Donor-acceptor Cyclopropanes Research Articles

Sn(OTf)2-Catalyzed (3 + 2) Cycloaddition/Sulfur Rearrangement Reaction of Donor-Acceptor Cyclopropanes with Indoline-2-thiones.

The (3 + 2) cycloaddition/sulfur rearrangement reaction of donor-acceptor cyclopropanes bearing a single keto acceptor with indoline-2-thiones has been realized. Under the catalysis of Sn(OTf)2, a series of functionalized 3-indolyl-4,5-dihydrothiophenes were synthesized with moderate to excellent yields.

Iron-catalyzed cascade C-C/C-O bond formation of 2,4-dienals with donor-acceptor cyclopropanes: access to functionalized hexahydrocyclopentapyrans.

Iron-catalyzed cascade C-C and C-O bond formation of 2,4-dienals with donor-acceptor cyclopropanes (DACs) has been developed to furnish hexahydrocyclopentapyrans. Optically active DACs can be coupled stereospecifically (>97% ee). Chirality transfer, use of iron-catalysis and substrate scope are the salient practical features.

Synthesis of β-enamino malonates through caesium carbonate-promoted reaction of nitro-substituted donor-acceptor cyclopropanes.

A caesium carbonate-promoted reaction of nitro-substituted donor-acceptor cyclopropanes (DACs) with primary aromatic amines in water provides a convenient access to β-enamino malonates under mild reaction conditions. The transformation takes place through the formation of allene intermediates from the DACs followed by the conjugate addition of various primary aromatic amines to the intermediates. The reaction proceeds more efficiently in water as compared with organic solvents and the products were isolated in good yields by filtering through a silica gel column without any prior extraction procedure.

Activation of donor–acceptor cyclopropanes under basic conditions: ring opening of 2-(p-siloxyaryl)cyclopropane 1,1-dicarboxylates with nitro compounds and other C-nucleophiles

A new activation mode for donor–acceptor cyclopropanes was proposed and implemented in their reaction with nitro compounds and other common C-nucleophiles.

Concise approach to γ-(het)aryl- and γ-alkenyl-γ-aminobutyric acids. Synthesis of vigabatrin.

γ-Aminobutyric acid (GABA) and GABA derivatives have attracted increased attention over the years in the fields of medicinal chemistry and chemical biology due to their interesting biological properties and synthetic relevance. Here, we report a short synthetic route to γ-(het)aryl- and γ-alkenyl-γ-aminobutyric acids, including the antiepileptic drug vigabatrin, from readily available donor-acceptor cyclopropanes and ammonia or methylamine. This protocol includes a facile synthesis of 2-oxopyrrolidine-3-carboxamides and their acid hydrolysis to γ-aryl- or γ-alkenyl-substituted GABAs, which can serve as perspective building blocks for the synthesis of various GABA-based N-heterocycles and bioactive compounds.

Catalytic stereoselective synthesis of cyclopentanones from donor-acceptor cyclopropanes and in situ-generated ketenes.

A dual InBr3-EtAlCl2 Lewis acidic system was found to be optimal for promoting the diastereoselective (3 + 2)-cycloaddition of donor-acceptor cyclopropanes with in situ-generated ketenes to form cyclopentanones. The desired products were formed in good to excellent yields (70-93% for 16 examples) and with good to excellent diastereoselectivity and enantiospecificity.

One-pot C-N/C-C bond formation and oxidation of donor-acceptor cyclopropanes with tetrahydroisoquinolines: access to benzo-fused indolizines.

One-pot C-N/C-C bond formation of donor-acceptor cyclopropanes (DACs) with tetrahydroisoquinolines (THIQs) has been achieved to furnish benzo-fused indolizines. These reactions involve a MgI2-catalyzed ring opening of DACs and oxidative annulation using Mn(OAc)3·2H2O. The substrate scope and functional group diversity are the important practical features.

Asymmetric [3 + 2] cycloaddition of donor–acceptor cyclopropanes with azadienes enabled by Brønsted base catalysis

A chiral bifunctional Brønsted base-catalyzed enantioselective [3 + 2] cycloaddition of D–A cyclopropanes and azadienes is reported. The protocol features broad substrate scope, mild reaction conditions and high functional group tolerance.

