Transition metal-catalyzed intermolecular [5+2] and [5+2+1] cycloadditions of allenes and vinylcyclopropanes

Initial examples of the intermolecular Rh(I)-catalyzed [5+2] cycloaddition reaction of bifunctional allenes and vinylcyclopropanes are described. The reactions proceed with facility and in yields of up to 99% with a variety of alkyne-, ester-, styrene-, or cyano-substituents on the allene to afford the corresponding cycloadducts. In the presence of CO, the reaction proceeds to an eight-membered ring cycloadduct and its transannularly closed product, providing the first example of a three-component [5+2+1] cycloaddition with allenes.     

An unexpected phosphine-catalyzed [3 + 2] annulation. Synthesis of highly functionalized cyclopentenes

An unexpected phosphine-catalyzed [3 + 2] annulation from electron-deficient allenes and substituted alkylidenemalononitriles was realized in which the allylic moiety of the substituted alkylidenemalononitriles served as the three carbon unit of the cyclopentenes instead of the electron-deficient allenes.     

Theoretical study of the [2+2+2+1] cycloaddition mechanism of enediynes and carbon monoxide catalyzed by rhodium

The [2+2+2+1] cycloaddition mechanism of enediynes and carbon monoxide catalyzed by the [Rh(CO)2Cl]2 rhodium dimer has been studied using density functional theory, comparing this multistep process with the two-step reaction in the absence of a catalyst. According to our results, the multistep mechanism agrees with that previously suggested. The great selectivity of this reaction and the influence of the chosen solvent in this selectivity were also analyzed.     

Specific synthesis of 1,2- and 1,3-dialkylidenecycloheptanes by [3+2+2] cyclization of alkenyl Fischer carbene complexes and allenes

The 1,2- and 1,3-dialkylidenecycloheptane rings are specifically assembled from chromium alkenyl Fischer carbene complexes and allenes via [3+2+2] cyclization reactions. The former cycloadducts are obtained when the cyclization is performed in the presence of 1 equiv of [Ni(cod)2], while the [Rh(cod)Cl]2-catalyzed cyclization leads to the latter cycloadducts.     

Highly regio- and chemoselective [2 + 2 + 2] cycloaddition of 1,6-heptadiynes with allenes catalyzed by cobalt complexes

The CoI2(PPh3)2/Zn system effectively catalyzes the [2 + 2 + 2] ene-diyne cycloaddition of 1,6-heptadiynes with allenes in a highly regio- and chemoselective fashion to yield substituted benzene derivatives in good to excellent yields.     

Alkenes in [2+2+2] Cycloadditions

Participation of alkenes and allenes in [2+2+2] cycloaddition reactions has attracted much attention recently. This version of the well‐established alkyne cyclotrimerization renders interesting products, such as cyclohexadienes and other polycycles, through cascade processes. Many mechanistic variations are observed when using certain metal complexes as catalysts. The frequent generation of stereogenic centers has prompted the development of efficient asymmetric versions. This Minireview summarizes the efforts reported to date on the use of double bonds as partners in [2+2+2] cyclotrimerizations.     

Fluorous mixture synthesis of 4-alkylidene cyclopentenones via a rhodium-catalyzed [2+2+1] cycloaddition of alkynyl allenes

Fluorous mixture synthesis was used to prepare a library of 4-alkylidene cyclopentenones starting from a mixture of four alpha-amino acid derivatives tagged with different fluorous benzyl carbamates ((F)CBz) of varying fluorine content. The amino acids were converted to the corresponding propargyl esters and then subjected to an ester-enolate Claisen rearrangement to give a mixture of allenic amino esters. The allenes were then split four ways and propargylated with different propargyl bromides to give four mixtures of alkynyl allenes. The 4-alkylidene cyclopentenones were formed by a formal [2+2+1] cycloaddition of the alkynyl allenes using catalytic [Rh(CO)2Cl]2 under CO atmosphere. Demixing by fluorous preparative HPLC, removal of the fluorous benzyl carbamates, and then exposure to HCl/ether gave the hydrochloride salts of 16 compounds as diastereomeric mixtures in 69-99% purity. Thus, after just 26 chemical steps, a library of 16 cyclopentenones was prepared by using fluorous mixture synthesis. By comparison, the same library would have required 112 steps if each compound were made individually by parallel synthesis.     

