Stereoselective Nickel‐Catalyzed [2+2] Cycloadditions of Ene‐Allenes

A stereoselective nickel‐catalyzed [2+2] cycloaddition of ene‐allenes is reported. This transformation encompasses a broad range of ene‐allene substrates, thus providing efficient access to fused cyclobutanes from easily accessed π‐components. A simple and inexpensive first‐row catalytic system comprised of [Ni(cod)₂] and dppf was used in this process, thus constituting an attractive approach to synthetically challenging cyclobutane frameworks under mild reaction conditions.     

Stereospecific and Stereoselective Rhodium(I)‐Catalyzed Intramolecular [2+2+2] Cycloaddition of Allene‐Ene‐Ynes: Construction of Bicyclo[4.1.0]heptenes

Treatment of the allene‐ene‐yne substrates with [{RhCl(CO)₂}₂] effected the intramolecular [2+2+2]‐type ring‐closing reaction to produce various of tri‐ and tetracyclic derivatives containing a cyclopropane ring. The reaction is highly stereoselective as well as stereospecific with good to excellent yields.     

Chemo‐ and Regioselective Rhodium(I)‐Catalyzed [2+2+2] Cycloaddition of Allenynes with Alkynes

A highly chemo‐ and regioselective partially intramolecular rhodium(I)‐catalyzed [2+2+2] cycloaddition of allenynes with alkynes is described. A range of diverse polysubstituted benzene derivatives could be synthesized in good to excellent yields, in which the allenynes served as synthetic equivalent to the diynes. A high regioselectivity could be observed when allenynes were treated with unsymmetrical alkynes.     

Stereoselective Rhodium‐Catalysed [2+2+2] Cycloaddition of Linear Allene–Ene/Yne–Allene Substrates: Reactivity and Theoretical Mechanistic Studies

Allene–ene–allene ( 2 and 5 ) and allene–yne–allene ( 3 and 7 ) N‐tosyl and O‐linked substrates were satisfactorily synthesised. The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh₃)₃] was evaluated. Substrates 2 and 5 , which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. The reaction of substrates 3 and 7 , which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. A Diels–Alder reaction on N‐tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction.     

Rhodium(I)‐Catalyzed Intramolecular Carbonylative [2+2+1] Cycloaddition of Bis(allene)s: Bicyclo[6.3.0]undecadienones and Bicyclo[5.3.0]decadienones

No templates needed : The title reaction makes it easy to construct the bicyclo[6.3.0]undecadienone framework in high yields (see scheme). A template effect is not required to achieve this ring‐closing reaction efficiently. The present method can be applied to the construction of bicyclo[5.3.0] and bicyclo[4.3.0] ring systems. Ts=p‐toluenesulfonyl.

     

Direct Detection of Key Intermediates in Rhodium(I)‐Catalyzed [2+2+2] Cycloadditions of Alkynes by ESI‐MS

The mechanism of the Rh‐catalysed [2+2+2] cycloaddition reaction of diynes with monoynes has been examined using ESI‐MS and ESI‐CID‐MS analysis. The catalytic system used consisted of the combination of a cationic rhodium(I) complex with bisphosphine ligands, which generates highly active complexes that can be detected by ESI(+) experiments. ESI‐MS on‐line monitoring has allowed the detection for the first time of all of the intermediates in the catalytic cycle, supporting the mechanistic proposal based mainly on theoretical calculations. For all ESI‐MS experiments, the structural assignments of ions are supported by tandem mass spectrometry analyses. Computer model studies based on density functional theory (DFT) support the structural proposal made for the monoyne insertion intermediate. The collective studies provide new insight into the reactivity of cationic rhodacyclopentadienes, which should facilitate the design of related rhodium‐catalysed C? C couplings.     

Stereocontrolled Syntheses of Seven‐Membered Carbocycles by Tandem Allene Aziridination/[4+3] Reaction

A tandem allene aziridination/[4+3]/reduction sequence converts simple homoallenic sulfamates into densely functionalized aminated cycloheptenes, where the relative stereochemistry at five contiguous asymmetric centers can be controlled through the choice of the solvent and the reductant. The products resulting from this chemistry can be readily transformed into complex molecular scaffolds which contain up to seven contiguous stereocenters.     

