Iron‐Catalyzed Synthesis of the Hexahydrocyclopenta[c]furan Core and Concise Total Synthesis of Polyflavanostilbene B

The first synthesis of polyflavanostilbene B ( 1 ), which has seven contiguous stereocenters including two quaternary carbon centers, from abundant polymeric (?)‐epicatechin gallate on a gram scale in three steps without the use of protecting groups is reported. The key transformations of this strategy include a regioselective and stereoselective substitution of resveratrol to give the 4‐derivative of (?)‐epicatechin 3‐gallate and an iron‐catalyzed cyclization reaction. The possible radical cyclization mechanism in the formation of the hexahydrocyclopenta[c]furan core is also discussed.     

Synthesis of Spirocyclic Cyclobutenes through Desulfinative Spirocyclisation of gem-Bis(triflyl)cyclobutenes

A two-step synthesis of less accessible spiro[cyclobutene-1,9′-fluorene] compounds from biaryl-alkynes and 2-(2-fluoropyridin-1-ium-1-yl)-1,1-bis((trifluoromethyl)sulfonyl)ethan-1-ide, which serves as a potent precursor for outstandingly electrophilic Tf₂C=CH₂, has been developed. This synthetic methodology includes selective formation of gem-bis(triflyl)cyclobutenes from biaryl-alkynes and Tf₂C=CH₂ followed by desulfinative spirocyclisation mediated by 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP). Besides, on the basis of the chameleonic reactivity of sulfone functionality, several derivatisations of triflylated spiro[cyclobutene-1,9′-fluorene] products have been successfully achieved.     

A New Cyclization/Decarboxylation Reaction of Isatins with Acyl Chlorides for the Facile Synthesis of 3‐Alkenyl‐Oxindoles

The first cyclization/decarboxylation reaction of isatins with acyl chlorides promoted by 4‐dimethylaminopyridine (DMAP) was described and a series of desired 3‐alkenyl‐oxindoles were obtained in good yields (up to 80%) and E/Z selectivities (up to 6.4/1). This protocol provided a new and feasible access to 3‐alkenyl‐oxindoles.     

Rhodium(III)‐Catalyzed [3+2] Annulation of 5‐Aryl‐2,3‐dihydro‐1H‐pyrroles with Internal Alkynes through C(sp2)H/Alkene Functionalization

This study describes a new rhodium(III)‐catalyzed [3+2] annulation of 5‐aryl‐2,3‐dihydro‐1H‐pyrroles with internal alkynes using a Cu(OAc)₂ oxidant for building a spirocyclic ring system, which includes the functionalization of an aryl C(sp²)? H bond and addition/protonolysis of an alkene C?C bond. This method is applicable to a wide range of 5‐aryl‐2,3‐dihydro‐1H‐pyrroles and internal alkynes, and results in the assembly of the spiro[indene‐1,2′‐pyrrolidine] architectures in good yields with excellent regioselectivities.     

Rhodium‐Catalyzed Synthesis of Chiral Spiro‐9‐silabifluorenes by Dehydrogenative Silylation: Mechanistic Insights into the Construction of Tetraorganosilicon Stereocenters

Mechanistic insight into the construction of quaternary silicon chiral centers by rhodium‐catalyzed synthesis of spiro‐9‐silabifluorenes through dehydrogenative silylation is reported. The C₂‐symmetric bisphosphine ligand, BINAP, was effective in controlling enantioselectivity, and axially chiral spiro‐9‐silabifluorenes were obtained in excellent yields with high enantiomeric excess. Monitoring of the reaction revealed the presence of a monohydrosilane intermediate as a mixture of two constitutional isomers. The reaction proceeded through two consecutive dehydrogenative silylations, and the absolute configuration was determined in the first silylative cyclization. Competitive reactions with electron‐rich and electron‐deficient dihydrosilanes indicated that the rate of silylative cyclization increased with decreasing electron density on the silicon atom of the starting dihydrosilane. Further investigation disclosed a rare interconversion between the two constitutional isomers of the monohydrosilane intermediate with retention of the absolute configuration.     

Titanocene(III)‐Catalyzed 6‐exo Versus 7‐endo Cyclizations of Epoxypolyprenes: Efficient Control and Synthesis of Versatile Terpenic Building Blocks

In this article, a complete study on the selectivity of titanocene(III) cyclization of epoxypolyprenes is presented. The requirements for the formation of six‐ or seven‐membered rings during these cyclizations are determined, taking into account the different substitution pattern in the epoxypolyprene precursor. Thus, a complete selectivity to 6‐exo or 7‐endo cyclization process has been achieved, yielding mono‐, bi‐, and even tricyclic compounds, constituting a new and efficient access to this type of derivative. Additionally, this procedure opens the possibility to prepare excellent building blocks for the synthesis of polycyclic compounds with a trisubstituted oxygenated function, which is present in several natural terpenes.     

