Copper(I)‐Catalyzed [3+2] Cycloaddition/Ring‐Opening Rearrangement/[4+2] Cycloaddition/Aromatization Cascade: An Unprecedented Chemo‐ and Stereoselective Three Component Coupling of Sulfonyl Azide,Alkyne and N‐Arylidenepyridin‐2‐ amine to Pyrido[1,2‐a]pyrimidin‐4‐imine

A novel synthetic protocol for the one‐pot chemo‐ and stereoselective construction of diversely functionalized pyrido[1,2‐a]pyrimidin‐4‐imines via copper(I)‐catalyzed [3+2] cycloaddition/ring‐opening rearrangement/[4+2] cycloaddition/aromatization cascade of sulfonyl azides, alkynes and N‐arylidenepyridin‐2‐amines under mild reaction conditions is reported. In addition, the catalytic activity of copper(I)‐modified zeolite, a recyclable, heterogeneous catalyst is also investigated, which gives improved yield compared to its homogeneous equivalents.     

Copper(I)‐Catalyzed Asymmetric 1,3‐Dipolar [3+4] Cycloaddition of Nitrones with Azoalkenes

The first copper(I)‐catalyzed asymmetric 1,3‐dipolar [3+4] cycloaddition of nitrones with azoalkenes has been developed, affording a variety of biologically important 1,2,4,5‐oxatriazepane derivatives in good yields with exclusive regioselectivities and excellent enantioselectivities.

     

Complete 2,5‐Diastereocontrol in the Organocatalytic Enantioselective [3+2] Cycloaddition of Enals with Azomethine Ylides Derived from α‐Iminocyanoacetates: Asymmetric Synthesis of Pyrrolidines with Four Stereocentres

Racemic α‐iminocyanoacetates have been used as azomethine ylide precursors in the catalytic enantioselective [3+2] cycloaddition with α,β‐unsaturated aldehydes catalyzed by (S)‐α,α‐diphenylprolinol leading to the fully stereocontrolled formation of pyrrolidine cycloadducts with four stereocentres, one of them being a quaternary one. The reaction proceeded with excellent yields, endo‐selectivities and enantioselectivities. Remarkably, complete 2,5‐diastereoselection has also been achieved under the optimized reaction conditions, which has been explained in terms of the participation of intramolecular H‐bonding interaction which contributes to stabilize one determined geometry for the in situ generated azomethine ylide.     

Copper(II)‐Catalyzed Asymmetric 1,3‐Dipolar [3+4] Cycloaddition and Kinetic Resolution of Azomethine Imines with Azoalkenes

An unprecedented copper(II)‐catalyzed enantioselective 1,3‐dipolar [3+4] cycloaddition of azomethine imines with in situ formed azoalkenes has been realized. This strategy provides a facile access to biologically important 1,2,4,5‐tetrazepine derivatives in high yield with exclusive regioselectivity and high stereoselectivity. Moreover, enantioenriched azomethine imines could be obtained via an efficient kinetic resolution using the same approach.

     

Microwave‐Assisted Facile Synthesis of Furo[3,2‐b]indole Derivatives via Silver(I)‐Mediated [3+2] Cycloaddition

A robust one‐pot process has been developed for the synthesis of a variety of furo[3,2‐b]indoles from readily available o‐propargylaminoacetophenones via silver(I)‐mediated [3+2] cycloaddition.     

Phosphite‐Gold(I)‐Catalyzed [2+2] Intermolecular Cycloaddition of Enol Ethers with N‐Allenylsulfonamides

Addition of catalytic amounts of a phosphite‐based gold(I) catalyst efficiently triggers the intermolecular [2+2] cycloaddition of allenes and alkenes substituted by electron‐donor groups. The reaction is fast and furnishes cyclobutane derivatives in a stereoselective manner using low catalyst loadings. Besides, the same catalyst selectively affords homodimerization products from the starting allene, a process that may be conveniently fine tuned by addition of norbornene.     

Cationic Gold(I)‐Catalyzed Intermolecular [4+2] Cycloaddition between Dienes and Allenyl Ethers

Simple allenyl ethers have been shown to be efficiently activated by cationic gold(I) catalysts to form reactive dienophiles in intermolecular Diels–Alder reactions. A range of different dienes give the cycloaddition products in moderate to excellent yields and good selectivity.     

