[2+2]-cycloadditions of cyclopentyne

Cyclopentyne, as generated from dibromomethylenecyclobutane, a formerly unknown cyclopentyne source, undergoes [2+2]-cycloadditions with various substituted olefins yielding bicyclo[3.2.0]hept-1(5)-ene derivatives.     

[2+2]-cycloadditions of alkenes with the triphenylallenyl cation

The triphenylallenyl cation (8), generated from triphenylpropynol (7) and FSO₃H, reacts with alkenes to give the allyl cations 12, which may be deprotonated to yield the methyleneccylobutenes 14. Alternatively, 12 can be converted into the 2-vinyl-indenes 13 $\text{via}$ two subsequent electrocyclic reactions.     

Studies in stereoselective [2+2]-cycloadditions with dichloroketene

During the investigation of the reaction of dichloroketene with cyclic enoxy-lactones and acyclic enoxy-ester substrates it was found that only the acylic variants effectively participated in the [2+2]-cycloaddition. Although a complete understanding of the reasons for this are lacking, molecular mechanics calculations do suggest that an out of plane twist of the cabonyl group in the acyclic compounds may be partially responsible. After screening a variety of chiral auxiliaries it was found that useful levels of diastereoselectivity (2.6-10.8:1) could be obtained in this cycloaddition reaction when (R)-2,2-diphenylcyclopentanol was used as the chiral auxiliary.     

Catalytic enantioselective [3 + 2]-cycloadditions of diazoketone-derived aryl-substituted carbonyl ylides

An evaluation of alpha-aryl-alpha-diazodiones in tandem carbonyl ylide formation-enantioselective [3 + 2]-cycloaddition reactions is described. Such substrates were designed to allow investigation of the electronic characteristics of the dipole upon asymmetric induction. Intramolecular cycloadditions (with a tethered alkene dipolarophile) were found to occur in good to quantitative yields, with a difference in ee exhibited by the two electronically different diazodiones 8 and 9. Intermolecular cycloadditions using diazodiones 12 and 13 with DMAD and arylacetylenes 16-18 again demonstrated that electronics play a key role in determining the outcome of the cycloaddition reactions. Enantioselectivities of up to 76% were observed.     

Kinetics studies of rapid strain-promoted [3 + 2]-cycloadditions of nitrones with biaryl-aza-cyclooctynone

Strain-promoted cycloadditions of cyclic nitrones with biaryl-aza-cyclooctynone (BARAC) proceed with rate constants up to 47.3 M(-1) s(-1), this corresponds to a 47-fold rate enhancement relative to reaction of BARAC with benzyl azide and a 14-fold enhancement over previously reported strain promoted alkyne-nitrone cycloadditions (SPANC). Studies of the SPANC reaction using the linear free energy relationship defined by the Hammett equation demonstrated that the cycloaddition reaction has a rho value of 0.25 ± 0.04, indicating that reaction is not sensitive to substituents and thus should have broad applicability.     

Efficient intermolecular 3+2 trapping of the Nazarov intermediate with vinyl sulfides

Cross-conjugated 1,4-pentadien-3-ones undergo electrocyclization to 2-oxidocyclopentenyl cations upon treatment with BF₃·OEt₂. When these reactions are carried out in the presence of electron-rich vinyl sulfides, nucleophilic trapping followed by ring-closure furnishes bridged bicyclic products that can be viewed as formal 3+2 cycloadducts. This process results in three new carbon-carbon bonds and establishes up to five new stereocenters.     

Synthesis of 2-azaspiro[4.4]nonan-1-ones via phosphine-catalysed [3+2]-cycloadditions

The phosphine-catalyzed [3+2]-cycloaddition of the 2-methylene γ-lactams 4 and 5 and the acrylate 6 with the ylides derived from the ethyl ester, the amide or the chiral camphor sultam derivative of 2-butynoic acid (7a-c) give directly, or indirectly after reductive cyclization, spiro-heterocyclic products. The acid 32 underwent Curtius rearrangement and then acid hydrolysis to give two novel spiro-cyclic ketones, 41 and 42.     

Thioallenoates in catalytic enantioselective [2+2]-cycloadditions with unactivated alkenes

The application of thioallenoates to catalytic enantioselective [2+2]-cycloadditions with unactivated alkenes is reported. In many cases, the thioallenoates examined exhibit superior reactivity and selectivity compared to the allenic esters generally used in these cycloadditions.     

Intramolecular photochemical [2 + 1]-cycloadditions of nucleophilic siloxy carbenes

Visible light induced singlet nucleophilic carbenes undergo rapid [2 + 1]-cycloaddition with tethered olefins to afford unique bicyclo[3.1.0]hexane and bicyclo[4.1.0]heptane scaffolds. This cyclopropanation process requires only visible light irradiation to proceed, circumventing the use of exogenous (photo)catalysts, sensitisers or additives and showcases a vastly underexplored mode of reactivity for nucleophilic carbenes in chemical synthesis. The discovery of additional transformations including a cyclopropanation/retro-Michael/Michael cascade process to afford chromanones and a photochemical C–H insertion reaction are also described.

