Enantioselective Synthesis of 3-Substituted Cyclobutenes by Catalytic Conjugate Addition/Trapping Strategies

A copper-catalyzed tandem process to generate chiral cyclobutene derivatives has been developed. It is based on an enantioselective conjugate addition or reduction of a cyclobutenone and sequential trapping with a chlorophosphate in a one-pot process. These phosphates are stable under mildly acidic conditions and serve as good electrophiles in Negishi coupling reactions.     

Enantioselective Synthesis of 3‐Substituted Cyclobutenes by Catalytic Conjugate Addition/Trapping Strategies

A copper‐catalyzed tandem process to generate chiral cyclobutene derivatives has been developed. It is based on an enantioselective conjugate addition or reduction of a cyclobutenone and sequential trapping with a chlorophosphate in a one‐pot process. These phosphates are stable under mildly acidic conditions and serve as good electrophiles in Negishi coupling reactions.     

High‐Throughput Ligand Screening Enables the Enantioselective Conjugate Borylation of Cyclobutenones to Access Synthetically Versatile Tertiary Cyclobutylboronates

Cyclobutane rings are important in medicinal chemistry, yet few enantioselective methods exist to access this scaffold. In particular, cyclobutylboronates are receiving increasing attention in the literature due to the synthetic versatility of alkylboronic esters and the increasing role of boronic acids in drug discovery. Herein, a conjugate borylation of α‐alkyl,β‐aryl/alkyl cyclobutenones is reported leading to the first synthesis of enantioenriched tertiary cyclobutylboronates. Cyclobutanones with two stereogenic centers are obtained in good to high yield, with high enantioselectivity and diastereoselectivity. Vital to this advance are the development of a novel approach to α,β unsymmetrically disubstituted cyclobutenone substrates and the use of a high‐throughput chiral ligand screening platform. The synthetic utility of both the boronic ester and ketone functionalities is displayed, with remarkable chemoselectivity for either group being possible in this small ring scaffold.     

Reactivity of organo lithium reagents on dimethyl squarate : a 1,2-addition process leading to new 2-hydroxy-3,4 dimethoxy 3-cyclobutenone

Lithium reagents react with dimethylsquarate at the carbonyl group according to a 1,2-addition process, leading to new 2-hydroxy-3,4 dimethoxy-3 cyclobutenone.     

Utilizing the high dielectric constant of water: efficient synthesis of amino acid-derivatized cyclobutenones

This work reports the use of water as a solvent to facilitate an efficient syntheses of amino acid-derivatized cyclobutenone. Kinetics studies in different solvents reveals that high dielectric constants of the solvents are the primary attribute for the high yielding and fast rate for this reaction. This class of substitution reactions in water also proceeds efficiently with a wide range of amino acids.     

Ring opening and ring enlargement of a cyclopropene carboxylic acid

3,3-Dimethyl-2-phenyl-cyclopropenecarboxylic acid 4 is prepared, starting with chlorophenyldiazirine 1. With acids 4 yields the open chain carboxylic acids 5, 6 and 7. Thionychloride leads to the cyclobutenone 10, DCC to the acid anhydrides 11 and 13.     

Efficient approach to 1,2-diazepines via formal diazomethylene insertion into the C-C bond of cyclobutenones

Efficient monocyclic 1,2-diazepine formation via a tandem electrocyclization reaction of cyclobutenones with lithiodiazoacetate is demonstrated. The reaction proceeds through an oxy anion-accelerated 4π-ring opening of cyclobutene followed by an 8π-ring closure of the resultant oxy anion-substituted diazo-diene under mild conditions to furnish a 1,2-diazepine via formal diazomethylene insertion into the C-C bond of cyclobutenone.     

Reaktionen von komplexliganden: XXVII. Cycloaddition von carbonyl-carben-komplexen mit alkinen: cyclobutenon-bildung versus carbenanellierung

Upon reaction with tolan pentacarbonyl[1,3-difluorophenyl(methoxy)carbene]-chromium undergoes a [2 + 1 + 1]cycloaddition to give the cyclobutenone skeleton while the 2,6-dimethyl(phenyl)carbene analogue leads to the carbene annulation product.     

Stereoselective synthesis of cis-1,3-disubstituted cyclobutyl kinase inhibitors

Two synthetic routes to a series of structurally novel kinase inhibitors containing a cis-1,3-disubstituted cyclobutane are described. The first route utilized addition of 3-aminocyclobutanol to 1,4-dinitroimidazole 5 as the crucial step in preparing 1, whereas the second route employed a novel 1,4-addition of 4-nitroimidazole 18 to in situ generated cyclobutenone 17 as the key reaction. This allowed for a stereoselective and shorter synthesis that eliminated the use of potentially explosive 1,4-dinitroimidazole 5. [structure: see text]     

Synthesis of cyclobuteniminium salts derived from aldo-keteniminium salts and study of their reactivity in Diels–Alder reaction

The synthesis of broad scope of novel monosubstituted cyclobuteniminium salts derived from aldo-keteniminium salts and acetylene or 1-propyne is described. The reactivity of cyclobuteniminium salts in Diels–Alder reactions has been studied in detail by DFT calculations and by performing competition reaction with cyclobutenone derivatives.     