A Highly Active 4‐Siloxyproline Catalyst for Asymmetric Synthesis

trans‐4‐tert‐Butyldimethylsiloxy‐L ‐proline displays a greater catalytic activity than the parent proline without compromising the enantioselectivity, which widens the substrate scope in the α‐aminoxylation of carbonyl compounds, as well as O‐nitroso‐aldol/Michael, and Mannich reactions.     

Stereoselective Synthesis of Hydropyrano[3,2‐b]indoles via Organocatalytic Asymmetric Inverse‐Electron‐Demand Oxa‐Diels–Alder Reaction

Enantio‐ and diastereoselective inverse‐electron‐demand oxa‐Diels–Alder reactions are described between (Z)‐2‐ylideneoxindoles and aldehydes in the presence of a chiral secondary amine catalyst. The corresponding hydropyrano[3,2‐b]indoles are produced in up to 77% yield with up to 99% ee. Convenient synthetic transformations of the products readily lead to pharmacologically interesting scaffolds bearing multiple functional groups. This method may also provide an alternative approach for the asymmetric synthesis of 2‐spirocyclo‐3‐oxindoles.

     

Superbase‐Catalyzed [4+2] Cycloaddition of Acetylenes to 3,6‐Di(pyrrol‐2‐yl)‐1,2,4,5‐tetrazine: A Facile Synthesis of 3,6‐Di(pyrrol‐2‐yl)pyridazines

Acetylenes undergo the [4+2] cycloaddition to 3,6‐di(pyrrol‐2‐yl)‐1,2,4,5‐tetrazine in the potassium hydroxide/dimethyl sulfoxide or potassium tert‐butoxide/dimethyl sulfoxide systems (80 °C, 2.5–4 h) to afford (after extrusion of the nitrogen molecule from the intermediate) 3,6‐di(pyrrol‐2‐yl)pyridazines in up to 73% yield, while under non‐catalytic conditions this reaction does not take place. This unusual result substantially extends the scope of synthetic application and mechanistic diversity of the Diels–Alder reaction. The step‐wise mechanisms involving the formation of [OH/tetrazine]⁻ or [t‐BuO/tetrazine]⁻ anionic intermediate complexes or cycloaddition of tetrazine to the acetylide anion are considered.     

Optically Pure 1,2‐Bis[(o‐alkylphenyl)phenylphosphino]ethanes and Their Use in Rhodium‐Catalyzed Asymmetric Hydrogenations of α‐(Acylamino)acrylic Derivatives

Optically pure (S,S)‐1,2‐bis[(o‐alkylphenyl)phenylphosphino]ethanes 1a–d were prepared in four steps from phenyldichlorophosphine via phosphine‐boranes as the intermediates. The rhodium complexes 5a–d of these diphosphines were used for the asymmetric hydrogenations of α‐(acylamino)acrylic derivatives including β‐disubstituted derivatives. Markedly high enantioselectivity (78–>99%) was observed for the reduction of β‐monosubstituted derivatives. β‐Disubstituted derivatives were also reduced in considerably high enantioselectivity (up to 90%). The single crystal X‐ray analysis of the rhodium complex 5c of (S,S)‐1,2‐bis[phenyl(5′,6′,7′,8′‐tetrahydronaphthyl)phosphino]ethane ( 1c) revealed its δ‐type structure with face orientation of the two tetrahydronaphthyl groups and edge orientation of the two phenyl groups. This conformation corresponds to that of the rhodium complex of 1,2‐bis[(o‐methoxyphenyl)phenylphosphino]ethane (DIPAMP); the rhodium complex of (R,R)‐DIPAMP, whose chirality at phosphorus is opposite that of 5c , exhibits a λ‐type structure with the face orientation of the two o‐methoxyphenyl groups and the edge orientation of the two phenyl groups. The conformational similarity of these rhodium complexes as well as the stereochemical outcome in the asymmetric hydrogenations means that the coordinative interaction of the methoxy group of DIPAMP with rhodium metal is not the main factor that affects asymmetric induction.     

Catalytic Asymmetric 1, 3‐Dipolar Cycloaddition Reaction of Nitrones with α′‐Phosphoric Enones by a Chiral Ligand‐ Copper(II) Triflate Complex

Using the C₂‐symmetric bis‐oxazoline copper(II) catalyst 6f as a chiral Lewis acid, α′‐phosphoric enones 2 undergo 1,3‐dipolar cycloaddition with nitrones 3 to provide isoxazolidines 4 with very high enantioselectivity and endo/exo selectivity.     

