Carbene transfer mechanism

The factors that direct a metallacyclobutane intermediate along one of these pathways are only partially understood. For example, in the case shown in Fig. 4.10, both metathesis and cyclopropanation are mediated by the same tungsten-carbene complex when the reaction is performed in a non-coordinating solvent [31]. These conditions are consistent with reaction via a metallacyclobutane because they allow the olefin to coordinate to the metal center, a prerequisite for [2 -I- 2] cycloaddition. In contrast, only cyclopropanation occurs when the reaction is performed in a coordinating solvent, presumably because formation of a metal-solvent adduct prevents olefin coordination and leaves only a direct carbene transfer mechanism available. 

Aryl(carbonyl)carbenes. The mechanism of proton transfer to the carbenes 168 was found to respond sensibly to the ApA"a of the reactants. LFP of 167a generated 168a (A. = 355 nm) whose absorption was quenched rapidly by... 

Vinyl Fischer carbenes can be used as three-carbon components in Ni(0)-mediated and Rh(l)-catalyzed [3 + 2 + 21-reactions with alkynes (Schemes 48 and 49)142 and with allenes (Schemes 50 and 51).143 All three of the proposed mechanisms for the [3 + 2 + 2]-cycloadditions involve an initial carbene transfer from chromium to nickel or rhodium (Schemes 49, 52, and 53). As is seen from the products of the two [3 + 2 + 2]-reactions with 1,1-dimethylallene, although the nickel and rhodium carbenes 147G and 147K appear similar, the initial insertion of the allene occurs with opposite regioselectivity. 

An understanding of the mechanism [10] for rhodium-mediated intramolecular C-H insertion begins with the recognition that these a-diazo carbonyl derivatives can also be seen as stabilized ylides, such as 15 (Scheme 16.4). The catalytic rhodium(II) car-boxylate 16 is Lewis acidic, with vacant coordination sites at the apical positions, as shown. The first step in the mechanism, carbene transfer from the diazo ester to the rhodium, begins with complexation of the electron density at the diazo carbon with an open rhodium coordination site, to give 17. Back-donation of electron density from the proximal rhodium to the carbene carbon, with concomitant loss of N2, then gives the intermediate rhodium carbene complex 18. 

The enol form of mandelic acid (101) has been generated by flash photolysis of phenyldiazoacetic acid in aqueous solution.101 The enol forms by hydration of the intermediate carbene (102). The reaction of chloramine-T (TsNClNa O) with methyl p-tolyl sulfide to give the corresponding sulfimide (103) appears to proceed via a nitrene-transfer mechanism in the presence of copper(I) and a second nitrogen ligand (such as acetonitrile).102... 

The nitrene transfer from PhI=NTos to alkenes catalyzed by the CpFe(CO)2+ fragment gave better results (85% for styrene) [25], but the characteristics of the chemistry of the cationic intermediates as postulated by the reaction mechanism are closely connected to the alternative formation of aziridines by a carbene transfer... 

The pattern of substituent effects on the magnitude of the isotope effects suggests a wide variation in transition state structure with changing structure of both the carbene and alcohol (Bethell, Howard and Newall, unpublished). At its limits, the range of structures could embrace both ylid and proton-transfer mechanisms. 

The mechanism of the Simmons-Smith reaction appears to be a carbene transfer from the metal to the aikene without any free carbene being released. It may look something like this. 

In certain cases the process analogous to the isonitrile synthesis for the preparation of phosphaalkenes, showing proton- and halogene-substituted C-bridged atoms, is a successful one. 2,4,6-tri-i-butylphenyl-phosphane can be transferred to the phosphaalkene using a strong alkaline solution of chloroform [Eq. (7)] or methylene chloride [Eq. (8)]. A carbene addition mechanism is involved in this reaction (36, 37). 

Figure 4.95 A tentative mechanism for the carbene transfer from sulfur to palladium.

There is thus to date no single general mechanism model for olefin cyclopropanation. The basic mode of ring closure in metal-catalyzed carbene transfer reactions must still be regarded as hypothetical in most cases. 

Substitution by the SN2 mechanism and -elimination by the E2 and Elcb mechanisms are not the only reactions that can occur at C(sp3)-X. Substitution can also occur at C(sp3)-X by the SRN1 mechanism, the elimination-addition mechanism, a one-electron transfer mechanism, and metal insertion and halogen-metal exchange reactions. An alkyl halide can also undergo a-elimination to give a carbene. 

