Diastereoselective synthesis of three-, five-, six-, and seven-membered rings from Fischer carbene complexes and 4-unsubstituted 1-amino-1,3-dienes

Fischer carbene complexes react with 4-unsubstituted 1-amino-1,3-dienes to give different carbocyclization products depending on the nature of the carbene complex and on the substitution pattern of the aminodiene. Thus, the reaction of arylcarbene chromium complexes and 1-aminodienes diastereoselectively affords cyclopropane derivatives by means of a formal [2+1] carbocyclization reaction. In particular, pentacarbonyl[(2-furyl)(methoxy)methylene]chromium complex furnishes formal [4+1] carbocyclization products. Starting from beta-substituted alkenylcarbene complexes, formal [4+1] reactions occur and cyclopentenamine derivatives are diastereoselectively formed. However, when the alpha,beta-disubstituted alkenylcarbene complex pentacarbonyl[(5,6-dihydro-2H-pyran-2-yl)(methoxy)methylene]tungsten is used, the outcome of the reaction depends on the substitution on the carbon atom at the 3-position of the aminodiene, generating the [3+2] or [4+3]-cyclization products if the substituent is or is not a hydrogen atom, respectively. Finally, when the reaction is performed with alkynylcarbene complexes, benzaldehyde derivatives are obtained if the triple-bond substituent is a phenyl group or indene derivatives if the group is an alkenyl moiety.     

Solvent-controlled diastereoselective synthesis of cyclopentane derivatives by a [3 + 2] cyclization reaction of alpha,beta-disubstituted (alkenyl)(methoxy)carbene complexes with methyl ketone lithium enolates

Reaction of alpha,beta-unsaturated methoxycarbene complexes 1 and 11 with methyl ketone lithium enolates 2 leads to the corresponding five-membered carbocyclic compounds 4 or diast-4 and 12. The influence of the solvent and/or cosolvent (PMDTA), which turned out to be crucial to direct the reaction to 4 or diast-4, is studied, and a tentative mechanism according to these facts is proposed. In addition, the reaction of carbene complex 1a with alkynyl methyl ketone lithium enolates can be directed to the formal [3 + 2] or [4 + 1] cyclization products by a slight variation of the reaction conditions. Finally, consecutive three-component coupling reactions with carbene complex 1a, lithium enolates 2, and aldehydes 18 to give, in a diastereoselective way, hydroxy carbonyl compounds 19 and tricyclic polyethers 20 are presented.     

Rhodium(I)-catalyzed [3+2+2]-cyclization of alkenyl Fischer carbene complexes with methyl buta-2,3-dienoate

A variety of alkenyl chromium Fischer carbene complexes react with methyl buta-2,3-dienoate in the presence of a rhodium catalyst to afford substituted cycloheptene derivatives 7, along with minor amounts of cyclopentene derivatives 6. Through this [3+2+2]-cyclization two allene units and one alkenyl carbene ligand are assembled in a selective manner.     

[8+2] and [8+3] Cyclization Reactions of Alkenyl Carbenes and 8‐Azaheptafulvenes: Direct Access to Tetrahydro‐1‐azaazulene and Cyclohepta[b]pyridinone Derivatives

The reactivity of Fischer alkenyl carbenes toward 8‐azaheptafulvenes is examined. Alkenyl carbenes react with 8‐azaheptafulvenes with complete regio‐ and stereoselectivity through formal [8+3] and [8+2] heterocyclization reactions, which show an unprecedented dependence on the C_β substituent at the alkenyl carbene complex. Thus, the formal [8+3] heterocyclization reaction is completely favored in carbene complexes that bear a coordinating moiety to give tetrahydrocyclohepta[b]pyridin‐2‐ones. Otherwise, alkenyl carbenes that lack appropriate coordinating groups undergo a formal [8+2] cyclization with 8‐azaheptafulvenes to give compounds that bear a tetrahydroazaazulene structure. A likely mechanism for these reactions would follow well‐established models and would involve a 1,4‐addition/cyclization in the case of the [8+2] cyclization or a 1,2‐addition/[1,2] shift–metal‐promoted cyclization for the [8+3] reaction. The presence of a coordinating moiety in the carbene would favor the [1,2] metal shift through transition‐state stabilization to lead to the [8+3] product. All these processes provide an entry into the tetrahydroazaazulene and cycloheptapyridone frameworks present in the structure of biologically active molecules.     