Sequential One-Pot Synthesis of β-Amino-γ-keto-malonates from Nitro-Substituted Donor–Acceptor Cyclopropanes

AbstractA sequential one-pot procedure has been developed to access β-amino-γ-keto-malonates from nitro-substituted donor–acceptor cyclopropanes and four different nitrogen heterocycles. The reaction proceeds through in situ generation of aroylmethylidene malonates from 1-aryl-2-nitrocyclopropanes via Kornblum-type ring-opening oxidation using DMSO and subsequent aza-Michael addition with the nitrogen heterocycles. To prove the synthetic utility of the resulting products, one of them was transformed into a pyridazinone derivative.

Electrocatalytic Synthesis of 1,2-Dioxolanes from Tetrasubstituted Donor–Acceptor Cyclopropanes

AbstractAn electrochemical method for the synthesis of 3,3,5,5-tetrasubstituted 1,2-dioxolanes from donor–acceptor cyclopropanes with quaternary donor positions is described. This catalyst-free strategy delivers radical cations after C(sp3)–C(sp3) cleavage by direct anodic oxidation of the strained carbocycle. A broad scope with regard to the cyclopropanes employed in the reaction is presented. Additionally, we propose a plausible mechanism for the reaction.

Yb(OTf)3-Catalyzed Formal (4 + 3) Cycloaddition Reactions of 3-Benzylideneindoline-2-thiones with Donor-Acceptor Cyclopropanes.

A Yb(OTf)3-catalyzed formal (4 + 3) cycloaddition reaction of donor-acceptor cyclopropanes with 3-benzylideneindoline-2-thiones as sulfur-containing 4π components has been successfully achieved. A series of functionalized 5,10-dihydro-2H-thiepino[2,3-b]indole derivatives were synthesized with good yields and moderate to good diastereoselectivity. The reaction described herein represented the inaugural (4 + 3) cycloaddition of 3-benzylideneindoline-2-thiones.

Recent Advances on High-Order Dipolar Annulations of Donor–Acceptor Cyclopropanes/Cyclobutanes

AbstractThis short review summarizes the recent impressive developments on the high-order dipolar annulations (HODAs) of donor–acceptor cyclopropanes (DACs) and donor–acceptor cyclobutanes (DABs) to afford medium-sized (hetero)cycles.1 Introduction2 (3+m) (m > 3) Annulations of Donor–Acceptor Cyclopropanes2.1 (3+4) Annulations2.2 (3+5) Annulations3 (4+m) (m > 2) Annulations of Donor–Acceptor Cyclobutanes4 Conclusion

Enantiospecific Total Synthesis of (−)‐Hyacinthacine A1 and (+)‐Hyacinthacine A1 and Their Homologues Using Nitrogen Substituted Donor–Acceptor Cyclopropane

AbstractA concise and efficient enantiospecific total synthesis of (−)‐hyacinthacine A1 and (+)‐hyacinthacine A1 was achieved from commercially available starting material L‐pyroglutamic acid and D‐glutamic acid, respectively. For the synthesis of this trihydroxylated pyrrolizidine ring, we employed the nitrogen‐substituted donor‐acceptor cyclopropane as a key intermediate. The synthetic approach relies on two crucial steps, highly stereo‐ and regioselective intramolecular cyclopropanation with Rh2(OAc)4 and regioselective ring opening of a nitrogen‐substituted donor‐acceptor cyclopropane.

Stereoselective Photoredox Catalyzed (3+3) Dipolar Cycloaddition of Nitrone with Aryl Cyclopropane.

By resorting to the principle of remote activation, we herein demonstrate the first photoredox catalyzed (3+3) dipolar cycloaddition of nitrones with aryl cyclopropanes. Key to the fidelity of the reaction resides in a facile manner of substrate activation by single-electron transfer (SET) oxidation with photoredox catalysis, and the reaction takes place through a stepwise cascade encompassing a three-electron-type nucleophilic substitution triggered cyclopropane ring-opening and a diastereoselective 6-endo-trig radical cyclization manifold. The reaction proceeds under mild conditions with excellent regio- and stereoselectivity, nicely complementing the well-developed Lewis acid catalyzed cycloaddition of donor-acceptor cyclopropanes. Other merits of the protocol include wide scope of aryl cyclopropanes with diversified substitution patterns and good functional-group compatibility. A mechanism involving an aryl radical cation promoted remote activation mode was also proposed and supported by mechanistic experiments.

Development of cationic gallium phthalocyanine catalysts for the chemistry of donor-acceptor cyclopropanes and its reactions with aldehydes

Cationic gallium phthalocyanine (RPcGa+) catalysts with SbF6– and Sb2F11–/Sb3F16– weakly coordinating anions were developed and used in the catalytic chemistry of donor-acceptor (D–A) cyclopropanes and related substrates. For the first time, these processes were implemented on the examples of [3 + 2]-cycloaddition/annulation reactions of D–A cyclopropanes and styrylmalonates with various aldehydes, as well as some other transformations with different substrates.