Visible light induced singlet nucleophilic carbenes undergo rapid [2 + 1]-cycloaddition with tethered olefins to afford unique bicyclo[3.1.0]hexane and bicyclo[4.1.0]heptane scaffolds.     

Electronic effects of ruthenium-catalyzed [3+2]-cycloaddition of alkynes and azides

A combined experimental and theoretical study of ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) reactions is presented and various electronic analyses were conducted to provide a basis in understanding the observed regioselectivity of the 1,2,3-triazole products. Computational studies using density functional theory (DFT) and atoms in molecules quantum theory (AIM) further yield fresh details on the electronic factors that determine the regioselectivity in the RuAAC. It is found that the formation of 1,2,3-triazole products is irreversible and from the Hammett study, the pathway involving a vinyl cationic intermediate is ruled out. The electronic effect favors the formation of 5-electron-donating-group substituted-1,2,3-trizoles.     

Catalyst-controlled diastereoselective ring-opening formal [3+2]-cycloadditions of arylvinyl oxirane 2,2-diesters with cyclic N-sulfonyl imines

A diastereoselectivity-controllable formal [3+2]-cycloaddition of arylvinyl oxirane 2,2-diesters with cyclic N-sulfonyl imines is developed, affording the corresponding tricyclic oxazolidine derivatives in moderate to excellent yields with excellent diastereoselectivities in the presence of palladium(0) or scandium(III) triflate. This protocol allows selective synthesis of diastereomers of tricyclic oxazolidine derivatives under switchable and mild conditions. Further transformations of the obtained products were conducted by removing ester groups and arylvinyl moieties.     

A new domino reaction based on [4+2]-cycloadditions of pyrido[1,2-a]pyrazines with azadienophiles

The reaction of pyrido[1,2-a]pyrazines 1 with nitroso compounds 2 provides pyridyl substituted 1,2,4-triazinones 4 via a domino reaction which involves a cycloaddition and a ring transformation reaction. The intermediate and regioselective formed oxadiazines 4′ were trapped by complexation yielding the (CO)₄Mo-complex 5. Derivatives of diazene such as N-phenyltriazolindione 6a , phthalazinedione 6b or esters of azodicarboxylic acid 6c-6f reacted with 1 to give different derivatives of 1,2,4-triazine 7a-f . The use of oxygen gave oxadiazinones 8 .     

Intermolecular gold-catalyzed diastereo- and enantioselective [2+2+3] cycloadditions of 1,6-enynes with nitrones

Going for gold: The title reaction has been developed and demonstrates a wide substrate scope with respect to the 1,6-enynes and nitrones (see scheme; DCE = 1,2-dichloroethane, Tf = trifluoromethanesulfonyl). The results for the enantioselective versions are also presented.     

Synthesis of carbocyclic hydantocidins via regioselective and diastereoselective phosphine-catalyzed [3 + 2]-cycloadditions to 5-methylenehydantoins

The phosphine-catalyzed [3 + 2]-cycloaddition of 5-methylenehydantoins 4 with the ylides 5, derived from addition of tributylphosphine to the 2-butynoic acid derivatives, 6a-d, gives spiro-heterocyclic products. The camphor sultam derivative 6b gives optically active products. Noteable was that the ylides derived from ethyl 2-butynoate and the 3-(2-butynoyl)-1,3-oxazolidin-2-one derivatives 6c and 6d gave spiro-heterocyclic products with reverse regioselectivities. The N,N-dibenzylprotected cycloadduct has been converted to carbocyclic hydantocidin and 6,7-diepi-carbocyclic hydantocidin.     

1.3.2.4.5-dioxadithiazin-2.2.4.4-tetraoxides - new reagents for [2+2] - and [2+4]-cycloadditions to olefins

The titled compounds react with olefins under mild conditions to give 1.2-thiazetidin-1.1-dioxides and/or 1.4.5-oxathiazin-4.4-dioxides being formal versatile sources of 1.2- and 1.4-dipoles. Relation of these paths changes widely depending upon structural effects of alkenes and conditions of the reaction.     

Gold-catalyzed synthesis of substituted 2-aminofurans via formal [4+1]-cycloadditions on 3-en-1-ynamides

Gold-catalyzed formal [4+1]-cycloadditions between 3-en-1-ynamides 1 and 8-methylquinoline oxide are reported. The success of this reaction relies on a hypothetic oxa-Nazarov cyclization on gold-stabilized allylic cations. Preliminary results on a new 1,2-difunctionalization of 3-en-1-ynamide are also reported.