Highly regio- and chemoselective [2 + 2 + 2] cycloaddition of electron-deficient diynes with allenes catalyzed by nickel complexes: a novel entry to polysubstituted benzene derivatives

Diynes 1a-c [X(CH(2)Ctbd1;CCO(2)Me)(2): X = (CH(2))(2), 1a, X = CH(2), 1b and X = O, 1c] undergo [2 + 2 + 2] ene-diyne cycloaddition reactions with a variety of allenes (n-butylallene 2a, phenylallene 2b, (4-chlorophenyl)allene 2c, (4-bromophenyl)allene 2d, (3-methoxyphenyl)allene 2e, 1-naphthylallene 2f, cyclohexylallene 2g and cyclopentylallene 2h) in the presence of Ni(dppe)Br(2) and Zn powder in CH(3)CN at 80 degrees C for 8 h to give the corresponding polysubstituted benzene derivatives 4a-l in good to excellent yields. Under similar reaction conditions, unsymmetrical diynes 5a-c (HCtbd1;CCH(2)XCH(2)Ctbd1;CCO(2)Me) react with allenes 2 to afford exclusively the corresponding meta-isomers 6a-g in 73-86% yields. The catalytic reaction is highly regioselective and completely chemoselective. This synthetic method is compatible with many functional groups such as Cl, Br, and OMe on the phenyl group of the allene moiety and an ether linkage in a diyne moiety. In this catalytic reaction, allenes are synthetically equivalent to terminal alkynes. Interestingly, unsymmetrical diyne 7 (MeCtbd1;C(CH(2))(4)Ctbd1;CCO(2)Me) undergoes 2:1 cocyclotrimerization with allenes 2a and 2g to afford the corresponding polysubstituted benzene derivatives 9a,b in 87% and 82% yields, respectively. A plausible mechanism involving a nickelacycloheptadiene intermediate is proposed to account for this nickel-catalyzed reaction.     

Single-Step Construction of a Nine-Membered Carbocycle by a New [4+4+1] Cycloaddition

A palladium catalyst serves as a template for the assembly of a nine-membered carbocycle from two molecules of vinylallene and one molecule of carbon monoxide [Eq. (a)]. This unprecedented [4+4+1] cycloaddition is in marked contrast to the [4+1] cycloaddition mediated by rhodium(I ) catalysts.     

Cycloadditions of 1-iminylphosphirane complexes with allenes

A cascade carbonylative ring expansion and [2+2]/[4+2] cycloaddition of strained 1-iminylphosphirane complexes with aryl allenes were reported.The carbonylative ring expansion of 1-iminylphosphirane complexes provides an azaphosphacyclohexone complex intermediate with a C=P double bond.The following [2+2] or dearomatic [4+2] cycloaddition of this intermediate with allenes is modulated by the aryl substituents on the imino carbon.The regioselective [2+2] cycloaddition with 1,1-diarylallene provides an entry to bicyclo[4.2.0]octan-4-one skeletons featuring a four-membered phosphacyclobutane moiety.While dearomatic [4+2] cycloaddition was preferred with less aromatic naphthalene and yielded octahydrochrysene skeleton containing heteroatoms.     

Diastereoselective intermolecular rhodium-catalyzed [4 + 2 + 2] carbocyclization reactions: computational and experimental evidence for the intermediacy of an alternative metallacycle intermediate

Intermolecular rhodium-catalyzed [m + n + o] reactions of 1,6-enynes and various pi-components (carbon monoxide, alkynes, 1,3-butadienes, etc.) provide an expeditious approach for the construction of polycyclic fragments that represent important synthons for target-directed synthesis. We present computational and experimental evidence for the existence of a previously undescribed reaction pathway for the rhodium-catalyzed [4 + 2 + 2] reaction involving a 1,6-enyne. This model clearly demonstrates the origin of the excellent diastereoselectivity in this type of reaction and the remarkable tolerance of both (E)- and (Z)-isomers within the 1,6-enyne, which is generally prone to competitive ene-cycloisomerization.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Highly chemo-, regio-, and stereoselective [3+2]-cyclization of activated and deactivated allenes with alkenyl Fischer carbene complexes: a straightforward access to alkylidenecyclopentanone derivatives