Regioselective C3-H Alkylation of Imidazopyridines with Donor-Acceptor Cyclopropanes.

Alkylated imidazopyridines are crucial structures for medicinal chemistry. Here, an efficient method for the C3-H alkylation of imidazopyridines was devised. Under Lewis acid-catalyzed conditions, reactions of imidazopyridines with different donor-acceptor cyclopropanes were carried out. Finally, 1,3-bisfunctionalizaton of donor-acceptor cyclopropanes was performed. In addition, synthesized C3-alkylated imidazopyridines are amenable for diverse synthetic applications.

Organocatalytic Activation of Donor-Acceptor Cyclopropanes: A Tandem (3 + 3)-Cycloaddition/Aryl Migration toward the Synthesis of Enantioenriched Tetrahydropyridazines.

An organocatalytic enantioselective (3 + 3)-cycloaddition reaction of racemic cyclopropane carbaldehydes and aryl hydrazones has been demonstrated for the first time. A wide range of enantioenriched tetrahydropyridazines with an exocyclic double bond were obtained with moderate to good yields and good to excellent enantiomeric excesses. Mechanistic investigations hinted toward a matched/mismatched kinetic resolution, and control experiments and DFT calculations unveiled that 1,3-aryl migration was concerted and intramolecular and proceeds via a four-membered transition state.

Efficient and versatile formation of glycosidic bonds via catalytic strain-release glycosylation with glycosyl ortho−2,2-dimethoxycarbonylcyclopropylbenzoate donors

Catalytic glycosylation is a vital transformation in synthetic carbohydrate chemistry due to its ability to expediate the large-scale oligosaccharide synthesis for glycobiology studies with the consumption of minimal amounts of promoters. Herein we introduce a facile and efficient catalytic glycosylation employing glycosyl ortho−2,2-dimethoxycarbonylcyclopropylbenzoates (CCBz) promoted by a readily accessible and non-toxic Sc(III) catalyst system. The glycosylation reaction involves a novel activation mode of glycosyl esters driven by the ring-strain release of an intramolecularly incorporated donor-acceptor cyclopropane (DAC). The versatile glycosyl CCBz donor enables highly efficient construction of O-, S-, and N-glycosidic bonds under mild conditions, as exemplified by the convenient preparation of the synthetically challenging chitooligosaccharide derivatives. Of note, a gram-scale synthesis of tetrasaccharide corresponding to Lipid IV with modifiable handles is achieved using the catalytic strain-release glycosylation. These attractive features promise this donor to be the prototype for developing next generation of catalytic glycosylation.

Synthesis of Heterocycles from Donor-Acceptor Cyclopropanes: A Five-Year Recap

AbstractThis review discusses the utility of donor-acceptor cyclopropanes (DACs) for the construction of heterocycles. In addition to (3+2), (3+3), and (4+3) cycloaddition pathways, nucleophilic ring-opening reactions, intramolecular transformations, and cycloisomerizations in the presence of suitable catalysts pave the way for the generation of heterocycles from DACs. The mild reactions conditions employed and the variety of starting materials that can be used as reaction partners make the DAC route for heterocycle synthesis attractive. The literature covered in this review is from the period 2018 to 2023.1 Introduction2 Synthesis of Nitrogen Heterocycles2.1 By Annulations with Anthranils and Azadienes2.2 By Nucleophilic Attack of Anilines and Hydrazones2.3 By Reaction with Ureas and Thioureas2.4 By Annulation Reactions Using an Azomethine Imine2.5 By Reaction with Other Nitrogen Heterocycles2.6 By Other Transformations3 Synthesis of Oxygen Heterocycles3.1 By Intramolecular Transformations3.2 By Intermolecular Reactions4 Synthesis of Sulfur and Selenium Heterocycles4.1 By Reaction with Thiocarbonyl Substrates4.2 By Reaction with Thio- and Selenocyanates and Thiosulfonate Salts5 Synthesis of N–S and N–O Heterocycles6 Conclusions

Triple role of thiocyanate-containing protic ionic liquids in chemodivergent ring-opening of 1,3-indanedione-derived donor–acceptor cyclopropanes

Triple-role thiocyanate-containing protic ionic liquids (PILs) were employed as a regenerable solvent, a Brønsted acid catalyst, and a source of the nucleophile for the ring-opening of 1,3-indanedione-based donor–acceptor cyclopropanes.