Density functional theory study of the mechanisms and stereochemistry of the rh(i)-catalyzed intramolecular [3+2] cycloadditions of 1-ene- and 1-yne-vinylcyclopropanes

The mechanisms, structures of all stationary points involved, and kinetic and thermodynamic parameters of the Rh(I)-catalyzed intramolecular [3+2] cycloaddition reactions of 1-ene- and 1-yne-vinylcyclopropanes (1-ene-VCPs and 1-yne-VCPs) have been investigated using density functional theory (DFT) calculations. The computational results showed that the [3+2] reactions of 1-ene/yne-VCPs studied here occur through a catalytic cycle of substrate-catalyst complex formation, cyclopropane cleavage, alkene/alkyne insertion, and reductive elimination. Alkene/alkyne insertion is the rate- and stereoselectivity-determining step of these multistep [3+2] cycloadditions. The experimentally observed high reactivity of 1-yne-VCPs compared to 1-ene-VCPs is well rationalized by the differences of steric effects in the alkyne/alkene insertion transition states. DFT calculations unveiled that the relative orientation of the tethers in the 1-ene/yne-VCPs plays a key role in controlling the stereochemistry of the [3+2] cycloadducts. In addition, DFT calculation results are used to explain why, in some cases, the formation of the β-hydride elimination byproduct can compete with the [3+2] pathway.     

Alkyne and alkene complexes of a d(0) zirconocene aryl cation

The generation and properties of nonchelated Zr-aryl-alkyne and Zr-aryl-alkene complexes that are stabilized by the presence of beta-Si-substituents in the alkyne and alkene ligands and fluorination of the aryl ligand are described. Reaction of [Cp'2Zr(OtBu)(ClCD2Cl)][B(C6F5)4] (1, Cp' = C5H4Me) with alkyne and alkene substrates (L) generates Cp'2Zr(OtBu)(L)+ adducts (L = HCCCH2SiMe3 (2); H2C=CHCH2SiMe3 (3); HCCMe (4); H2C=CHCH2CMe3 (5)). Equilibrium constants for substrate binding (Keq = [Zr-L][1]-1[L]-1; CD2Cl2, -89 degrees C) are much larger for the beta-Si-substituted compounds 2 (1.0(2) x 105 M-1) and 3 (1.7(4) x 103 M-1) than for hydrocarbon analogues 4 (3.6(7) x 102 M-1) and 5 (1.9(1) M-1), which is ascribed to beta-Si stabilization of the partial positive charge on Cint of the bound substrate. [Cp2Zr(C6F5)][B(C6F5)4] (7, Cp = C5H5) was generated by the reaction of Cp2Zr(C6F5)Me with [Ph3C][B(C6F5)4] in C6D5Cl. Reaction of 7 with alkyne and alkene substrates (L) generates Cp2Zr(C6F5)(L)+ adducts (L = HCCCH2SiMe3 (8); H2C=CHCH2SiMe3 (10)). No insertion of the substrate into the Zr-C6F5 bond is observed in 8 (at -38 degrees C) or 10 (up to 22 degrees C). The allyltrimethylsilane ligand in 10 undergoes nondissociative alkene face exchange ("alkene flipping", i.e., exchange of the Cp2Zr(C6F5)+ unit between the two alkene enantiofaces without alkene dissociation), with a first-order rate constant kflip = 23(1) s-1 (C6D5Cl, -38 degrees C). 10 also undergoes slower reversible decomplexation of the alkene (kdissoc = 5.0(8) s-1; C6D5Cl, -38 degrees C).     

Formation of bridging alkene and conjugated dialkenes exclusively generated from alkynes on the [3,3'-Co(1,2-C2B9H11)2]- platform. The unique hydroboration role of [3,3'-Co(1,2-C2B9H11)2]-

The unprecedented metal-mediated transformation of an alkyne into a B,B' bridging alkene is reported. Also, the unprecedented synthesis of a conjugated dialkene derivative of [3,3'-Co(1,2-C2B9H11)2]- generated only from an alkyne, contrary to the usual case where an alkyne and an alkene are needed, is described. This has been possible through the singular capacity of a B-H to produce hydroboration.     

