Cyclopropyl Substrates Research Articles

A Redox Auxiliary Strategy for Pyrrolidine Synthesis via Photocatalytic [3+2] Cycloaddition.

Cycloaddition reactions can be used to efficiently assemble pyrrolidine rings that are significant in a variety of chemical and biological applications. We have developed a method for the formal cycloaddition of cyclopropyl ketones with hydrazones that utlizes photoredox catalysis to enable the synthesis of a range of structurally diverse pyrrolidine rings. The key insight enabling the scope of photoredox [3+2] cycloadditions to be expanded to C=N electrophiles was the use of a redox auxiliary strategy that allowed for photoreductive activation of the cyclopropyl ketone without the need for an exogenous tertiary amine co-reductant. These conditions prevent the deleterious reductive ring-opening of the cyclopropyl substrates, enabling a range of less-reactive coupling partners to participate in this cycloaddition.

ChemInform Abstract: N‐Heterocyclic Carbene‐Catalyzed Ireland—Coates Claisen Rearrangement: Synthesis of Functionalized β‐Lactones.

AbstractFormal [3 + 2]‐annulation is achieved between a range of α,β‐unsaturated acyl fluorides and cyclopropyl substrates bearing C2‐ and C4‐oxygenation.

Oxidation of N-Methylanilines by a Nonheme Iron(IV)-Oxo Complex

High-valent iron-oxo species have been frequently employed in heme and nonheme iron enzymes to carry out catalytic oxygenation reactions. In heme-based systems, biological and synthetic oxoiron(IV) porphyrin π-cation radicals are believed to carry out the catalytic oxidations of organic substrates. In the nonheme iron enzymes, oxoiron(IV) intermediates have recently been identified by spectroscopic methods in the catalytic cycle of taurine dioxygenase, and synthetic nonheme oxoiron(IV) species bearing tetradentate and pentadentate ligands were also isolated and characterized. In addition, it has been demonstrated that the nonheme oxoiron(IV) species were capable of conducting the conversion of diverse organic subsatrates such as PPh3, thioanisole, alcohol, and alkanes. The molecular mechanisms of oxidative N-demethylation of N,N-dimethylanilines by heme enzymes such as peroxidases and cytochrome P-450 have been studied for the past twenty years. However, two possible mechanisms, electron transfer followed by proton transfer and hydrogen transfer from α-C-H bonds of the methyl group in N,Ndimethylanilines, are still under debate. Recently, we also reported the oxidative N-dealkylation of N,N-dialkylanilines and demonstrated that the oxidative N-dealkylation reactions occurred via a proton-coupled electron transfer process. Meanwhile, secondary amine substrates bearing a cyclopropyl group have been used in the relation to a mechanismbased inactivation of heme enzymes, and the formation of a highly reactive carbon-centered radical was reported in the oxidation of heteroatom-containing cyclopropyl substrates. Relatively, a few studies for the oxidation of Nmethylanilines as substrate were reported using iron, cobalt, and copper complexes. However, no detailed mechanistic study in the oxidation of secondary amines with nonheme Fe(IV)-oxo species has been reported until now. Presented in this study is a kinetic examination of the oxidation of N-methylanilines with [(tmc)Fe=O] (tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), which yields N,N'-dimethyl-N,N'-diphenylhydrazine formed by the coupling of two N-methylaniline molecules. By determining the rate constants for the step of electron transfer from N-methylaniline to the iron(IV)-oxo species, we suggest that the oxidation of N-methylaniline occurs via an electron transfer. Experimental Procedure

On the regioselectivity of the Ru-catalyzed intramolecular [5 + 2] cycloaddition.

The influence of substituents on which cyclopropyl bond cleaves in the cycloisomerization of cyclopropylenynes catalyzed by CpRu(N&tbd1;CCH(3))(3)(+)PF(6)(-) is compared to the corresponding Rh-catalyzed reaction. With the trans cyclopropyl substrates, the bond energy of the cleaving bond appears to be an important factor. With cis cyclopropyl substrates, steric effects appear to dominate.

