Showing papers on "Cyclopropane published in 2011"

Asymmetric Rh(II)-Catalyzed Cyclopropanation of Alkenes with Diacceptor Diazo Compounds: p-Methoxyphenyl Ketone as a General Stereoselectivity Controlling Group

Abstract: Different diacceptor diazo compounds bearing an α-PMP-ketone group were found to be effective carbene precursors for the highly stereoselective Rh2(S-TCPTTL)4-catalyzed cyclopropanation of alkenes (EWG = NO2, CN, CO2Me). The resulting products were readily transformed into a variety of biologically relevant enantiopure molecules, such as cyclopropane α- and β-amino acid derivatives. Different mechanistic studies carried out led to a rationale for the high diastereo- and enantioselectivity obtained, where the PMP-ketone moiety was found to play a critical role in the stereoinduction process. Additionally, the use of catalytic amounts of achiral Lewis bases to influence the enantioinduction of the reactions developed is documented.

Oxazaborolidinium ion-catalyzed cyclopropanation of α-substituted acroleins: enantioselective synthesis of cyclopropanes bearing two chiral quaternary centers.

Abstract: A catalytic synthetic route to highly functionalized chiral cyclopropane derivatives was developed by Michael-initiated cyclopropanation of α-substituted acroleins with aryl- and alkyl diazoacetates. In the presence of chiral (S)-oxazaborolidinium cation 1b as a catalyst, the reaction proceeded in high yield (up to 93%) with high to excellent diastereoselectivity (up to 98% de) and enantioselectivity (up to 95% ee).

Formal Homo‐Nazarov and Other Cyclization Reactions of Activated Cyclopropanes

Abstract: The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo-Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl-cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three-membered ring of vinyl-cyclopropyl ketones to allow the formal homo-Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non-electron-rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo-Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with Bronsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported.

Asymmetric cyclopropanation of β,γ-unsaturated α-ketoesters with stabilized sulfur ylides catalyzed by C2-symmetric ureas.

Abstract: A novel organocatalytic asymmetric cyclopropanation of β,γ-unsaturated α-ketoesters with stabilized sulfur ylides using C(2)-symmetric urea as a hydrogen-bond catalyst has been described. This reaction allows an efficient access to 1,2,3-trisubstituted cyclopropane derivatives in moderate to good yields with up to 16:1 dr and 90:10 er under mild reaction conditions. The mechanism study proved that the high stereoinduction originated from the cooperative effect of the hydrogen-bond catalyst.

Potential Energy Surface for (Retro-)Cyclopropanation: Metathesis with a Cationic Gold Complex

Abstract: The gas-phase cyclopropanation and apparent metathesis reactivity of ligand-supported gold arylidenes with electron-rich olefins is explained by quantum-chemical calculations. A deep potential minimum corresponding to a metal-bound cyclopropane adduct is in agreement with the measured absolute energies of the cyclopropanation and metathesis channels and is also consistent with previously reported electronic effects of arylidenes and supporting phosphorus ylid ligands on the product ratios. In the gas phase, the rate-determining step for the cyclopropanation is dissociation of the Lewis-acidic metal fragment, whereas the metathesis pathway features several rate-limiting transition states that are close in energy to the final product dissociation and hence contribute to the overall reaction rate. Importantly, the presented potential energy surface also accounts for the recently reported gold-catalyzed solution-phase retro-cyclopropanation reactivity.

Lewis Acid‐Catalyzed [3+4] Annulation of 2‐(Heteroaryl)‐ cyclopropane‐1,1‐dicarboxylates with Cyclopentadiene

Abstract: A novel Lewis acid-catalyzed [3+4] annulation of 2-(heteroaryl)cyclopropane-1,1-dicarboxylates with cyclopentadiene is reported. This reaction proceeds via an electrophilic attack of the Lewis acid-activated donor-acceptor cyclopropane onto cyclopentadiene followed by Friedel–Crafts intramolecular alkylation of the heteroarene substituent. This is the first general example of reactions of donor-acceptor cyclopropanes wherein the donor substituent serves as a nucleophile. The described annulation represents a convenient approach to bicyclo[3.2.1]octa-2,6-dienes with heteroarenes annulated to C(2)-C(3) bond. Its efficiency was demonstrated for a series of furyl, thienyl, pyrrolyl, benzofuryl, benzothienyl, and indolyl substituted cyclopropanes. Additionally, in the case of 2-(5-methyl-2-furyl)cyclopropane-1,1-diester we observed the predominant formation of product of the [3+4] annulation or the tetracyclic 5,8-methanocyclopenta[a]azulene derivative, depending on the reaction conditions.