Ruthenium-catalyzed [2 + 2] cycloadditions between 7-substituted norbornadienes and alkynes: an experimental and theoretical study

The ruthenium-catalyzed [2 + 2] cycloadditions of 7-substituted norbornadienes with an alkyne have been investigated. The cycloadditions were found to be highly regio- and stereoselective, giving only the anti-exo cycloadducts as the single regio- and stereoisomers in good yields. The results on the relative rate of different 7-substituted norbornadienes in the Ru-catalyzed [2 + 2] cycloadditions with an alkyne indicated that the reactivity of the alkene component decreases dramatically as the alkene becomes more electron deficient. Ab initio computational studies on the ruthenium-catalyzed [2 + 2] cycloadditions provided important information about the geometries and the arrangements of the four different groups on the Ru in the initial Ru-alkene-alkyne pi-complex, 14, and in the metallacyclopentene 15. Based on our computational studies, we also found that the first carbon-carbon bond formed in the [2 + 2] cycloaddition is between the C(5) of the alkene and the C(b) (the acetylenic carbon attached to the ester group) of the alkyne 8. Our computational studies on the potential energy profiles of the cycloadditions showed that the activation energy relative to the reactants for the oxidative addition step is in the range of 9.3-9.8 kcal/mol. The activation energy relative to the metallacyclopentene for the reductive elimination step is much higher than for the oxidative addition step (in the range of 25.9-27.6 kcal/mol).     

Rhodium‐Catalyzed Intramolecular [5+2] Cycloaddition of Inverted 3‐Acyloxy‐1,4‐enyne and Alkyne: Experimental and Theoretical Studies

By switching the position of the alkene and alkyne, a new type of 3‐acyloxy‐1,4‐enyne (ACE) five‐carbon building block was developed for Rh‐catalyzed intramolecular [5+2] cycloaddition. An electron‐withdrawing acyl group on the alkyne termini of the ACE was essential for a regioselective 1,2‐acyloxy migration. This new method provided bicyclic [5.3.0]decatrienes that are different from previous methods because of the positions of the alkenes and the acyloxy group. Multiple mechanistic pathways become possible for this new [5+2] cycloaddition and they are investigated by computational studies.     

Mechanism of enyne metathesis catalyzed by Grubbs ruthenium-carbene complexes: a DFT study

The complete catalytic cycle of the reaction of alkenes and alkynes to dienes by Grubbs ruthenium carbene complexes has been modeled at the B3LYP/LACV3P**+//B3LYP/LACVP level of theory. The core structures of the substrates and the catalyst were used as models, namely, ethene, ethyne, hept-1-en-6-yne, (Me(3)P)(2)Cl(2)Ru=CH(2), and [C(2)H(4)(NMe)(2)C](Me(3)P)Cl(2)Ru=CH(2). Insight into the electronically most preferred mechanistic pathways was gained for both intermolecular as well as for intramolecular enyne metathesis. Alkene metathesis is predicted to proceed fast and reversible, while the insertion of the alkyne substrate is slower, irreversible, and kinetically regioselectivity determining. Ruthenacyclobut-2-ene structures do not exist as local minima in the catalytic cycle. Instead, vinylcarbene complexes are formed directly. The alkyne insertion step and the cycloreversion of 2-vinyl ruthenacyclobutanes feature comparable predicted overall barriers in intermolecular enyne metathesis. For intramolecular enyne metathesis, a noncyclic alkene fragment of the enyne substrate is first incorporated into the Grubbs catalyst by an alkene metathesis reaction. The subsequent insertion of the alkyne fragment then proceeds intramolecularly. Alkene association, cycloaddition, and cycloreversion to the diene product complex close the catalytic cycle. Rate enhancement by an ethene atmosphere (Mori's conditions) originates from a constantly higher overall alkene concentration that is necessary for the rate-limiting [2 + 2] cycloreversion step to the diene product complex.     

Rhodium catalysed dehydrogenative borylation of vinylarenes and 1,1-disubstituted alkenes without sacrificial hydrogenation--a route to 1,1-disubstituted vinylboronates

The complex trans-[Rh(Cl)(CO)(PPh3)2] (1) is an efficient catalyst precursor for the dehydrogenative borylation of alkenes without consumption of half the alkene substrate by hydrogenation, giving useful vinylboronate esters including 1,1-disubstituted derviatives that cannot be made by alkyne hydroboration.     

Cobalt-catalyzed intermolecular [2 + 2 + 2] cycloaddition for the synthesis of 1,3-cyclohexadienes

A cobalt(I)-catalyzed [2 + 2 + 2] cycloaddition reaction between an internal acceptor-substituted alkyne and a terminal alkene leads to the formation of regiochemically enriched polysubstituted 1,3-cyclohexadiene derivatives in acceptable yields when methyl butynoate is used, whereas regiochemically pure products are formed in good yields form phenyl propyonate. The concurrent cyclotrimerization reaction of the alkyne to the corresponding benzene derivative is dependent on the sterical bulk of the alkyne and is considerably reduced with the sterically more hindered alkyne.     

