Carbenes insertion into a C—H bond

II. Regioselectivity of the Carbene Insertion into a C-H Bonds of Alkoxides. 289... 

II. REGIOSELECTIVITY OF THE CARBENE INSERTION INTO a C-H BONDS OF ALKOXIDES... 

These same pyridinium ylides have been generated photochemically. The irradiation of diazomethane in pyridine gave 2-picoline (199) in 83% yield.107 The high yield and specificity of attack at the 2-position of the ring seem to be at variance with electrophilic carbene insertion into a C-H bond as the preferred site of this reaction is at the 3-position. This result is consistent, however, with initial electrophilic attack of the... 

Efficient syntheses of tetrahydrothiopyran-4-one and 3,6-dihydro-4-trimethylsilyloxy-277-thiopyran 58 from dimethyl 3,3 -thiobispropanoate have been described <07S1584>. Carbene insertion into a C-H bond of diazosulfones leads to tetrahydrothiopyran sulfones 59 with stereoselectivity for the trans disposition of the 2- and 3-substituents. When applied to diazosulfonates, the corresponding 1,2-oxathianes are produced <07OL61>. 

Carbene cyclization reactions offer a convenient and efficient method for the synthesis of five-membered sulfur-containing rings. These may involve both carbene insertion into a C—H bond and ylide formation. 

The model predicts k2l). This is found to be consistent with the fact that carbene insertion into a C-H bond is slower than carbene addition to double bonds. The agreement with experimental data was satisfactory. The carbene insertion reaction in olefins, as described by Chang,predicts a redistribution of olefinic species, but no net increase in the production of olefins. This was corrected for by Anthony. 

Rhodium-Catalyzed Reactions via Zwitterionic Intermediates Diazo compounds are also known to undergo insertion into C—H bonds by action of a rhodium-based catalyst, giving rise to a zwitterionic species characterized by a similar reactivity to that of onium ylide species [170]. Recently, Hu et al. [171] have described that zwitterionic intermediates 150, obtained by carbene insertion into a C—H bond in indoles, can be trapped by imine 151 activated by a chiral Brpnsted acid. After optimization of conditions, three-component reactions carried out at -10 °C in toluene afforded the desired products 152 in high yields, >20 1 diastereoselectivities for the flnft-isomer, and 84-99% ee (Scheme 3.66). 

An attempt to measure the IR spectrum of the hydroxy carbene [28] after UV photolysis (A>220 nm) of formaldehyde isolated in an argon matrix was unsuccessful (Sodeau and Lee, 1978). Instead of [28] only hydroxyacetal-dehyde resulting from carbene insertion into the C—H bond of the starting formaldehyde was found in the reaction products. Due to its small size, the... 

Carben.es insert into a C — H bond of a cyclobutane.157 When there is a choice between a cyclopropane and a cyclobutane C — H bond, as in bicyclo[2.1. OJpentane, the insertion of phenylcarbe-ne takes place at a cyclobutane methylene position to give 2-benzylbicyclo[2.1.0]pentane (l).157... 

Usually, carbon-carbon bonds are formed by coupling two carbons each of which are already functionalized in some way, as with the displacement of a C-Br with NaCN to form C-CN. It would be more efficient, and potentially less expensive and less polluting, if one of the partners could be an ordinary C-H bond. Intramolecular processes for carbene insertion into unactivated C-H bonds have been known for years. Practical intermolecular processes for C-C bond formation to a C-H bond are just starting to appear. 

The diverse chemistry of carbenes is beyond the scope of this account, but a few typical reactions are shown here to illustrate the usefulness of the photochemical generation of these reactive species. A carbene can insert into a C—H bond, and this finds application in the reaction of an a-diazoamide to produce a P-lactam (5.29). Carbenes derived from o-diazoketones can rearrange to ketenes, and thus a route is opened up to ring-contraction for making more highly strained systems <5.301. Carbenes also react with alkenes, often by cycloaddition to yield cyclopropanes in a process that can be very efficient (5.31) and highly stereoselective (5.321. 

CARBENE. The name quite generally used for the methylene radical, CH,. It is formed during a number of reactions. Thus the flash photochemical decomposition of ketene (CH2=C=0) has been shown to proceed in two stages. The first yields carbon monoxide and CHj. the latter then reacting with more ketene to form ethylene and carbon monoxide. Carbcne reacts by insertion into a C- H bond to form a C-CH, bond. Thus carbene generated from ketene reacts with propane to form, i-butane and isobutane. Carbene generated by pyrolysis uf diazomethane reacts with diethyl ether to form ethylpropyl ether and ethylisopropyl ether. 

Because these insertion reactions create new bonds at completely unfunctionalized centres, they can be very useful in synthesis. This next carbene is created between two carbonyl groups from a diazocompound with rhodium catalysis and selectively inserts into a C-H bond five atoms away to form a substituted cyclopentanonc. 

In principle, triplet carbene insertions should follow a two-step radical pathway analogous to their insertion into alkenes. However, very few triplet carbene insertions into C-H bonds have been observed, and the stereochemical consequence of the two-step mechanism (which should result in mixtures of stereoisomers on insertion into a C-H bond at a stereogenic centre) has never been verified. 

Subsequent abstraction of hydrogen atoms from the substrate by the triplet carbene or insertion into a C—H bond by the singlet species can occur ... 

When the dichlorocarbene adduct 231 of 9-methoxyphenanthrene is reacted with 2 equivalents of (-BuOK in tetrahydrofuran in the presence of a crown ether, the phenanthro[9,10-b]furan 232 is obtained in 80% yield. The intermediate methoxy-substituted chlorocarbene is derived from cyclo-propene. The key step consists in an intramolecular carbene insertion into the C—H bond of the methoxy group (84C79). 

A review has discussed the photochemical cyclization of a variety of aryl- and heteroaryl-prop-2-enoic acids. Irradiation (A,>340nm) of the cyclohexenone (119) in argon purged benzene solution affords the cyclized derivatives (120) as a 3 1 mixture of diastereoisomers. The formation of the cyclopropyl group arises via the carbene (121) and insertion into a C-H bond of a neighbouring methyl group. This carbene is formed, presumably, from the biradical (122) which arises by addition of the alkene to the excited state of the enone. Further evidence for the carbene intermediate comes from a reaction in methanol when the diastereo-isomeric mixture of the ethers (123) and (124) is obtained." ... 

Alkenes with a fairly unreactive double bond additionally form the products of carbene insertion into the C-H bond (see Houben-Weyl, Vol. E19b, pp 1494 and 1495), e.g. formation... 

Allylic ethers, particularly cyclic allylic ethers, may enter a competitive reaction with dibromo-carbene of insertion into a C H bond. In the example of the formation of 3 and 4, a suitable workup of the reaction mixture allows isolation of pure cyclopropane 3.71... 

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