Iridium‐Catalyzed Asymmetric Allylic Etherification and Ring‐Closing Metathesis Reaction for Enantioselective Synthesis of Chromene and 2,5‐Dihydrobenzo[b]oxepine Derivatives

Iridium‐catalyzed asymmetric etherifications of allylic carbonates with 2‐vinylphenols and 2‐allylphenols were realized. With a catalyst generated from 2 mol% of [Ir(cod)Cl]₂ (cod=cycloocta‐1,5‐diene) and 4 mol% of the phosphoramidite ligand L2 , the etherification products were obtained in excellent ees and then subjected to the ring‐closing metathesis reaction providing an efficient synthesis of enantioenriched 2H‐chromene and 2,5‐dihydrobenzo[b]oxepine derivatives.     

Gold(I)‐Catalyzed [4+2] Annelation/Nucleophilic Addition Sequence: Stereoselective Synthesis of Functionalized Bicyclo[4.3.0]nonenes

The gold(I)‐catalyzed isomerization of readily available 1,8‐dien‐4‐ynes allows the rapid construction of a variety of synthetically useful bicyclo[4.3.0]nonenes by a stereoselective sequence involving a [4+2] annelation/nucleophilic addition process.     

Chiral Dirhodium(II) Carboxamidate‐Catalyzed [2+2]‐Cycloaddition of TMS‐Ketene and Ethyl Glyoxylate

The [2+2]‐cycloaddition reaction between ethyl glyoxylate and trimethylsilylketene is reported. Enantiomeric excesses up to 83% have been achieved with the use of only 1.0 mol % of a previously unreported chiral imidazolidinone‐ligated dirhodium(II) carboxamidate catalyst. An extensive survey of chiral catalysts has shown that enantiocontrol for cycloaddition increases as the steric bulk of the ligand is increased. However, enantioselectivity is increased to 99% ee by the addition of 10 mol % of quinine as a co‐catalyst with a chiral dirhodium(II) azetidinone‐ligated catalyst, and there is a significant decrease in reaction time.     

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

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 [5+2] Cycloaddition of 3‐Acyloxy‐1,4‐enyne with Alkene or Allene

We recently developed a completely new type of Rh‐catalyzed [5+2] cycloaddition by using 3‐acyloxy‐1,4‐enyne (ACE) as the 5‐carbon building block. In this update, we show that ACE can undergo intramolecular [5+2] cycloaddition with either an alkene or an allene in the presence of an appropriate rhodium catalyst and ligands to afford bicyclic compounds with multiple stereogenic centers. In most cases, cis‐fused bicyclo[5.3.0]decadienes are prepared highly diastereoselectively.

     

Catalytic Asymmetric [3+2] Cycloadditions of C‐3 Unsubstituted 2‐Indolylmethanols: Regio‐, Diastereo‐ and Enantioselective Construction of the Cyclopenta[b]indole Framework

The first catalytic asymmetric [3+2] cycloaddition of 2‐indolylmethanols with 3‐vinylindoles has been established, which makes use of C‐3 unsubstituted 2‐indolylmethanol as a C₃ building block in the presence of a chiral phosphoric acid. By using this strategy, biologically important cyclopenta[b]indole frameworks were efficiently constructed with regiospecificity in high yields (up to 99%), excellent diastereo‐ and enantioselectivities (up to >95:5 dr, 96:4 er). This reaction not only represents the first catalytic asymmetric [3+2] cycloaddition of C‐3 unsubstituted 2‐indolylmethanols, but also has confronted the great challenges in 2‐indolylmethanol‐involved enantioselective transformations.

     

Beyond the Limits: Palladium‐N‐Heterocyclic Carbene‐Based Catalytic System Enables Highly Efficient [4+2] Benzannulation Reactions

A highly efficient catalytic system for the palladium‐catalyzed [4+2] benzannulation reaction of enynes and enynophiles has been developed. The use of an N‐heterocyclic carbene‐based palladium precursor allowed us to achieve turnover numbers up to 1800. The new catalytic system has enabled an expansion of the scope of the [4+2] homo‐benzannulation reaction.     

Organocatalytic Asymmetric Formal [3+3] Cycloaddition Reactions of α,β‐Unsaturated Aldehydes with Nazarov Reagents

An organocatalytic asymmetric formal [3+3] cycloaddition reaction of α,β‐unsaturated aldehydes with Nazarov reagents promoted by prolinol derivatives afforded, after oxidation, 3,4‐dihydropyranones in good yields with high enantioselectivities of up to 97% ee.