Diazomethane insertion reactions

Owing to the high reactivity of the intermediates involved, intermolecular carbene insertion reactions are not very selective. The distribution of products from the photolysis of diazomethane in heptane, for example, is almost exactly that expected on a statistical basis.211... 

Hydride 38 is converted to the methyl derivative 40 upon treatment with diazomethane in the presence of Cu (equation 8)21. Presumably this insertion reaction proceeds with retention of configuration. 

An interesting Fe-catalyzed SN2 -like carbene insertion reaction using diazo compounds and allyl sulfides (the Doyle-Kirmse reaction) was reported by Carter and Van Vranken in 2000 [20], Various allyl thioethers were reacted with TMS-diazomethane in the presence of catalytic amounts of Fe(dppe)Cl2 to furnish the desired insertion products with moderate levels of stereocontrol [Equation (7.6), Scheme 7.14]. The products obtained serve as versatile synthons in organic chemistry, e.g. reductive desulfurization furnishes lithiated compounds that can be used in Peterson-type oleftnations to yield alkenes [Equation (7.7), Scheme 7.14] [21]. 

It would be impossible to obtain this product with diazomethane. In Section 14.3.2 (Figure 14.25), a third method will be described for the insertion of a CH2 group into a cycloalka-none. Again, a [1,2]-rearrangement will be part of that insertion reaction. 

Recently, Kistiakowsky and co-workers8 found that reactions of methylene, formed by photochemical decomposition of ketene or diazomethane, produce hydrocarbon molecules with considerable excess vibrational energy. The C—H insertion reaction is represented by reaction (3) ... 

Formally, the insertion of a carbene(oid) into the 2,3-doubIe bond of the thiophene ring should result in the formation of the 2-thiabicyclo [3.1.0] hex-3-ene ring system. Copper(II)-catalyzed reaction of thiophene with diazomethane results in the formation of 24 (R = H) in modest yield (63TL1047). Analogously, the reaction of thiophene with ethyl diazoacetate yields 24 (R = COjEt) (22LA154). Although these reactions appear to be simple carbene insertion reactions, it is probable that this simple mechanism is not in operation. Rather, the cyclopropane derivatives 24 probably result from the initial formation of the ylid (e.g., 18), which subsequently rearranges. 

Methylene insertion reactions into the olefinic CH bond of 164, 168 and 171/172 by diazomethane have been reported several times 292-294.29s. 305. these cases... 

Now, you saw a similar insertion reaction earlier in the chapter, and the mechanism here is not dissimilar. Both peracids and diazomethane contain a nucleophilic centre that carries a good leaving group, and addition of peracid to the carbonyl group gives a structure that should remind you of a semipinacol intermediate with one of the carbon atoms replaced by oxygen. 

A diazomethane-iminium insertion reaction was utilized during the formation of a methylene bridge in the synthesis of a morphinan-type compound from a corresponding octahydroisoquinoline (Scheme 17). The requisite octahydroisoquinoline (85) was prepared from the tetrahydropyri-... 

Metal-catalyzed decomposition of diazomethane in the presence of 1,2,3,4,5,6-hexamethyl-bicyclo[2.2.0]hexa-2,5-diene (11, hexamethyl Dewar benzene) has been shown to give the simple or double cycloaddition products with exo configuration. When the reaction was carried out in the absence of a metal catalyst, the products of C-H insertion to allylic C-H bonds were also observed, in addition to cycloaddition to the double bond to an extent of 25%. A C-C insertion reaction at the unusually long central bond of hexamethyl Dewar benzene was not detected. The reaction conditions were designed to generate methylene in the singlet state, and the observed products were those that would be expected for the reaction of singlet methylene with hexamethyl Dewar benzene. 

An attractive route to spiropentane and triangulane systems is by the reaction of carbenes with methylenecyclopropanes. When a heptane solution of diazomethane and methylenecy-clopropane was irradiated, spiropentane (1) was formed as the main product. The byproducts, l-methyl-2-methylenecyclopropane (2) and vinylidenecyclopropane (3), derive from an insertion reaction of the carbene into C-H bonds. 

