Buchner Reaction Research Articles

Intramolecular Buchner Reaction: Experimental and Theoretical Comparison of the Effect of the Carbene Substituent on the Chemoselectivity

AbstractThe intramolecular Buchner reaction is a powerful transformation able to dearomatize benzenic rings. However, the competitive C−H insertion of the carbene moiety into benzylic positions still remains a limitation, and the reasons governing this uncomplete chemoselectivity are poorly understood. The carbene substitution, in particular, has been observed to influence the selectivity strongly, though the currently proposed explanation relying on the electrophilicity of the metallocarbene hardly describes some experimental results reported in the literature. In this article, we present our experimental observations of intramolecular rhodium‐catalyzed Buchner reactions, combined with DFT calculations on selected carbene substituents, to propose a complementary explanation for the observed chemoselectivity modification.

Selective ring expansion and C−H functionalization of azulenes

We report a transition metal-catalyzed ring expansion of azulene that can be contrasted with C–H functionalization. This study represents the first example of the successful ring expansion of azulene using Cu(hfacac)2 (hfacac: hexafluoroacetylacetonate) with a diazo reagent. This result is notable for extending the Buchner reaction, previously limited to benzenoid aromatics, to nonbenzenoid compounds. The chemoselectivity of the reaction can be directed towards C–H functionalization by substituting the Cu catalyst with AgOTf. This approach does not require the addition of phosphine, NHC, or related ligands, and prefunctionalization of azulenes is unnecessary. Furthermore, the method exhibits excellent functional group tolerance, allowing for the synthesis of a wide range of 6,7-bicyclic compounds and C–H functionalized azulenes. We also present a theoretical study that explains the experimental observations, explaining why copper afford the ring expansion product while silver forms the C–H alkylation product.

Silver-Exchanged Zeolite Y Catalyzes a Selective Insertion of Carbenes into C–H and O–H Bonds

Silver-Exchanged Zeolite Y Catalyzes a Selective Insertion of Carbenes into C–H and O–H Bonds

A Mn(OAc)3-Triggered Formation of Cyclopropanes from Ugi Adducts

AbstractUgi adducts involving malonic acid monoesters and dialkoxy-substituted aromatic aldehydes can undergo an oxidative dearomatization when treated with Mn(OAc)3 leading to the formation of fused cyclopropanes as observed in the Buchner reaction of diazo compounds.

Phosphine-catalyzed formal Buchner [6+1] annulation: de novo construction of cycloheptatrienes.

An unprecedented phosphine-catalyzed formal Buchner [6+1] annulation of a newly designed allenoate has been developed, providing a series of cycloheptatriene derivatives in moderate to good yields (up to 99%). This reaction demonstrates that the introduction of an electrophilic allylic group to allenoates effectively extends the reaction scope of phosphine-catalyzed annulation, providing a concise route to cycloheptatrienes. Mechanistic study indicated that this reaction involves a [4+2] Diels-Alder reaction and ring expansion of the bicyclo[4.1.0] moiety, which is similar to the Buchner reaction. Notably, an enantioselective variant of this [6+1] annulation can also be performed using a chiral iminophosphine catalyst.

Dearomative Ring Expansion of Polycyclic Arenes

Benzocycloheptenes constitute a common structural motif embedded in many natural products and biologically active compounds. Herein, we report their concise preparation from non-activated polycyclic arenes using a two-step sequence involving dearomative [4+2]-cycloaddition with arenophile in combination with palladium-catalyzed cyclopropanation, followed by cycloreversion-initiated ring expansion. The described strategy provides a working alternative to the Buchner reaction, which is limited to monocyclic arenes. Overall, this methylene-insertion molecular editing approach enables rapid and direct conversion of simple (hetero)arenes into a range of substituted (aza)benzocycloheptatrienes, which can undergo a myriad of downstream functionalizations.

Dearomative Ring Expansion of Polycyclic Arenes.

