Stereoselective formation and rearrangement of morpholinium ylides derived from copper carbenoids

Amino diazoacetoacetates 4a–e and 7a,b were prepared from readily available amino alcohols and subjected to copper-catalyzed carbene-transfer reaction. Substrates 4c–e furnished the morpholin-2-ones 5c–e in good yield via the corresponding cyclic ammonium ylides, albeit with poor diastereoselectivity. Substrates 4a,b failed to provide the corresponding morpholinones, perhaps as a result of steric congestion. Cyclic substrates 7a,b underwent conversion to bicyclic morpholinones 8 and 9 in good yield and with moderate to good diastereoselectivity. This result is rationalized via control of the transiently stereogenic ammonium center of the intermediate bicyclic ylides.     

Ligand-induced control of C-H versus aliphatic C-C migration reactions of Rh carbenoids

The reaction of lithiated trimethylsilyldiazomethane (LTMSD) with aldehydes and subsequent quenching with TMSCl furnished relatively stable alpha-silylated diazocompounds. Upon treatment of the alpha-silylated diazocompounds with Rh2(OAc)4 in refluxing toluene, alpha-silyl silyl enol ethers were formed from unbranched and branched aliphatic aldehydes through predominantly 1,2-migration of the C-H bond. In contrast, treatment of the alpha-silylated diazocompounds with Rh2(tfa)4 at room temperature gave alpha-silyl silyl enol ethers through exclusive and unusual 1,2-migration of the C-C bond. The origin of the selectivity observed from the two catalysts is discussed in relation to early and late transition states.     

Highly stereoselective C-C bond formation by rhodium-catalyzed tandem ylide formation/[2,3]-sigmatropic rearrangement between donor/acceptor carbenoids and chiral allylic alcohols

The tandem ylide formation/[2,3]-sigmatropic rearrangement between donor/acceptor rhodium carbenoids and chiral allyl alcohols is a convergent C-C bond forming process, which generates two vicinal stereogenic centers. Any of the four possible stereoisomers can be selectively synthesized by appropriate combination of the chiral catalyst Rh(2)(DOSP)(4) and the chiral alcohol.     

Aluminum carbenoids in the cyclopropanation of fulvenes

Aluminum carbenoid Et₂AlCH₂I reacts with 6-substituted fulvenes to give tricyclopropanes in high yields. Calculations at the B3LYP/6-31G(d) level of theory show that coplanar arrangement of the double bonds facilitates cyclopropanation due to conjugation in the transition state. Aluminum carbenoid Et₂AlCH₂I was generated by either the reaction of equimolar amounts of Et₃Al and CH₂I₂ in hexane or treatment of Et₂AlI with CH₂N₂ in dichloromethane.     

Synthesis of spiroacetals using functionalised titanium carbenoids

Alkylidenation of lactones with functionalised titanium carbenoid reagents (Schrock carbenes) followed by acid-induced cyclisation of the resulting enol ethers constitutes a new method for the preparation of [4.4], [4.5] and [5.5] spiroacetals (1,6-dioxaspiro[4.4]nonanes, 1,6-dioxaspiro[4.5]decanes and 1,7-dioxaspiro[5.5]undecanes, respectively, sometimes termed 5,5-, 5,6- and 6,6-spiroketals). The titanium carbenoids are easily generated from readily available thioacetals.     

Catalytic and enantioselective allylic C-H activation with donor-acceptor-substituted carbenoids

In this perspective we give an overview of enantioselective C-H activation at allylic sites by means of rhodium(II)-stabilized donor-acceptor-substituted carbenoids. This methodology has been proven to be both an equivalent to established asymmetric reaction sequences and a new synthetic approach with no established counterpart in organic synthesis.     

Intermolecular reactions of electron-rich heterocycles with copper and rhodium carbenoids

This tutorial review describes the reactions of the electron-rich heterocycles pyrrole, furan, indole and benzofuran with copper and rhodium carbenoids. Two main reaction pathways are possible, involving either a concerted non-synchronous cyclopropanation or zwitterionic intermediates. A diverse range of products are possible and the outcome is very dependent on the structure of the heterocycle and the carbenoid. To emphasize this point the carbenoids are considered in terms of three classes: acceptor, acceptor-acceptor and donor-acceptor carbenoids. Unusual catalytic asymmetric transformations can be achieved with this chemistry while the asymmetric induction is strongly influenced by how the carbenoid can approach the heterocycles. This tutorial review gives an overview of the general features that govern the chemistry of metal carbenoids with heterocycles and presents a mechanistic rationale for the range of products that can be formed.     

