Carbenes generation reactions

Ordinarily water must be scrupulously excluded from carbene-generating reactions. Both the intermediate trichloromethyl anion (3) and dichlorocarbene (4) react with water. But in the presence of a phase transfer... 

Tnmethyl(trifluororaethyl)tin can also be prepared via in situ formation and capture of tnfluorometbide by trimethyltin chlonde [13, 14] (equation 9) This tin analogue has been used as a precursor for difluorocarbene either by thermal decomposition or by reaction with sodium iodide m 1,2-dimethoxyethane This carbene generation procedure has been used to study difluorocarbene selectivity with steroidal olefins [75] (equation 10). 

The Ciamician-Dennstedt reaction involves the reaction of a pyrrole (1) with the carbene generated from chloroform and a base to provide a 3-chloropyridine (2, Scheme 8.3.1). 

Due to the commercial availability of EMME in good purity, there has not been a need to develop new methods to prepare 3-anilino-acrylates therefore, only a few alternatives have been reported. One approach described thermal carbene generation from 37, and rearrangement to form 38. Cyclization in refluxing 1,2-dichlorobenzene (1,2-DCB) provided the 2, 3, 4-trisubstituted quinolines. An electron-withdrawing group (EWG) on the carbene carbon was required for this reaction, and therefore led to the EWG substitution in the 2-position of the quinoline. 

The imidazoline denvative cibeiuoline (64) is a class I antiarrhythmic agent which has undergone clinical trials in the United States with apparently satisfactory results It is synthesized by diphenylcyclopropananon of acrylonitrile by thermal carbene generation from diphenyldiazo methane (62) to give 1 cyano 2,2 diphenylc>clopropane (63) Reaction of this with ethylenedia mine tosylate completes the synthesis of ciben/oline (64) [221... 

Hindered lithium dialkylamides can generate aryl-substituted carbenes from benzyl halides.162 Reaction of a,a-dichlorotoluene or a,a-dibromotoluene with potassium r-butoxide in the presence of 18-crown-6 generates the corresponding a-halophenylcarbene.163 The relative reactivity data for carbenes generated under these latter conditions suggest that they are free. The potassium cation would be expected to be strongly solvated by the crown ether and it is evidently not involved in the carbene-generating step. 

Reactions involving free carbenes are very exothermic since two new theoretical treatment of the addition of singlet methylene to ethylene suggests that there is no activation barrier.168 The addition of carbenes to alkenes is an important method for synthesis of many types of cyclopropanes and several of the methods for carbene generation listed in Scheme 10.8 have been adapted for use in synthesis. Scheme 10.9, at the end of this section, gives a number of specific examples. 

The addition of dichlorocarbene, generated from chloroform, to alkenes gives dichlorocyclopropanes. The procedures based on lithiated halogen compounds have been less generally used in synthesis. Section D of Scheme 10.9 gives a few examples of addition reactions of carbenes generated by a-elimination. 

The most common rearrangement reaction of alkyl carbenes is the shift of hydrogen, generating an alkene. This mode of stabilization predominates to the exclusion of most intermolecular reactions of aliphatic carbenes and often competes with intramolecular insertion reactions. For example, the carbene generated by decomposition of the tosylhydrazone of 2-methylcyclohexanone gives mainly 1- and 3-methylcyclohexene rather than the intramolecular insertion product. 

The difference in reactivity between isoprenol and isoprenyloxide, methal-lyl methyl ether and methallyloxide were investigated in the reaction with (phenylthio)carbene generated under phase-transfer conditions. With isoprenol, (phenylthio)methyl ether (41%) was the major product, whereas with methyl ether cyclopropanation (36%) was the sole reaction.1519 With alkoxides, in contrast, the major product was the C-H insertion product (45%) and (phenyl-... 

Vinylidenecarbene or allenylidene3 (R)2C=C=C has a lance-shaped, unsubstituted and sp-hybridized carbene center and, therefore, will not be easily subject to steric hindrance in its insertion reactions. On this assumption, (2-methyljpropenylidenecarbene or its carbenoid was chosen as a prototype of typical vinylidenecarbenes and its insertion reaction with several different types of alkoxides was investigated by employing two methods (A and B, Scheme 10) for carbene generation.20 The insertion products 20 were obtained almost exclusively except lithium allyloxide (Table 4, entry 10).21 By-products such as propargyl ether and allenyl ether were not formed at all. To be noted here, in... 

Since alkyllithium compounds and their carbanions have an isoelectronic structure with alkoxides, their reaction behavior with carbenes is expected to be similar to that of alkoxides, showing enhanced reactivity in both C-H insertion and hydride abstraction.35 In this reaction, the hydride abstraction cannot be followed by recombination and, therefore, can be differentiated from the insertion. Indeed, the reaction of alkyllithium compounds 70 or nitrile anions (see Section IV.B) with ethyl(phenylthio)carbenoid, which is generated by the reaction of 1-chloropropyl sulfide 69 with BuLi, takes place at the -position of 70 more or less in a similar manner giving both insertion product 71 and hydride abstraction products 72 and 73, respectively. This again supports a general rule C-H bonds at the vicinal position of a negatively charged atom are activated toward carbene insertion reactions (Scheme 22). 

The addition of carbenes is also a stereospecific reaction, each geometrical isomer forms the cis addition product. Thus carbene generated from the photolysis of diazomethane adds in a cis manner to both cis and trans butene-2. 

Nucleophilic substitution 313 Nucleophilic addition 337 Hydrogen-abstraction reactions 343 Carbene generation 355 Oxidation reactions 356 Reduction reactions 358 Miscellaneous reactions 360... 

Carbenes and transition metal carbene complexes are among the few reagents available for the direct derivatization of simple, unactivated alkanes. Free carbenes, generated, e.g., by photolysis of diazoalkanes, are poorly selective in inter- or intramolecular C-H insertion reactions. Unlike free carbenes, acceptor-substituted carbene complexes often undergo highly regio- and stereoselective intramolecular C-H insertions into aliphatic and aromatic C-H bonds [995,1072-1074,1076,1085,1086],... 

The absolute rate constants for reaction of /t-tolyl(trifluoromethyl)carbene, generated by laser flash photolysis of the corresponding diazirine, with pyridine (4 x lO lmor s ... 

A detailed reinvestigation of the products and kinetics of reactions of benzylchloro-carbene, generated by photolysis of the corresponding diazirine, indicated that the... 

Yields of dichlorocyclopropanes from reaction of alkencs with dichloro-carbene generated at a lead cathode in dichloromethane containing tetxa-butylammonium bromide. Ref. [79]. 

There is just one example of the reaction of thianthrene with a carbene, generated either by decomposition of diethyl diazomalonate at 140°C in the presence of CUSO4 (82JHC833) or using PhI" -C (CN)2 as a precursor [87JCR(S)374] and producing 50. 

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