The [2 + 1] and [4 + 3] cyclization reactions of fulvenes with Fischer carbene complexes: new access to annulated cyclopentanones

Pentafulvenes are regioselectively cyclopropanated with group 6 Fischer carbene complexes leading to the homofulvene ring with complete endo selectivity. The homofulvene adducts undergo in turn a further cyclopropanation with ethyl diazoacetate or cyclopentannulation with a Fischer alkenyl carbene complex to provide substituted cyclopentanones after ozonolysis of the exocyclic carbon=carbon double bond. Fischer alkynyl carbene complexes also produce the corresponding alkynyl homofulvenes, albeit the exo stereoisomer is in this case exclusively or preferentially formed. Under moderate CO pressure, tungsten alkynyl carbene complexes cycloadd to pentafulvenes in a [4 + 3] fashion, giving rise to bicyclo[3.2.1]octadien-2-ones.     

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.     

3 + 2] Annulation of beta-heteroatom-substituted alpha,beta-unsaturated acylsilanes with methyl ketone enolates: scope and investigation of the reaction course

A new route to (Z)-beta-silylacryloylsilanes 10 and the improved conditions for the [3 + 2] annulation using 10 and alkyl methyl ketone enolates are reported. Also, details of investigations defining a reaction course of the [3 + 2] annulation using beta-phenylthio- and beta-trimethylsilyl-acryloylsilanes 1 (X = SPh, SiMe(3)) and alkyl methyl ketone enolates are described.     

Stereocontrolled construction of seven-membered carbocycles using a combination of Brook rearrangement-mediated [3 + 4] annulation and epoxysilane rearrangement

Reactions of delta-silyl-gamma,delta-epoxy-alpha,beta-unsaturated acylsilane with alkenyl methyl ketone enolate afford highly functionalized cycloheptenone derivatives via a tandem sequence featuring the combination of Brook rearrangement-mediated [3 + 4] annulation and epoxysilane rearrangement. The reactions using an opposite combination of three and four carbon units, in which an epoxysilane moiety was incorporated in the four-carbon unit, also give satisfactory results. Also, the possibility of chirality transfer from epoxide to remote positions via the tandem sequence using an optically active epoxide has been demonstrated.     

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.     

A general and regioselective synthesis of cyclopentenone derivatives through nickel(0)-mediated [3 + 2] cyclization of alkenyl Fischer carbene complexes and internal alkynes

A broad range of substituted 2-cyclopentenone derivatives 3-6 are synthesized by the nickel(0)-mediated [3 + 2] cyclization reaction of chromium alkenyl(methoxy)carbene complexes 1 and internal alkynes 2. The reaction takes place with complete regioselectivity with both unactivated alkynes and activated alkynes (electron-withdrawing and electron-donating substituted alkynes). Representative cycloadducts containing boron and tin substituents are further demonstrated to be active partners in classical Pd-catalyzed C-C coupling processes to allow the production of 2-aryl- and 2-alkynyl-substituted cyclopentenones 9-13.     

Regioselective and Stepwise [8 + 2] Cycloaddition Reaction between Alkynyl-Fischer Carbene Complexes and Tropothione

The formal [8 + 2] cycloaddition reaction between alkynyl Fischer carbene complexes and tropothione leads to the regioselective formation of novel 3aH-cyclohepta[b]thiophene carbene complexes. Computational DFT calculations indicate that the process proceeds stepwise via antiaromatic zwitterionic intermediates.     

Diastereoselective metal-catalyzed [4 + 2 + 2] carbocyclization reactions utilizing a rhodium N-heterocyclic carbene (NHC) complex: the first example of a rhodium NHC-catalyzed [m + n + o] carbocyclization

The air and moisture stable rhodium N-heterocyclic carbene (NHC) complex, RhCl(IMes)(COD)(IMes =N,N[prime or minute]-bis(2,4,6-trimethylphenyl)imidazole-2-ylidine; COD = 1,5-cyclooctadiene), facilitates a diastereoselective metal-catalyzed [4 + 2 + 2] carbocyclization of 1,6-enynes in the presence of silver triflate and 1,3-butadiene.     

Diastereoselective cyclopropanation of ketone enols with Fischer carbene complexes

Treatment of aryl/heteroaryl methoxycarbene complexes of chromium with -substituted ketone lithium enolates between -78 degrees C and room temperature resulted in the diastereoselective synthesis of 1,2,2,3-tetrasubstituted cyclopropanols. An exception has been observed in the reaction with cyclohexanone lithium enolate that yielded a bicyclic 2-buten-4-olide. 1,2-Dimethoxycyclopropanes and 1-methoxy-2-trimethylsilyloxycyclopropanes were isolated by quenching the reactions with MeOTf or Me3SiCl, respectively. This novel cyclopropanation process involves formation of lithium (3-oxoalkyl)pentacarbonylchromate intermediates which on warming undergo intramolecular addition to the carbonyl group. This cyclization is equivalent to the cyclopropanation in smooth conditions of electron-rich alkenes with Fischer carbene complexes.     

