.…”