Mechanistic Study of the Rhodium‐Catalyzed [3+2+2] Carbocyclization of Alkenylidenecyclopropanes with Alkynes

A systematic theoretical study has been performed on the recently reported Rh^I‐catalyzed [3+2+2] carbocyclization reactions between alkenylidenecyclopropanes (ACPs) and alkynes. With the aid of theoretical calculations, two possible mechanisms, that is, alkene‐carbometalation‐first and alkyne‐carbometalation‐first mechanisms, are examined in this study. In the oxidative addition step, the possibility of reaction on either the distal or proximal C? C bond of the cyclopropane group has been evaluated. The calculations indicate that the alkene‐activation‐first mechanism is more favored for the overall catalytic cycle. This mechanism involves four steps, that is, oxidative addition of the distal (rather than the proximal) C? C bond of cyclopropane group, alkene carbometalation, alkyne carbometalation, and reductive elimination. The rate‐determining step in the overall catalytic cycle is the carbometalation of the alkyne (i.e., the alkyne‐insertion step) and this step also determines the regioselectivity. Finally, the origin of the regioselectivity is determined by the steric effect (i.e., the steric crowding between the electron‐withdrawing group on alkyne and other ligands on the rhodium center) in the alkyne‐insertion step.     

Synthesis of functionalized hydroquinones via [Cp*RuCl2]2-catalyzed cocyclization of alkynes, alpha,beta-unsaturated carbonyl compounds, and carbon monoxide

[reaction: see text] Catalytic [2 + 2 + 1 + 1] cocyclization reaction of an alkyne, an alkene, and two molecules of carbon monoxide, leading to functionalized hydroquinones, was studied. Using [Cp*RuCl2]2 as a catalyst, we found that a variety of electron-deficient alkenes, such as alpha,beta-unsaturated ketones, esters, amides, and nitriles, can be employed as an alkene coupling partner to give the corresponding hydroquinones.     

Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols

Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endo-hydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo[2.1.1]-hexan-5-ols 15a,b and 15d-g.     

Catalytic enantioselective intermolecular [2 + 2 + 2] cycloaddition of an alkene and two alkynes

A catalytic enantioselective intermolecular [2 + 2 + 2] cycloaddition of one molecule of alkene (enone) and two molecules of alkyne was developed in the presence of a nickel complex modified by chiral monodentate oxazoline ligands, which have not previously been used as chiral ligands for transition metals in asymmetric catalysts, and an aluminium phenoxide.     

A Pauson-Khand-type reaction between alkynes and olefinic aldehydes catalyzed by rhodium/cobalt heterobimetallic nanoparticles: an olefinic aldehyde as an olefin and CO source

Co/Rh (Co:Rh = 2:2) heterobimetallic nanoparticles derived from Co(2)Rh(2)(CO)(12) react with alkynes and alpha,beta-unsaturated aldehydes such as acrolein, crotonaldehyde, and cinnamic aldehyde and release products resulting from [2 + 2 + 1]cycloaddition of alkyne, carbon monoxide, and alkene. alpha,beta-Unsaturated aldehydes act as a CO and alkene source. These reactions produce 2-substituted cyclopentenones.     

One‐pot four component condensation for the synthesis of novel dispirooxindole pyrrolidine linked 1,2,3‐triazoles via stereo‐ and regioselective [3 + 2] cycloaddition reaction in PEG‐400

A one‐pot four component condensation of isatin, sarcosine, 2‐[2‐oxo‐1‐(prop‐2‐ynyl)indolin‐3‐ylidene]malononitrile and aryl azides has been reported for the synthesis of novel dispirooxindole pyrrolidine linked 1,2,3‐triazole conjugates using Cu(I) as a catalyst in PEG‐400 by stereoselective [3 + 2] azide‐alkyne cycloaddition followed by [3 + 2] azomethine ylide and alkene cycloaddition. Structures have been confirmed by spectral and X‐ray studies. Crystal packing of 5a has also been reported. Rapid reaction, easy work‐up and high yields are the salient features of the present protocol.     

Boron-directed regio- and stereoselective enyne cross metathesis: efficient synthesis of vinyl boronate containing 1,3-dienes

[reaction: see text] Regio- and stereoselective enyne cross metathesis reactions between borylated alkynes and terminal alkenes were realized to provide a variety of functionalized vinyl boronates. High chemical yield and regioselectivity was achieved irrespective of substituents on the alkyne and alkene counterparts, whereas Z/E-selectivity was found to be dependent upon the substituents both on the alkyne and alkene.     

