Carbenoids, production

Dipoles can also be generated from rearrangements that take place after the formation of an initial rhodium carbenoid product ]40, 70, 71]. One example of this type of transmutation, also known as a dipole cascade process, involves the formation of an azomethine ylide via the initial formation of a carbonyl ylide [72]. This process was... 

Dirhodium(ll) tetrakis[methyl 2-pyrrolidone-5(R)-oarboxylate], Rh2(5R-MEPV)4, and its enantiomer, Rh2(5S-MEPY)4, which is prepared by the same procedure, are highly enantioselective catalysts for intramolecular cyclopropanation of allylic diazoacetates (65->94% ee) and homoallylic diazoacetates (71-90% ee),7 8 intermolecular carbon-hydrogen insertion reactions of 2-alkoxyethyl diazoacetates (57-91% ee)9 and N-alkyl-N-(tert-butyl)diazoacetamides (58-73% ee),10 Intermolecular cyclopropenation ot alkynes with ethyl diazoacetate (54-69% ee) or menthyl diazoacetates (77-98% diastereomeric excess, de),11 and intermolecular cyclopropanation of alkenes with menthyl diazoacetate (60-91% de for the cis isomer, 47-65% de for the trans isomer).12 Their use in <1.0 mol % in dichloromethane solvent effects complete reaction of the diazo ester and provides the carbenoid product in 43-88% yield. The same general method used for the preparation of Rh2(5R-MEPY)4 was employed for the synthesis of their isopropyl7 and neopentyl9 ester analogs. 

The reaction of oxiranes with base can follow several paths, giving products of type (34-38 Scheme 27). (a) Formation of an oxiranyl anion (34) is rare (Section 5.05.3.5). (b) Nucleophilic ring opening to give (35) is common with unhindered bases (Section 5.05.3.4). (c) a-Elimination to give a carbene or carbenoid (36) is favored by alkyllithium bases and... 

The possibility of a radical mechanism is supported by the observation of the accelerating effect of molecular oxygen on the cyclopropanation. Miyano et al. discovered that the addition of dioxygen accelerated the formation of the zinc carbenoid in the Furukawa procedure [24a, b]. The rate of this process was monitored by changes in the concentration of ethyl iodide, the by-product of reagent formation. Comparison of the reaction rate in the presence of oxygen with that in the... 

In 1963, Dauben and Berezin published the first systematic study of this syn directing effect (Scheme 3.15) [37]. They found that the cyclopropanation of 2-cyclohexen-l-ol 32 proceed in 63% yield to give the syn isomer 33 as the sole product. They observed the same high syn diastereoselectivity in a variety of cyclic allylic alcohols and methyl ethers. On the basis of these results, they reasonably conclude that there must be some type of coordinative interaction between the zinc carbenoid and the substrate. 

An alternative approach to asymmetric synthesis that avoids covalent modification of the substrate is chiral modification of the active reagent. This not only streamlines the number of synthetic manipulations, but it simplifies the isolation of the desired product. In the case of zinc carbenoids, such modifications are feasible alternatives to the use of a standard chiral auxiliary. Two important factors combine... 

Finally, metalated epoxides undergo isomerization processes characteristic of traditional carbenoids (Scheme 5.2, Path C). The structure of a metalated epoxide is intermediate in nature between the structures 2a and 2b (Scheme 5.2). The existence of this intermediacy is supported by computational studies, which have shown that the a-C-O bond of oxirane elongates by -12% on a-lithiation [2], Furthermore, experimentally, the a-lithiooxycarbene 4a (Scheme 5.3) returned cydo-pentene oxide 7 among its decomposition products indeed, computational studies of singlet 4a suggest it possesses a structure in the gas phase that is intennediate in nature between an a-lithiocarbene and the lithiated epoxide 4b [3],... 

Base-induced rearrangement of bicyclo[2.2.2]octane oxide 67 gives predominantly bicyclo[2.2.2]octanone 68 (Scheme 5.15), which once again indicates that close proximity between the carbenoid center and the C-H bond into which it may insert is important if such an insertion is to occur [30]. In comparison, the sense of product distribution is reversed for the related substrate bicyclo[2.2.2]octadiene oxide 70 on treatment with LDA [15, 22], alcohol 72 being the favored product. 

The reaction between CHCI3 and OH is often carried out under phase-transfer conditions. It has been shown that the reaction between PhCHCl2 and t-BuOK produces a carbenoid, but when the reaction is run in the presence of a crown ether, the free PhCCl is formed instead.Dihalocyclopropanes are very useful compoundsthat can be reduced to cyclopropanes, treated with magnesium or sodium to give allenes (18-3), or converted to a number of other products. 

Interestingly, [Ee(F20-TPP)C(Ph)CO2Et] and [Fe(p2o-TPP)CPh2] can react with cyclohexene, THF, and cumene, leading to C-H insertion products (Table 3) [22]. The carbenoid insertion reactions were found to occur at allylic C-H bond of cyclohexene, benzylic C-H bond of cumene, and ot C-H bond of THF. This is the first example of isolated iron carbene complex to undergo intermolecular carbenoid insertion to saturated C-H bonds. 

Carbenoid N-H insertion of amines with diazoacetates provides a useful means for the synthesis of ot-amino esters. Fe(III) porphyrins [64] and Fe(III/IV) corroles [65] are efficient catalysts for N-H carbenoid insertion of various aromatic and aliphatic amines using EDA as a carbene source (Scheme 16). The insertion reactions occur at room temperature and can be completed in short reaction times and with high product yields. It is performed in a one-pot fashion without the need for slow... 

At 22 °C the overall second-order coefficient for reductions by Fe(n) and Cu(I) are, respectively, 4x10 and 5xl0 l.mole .sec Products in the presence of olefins demonstrate unequivocally the intermediacy of carbenoid transients, and a complex mechanism is put forward, viz. 

Esters of a-diazoalkylphosphonic acids (95) show considerable thermal stability but react with acids, dienophiles, and triphenylphosphine to give the expected products. With olefinic compounds in the presence of copper they give cyclopropane derivatives (96), but with no such compounds present vinylphosphonic esters are formed by 1,2-hydrogen shift, or, when this route is not available, products such as (97) or (98) are formed, resulting from insertion of a carbenoid intermediate into C—C or C—H bonds. The related phosphonyl (and phosphoryl) azides (99) add to electron-rich alkynes to give 1,2,3-triazoles, from which the phosphoryl group is readily removed by hydrolysis. 

Rhodium carboxylates have been found to be effective catalysts for intramolecular C—H insertion reactions of a-diazo ketones and esters.215 In flexible systems, five-membered rings are formed in preference to six-membered ones. Insertion into methine hydrogen is preferred to a methylene hydrogen. Intramolecular insertion can be competitive with intramolecular addition. Product ratios can to some extent be controlled by the specific rhodium catalyst that is used.216 In the example shown, insertion is the exclusive reaction with Rh2(02CC4F9)4, whereas only addition occurs with Rh2(caprolactamate)4, which indicates that the more electrophilic carbenoids favor insertion. 

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