Rhodium-Catalyzed Ring Expansion of Cyclopropanes to Seven-membered Rings by 1,5 C ? C Bond Migration

Abstract: Selective cleavage and subsequent elaboration of carbon–carbon σ bonds into complex molecules represents a fundamental challenge in chemistry. The C–C σ bonds of cyclopropanes are activated owing to ring strain, and the ring expansion of cyclopropanes is an attractive route to other ring systems because of the well-documented stereoselective methods for cyclopropanation.[1] Indeed, ring expansion of cyclopropanes to four- or five-membered rings by 1,2 or 1,3 migration is routinely practiced in organic synthesis [Eq. (1)].[2] In contrast, ring expansion of cyclopropanes to seven-membered rings by 1,5 C–C bond migration has not been developed as a general method, in spite of the prevalence of cycloheptane skeletons in natural products and pharmaceutical agents.[3] The 1,5 migration of a cyclopropane C–C bond has been mainly studied in bicyclo-[4.1.0]heptadienes and a few other conformationally constrained bicyclic compounds under thermal conditions.[4] In fact, it was reported that simple 1,3-dienylcyclopropanes underwent 1,3 C–C bond migration to form vinylcyclopentenes in the presence of Ni or Pd catalysts.[5]

Base-Controlled Selective Conversion of Michael Adducts of Malonates with Enones in the Presence of Iodine

Abstract: An efficient base-controlled selective conversion of the Michael adducts of malonates with enones in the presence of iodine is reported. Highly functionalized cyclopropane, oxetane, and α-hydroxylmalonate derivatives are obtained selectively using DBU, Na2CO3, and NaOAc as the base, respectively. O2 was identified to be crucial to the formation of oxetane and α-hydroxylmalonate derivatives.

Cyclopropyl carbinol rearrangement for benzo-fused nitrogen ring synthesis.

Abstract: A synthetic method that relies on gold-catalysed cyclopropyl carbinol rearrangement of 2-tosylaminophenyl cyclopropylmethanols to prepare 2,3-dihydro-1H-benzo[b]azepines and 2-vinylindolines efficiently is reported. The reactions were shown to be chemoselective, with secondary and tertiary alcohol substrates exclusively providing benzo-fused five- and seven-membered ring products, respectively. The ring-forming process was also found to proceed in moderate to excellent yields under mild conditions only in the presence of the gold and silver catalyst combination. The mechanism is thought to involve activation of the alcohol by the (p-CF(3)C(6)H(4))(3)PAuCl/AgOTf (Tf = triflate) catalyst, resulting in ionization of the starting material. The tertiary carbocationic intermediate generated in situ in this manner then triggers ring-opening of the cyclopropane moiety and trapping by the tethered aniline group to give the 2,3-dihydro-1H-benzo[b]azepine. Cyclopropane ring fragmentation of the secondary carbocationic analogue, on the other hand, results in diene formation followed by subsequent intramolecular hydroamination to afford the 2-vinylindoline.

Density Functional Theory Study of the Mechanism and Origins of Stereoselectivity in the Asymmetric Simmons-Smith Cyclopropanation with Charette Chiral Dioxaborolane Ligand

Abstract: Asymmetric Simmons–Smith reaction using Charette chiral dioxaborolane ligand is a widely applied method for the construction of enantiomerically enriched cyclopropanes. The detailed mechanism and the origins of stereoselectivity of this important reaction were investigated using density functional theory (DFT) calculations. Our computational studies suggest that, in the traditional Simmons–Smith reaction conditions, the monomeric iodomethylzinc allyloxide generated in situ from the allylic alcohol and the zinc reagent has a strong tendency to form a dimer or a tetramer. The tetramer can easily undergo an intramolecular cyclopropanation to give the racemic cyclopropane product. However, when a stoichiometric amount of Charette chiral dioxaborolane ligand is employed, monomeric iodomethylzinc allyloxide is converted into an energetically more stable four-coordinated chiral zinc/ligand complex. The chiral complex has the zinc bonded to the CH2I group and coordinated by three oxygen atoms (one from the allyli...