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.     

Nickel-catalyzed [3+1+1] cycloaddition reactions of alkenyl Fischer carbene complexes with methylenecyclopropanes

Methylenecyclopentanones were synthesized by the nickel-catalyzed [3+1+1] cycloaddition reactions of alkenyl Fischer carbene complexes with methylenecyclopropanes. The methylenecyclopropane was transformed into the C(2)-symmetric bis-cyclopentapyridazine derivative by reacting with p-toluenesulfonyl hydrazine.     

CH3--MoF], [CH2=MoHF], and [CH[triple bond]MoH2F] formed by reaction of laser-ablated molybdenum atoms with methyl fluoride: persistent photoreversible interconversion through alpha-hydrogen migration and agostic interaction

Simple molybdenum methyl, carbene, and carbyne complexes, [CH3--MoF], [CH2=MoHF], and [CH[triple chemical bond]MoH(2)F], were formed by the reaction of laser-ablated molybdenum atoms with methyl fluoride and isolated in an argon matrix. These molecules provide a persistent photoreversible system through alpha-hydrogen migration between the carbon and metal atoms: The methyl and carbene complexes are produced by applying UV irradiation (240-380 nm) while the carbyne complex is depleted, and the process reverses on irradiation with visible light (lambda>420 nm). An absorption at 589.3 cm(-1) is attributed to the Mo--F stretching mode of [CH3--MoF], which is in fact the most stable of the plausible products. Density functional theory calculations show that one of the alpha-hydrogen atoms of the carbene complex is considerably bent toward the metal atom (angle-spherical HCMo=84.5 degrees ), which provides evidence of a strong agostic interaction in the triplet ground state. The calculated C[triple chemical bond]Mo bond length in the carbyne is in the range of triple-bond values in methylidyne complexes.     

Nickel(0)-mediated [2+2+1] cyclization reaction of chromium carbene complexes and internal alkynes

Alkyl, aryl, and heteroaryl chromium Fischer carbene complexes undergo Ni(0)-mediated [2+2+1] cyclization reaction with internal unactivated and electron-poor internal alkynes to yield highly substituted cyclopentadienes with complete regioselectivity in most cases. The intramolecular version of this cyclization has been accomplished with 1,8-diphenyl-1,7-octadiyne to produce indene derivatives. This three-component [2+2+1] cyclization represents a very uncommon process in the chemistry of Fischer carbene complexes.     

Diastereoselective intramolecular temporary silicon-tethered rhodium-catalyzed [4+2+2] cycloisomerization reactions: regiospecific incorporation of substituted 1,3-butadienes

Transition metal-catalyzed carbocyclization reactions represent powerful methods for the construction of complex polycyclic systems. We have developed a regiospecific and diastereoselective intramolecular temporary silicon-tethered rhodium-catalyzed [4+2+2] cycloisomerization reaction of a tethered enyne for the construction of tricyclic eight-membered heterocycles and carbocycles. This methodology also allows (E)- and (Z)-olefins to be utilized in a stereospecific manner. The incorporation of either alkene geometry is particularly significant, since related carbocyclization reactions are often limited in this respect. Finally, the ability to utilize carbon-tethered 1,6-enynes and to regiospecifically incorporate substituted 1,3-butadiene derivatives provides exciting opportunities for future applications toward the total synthesis of cyclooctanoid containing diterpenes.     

Stereoselective [3+2+2] cycloaddition utilizing optically active binuclear Fischer carbene complexes with alkynes

The reaction of optically active α,β-unsaturated binuclear Fischer carbene complexes with alkynes gave planar chiral cycloheptatriene chromium complexes via [3+2+2] cycloaddition with high diastereoselectivity.     

Study of the reactivity of ketone enolates with 3-halo-2-amino derivatives of benzo[b]thiophene under photostimulated sRN1 reaction conditions

Reactivity of the 3-halo-2-amino derivatives of benzo[6]thiophene 1a-c and 2 with several ketone enolates 3–5 have been studied under photostimulated S_RN1 reaction conditions. The normal substitution product 6 only was obtained in low yields using potassioacetophenone 3 as the enolate ion and 2-(tert-butoxycarbonylamino)-3-chlorobenzo[b]thiophene ( 1a ) and 2-(tert-butoxycarbonylamino)-3-iodobenzo[b]thiophene ( 1c ) as substrates. In all reactions the main product was the corresponding dehalogenated substrate 7a-b , thus indicating that reduction of the substrate strongly competes with the desired substitution reaction.