Benzocycloheptenes constitute a common structural motif embedded in many natural products and biologically active compounds. Herein, we report their concise preparation from non‐activated polycyclic arenes using a two‐step sequence involving dearomative [4+2]‐cycloaddition with arenophile in combination with palladium‐catalyzed cyclopropanation, followed by cycloreversion‐initiated ring expansion. The described strategy provides a working alternative to the Buchner reaction, which is limited to monocyclic arenes. Overall, this methylene‐insertion molecular editing approach enables rapid and direct conversion of simple (hetero)arenes into a range of substituted (aza)benzocycloheptatrienes, which can undergo a myriad of downstream functionalizations.

Synthesis of Cycloheptatriene-Containing Azetidine Lactones.

We prepared a collection of complex cycloheptatriene-containing azetidine lactones by applying two key photochemical reactions: "aza-Yang" cyclization and Buchner carbene insertion into aromatic rings. While photolysis of phenacyl amines leads to a rapid charge transfer and elimination, we found that a simple protonation of the amine enables the formation of azetidinols as single diastereomers. We provide evidence, through ultrafast spectroscopy, for the electron transfer from free amines in the excited state. Further, we characterize the aza-Yang reaction by establishing the dependence of the initial reaction rates on the rates of photon absorption. An unanticipated change in reactivity in morpholine analogues is explained through interactions with the tosylate anion. The Buchner reaction proceeds with a slight preference for one diastereomer over the other, and successful reaction requires electron-donating carbene-stabilizing substituents. Overall, 16 compounds were prepared over seven steps. Guided by an increase in structural complexity, efforts such as this one extend the reach of chemists into unexplored chemical space and provide useful quantities of new compounds for studies focused on their properties.

One‐Pot Synthesis of α‐Diazo‐γ,δ‐unsaturated Esters as Versatile Building Blocks for Functionalized Dienes, Cyclopentenes, and 5,7‐Fused Bicycles

AbstractThe synthesis of novel allylic α‐diazo carbonyl compounds was achieved through a one‐pot strategy involving base‐catalyzed allylation of 1,3‐dicarbonyls with readily available allylic bromides followed by the deacylative diazo transfer reaction. Besides the broad substrate scope related to this method, other relevant features include the use of simple and inexpensive reagents, non‐toxic solvents and mild reaction conditions. The synthetic utility of these α‐diazo‐γ,δ‐unsaturated esters was further demonstrated through rhodium‐catalyzed transformations, where the type of product formed is dependent on both the substrate and catalyst employed. Thus, treating α‐diazo‐γ,δ‐unsaturated esters with catalytic Rh2(pfb)4 in acetonitrile under reflux resulted in a diastereoselective β‐hydride migration to give 2Z,4E‐dienes in good yields. On the other hand, the combination of Rh2(OAc)4 as the catalyst in toluene under reflux for 10 min led the aryl‐substituted diazo compounds to a regioselective intramolecular Buchner reaction to furnish 5,7‐fused bicyclic tetraenes in high yields, while the alkyl‐substituted analogues undergo intramolecular C–H insertion to give functionalized cyclopentenes of anti‐configuration.

Product selectivity of thermal Buchner reaction of methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates with benzene, naphthalene and mesitylene, and ring-opening/closing reaction of products

Methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates were synthesized and the product selectivity of their thermal Buchner reaction with benzene, naphthalene and mesitylene was studied. The reaction of the isoxazolyl-substituted diazoacetates with benzene gave a mixture of cycloheptatriene/norcaradiene isomeric adducts, which are in a rapid equilibrium. Heating the same diazo compounds with naphthalene led exclusively to stable norcaradiene adducts. In contrast, their thermal reaction with mesitylene gave only the products of carbene insertion into C–H bond of mesitylene. According to DFT calculations, such a difference in the product selectivity of the thermal Buchner reaction of the diazoacetates with benzene, naphthalene and mesitylene is associated with the fact that the first two reactions proceed under kinetic control, and the last one under thermodynamic control. Isoxazoles synthesized were converted to a new family of functionalized enaminones, ( Z )-methyl 5-amino-2,5-diaryl-3-oxo-2-phenylpent-4-enoates, by reaction with Mo(CO) 6 /H 2 O hydrogenative reagent, wherein Mo(CO) 6 catalyzes also the retro-Buchner reactions of the norcaradiene moiety of the starting compounds. The obtained enaminones are convenient precursors of 3,6-diaryl-4-hydroxy-3-phenylpyridin-2(1 H )-ones, which were prepared from them under thermal conditions in high yields.