Gold‐Catalyzed Rearrangements: Reaction Pathways Using 1‐Alkenyl‐2‐alkynylcyclopropane Substrates

Abstract: ) allowed to design useful trans-formations based on the cleavage of the cyclopropane ring.Inthisscenario,itseemedtousthatthecatalytictransformationsof substrates containing the alkene–cyclopropane–alkyneconnectivity might be a promising approach. Surprisingly,transformations based on the 1-alkenyl-2-alkynylcyclopro-pane framework (1,5-enyne arrangement) are very rare.

The Michael Reaction

Abstract: The Michael condensation in its original scope is the addition of an addend or donor containing an alpha-hydrogen atom in the system OCCH to a carbon-carbon double bond that forms part of a conjugated system of the general formula CCCO in an acceptor The condensation takes place under the influence of alkaline reagents, typically alkali metal alkoxides The range of addends is very broad Typical acceptors are alpha, beta-unsaturated aldehydes, keotnes, and acid derivatives As an extension of the original scope, the Michael condensation has come to be understood to include addends and acceptors activated by groups other than carbonyl and carboxalkoxy The wider scope is encompassed in this survey Keywords: Michael reaction; side reaction; adduct; bridged intermediates; cyclopropane derivatives; Michael condensation; ketones; esters; cycloalkanones; cycloalkenes; Robinson's modification; aromatic rings systems; rings; pyrroles; piperidines; pyrrolizidines; amino salts; experimental conditions

Mechanism of mycolic acid cyclopropane synthase: a theoretical study.

Abstract: The reaction mechanism of mycolic acid cyclopropane synthase is investigated using hybrid density functional theory. The direct methylation mechanism is examined with a large model of the active site constructed on the basis of the crystal structure of the native enzyme. The important active site residue Glu140 is modeled in both ionized and neutral forms. We demonstrate that the reaction starts via the transfer of a methyl to the substrate double bond, followed by the transfer of a proton from the methyl cation to the bicarbonate present in the active site. The first step is calculated to be rate-limiting, in agreement with experimental kinetic results. The protonation state of Glu140 has a rather weak influence on the reaction energetics. In addition to the natural reaction, a possible side reaction, namely a carbocation rearrangement, is also considered and is shown to have a low barrier. Finally, the energetics for the sulfur ylide proposal, which has already been ruled out, is also estimated, showing a large energetic penalty for ylide formation.

Deactivation of Ru-benzylidene Grubbs catalysts active in olefin metathesis

Abstract: In this work, we explore the reactivity induced by coordination of a CO molecule trans to the Ru-benzylidene bond of a prototype Ru-olefin metathesis catalyst bearing a N-heterocyclic carbene (NHC) ligand. DFT calculations indicate that CO binding to the Ru center promotes a cascade of reactions with very low-energy barriers that lead to the final crystallographically characterized product, in which the original benzylidene group has attacked the proximal aromatic ring of the ligand leading to a cycloheptatriene ring through a Buchner ring expansion. In conclusion, the overall mechanism is best described as a carbene insertion into a C–C bond of the aromatic N-substituent of the NHC ligand, forming a cyclopropane ring. This cyclopropanation step is followed by a Buchner ring expansion reaction, leading to the experimentally observed product presenting a cycloheptatriene ring.

TfOH-catalyzed tandem cyclopropane ring enlargement/C–C formation/etherification of alkynylcyclopropanes and 1,3-diketones to cyclobutane-fused dihydrofurans

Abstract: A new type of TfOH-catalyzed tandem cyclopropane ring enlargement/C–C formation/etherification reaction between alkynylcyclopropanes and 1,3-diketones to cyclobutane-fused dihydrofurans is described. The reaction tolerates a range of aryl and alkyl substituents with moderate to good yields.