Alpha-arylsulfanyl-alpha-fluoro carbenoids: their novel chemistry and synthetic applications

The bromine-magnesium exchange reactions of arylthiobromodifluoromethanes with Grignard reagents have been studied. Upon trapping with electrophiles, alkyl aryl sulfides and ketenedithioacetals are obtained. The reaction is proposed to occur via novel alpha-arylsulfanyl-alpha-fluoro carbenoids. The first examples of arylthiomethane multipole synthons are also reported. [reaction: see text]     

Recent advances in the chemistry of magnesium carbenoids

This tutorial review deals with recent advances in the chemistry and synthetic use of magnesium carbenoids. The reactivity of traditional carbenoids (alpha-haloalkyllithium species) was successfully reduced by using magnesium as the metal instead of lithium. Properties of these relatively stable carbenoids, magnesium carbenoids, were widely investigated and it was found that the magnesium carbenoids have very interesting reactivity toward several nucleophiles. The magnesium carbenoids, magnesium cyclopropylidenes, magnesium alkylidene carbenoids, and magnesium beta-oxido carbenoids are generated from alpha-chloroalkyl (or alpha-chloroalkenyl) aryl sulfoxides with a Grignard reagent at low temperature by sulfoxide-magnesium exchange reaction. The stability of the generated magnesium carbenoids and several new reactions based on the electrophilicity of the magnesium carbenoids, including 1,3-CH insertion, are reviewed. Magnesium carbenoids open up the new world of the chemistry of carbenoids.     

Direct N- and C-alkenylation of nitrogen-containing heterocycles with magnesium alkylidene carbenoids

Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride at −78 °C in toluene, with N-lithio nitrogen-containing heterocycles gave N-alkenylated products in moderate to good yields. Also, the reaction of C-lithio indoles, which were generated from N-protected indoles, with magnesium alkylidene carbenoids gave C-2 or C-3 alkenylated products, corresponding to the protective group. The intermediate of these reactions were found to be the alkenyl anion, which could be trapped with electrophiles to give the heterocycles having fully substituted alkenes.     

Insertion of organoindium carbenoids into rhodium halide bonds: revisiting a classic type of transition metal-group 13 metal bond formation

Insertion of the carbenoid group 13 metal species InCp* (Cp* = pentamethylcyclopentadienyl) and InC(SiMe3)3 into the Rh-Cl bonds of [[RhCp*Cl2]2] yields the new complexes [Cp*Rh(InCp*)3(Cl)2] 1 and [Cp*Rh(mu2-Cl)2(InC(SiMe3)3)3] 2, respectively, exhibiting novel cage-like intermetallic complexes with In-Cl-In bridges.     

Diastereoselective zinco-cyclopropanation of chiral allylic alcohols with gem-dizinc carbenoids

The highly diastereoselective zinco-cyclopropanation of chiral allylic alcohols using gem-dizinc carbenoids is described. The reaction produces three contiguous stereogenic centers, and the resulting chiral cyclopropylzinc derivatives can be trapped with electrophiles with retention of configuration. Simple functional group manipulations lead to the efficient synthesis of orthogonally protected 1,2,3-substituted cyclopropane derivatives.     

Observations on the direct amidocyclopropanation of alkenes using organozinc carbenoids

A series of amidocyclopropanes were prepared by direct amidocyclopropanation of alkenes, using organozinc carbenoids generated from readily available diethoxymethylamides. The amidocyclopropanation of monosubstituted alkenes led to selective formation of the trans-amidocyclopropane in most cases, but with more substituted alkenes, the stereochemical outcome of the cyclopropanation reactions was unpredictable. The amidocyclopropane products can be readily elaborated to structurally interesting cyclopropane containing amino acids or amino alcohols.     

Cyclopropylation of arylamines at the 2-position with cyclopropylmagnesium carbenoids

Direct cyclopropylation of arylamines at the 2-position with 1-chlorocyclopropyl phenyl sulfoxides was achieved. The reaction of N-lithio arylamines with cyclopropylmagnesium carbenoids, which are generated from 1-chlorocyclopropyl phenyl sulfoxides with i-PrMgCl via the sulfoxide-magnesium exchange reaction, is the key of this procedure. This method offers an unprecedented way for the synthesis of arylamines having a cyclopropane ring at the 2-position directly from arylamines.     

Metal salt catalyzed carbenoids—XII: General considerations

A systematology for carbene transfer (MT) processes based on apparent molecularities of the product determining step is proposed. An analysis is made of potential conformation effects for copper(I) and copper(II) based carbenoids and a systematology for purposes of nomenclature is proposed for conformations of penta-coordinated systems based upon trigonal bipyramides and tetragonal pyramides. The possible role of valence state is examined and the hazards of applying spin state correlations to carbenoids in parallel with the methods used for carbenes is discussed. Basic guidelines for generating data suitable for internal and external comparisons are given.     

Theoretical studies of carbenes and carbenoids. 5. Intramolecular reactions of cyclopropylcarbene

Intramolecular reactions of cyclopropylcarbene in singlet ground state have been studied using HF/3-21G- gradient methods. Relative energies are estimated with 6–31G^**. The “super-conjugation” between the cyclopropyl and the p AO at the carbene site stabilizes the carbene and retards its exo-endo isomerization with a barrier of 13.7 kcal/mol. The ring expansion occurs preferably from the exo conformation with a barrier of 12.9 kcal/mol. Two terminals disrotate in different rotation directions before and after the transition state. The ring expansion from the endo conformation is a more energetic pathway. The 1,2 H shift is not competitive to the ring expansion for its much higher barrier.