Buchner Reaction/Azirine Modification Approach Toward Cycloheptatriene Containing Nitrogen Heterocyclic Scaffolds.

The reaction conditions for the Buchner reaction of 2-(diazoacetyl)-2H-azirines with benzene leading to 2-(cyclohepta-2,4,6-trien-1-yl)-2H-azirines have been found. The azirine fragment of these compounds was subsequently used to prepare 5-(cyclohepta-2,4,6-trien-1-yl)isoxazoles and α-(cyclohepta-2,4,6-triene-1-ylcarbonyl)-1H-pyrroles. NMR and DFT calculations showed that the cycloheptatriene-norcaradiene valence isomerization in the corresponding moieties of synthesized azirines, isoxazoles, and pyrroles is very fast at room temperature. Cycloheptatriene valence isomer predominates in azirines and pyrroles, while 5-(cycloheptatrienyl)isoxazoles exist in a pure cycloheptatriene form at 25 °C in chloroform solution. In accordance with the X-ray analysis, two of the synthesized pyrroles crystallized as norcaradiene isomers from a solution of equilibrium mixture of valence isomers. Reductive isoxazole ring opening using the Mo(CO)6/H2O reductive system afforded (Z)-3-amino-3-aryl-1-(cyclohepta-2,4,6-trien-1-yl)prop-2-en-1-ones, which are pure cycloheptatriene isomers. α-(Cycloheptatrieneylcarbonyl)-1H-pyrroles were transformed into the α-(benzylcarbonyl)-1H-pyrroles under cooperative TFA/Rh2(TFA)4 catalysis.

Asymmetric Intramolecular Buchner Reaction: From High Stereoselectivity to Coexistence of Norcaradiene, Cycloheptatriene, and an Intermediate Form in the Solid State.

Bicyclic compounds bearing a quaternary stereogenic center have been obtained using asymmetric intramolecular Buchner reaction with excellent yields and level of enantioselectivity. X-ray crystallography determination of the absolute configuration of one product has led to the serendipitous observation of an unusual behavior within the crystal structure, with equilibrating norcaradiene and cycloheptatriene valence isomers at the solid state, as well as an even more unexpected intermediate form. DFT calculations were performed to support these observations.

Asymmetric Synthesis of a 5,7-Fused Ring System Enabled by an Intramolecular Buchner Reaction with Chiral Rhodium Catalyst.

A Rh-catalyzed asymmetric intramolecular Buchner ring expansion of α-alkyl-α-diazoesters has been developed. The present protocol generates a 5,7-fused ring system in an enantioselective manner while minimizing β-hydrogen migration, which has been a competing reaction when using α-alkyl-α-diazoesters. The ester functionality at the bridgehead position would be a useful synthetic handle for further derivatization to complex molecules including natural products.

Copper-catalyzed carbene/alkyne metathesis terminated with the Buchner reaction: synthesis of dihydrocyclohepta[b]indoles.

A copper-catalyzed selective cascade reaction of alkyne-tethered diazo compounds is reported for the direct and efficient construction of dihydrocyclohepta[b]indole skeletons under mild reaction conditions. A vinyl copper carbene is the key intermediate, which is generated in situ via carbene/alkyne metathesis (CAM) and terminated with the Buchner reaction.

Highly stereoselective intramolecular Buchner reaction of diazoacetamides catalyzed by a Ru(ii)-Pheox complex.