A broad range of functionalized 5-alkylidenecyclopentene derivatives are synthesized by the rhodium(I)-catalyzed [3+2]-cyclization reaction of chromium alkenyl(methoxy)carbene complexes 1 and activated allenes. Thus, amidocyclopentenes 4a-n are readily available from N-allenylamides 2a-c, while phenoxyallene 2e gives access to phenoxycyclopentenes 6. In turn, the cyclization reaction with (alkoxycarbonyl)allenes 3 leads to (alkoxycarbonyl)methylidenecyclopentenes 7-10. In terms of selectivity, most cyclization reactions take place with complete chemo-, regio-, and diastereoselectivity. Representative cycloadducts are efficiently hydrolyzed to the corresponding 2-alkylidenecyclopentanones 11a-e without tautomerization or isomerization. Finally, a tentative reaction pathway is proposed that involves the rhodium(I) carbene complexes as the species responsible for the [3+2]-cyclization.     

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.     

Ruthenium-catalyzed (2 + 2) intramolecular cycloaddition of allenenes

We report a ruthenium-catalyzed (2 + 2) intramolecular cycloaddition of allenes and alkenes. We have found that the use of the ruthenium complex RuH(2)Cl(2)(P(i)Pr(3))(2), which has previously gone unnoticed in catalytic applications, is crucial for the observed reactivity. The reaction proceeds under mild conditions and is fully diastereoselective, providing a practical entry to a variety of bicyclo[3.2.0]heptane skeletons featuring cyclobutane rings.     

Metal-controlled selective [3+2] cyclization reactions of alkenyl Fischer carbene complexes and allenes

Chromium alkenyl Fischer carbene complexes undergo selective [3+2] cyclization reactions to allenes in the presence of nickel(0) or rhodium(I) catalysts. Interestingly, the chemo- and regioselectivity of the process are entirely dependent on the nature of the metal.     

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.     

A highly regio- and stereoselective formation of bicyclo[4.2.0]oct-5-ene derivatives through thermal intramolecular [2 + 2] cycloaddition of allenes

Thermal [2 + 2] cycloaddition of allenes with an additional multiple bond is described. By simply heating the allenenes or allenynes having a three-atom tether in an appropriate solvent such as dioxane or DMF, the distal double bond of the allenic moiety regioselectively participates in the cycloaddition to form bicyclo[4.2.0]oct-5-ene derivatives in good to excellent yields. In all the reactions of allenenes, the olefin geometry was completely transferred to the cycloadducts. While the reaction of terminal allenes afforded bicyclic cyclobutane derivatives as a single isomer, the cycloaddition of some internal allenes with axial chirality yielded a diastereomeric mixture of cycloadducts. These results are in good accordance with the stepwise mechanism through a biradical intermediate with a coplanar allyl radical.     

Phenylsulfonyl ene-allenes as efficient precursors to bicyclic systems via intramolecular [2 + 2]-cycloaddition reactions

Various phenylsulfonyl allene derivatives were prepared with double bonds tethered either to the alpha-position or the gamma-position of the allene. These substrates underwent a highly regio- and stereospecific thermal [2 + 2]-cycloaddition across the nonactivated cumulene double bond, forming distal cycloadducts (i.e., 57) in the case of alpha-tethered allenes and proximal adducts (i.e., 25) in the case of gamma-tethered allenes. The mechanistic rationale for the observed stereospecificity involves initial diradical formation, followed by a rapid ring closure to the more stable cis-fused ring system. The tether may be equipped with heteroatoms, allowing for the formation of fused heterocycles (e.g., 61), and the cycloaddition can be facilitated by the introduction of sterically bulky groups and/or by conformational rigidity to the tether. Other modes of cyclization were observed in the presence of sodium benzenesulfinate or Lewis acids, in which cases polar mechanisms prevail. The chemoselectivity is reversed for [4 + 2]-cycloadditions, which prefer instead to engage the vinyl sulfone moiety, independent of whether the tether is attached to the alpha- or gamma-position of the allene.     

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.