The photochemistry of 4-chloroanilines in methanol, dioxane-water and diox-ane-methanol solvents has been investigated for more than thirty years by Latowski185,186. Large quantum yields of HC1 formation (hci) have been observed for the photolysis of 91a in protic solvents (e.g. Hci = 0.78 in methanol at 254 nm). However, the values of 4>hx are relatively small for 4-bromoaniline (HBt = 0.19), 4-iodoaniline (cbm = 0.29), 2-chloroaniline (hci < 0.02) and 3-chloroaniline (hci = 0.02) under the same condition. N-Acetylation of 91a to 4-chloroacetanilide also inhibits the photolytic process. In conjunction with the solvent- and concentration-dependent photolysis rates of 91a, these results indicate an electron-transfer mechanism for the photochemical reaction electron transfer occurred from an excited 91a to an unexcited 91a molecule, followed by ionization reactions. However, recent analysis of photoproducts from 91a in water/methanol mixtures has shown that benzidine (92) is a major product along with aniline (equation 29)187. As a result, a carbene mechanism that leads to the formation of aniline radicals was put forward in analogy to the photochemistry of 4-halophenols188,189. For example, the photolysis of 91a in aqueous solution first results in the transient species carbene 93 followed by the formation of the aniline radical 94 that was observed as the primary product (Scheme 13)190. In addition to la and 92, other identified secondary products include 4-aminodiphenylamine, 2-aminodiphenylamine, hydrazobenzene, 4-chloronitrosobenzene and 4-chloronitrobenzene, but they are all in low yields191. 

However, at this stage relatively little progress has been made in research on asymmetric catalytic carbene transfer to imines. In 1995, Jacobsen and Jorgensen reported independently that reaction of ethyl diazoacetate with selected imines can be catalyzed by copper salts [27,28]. In the former case [27], moderate levels of enantioselection were found to be imparted by bisoxazoline ligands associated with the copper catalyst (Scheme 11). The observation of racemic pyrrolidine byproducts in the reaction was taken to support a mechanism of catalysis involving initial formation of a copper-bound azomethine yhde intermediate (Scheme 12 ). Collapse of this intermediate to the optically active aziridine apparently competes with dissociation of the copper to a free azomethine ylide. The latter can react with fumarate formed by diazoester decomposition in a dipolar cycloaddition to afford racemic pyrrolidine. 

While many examples are available demonstrating the mechanism-based stereoselectivity in carbene transfer reactions, knowledge of the simple diastereoselectivity exhibited by alkylcarbenoids is rather limited. A few typical reactions (Table 1) arc sufficient to demonstrate the basic principles (for further examples, see Vol. E 19h, pp 165-390). Thus, photolysis of diiodomethane in the presence of (E)- or (Z)-3-hexene stereospecifically provides /r ns-l,2-diethylcyclopropane and cM-l,2-diethylcyclopropane, respectively1. For a general procedure for this photocyclopropa-nation method, which proceeds via the iodomethyl cation, see Vol. E 19b, p 190. 

Cyclopropanation reactions employing an a-diazo carbonyl compound as precursor are almost exclusively performed in the presence of a metal catalyst, The intermediacy of highly reactive metal-carbene complexes is generally accepted, but the details of the carbene transfer are still under discussion7,s. Many examples prove that the configuration of the olefin is maintained during these cyclopropanations (see Vol. E19b, p 1099). This mechanism-bascd stereoselectivity is therefore not further discussed in this section. 

Due to their singlet character, carbenes with sulfur-, selenium-, silicon-, or tin-substituents add to olefins with high stereospecificity, thus guaranteeing mechanism-based stereoselectivity. While high simple diastereoselectivity has been observed in certain examples, the diastereofacial selectivity of these carbenes is almost unknown, and examples of enantioselective carbene transfer reactions are completely lacking. 

Enantiomerically pure iron carbene complexes have been used for carbene transfer reactions to alkenes, e.g. vinyl acetate and styrene, at low temperature to furnish cyclopropanes with moderate cis/trans selectivity in high optical yield (75-95% ee). A two-step reaction mechanism has been proposed to explain the origin of enantioselectivity. ... 

Ru=CH-, <5h=21.7 ppm (s), <5 =305.7 ppm (7c-h= 142.4 Hz) [57]. Complex24released only trans-phenylcyclopropanecarboxylate at 60 °C by tbe reaction with styrene in 82% yield and 97% ee. Moreover, complex 24 acted as a catalyst in tbe same way as tbe etbylene complex 8 at 50 °C, 95% yield, 98 2 trans-to-cis ratio with 93% ee for tbe trans form. Thus, tbe mechanism of AGP catalyzed by Ru Pybox was explained by isolation of tbe corresponding carbene complexes and realization of tbe asymmetric carbene transfer reaction. 

A modified version of the Simmons-Smith reaction uses dibromomethane and in situ generation of the Cu-Zn couple. Sonication is used in this procedure to promote reaction at the metal surface. Cyclopropanation can also be affected with a combination of CH2I2 and an alkylzinc reagent. The reaction is stereospecific and strongly regioselective. Thus, it has been found that cyclopentenol gives only the mdo-bicyclic alcohol (Scheme 5.34). The mechanism of the Simmons-Smith reaction appears to be carbene transfer from the metal to the alkene without any free carbene being released (Scheme 5.35). 

Simmons-Smith reaction Areactionin which a cyclopropane ring is produced from an alkene. It uses the Simmons-Smlth recent, which was originally diiodo-methane (CH2I2) with aZn/Cu couple. Usually, diethyl zinc is used rather than Zn/Cu. The mechanism involves the formation of H2C(I) (Znl) and carbene transfer from the zinc to the double bond of the alkene. 

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