This work reports the first efficient enantioselective intramolecular Buchner reaction of diazoacetamides. The Ru(ii)-Pheox catalyst was shown to be highly efficient in this transformation in terms of both the regio- and enantioselectivity (up to 99% ee) giving the desired products in quantitative yield.

Mechanism of the Selective Fe-Catalyzed Arene Carbon–Hydrogen Bond Functionalization

The complete chemoselective functionalization of aromatic C(sp2)–H bonds of benzene and alkyl benzenes by carbene insertion from ethyl diazoacetate was unknown until the recent discovery of an iron-based catalytic system toward such transformation. A Fe(II) complex bearing the pytacn ligand (pytacn = L1 = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane) transferred the CHCO2Et unit exclusively to the C(sp2)–H bond. The cycloheptatriene compound commonly observed through Buchner reaction or, when employing alkyl benzenes, the corresponding derivatives from C(sp3)–H functionalization are not formed. We herein present a combined experimental and computational mechanistic study to explain this exceptional selectivity. Our computational study reveals that the key step is the formation of an enol-like substrate, which is the precursor of the final insertion products. Experimental evidences based on substrate probes and isotopic labeling experiments in favor of this mechanistic interpretation are provided.

Cyclopropanation of Benzene Rings by Oxidatively Generated α-Oxo Gold Carbene: One-Pot Access to Tetrahydropyranone-Fused Cycloheptatrienes from Propargyl Benzyl Ethers.

Cyclopropanations of benzene rings by oxidatively generated α-oxo gold carbenes are for the first time demonstrated in a Buchner reaction, in which readily available propargyl benzyl ethers are converted in one-pot to tetrahydropyranone-fused cycloheptatrienes via sequential oxidative gold catalysis and base-promoted isomerization. Additional examples of arene cyclopropanations without fragmentation of the cyclopropane ring are also realized.

Regioselective and Enantioselective Intermolecular Buchner Ring Expansions in Flow.

The first example of a regioselective and enantioselective intermolecular Buchner ring expansion is reported using continuous flow. The practicality and scope of the reaction are greatly improved under flow conditions. Reactions of ethyl diazoacetate with symmetric and nonsymmetric arenes afford cycloheptatrienes in good yield and excellent regioselectivity. The first example of an asymmetric intermolecular Buchner reaction is demonstrated with disubstituted diazo esters in good to excellent enantioselectivity. The asymmetric reactions proceed with absolute regioselectivity to afford cycloheptatrienes with an all-carbon quaternary center.

Improved Buchner reaction selectivity in the copper-catalyzed reactions of ethyl 3-arylmethylamino-2-diazo-3-oxopropanoates

Ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates (diazo amidoacetates) generate generally both cyclohepta[c]pyrrolones (Buchner products) and β-lactams (1,4-insertion products), and show obvious N-substituent-controlled chemoselectivity between the intramolecular Buchner reaction and aliphatic 1,4-C-H insertion under the catalysis of copper salts. The less steric N-alkyl substituents in the amide moiety generally favor the aliphatic 1,4-C-H insertion, while the more steric N-alkyl substituents generally favor the Buchner reaction. Compared with rhodium and ruthenium-catalyzed conditions, the current copper-catalyzed conditions improved the Buchner reaction selectivity of ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates.

Cobalt‐Porphyrin‐Catalyzed Intramolecular Buchner Reaction and Arene Cyclopropanation of In Situ Generated Alkyl Diazomethanes

AbstractCobalt(II)‐porphyrin catalyzed intramolecular Buchner reaction and arene cyclopropanation of alkyl diazomethanes generated in situ from N‐tosylhydrazones gave a range of bicyclic cycloheptatriene fused pyrrolidines and tetracyclic cyclopropane fused pyrrolidines in good to high yields and with high chemo‐ and regioselectivities. The obtained cyclopropane fused pyrrolidines can be readily converted into other N‐heterocycles with potential synthetic and biological interest.magnified image