Rh-catalyzed reagent-free ring expansion of cyclobutenones and benzocyclobutenones

Here we report a reagent-free rhodium-catalyzed ring-expansion reaction via C–C cleavage of cyclobutenones. A variety of poly-substituted cyclopentenones and 1-indanones can be synthesized from simple cyclobutenones and benzocyclobutenones. The reaction condition is near pH neutral without additional oxidants or reductants. The potential for developing a dynamic kinetic asymmetric transformation of this reaction has also been demonstrated. Further study supports the proposed pathway involving Rh-insertion into the cyclobutenone C–C bond, followed by β-hydrogen elimination, olefin insertion and reductive elimination.     

Formal Synthesis of (±)‐Isodihydronepetalactone

A formal synthesis of (±)‐isodihydronepetalactone ( 1 ) from cyclobutenone 5 was de scribed. Baeyer‐Villiger lactonization of cyclobutanone 8 followed by decholorination led to lactone 4 , which under went a series of functional group trans formations, furnished cyclopentanone derivative 15 . Shapiro reaction on hydrazone derivative in the presence of excess dry ice gave lactone 2 . Lactone 2 had previously been converted to isodihydronepetalactone ( 1 ).     

(2-Aryl-2-cyanoethenyl)ketenes---annulated cyanophenols from azidoquinones

Annulated cyanophenols are the products derived from the thermolysis of 3,6-diaryl-2,5-diazido-1,4-benzoquinones in the presence of an alkyne. The transformation is envisaged to involve the following steps: 1)thermal fragmentation of the azidoquinones to arylcyanoketenes, 2) cycloaddition of the ketenes to an alkyne to give 4-aryl-4-cyanocyclobutenones, 3) electrocyclic ring opening of the cyclobutenone to generate (2-aryl-2-cyanoethenyl)ketenes, and 4) ring closure of the conjugated ketenes to give the annulated cyanophenol products. Similarly, analogous products are obtained from the thermolysis of 4-aryl-3-azido-6-chloro-5-ethoxy-1,2-benzoquinones.     

A straightforward synthesis of cyclobutenones via a tandem Michael addition/cyclization reaction of 2,3-allenoates with organozincs

An efficient method for synthesis of polysubstituted cyclobutenones, which are not readily available from traditional methods due to the intrinsic ring strain, is described. The reaction of 2,3-allenoates and organozinc reagents proceeds via a tandem Michael addition/cyclic 1,2-addition/elimination mechanism with the functional groups from the organozinc reagents being introduced to the 3-position of the cyclobutenone products regiospecifically in moderate to excellent yields. Application to the synthesis of stereodefined β,γ-unsaturated enones is demonstrated.     

Synthesis of Silylated Cyclobutanone and Cyclobutene Derivatives Involving 1,4-Addition of Zinc-Based Silicon Nucleophiles

A copper-catalyzed conjugate silylation of various cyclobutenone derivatives with Me₂PhSiZnCl ⋅ 2LiCl or (Me₂PhSi)₂Zn ⋅ xLiCl (x≤4) to generate β-silylated cyclobutanones is reported. Trapping the intermediate enolate with ClP(O)(OPh)₂ affords silylated enol phosphates that can be further engaged in Kumada cross-coupling reactions to yield silylated cyclobutene derivatives.     

Delving noble metal and semiconductor nanomaterials into enantioselective analysis

The chiroplasmonic and chiroexcitonic platform constructed from noble metal and semiconductor nanomaterials have significantly advanced enantioselective analysis. In this paper, we summarized the exciting progresses and contributions by the peers in the field.     

Delving noble metal and semiconductor nanomaterials into enantioselective analysis

With growing interests paid to the enantioselective analysis of chiral molecules, roles played by noble metal and semiconductor nanomaterials surface gradually. Given the unique physicochemical properties of noble metal and semiconductor nanomaterials, the enantioselective analyses are classified into three categories: ?uorescence-based, colorimetry-based, and circular dichroism-based ones. In this paper, we review the existing progresses on enantioselective analysis, thanks to noble metal and semiconductor nanomaterials. Finally, the prospect of enantioselective analysis based on noble metal and semiconductor are discussed.     

Catalytic enantioselective fluorination of oxindoles

We have developed a highly efficient catalytic enantioselective fluorination of oxindole derivatives. In the presence of a catalytic amount of chiral Pd complex 2 (2.5 mol %), various substrates, including aryl- and alkyl-substituted oxindoles, were fluorinated in a highly enantioselective manner (up to 96% ee). In addition, when R was a hydrogen atom, enantioselective fluorination followed by solvolysis gave a monofluorinated ester with up to 93% ee. To our knowledge, this is the first example of catalytic enantioselective fluorination of oxindoles.     

A general enantioselective route to the chamigrene natural product family

Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.     

Enantioselective organocatalytic intramolecular Diels-Alder reactions. The asymmetric synthesis of solanapyrone D

The first direct enantioselective organocatalytic intramolecular Diels-Alder reaction has been accomplished. The use of iminium catalysis has provided a new catalytic strategy for the enantioselective [4 + 2] cycloisomerization of a wide variety of tethered diene-enal systems. The use of imidazolidinones 1 and 2 as the asymmetric catalysts has been found to mediate the enantioselective construction of [4.4.0] and [4.3.0] ring systems. Application of this methodology to the highly efficient asymmetric synthesis of the marine metabolite solanpyrone D has also been accomplished. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. Importantly, this technology has been utilized to execute the first enantioselective, catalytic Type II IMDA reaction.