Methylene-insertion

The highly reactive species methylene inserts into C—H bonds,both aliphatic and aromatic,though with aromatic compounds ring expansion is also possible (see 15-62). This version of the reaction is useless for synthetic purposes because of its nonselectivity (see p. 248). This contrasts with the metal carbene insertion reaction, which can be highly selective, and is very useful in synthesis. Alkylcarbenes usually rearrange rather than give insertion (p. 249), but, when this is impossible. 

The nature of the photochemically produced methylene has been the subject of considerable study. Evidence tends to indicate that this species is produced in its singlet state photochemically. Photolysis of diazomethane in the gas phase or in solution in the presence of excess cis- or trans-2-butene produces cyclopropane products due to methylene insertion in which the... 

Methylene insertion into C—H bonds is believed to be concerted for the singlet species and stepwise for the triplet.<164,156) The C—H insertion of methylene into the 14C-labeled isobutylene shown below results in 92% unrearranged isopentenes and 8% rearranged isopentene [Eq. (11.22)]. Assuming that an additional 8% of the unrearranged isopentene arises from the stepwise addition, it is clear that 84% of the insertion products result from insertion by singlet methylene and 16% by triplet methylene ... 

An interesting report has been made of methylene insertion into the P-C linkage of a-(acyloxy)iminoalkylphosphonates derived from carbohydrates.181 This reaction system, using diazomethane, allows extension of the chain by a single carbon atom, with that atom (methylene group) attached directly to the phosphorus. 

The product esters could not be separated analytically, so we reduced the cmde product from the cyclizations to the corresponding alcohols. We observed both diastereo-mers 39 and 40 of the methine insertion product, and three of the four possible dia-stereomers 41a, 41b, and 41c of the methylene insertion product interestingly alcohol 41d was not detected. The five alcohols could be resolved by HPLC and by H-NMR. While the HPLC ratios were more precise, the H-NMR ratios tracked reasonably well, and could be sufficient if a new rhodium(II) catalyst was to be characterized. 

In the carboxylate series, the TPA catalyst (entry 4) was the most selective for methine over methylene insertion. Should this remarkable chemoselectivity prove to be general, this complex may add a possibility for high chemoselectivity not previously observed with rhodium(ll) catalysts. The other carboxylate catalysts show less preference for CH over CH2 insertion. We expect that the CH/CH2 ratios would be more pronounced with a less carefully balanced substrate. In the carboxamidate class, MPPIM catalyst (entry 9) was more selective than the corresponding MeOX catalyst (entry 10), with the MEPY catalyst (entry 8) being the least discriminating for CH over CH2 insertion. 

The zinc-mediated reaction tolerates a variety of functionality in the p-keto ester. In fact, the method described above has been applied successfully to p-keto amides and p-keto phosphonates, Unsubstituted p-keto esters, amides and phosphonates have been chain-extended in yields that ranged from 58% to 98% (Table I). The primary limitation to this method is the inefficiency with which a-substituted esters and amides undergo methylene insertion. The zinc carbenoid must be employed in at least a threefold excess h... 

Both stereoisomers of a 4-(a-arylethylidene)-5(477)-oxazolone 441 and 443, undergo stereospecihc hydrolysis-methanolysis to furnish the corresponding (Z) and (E) isomers of 2-acetylamino(or benzoylamino)-3-aryl-2-butenoic acid or methyl ester, 442 and 444, respectively (Scheme 7.146). ° The requisite starting oxazolones were prepared by condensation of an acetophenone with an acylglycine or by methylene insertion into the vinyl C—H bond of a 4-arylidene-5(4//)-oxazolone. 

These include the four possible diastereomeric spirocyclopropane derivatives 633, 685, 634, and 686 resulting from methylene insertion into the double bond and a spirocyclopropane 687 derived from methylene insertion into the double bond of a homologated 5(4f/)-oxazolone. The amount of 687, the cis/trans selectivity and both the cis and trans diastereoselectivities depend on the reaction conditions. Use of nonpolar solvents avoids formation of 687. In addition, the cis/trans selectivity and both cis and trans diastereoselectivities are very high such that the major compound 633 can be isolated in 75% yield (Scheme 7.216). ... 

Methylene insertion in the ring of the perfluorodiketene (48) by means of diazomethane has been observed between the ring oxygen atom and C-4 (73IZV2562). Benzoylnitrene insertion in diketene, on the other hand, has been found to take place between the carbonyl group and C-3 (equation 68) (78CL697). 

Determine the selectivity and reactivity of. CH, from the yields of products from methylene insertion in pentane ... 

The reaction of stereomerically well-defined alkenylcopper species 91 obtained by a carbocupration followed by treatment with (KTFjiZn leads to a selective double methylene insertion providing the chelate-stabiUzed alkylzinc reagent 92, which leads after deuteriation with D2O to the unsaturated sulfoxide 93 in 80% yield. This method has been elegantly extended by Marek, Knochel and coworkers (Scheme 32). ... 

Employment of Zn—Cu couple is representative of another approach. For example, reaction of perfluoroalkyl iodides with carbonates gives fluorocarboxylic esters (equation 107)132. Similarly, reaction of perfluoroalkyl iodides with Zn—Cu couple and C02 or S02 in DMSO affords the perfluorocarboxylic acids and sulfonyl chlorides, respectively133. A double methylene inserted product is formed when dibromomethane is used as a substrate (equation 108)134. 

Carbenes 100, generated by UV irradiation of methyl (alkoxysilyl)diazoacetates 99, furnish l-oxa-2-silacyclopentanes 101 by 1,5-C,H insertion (equation 25)60. In order to suppress competing reaction pathways of the carbene intermediate (e.g. formation of a ketazine with excess diazo compound), the photolysis was carried out at high dilution, but, even then, yields were rather modest. Carbene insertion at CH2 seems to occur much more easily than at CH3 a preference of 3 0.6 1 for methylene insertion can be calculated from the isolated yields after correction for the number of C—H bonds. It should be noted that for both carbenes, 96 and 100, C,H insertion occurs only in the 1,5 mode whereas no 1,3-, 1,4- or 1,6-C,H insertion products could be detected. 

The synthetic method (c), is a base-catalysed ring opening of an oxirane.246 Since the oxirane may be formed by the epoxidation of an olefin (Section 8.1.3, p. 1132), or by a methylene insertion reaction into a carbonyl group (Section 8.1.2, p. 1131), this method is of some versatility. 

The use of dimethylsulphoxonium methylide, as a specific methylene insertion reagent for a, /J-unsaturated ketones and esters, is illustrated by its reaction with ethyl crotonate in dimethylformamide solution to form (39) (Expt 7.16).12 The sulphur ylide initially attacks the /J-carbon of the conjugated system (Michael acceptor site), and this is followed by cyclisation and loss of dimethyl sulphoxide. 

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