Thus, the glycosidation of 190 followed by oxidation led to the corresponding 2-oxopropyl glycosides 191, which on treatment with [(trimethylsilyl)diazomethane]lithium at low temperature underwent insertion reaction to provide spiroketal derivative 192. Subsequent ozonolysis of 192 liberated an unstable ketoaldehyde, which was immediately oxidized to the carboxylic acid, isolated as its methyl ester 193. Removal of the 2-oxopropyl group was accomplished using Sml2, to afford DAH derivative 194. 

Diazoalkanes are well known as reagents for carbon insertion reactions through the intermediacy of carbenes. Here, diethyl acetylphosphonate has been shown to react with diazomethane to give a mixture of 2-(diethoxyphosphinoyl)-2-methyloxirane (the major product) together with traces of diethyl (2-oxopropyl)phosphonate the reaction between dimethyl acetylphosphonate and diazoethane and that between diethyl ben-zoylphosphonate and diazomethane both afford only the (2-oxoalkyl)phosphonic... 

Decomposition of the sodium salt of the tosylhydrazone (203) in refluxing CCI4 produces a diazomethane intermediate which undergoes an internal insertion reaction to form (204) (73%). The normal reaction of diazomethane-type intermediates with double bonds would be 1,3-cycloaddition the reaction... 

Insertion reactions of alkylidene carbenes offer a useful entry to cyclopentene ring systems (4.81). Insertion is most effective with dialkyl-substituted alkylidene carbenes (R = alkyl), since rearrangement of the alkylidene carbene to the alkyne occurs readily when R = H or aryl. A number of methods have been used to access alkylidene carbenes. One of the most convenient uses a ketone and the anion of trimethylsilyl diazomethane. Addition of the anion to the ketone and eUmination gives an intermediate diazoalkene, which loses nitrogen to give the alkylidene carbene. For example, a synthesis of the antibiotic (-)-malyngolide started from the ketone 102 (4.82). The insertion reaction takes place with retention of configuration at the C—H bond. 

Addition of carbenes to aromatic systems leads to ring-expanded products. Methylene itself, formed by photolysis of diazomethane, adds to benzene to form cycloheptatriene in 32% yield a small amount of toluene is also formed by an insertion reaction. The cycloheptatriene is formed by a Cope rearrangement of the intermediate cyclopropane (a norcaradiene). More satisfactory is the reaction of benzene with diazomethane in the presence of copper salts, such as copper(I) chloride, which gives cycloheptatriene in 85% yield (4.87). The reaction is general for aromatic systems, substituted benzenes giving mixtures of the corresponding substituted cycloheptatrienes. 

The diazomethane-keten reaction gave no 1,3-dipolar adducts, such as those obtained readily enough from the corresponding thioketen (see Vol. 1, p. 44), even at low temperatures. The 2 1 adduct obtained (165) cannot arise by prior dimerization of the keten, whose jS-lactone dimer (166) reacts to give a y-lactone (167) by methylene insertion at the C—O bond, so that quite different hydrolysis products are obtained (see Scheme 48). ... 

Insertion reactions are particularly unprofitable for disulphides and diazomethane, though under irradiation moderate yields may be obtained (RSSR + CH2N2 RSCHjSR 4- N2). Diselenides give quantitative yields under these conditions, and ditellurides are easily inserted, in a dark... 

Kametani s group has applied the diazomethane ring expansion reaction of 3,4-dihydroisoquinoline methiodides to the preparation of isopavines. The carbon insertion reaction with the 3-aryl-3,4-dihydroisoquinoline methiodide 13 supplied a crude aziridinium iodide which upon standing in 6N hydrochloric acid for a week underwent successive ring expansion and closure, probably through the quinone methide 14, to furnish reframidine in 20% yield from the aziridine salt ... 

There are few examples of this variation in the literature. The variation relies on the alkylation of thiolactams (in replacement of cyclohexanones) by the Michael addition of diazomethyl vinyl ketone (in replacement of methyl vinyl ketones) followed by ring closure using rhodium(II) acetate mediated diazomethane insertion. The diazomethyl entity can also be added after the Michael addition step. The reaction affords six-membered rings with... 

---