Addition reactions carbene-mediated

Although there is some experimental evidence for the formation of hypervalent silicon species (Fukada et al. 2006) an alternative reaction pathway via preliminary carbene-mediated activation of the carbonyl or imine species respectively (1,2-addition), and subsequent reaction of the anionic species with TMSCN etc. (electrophilic trapping of the alkoxide) has been proposed (Suzuki et al. 2006b Marion et al. 2007). 

Transition metal-carbene complexes undergo many more reactions in addition to these three and have been widely applied to the synthesis of organic molecules. Because this material is outside the scope of the chapter, we direct the interested reader to reviews on other carbene-mediated transformations [19-21]. 

Crystal structures of ethylmagnesium bromide Crystal structure of tetrameric phenyllithium etherate Representation of tt bonding in alkene-transition-metal complexes Mechanisms for addition of singlet and triplet carbenes to alkenes Frontier orbital interpretation of radical substituent effects Chain mechanism for radical addition reactions mediated by trialkylstannyl radicals... 

An alternative to the synthesis of epoxides is the reaction of sulfur ylide with aldehydes and ketones.107 This is a carbon-carbon bond formation reaction and may offer a method complementary to the oxidative processes described thus far. The formation of sulfur ylide involves a chiral sulfide and a carbene or carbenoid, and the general reaction procedure for epoxidation of aldehydes may involve the application of a sulfide, an aldehyde, or a carbene precursor as well as a copper salt. This reaction may also be considered as a thiol acetal-mediated carbene addition to carbonyl groups in the aldehyde. 

Stang etal. (94JA93) have developed another alkynyliodonium salt mediated approach for the synthesis of y-lactams including bicyclic systems containing the pyrrole moiety. This method is based on the formation of 2-cyclopentenones 114 via intramolecular 1,5-carbon-hydrogen insertion reactions of [/3-(p-toluenesulfonyl)alkylidene]carbenes 113 derived from Michael addition of sodium p-toluenesulfinate to /3-ketoethynyl(phenyl) iodonium triflates 112 (Scheme 32). Replacing 112 by j8-amidoethynyl (phenyl)iodonium triflates 115-119 provides various y-lactams as outlined in Eqs. (26)-(30). 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

Reactions of alkynyliodonium salts 119 with nucleophiles proceed via an addition-elimination mechanism involving alkylidenecarbenes 120 as key intermediates. Depending on the structure of the alkynyliodonium salt, specific reaction conditions, and the nucleophile employed, this process can lead to a substituted alkyne 121 due to the carbene rearrangement, or to a cyclic product 122 via intramolecular 1,5-carbene insertion (Scheme 50). Both of these reaction pathways have been widely utilized as a synthetic tool for the formation of new C-C bonds. In addition, the transition metal mediated cross-coupling reactions of alkynyliodonium salts are increasingly used in organic synthesis. 

Silver can mediate oxidation reactions and has shown unique reactivity. In a few cases, namely, nitrene-, carbene-, and silylene-transfer reactions, novel reactivity was found with homogeneous silver catalysts. Some of these reactions are uniquely facilitated by silver, never having been reported with other metals. While ligand-supported silver catalysts were extensively utilized in enantioselective syntheses as Lewis acids, disappointingly few cases were reported with oxidation reactions. Silver-catalyzed oxidation reactions are still underrepresented. Silver-based catalysts are cheaper and less toxic versus other precious metal catalysts. With the input of additional effort, this field will undoubtedly give more promising results. 

Others have investigated the kinetics of amination reactions mediated by catalyst systems employing the new electron-rich monodentate ligands. In particular, Hartwig has shown that for catalysis by a 1 1 palladium to Xn tert-butyl)phosphine system, a mechanism in which oxidative addition of aryl chlorides follows coordination of base to the palladium competes with the standard nonanionic pathway. Finally, Caddick, Cloke, and coworkers have studied amination reactions of aryl chlorides performed by palladium complexes of N-heterocyclic carbene ligands. They found the rate to be limited by the oxidative addition step, which occurs first through the dissociation of an NHC ligand. 

A rhodium-mediated carbene addition has been employed as the key step in a synthesis of furans. The precursors were synthesized on TentaGel-NHi resin, which was transformed into an amide (135). Subsequent formation of imides 136 with malonic ethyl ester chloride and reaction with tosyl azide gave solid-phase-bound diazo imides 137. Reaction with Rh2(OAc)4 in the presence of electron-deficient alkynes produced substituted furans 139 via the intermediate isomiinch-none 138 through a sequence of a [2-i-3]-cycloaddition to the alkyne and subsequent cycloreversion. The yields of the reaction varied in the range 50-70% (Scheme 36) [52]. 

Because of the extraordinary strength of the carbon-fluorine bond, transition metal-mediated activation of fluoroalkanes and arenes is not easy to achieve. Nevertheless, activation of the C-F bond in highly electron-deficient compounds such as 2,4,6-trifluoropyrimidine, pentafluoropyridine, or hexafluorobenzene is possible with stoichiometric amounts of bis(triethylphosphano) nickel(O) [101] (Scheme 2.45). More recently Herrmann and coworkers [102] have described a variant of the Kumada-Corriu cross-coupling reaction [103] between fluorobenzene and aryl Grignard compounds which uses catalytic amounts of nickel carbene complexes. Hammett analysis of the relative kinetic rate constants indicated that the reaction proceeds via initial oxidative addition of the fluoroaromatic reactant to the nickel(O) species. 

An important factor in the efficiency of this reaction may well be complexation between the rhodium carbene and the bond into which carbene insertion is to take place certainly rhodium mediated C—H bond activation is known to take place. The addition to alkenes can also be catalysed " rearrangement of the product provides a useful route to cyclopentane rings. 

JV-carbamoyl-substituted heterocyclic carbene/Pd(II) complexes in the presence of PPh3 and Cul are reported to mediate the cross-coupling of aryl iodides with terminal alkynes at very mild temperature [67]. The system is compatible with aryl bromides however, the temperature then required is 80 °C. In all reactions, the addition of 1 mol% of phosphine increased the yield of product. The role of the phosphine ligand is not completely understood but may facilitate the initial generation of a Pd(0) species. 

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