Unexpected formation of N-(2-cyclopropenyl)phthalimides in the photosensitized decarboxylation of N-(2-cyclopropenylcarbonyloxy)phthalimides

The photosensitized decarboxylation of N-(2-cyclopropenylcarbonyloxy)phthalimides 1 smoothly generates N-(2-cyclopropenyl)phthalimides 3 instead of the corresponding 3-unsubstituted cyclopropene derivatives. On the other hand, the photolytic reaction of cyclopropyl substrate 5 proceeds as expected to give cyclopropane derivative 6, thus suggesting a different reactivity of cyclopropen-3-yl and cyclopropyl putative intermediate radicals in this decarboxylation process.

REACTION OF CYCLOPROPYLBENZENE AND CYCLOPROPYL PHENYL KETONE WITH SULFUR TRIOXIDE1–3

Abstract The sulfonation of cyclopropylbenzene (1a) and cyclopropyl phenyl ketone (5) with sulfur trioxide in both nitromethane and 1,4-dioxane as solvent has been studied. Sulfonation of cyclopropylbenzene (1a) with up to 2.0 mol-equiv. of SO3 in dioxane leads to the initial formation of 3-phenyl-1,3-propanesultone (2a) which product subsequently slowly isomerizes to 3-phenyl-2-propene-1-sulfonic acid (4a). Sulfonation of 1a with 4.0 mol-equiv. of SO3 in nitromethane gives the corresponding 4-sulfo derivatives 2b and 4b, of which the former product also slowly isomerizes to give the latter. Reaction of cyclopropyl phenyl ketone (5) with SO3 in nitromethane yields quantitatively 1-benzoyl-1,3-propanesultone (6). Upon aqueous alkaline work-up of the reaction mixtures, the γ-sultones 2a and 6 are quantitatively converted into the corresponding potassium hydroxypropanesulfonates 3 and 7, respectively. Mechanisms for the formation of the various products from the starting cyclopropyl substrates are proposed.

Chemistry of dicyclopropylcarbene and related intermediates in dimethyl sulfoxide

The potassium salts of the anions of (phenylsulfonyl)hydrazones of diisopropyl, isopropyl cyclopropyl, and dicyclopropyl ketone were decomposed in dimethyl sulfoxide in the temperature range of 110-130°C. The diisopropyl phenylsulfonyl anion decomposes to form 2,4-dimethyl-2-pentene and diisopropyl ketone. Similar decomposition of the isopropyl cyclopropyl substrate forms 1-cyclopropyl-2-methylpropene, 1-isopropylcyclobutene, and isopropyl cyclopropyl ketone, while thermal decomposition of the dicyclopropyl ketone (phenylsulfonyl)-hydrazone anion forms cyclopropylcyclobutene and dicyclopropyl ketone

Cyclopropylglyoxylate as a mechanistic probe of thiamine pyrophosphate dependent pyruvate-metabolizing enzymes

Four pyruvate-decarboxylating enzymes with thiamine pyrophosphate (TPP) cofactors catalyze the decarboxylation of the cyclopropyl substrate analog cyclopropylglyoxylate. Pyruvate: ferredoxin oxidoreductase, an archaebacterial enzyme which catalyzes oxidation of the hydroxyethyl-TPP (HETPP) intermediate by two one-electron transfers to an iron-sulfur center, generates the coenzyme A thioester of cyclopropylcarboxylic acid. A long-lived free radical, HETPP is thought to be an intermediate in the pyruvate to acetyl-CoA conversion; however, cleavage of the cyclopropyl ring was not detected. Pyruvate decarboxylase, pyruvate oxidase, and pyruvate dehydrogenase also generate the corresponding cyclopropyl products. The applicability of cyclopropyl substrate analogs as indicators of free-radical enzyme mechanisms is discussed in light of these results.