Total Synthesis of (+)‐Asteriscanolide: Further Exploration of the Rhodium(I)‐Catalyzed [(5+2)+1] Reaction of Ene‐Vinylcyclopropanes and CO

The total synthesis of (+)‐asteriscanolide is reported. The synthetic route features two key reactions: 1) the rhodium(I)‐catalyzed [(5+2)+1] cycloaddition of a chiral ene‐vinylcyclopropane (ene‐VCP) substrate to construct the [6.3.0] carbocyclic core with excellent asymmetric induction, and 2) an alkoxycarbonyl‐radical cyclization that builds the bridging butyrolactone ring with high efficiency. Other features of this synthetic route include the catalytic asymmetric alkynylation of an aldehyde to synthesize the chiral ene‐VCP substrate, a highly regioselective conversion of the [(5+2)+1] cycloadduct into its enol triflate, and the inversion of the inside–outside tricycle to the outside–outside structure by an ester‐reduction/elimination to enol‐ether/hydrogenation procedure. In addition, density functional theory (DFT) rationalization of the chiral induction of the [(5+2)+1] reaction and the diastereoselectivity of the radical annulation has been presented. Equally important is that we have also developed other routes to synthesize asteriscanolide using the rhodium(I)‐catalyzed [(5+2)+1] cycloaddition as the key step. Even though these routes failed to achieve the total synthesis, these experiments gave further useful information about the scope of the [(5+2)+1] reaction and paved the way for its future application in synthesis.     

Rhodium‐Catalyzed Intramolecular [3+2+2] Cycloadditions between Alkylidenecyclopropanes,Alkynes, and Alkenes

A Rh‐catalyzed intramolecular [3+2+2] cycloaddition is reported. The cycloaddition affords synthetically relevant 5,7,5‐fused tricyclic systems of type 2 from readily available dienyne precursors. The transformation takes place with moderate or good yields, high diastereoselectivity, and total chemoselectivity.     

Gold‐Catalyzed Intramolecular [3+2] Cycloadditions of 1‐Aryl‐1‐allene‐6‐enes

Treatment of 1‐aryl‐1‐allen‐6‐enes with [PPh₃AuCl]/AgSbF₆ (5 mol %) in CH₂Cl₂ at 25 °C led to intramolecular [3+2] cycloadditions, giving cis‐fused dihydrobenzo[a]fluorene products efficiently and selectively. The reactions proceeded with initial formation of trans/cis mixtures of 2‐alkyl‐1‐isopropyl‐2‐phenyl‐1,2‐dihydronaphthalene cations B, which were convertible into the desired cis‐fused cycloadducts through the combined action of a gold catalyst and a Brønsted acid. Theoretic calculation supports the participation of the trans‐B cation as reaction intermediate. Although HOTf showed similar activity towards several 1‐aryl‐1‐allen‐6‐enes, it lacks generality for this cycloaddition reaction.     

Regiodivergent Intermolecular [3+2] Cycloadditions of Vinyl Aziridines and Allenes: Stereospecific Synthesis of Chiral Pyrrolidines

The first rhodium‐catalyzed intermolecular [3+2] cycloaddition reaction of vinyl aziridines and allenes for the synthesis of enantioenriched functionalized pyrrolidines was realized. [3+2] cycloaddition with the proximal C=C bond of N‐allenamides gave 3‐methylene‐pyrrolidines in high regio‐ and diastereoselectivity, whereas, 2‐methylene‐pyrrolidines were obtained as the major products by the cycloadditions of vinyl aziridines with the distal C=C bond of allenes. Use of readily available starting materials, a broad substrate scope, high selectivity, mild reaction conditions, as well as versatile functionalization of the cycloadducts make this approach very practical and attractive.     

Rhodium(I)-Catalyzed Bridged [5+2] Cycloaddition of cis-Allene-vinylcyclopropanes to Synthesize the Bicyclo[4.3.1]decane Skeleton

Previously reported was that cis-ene-vinylcyclopropanes (cis-ene-VCPs) underwent Rh-catalyzed [5+2] reaction to give 5,7-fused bicyclic products, where vinylcyclopropane (VCP) acts as five-carbon synthon. Unfortunately, this reaction had very limited scope. Replacing the 2π component of cis-ene-VCPs to allene moiety, the corresponding cis-allene-VCPs did not undergo the expected normal [5+2] cycloaddition to give 5,7-fused bicyclic products. Instead, the challenging bicyclo[4.3.1]decane skeleton was obtained via an unprecedented bridged [5+2] cycloaddition. DFT calculations were applied to understand why this bridged [5+2] reaction is favored over the anticipated but not realized normal [5+2] reaction.