Carbene, attack

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

In isolated examples, reactions of specific amides and thioamides with dihalo-carbenes can take unusual pathways. Thus, for example, using procedure 7.1.1, A,A-dialkylamides are converted into a-chloromethylene derivatives of the amides [48]. The initial step in which the carbene attacks the carbonyl oxygen atom is the same as for the dehydration of the A-alkyl amides, but subsequent steps, for which there is evidence from 2H/ H labelling experiments, lead to the formation of an enamine and further reaction with the carbene (Scheme 7.34). 

The most convincing evidence for this mechanism is that in the reaction between isobutene-1-I4C and carbene the product 2-methyl-1-butene was labeled only in the 1 position.236 This rules out a free radical or other free intermediate such as a carbocation or carbanion. If 28 (or a corresponding ion) were an intermediate, resonance would ensure that some carbene attacked at the 1 position ... 

Stepwise, but heterolytic, mechanisms have been suggested in the insertion of carbenes into oxygen-hydrogen bonds. The reactivity of water and halide ions towards dihalomethylenes parallels their reactivity in Sn2 displacements (Hine and Dowell, 1954), suggesting that an electrophilic carbene attacks water initially by way of the non-bonded electron pair on oxygen giving an ylid (equation 21). An analogous mechanism could be followed in the insertion of carbenes into the... 

The differences in deuterium and carbon isotope effects indicate the asymmetric transition state with more advanced carbon-carbon bond formation to the terminal Cl atom. The difference between deuterium isotope effects for HCI-S and Htmns hydrogens probably originates from experimental uncertainty. Theoretical calculations (B3LYP/6-31G, B3LYP/6-311+G ) for carbene addition to 1-butene were carried out for two modes with carbene approaching carbon atom Cl or C2. The best agreement for experimental isotope effects is for carbene attack on terminal carbon atom and the carbene-alkene separation in the transition state of 2.5 A. 

Carbene attack is followed by proton transfer to generate a neutral molecule from the first formed zwitterion (or ylid ). However, if the heteroatom does not carry a hydrogen, attack on its lone pair generates an ylid that cannot rearrange in this way. Reaction of a carbene with a neutral nucleophile forms an ylid. This type of reaction is, in fact, a very useful way of making reactive ylids that are inaccessible by other means. 

Halogen-substituted carbenes attack olefins from their sterically less hindered face, however, exceptions are known for alkenes with oxygen substituents (vide infra). Two of numerous examples demonstrate the directive power of steric effects. Thus, spiro compound 1 and dichlorocarbene combine to provide the product 2 with the dichloromcthylcnc unit exclusively trans to the phenyl group14. 

In the first edition (CHEC-I) <84CHEC-I(4)74i> it was mentioned that three types of products were identified in the reaction of thiophenes with carbenes generated from diazo compounds, cyclopropanes, 5,C-ylides, and 2-substituted thiophenes, corresponding to carbene attack at the 2,3-double bond, ring sulfur or at C-2, respectively. However, it now appears very likely that the... 

The reaction of the dimethyoxytetrahydronaphthalene (70) with dibromocarbene results only in bis-addition, to give the syn- and anti-adducts (71) and (72). Addition to the tetrasubstituted double bond, the normal site for carbene attack in the absence of electron-donating substituents, is not observed either in the form of a mono- or a tris-addition product. Dichlorocarbene additions to naphthalene, phenanthrene, and anthracene have been reported, and only the product of addition to the 9,10-... 

Reaction of the 7,7r-acetylide Fe2(CO)e(CaPh)(PPh2) with cyclohexylamine results in addition across the acetylenic bond to yield the zwitterionic complexes (141) and (142), both characterized crystallographically. Reaction with dicyclohexylphosphine yields the structurally related (143), while carbene attack occurs to yield (144). Reaction of Fe2(CO), with t-butylethynyldiphenyl-phosphine yields (PhaPC CBu )Fe2(CO)8 containing Fe(CX))4(P) and Fe(CO)4-(acetylene) moieties the geometry of the latter resembles that found for (alkene)-Fe(CO)4 complexes. ... 

Ando et aU have published details of the thermal reaction of diazo-com-pounds with sulphides. For the reaction to be of use, a stabilized diazo-compound and a dialkyl sulphide must be employed, but some aryl sulphides have been used successfully. Thus, diazomalonate and dimethyl sulphide afforded the ylide in 75% yield, and the use of diphenyl sulphide afforded ylide in 85% yield. The use of olefinic sulphides afforded two competitive sites for attack by the carbene presumably formed from the diazo-compound. Diazoacetate and the vinyl sulphide (2) produced a 5% yield of the cyclopropane, resulting from carbene attack at the double bond, and a 39% yield of a rearranged vinyl sulphide (3), resulting from carbene... 

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