Non-stabilized transition metal carbenes as intermediates in intramolecular reactions of alkynes with alkenes

In this tutorial review we summarize the two major pathways followed in the reaction of alkenes with alkynes catalysed by electrophilic transition metals. If the metal coordinates simultaneously to the alkyne and the alkene, an oxidative cyclometallation can ensue to give a metallacyclopentene, which usually evolves by [small beta]-hydrogen elimination to give Alder-ene cycloisomerisation derivatives. On the other hand, coordination of the metal to the alkyne promotes the attack of the alkene to give metal cyclopropyl carbenes.     

Ruthenium-catalyzed cross-coupling of 7-Azabenzonorbornadienes with alkynes. an entry to 3a,9b-dihydrobenzo[g]indoles

Electron-rich half-sandwich ruthenium complex CpRuI(PPh3)2, generated in situ, catalyzed the coupling reaction of 7-azabenzonorbornadienes with alkynes to form 3a,9b-dihydrobenzo[g]indoles. This transformation involves the cleavage of one C-N bond of the bicyclic alkene and formation of two (C-C and C-N) bonds at the acetylenic carbons. The scope and limitations of the reaction are addressed according to the substitution patterns of the alkyne and of the substituent at the nitrogen atom of the azabenzonorbornadiene.     

Exploring Bis(cyclometalated) Ruthenium(II) Complexes as Active Catalyst Precursors: Room‐Temperature Alkene–Alkyne Coupling for 1,3‐Diene Synthesis

Described is the development of a new class of bis(cyclometalated) ruthenium(II) catalyst precursors for C? C coupling reactions between alkene and alkyne substrates. The complex [(cod)Ru(3‐methallyl)₂] reacts with benzophenone imine or benzophenone in a 1:2 ratio to form bis(cyclometalated) ruthenium(II) complexes ( 1 ). The imine‐ligated complex 1 a promoted room‐temperature coupling between acrylic esters and amides with internal alkynes to form 1,3‐diene products. A proposed catalytic cycle involves C? C bond formation by oxidative cyclization, β‐hydride elimination, and C? H bond reductive elimination. This Ru^II/Ru^IV pathway is consistent with the observed catalytic reactivity of 1 a for mild tail‐to‐tail methyl acrylate dimerization and for cyclobutene formation by [2+2] norbornene/alkyne cycloaddition.     

Cycloisomerization of enynes catalyzed by iron(0)-ate complexes

The 18-electron half-sandwich iron(0) complex [CpFe(C2H4)2] [Li(tmeda)] (1a), which is readily available in multigram quantities from inexpensive starting materials (ferrocene, ethylene, Li sand), is shown to be an efficient catalyst for the Alder-ene reaction of various 1,6(7)-enynes. Thereby, the presence of the labile alkene ligands in the ferrate catalyst is essential since the analogous complex [CpFe(CO)2]Na is catalytically incompetent. The cycloisomerizations catalyzed by 1a are compatible with various functional groups and turned out to be highly diastereoselective with regard to the configuration of the newly formed alkenes as well as relative stereochemistry at the ring junction. The alkyne moiety in the substrates may be terminal, silylated, or substituted with various groups, including cyclopropane rings. Likewise, the alkene substructure can be varied to a large extent, with cycloalkenes of ring sizes >/=7 being particularly suitable.     

Rhodium(II) mediated cyclizations of diazo alkynyl ketones

The rhodium(II)-catalyzed reaction of -diazo ketones bearing tethered alkyne units represents a new and useful method for the construction of a variety of substituted cyclopentenones. The process proceeds by addition of the rhodium-stabilized carbenoid onto the acetylenic π-bond to give a vinyl carbenoid intermediate. The resulting rhodium complex undergoes a wide assortment of reactions including cyclopropanation, 1,2-hydrogen migration, CH-insertion, addition to tethered alkynes and ylide formation. The exact pathway followed is dependent on the specific metal/ligand employed and is also influenced by the nature of the solvent. Sulfonium ylide formation occurred both intra and intermolecularly when the reaction was carried out in the presence of a sulfide. In the case where an ether oxygen was present on the backbone of the vinyl carbenoid, cyclization afforded an oxonium ylide which underwent a [1,2] or [2,3]-sigmatropic shift to give a rearranged product. These cyclic metallocarbenoids were also found to interact with a neighboring carbonyl π-bond to produce carbonyl ylide dipoles that could be trapped with added dipolarophiles. The domino transformation was also performed intramolecularly by attaching an alkene directly to the carbonyl group. When 2-alkynyl-2-diazo-3-oxobutanoates were treated with a Rh(II)-catalyst, furo[3,4-c]furans were formed in excellent yield. The 1,5-electrocyclization process involved in furan formation has also been utilized to produce indeno[1,2-c]furans. Rotamer population was found to play a significant role in the cyclization of -diazo amide systems containing tethered alkynes. In this account, an overview of our work in this area is presented.