Synthesis and Antiviral Properties of Spirocyclic [1,2,3]‐Triazolooxazine Nucleosides

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β‐D ‐psicofuranose to the corresponding azido‐derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3‐dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.     

DFT Study of a 5‐endo‐trig‐Type Cyclization of 3‐Alkenoic Acids by Using Pd–Spiro‐bis(isoxazoline) as Catalyst: Importance of the Rigid Spiro Framework for Both Selectivity and Reactivity

The reaction pathway of an enantioselective 5‐endo‐trig‐type cyclization of 3‐alkenoic acids catalyzed by a chiral palladium–spiro‐bis(isoxazoline) complex, Pd–SPRIX, has been studied by density functional theory calculations. The most plausible pathway involves intramolecular nucleophilic attack of the carboxylate moiety on the C?C double bond activated by Pd–SPRIX and β‐H elimination from the resulting organopalladium intermediate. The enantioselectivity was determined in the cyclization step through the formation of a π‐olefin complex, in which one of the two enantiofaces of the olefin moiety was selected. The β‐H elimination occurs via a seven‐membered cyclic structure in which the acetate ligand plays a key role in lowering the activation barrier of the transition state. In the elimination step, the SPRIX ligand was found to behave as a monodentate ligand due to the hemilability of one of the isoxazoline units thereby facilitating the elimination. Natural population analysis of this pathway showed that the more weakly electron‐donating SPRIX ligand, compared with the bis(oxazoline) ligand, BOX, facilitated the formation of the π‐olefin complex intermediate, leading to a smaller overall activation energy and a higher reactivity of the Pd–SPRIX catalyst.     

Efficient and Convenient Polyethylene Glycol (PEG)‐Mediated Synthesis of Spiro‐oxindoles

Polyethylene glycol (PEG) has been reported as an efficient and convenient medium for the three‐component synthesis for spiro‐oxindole.     

FeIII‐Catalyzed Cross‐Dehydrogenative Arylation (CDA) between Oxindoles and Arenes under an Air Atmosphere

An efficient Fe^III‐catalyzed cross‐dehydrogenative arylation (CDA) of 3‐substituted oxindoles with activated arenes under an air atmosphere was developed to provide 3,3′‐disubstituted oxindoles in good yields.     

Hypervalent‐Iodine(III)‐Mediated Oxidative Methodology for the Synthesis of Fused Triazoles

The organic chemistry of hypervalent organoiodine compounds has been an area of unprecedented development. This surge in interest in the use of hypervalent iodine compounds has mainly been owing to their highly selective oxidizing properties, environmentally benign character and commercial availability. Hypervalent iodine reagents have also been used as an alternative to toxic heavy metals, owing to their low toxicity and ease of handling. Hypervalent organoiodine(III) reagents are versatile oxidants that have been successfully employed to extend the scope of selective oxidative transformations of complex organic molecules in synthetic chemistry. This Focus Review concerns the tandem in situ generation and 1,5‐electrocyclization of N‐heteroaryl nitrilimines into fused triazoles. We describe the importance of recently developed hypervalent‐organoiodine(III)‐catalyzed oxidative cyclization reactions, building towards the conclusion that hypervalent iodine chemistry is a promising frontier for oxidative cyclization, in particular of hydrazones, for the synthesis of fused triazoles.     

Palladium‐Titanium Relay Catalysis Enables Switch from Alkoxide‐π‐Allyl to Dienolate Reactivity for Spiro‐Heterocycle Synthesis

Reported herein is the divergent syntheses of [5,5] and [6,5] spiro‐heterocycles under Lewis‐acid‐assisted palladium catalysis. In particular, an unprecedented switch from alkoxide‐π‐allyl to dienolate reactivity was achieved by the use of palladium‐titanium relay catalysis, and represents umpolung reactivity of vinylethylene carbonates. This method uses a simple procedure and commercially available catalysts, and delivers both classes of spiro‐heterocycles, bearing three contiguous stereocenters, in high yield and uniformly excellent diastereoselectivity.     

Amine‐bis(phenolate) Iron(III)‐Catalyzed Formal Hydroamination of Olefins

A practical synthesis of highly functionalized amines by the formal hydroamination reaction of alkenes with nitroarenes catalyzed by an air stable amine‐bis(phenolate) iron(III) complex is reported. The reaction uses an easily handled silane, low catalyst loadings, and mild reaction conditions. A wide range of substrates are transformed with synthetically useful yields (21 examples).