Carbenes chloro-substituted

A more general method for preparing carbenes often involves the a elimination of halides from carbanions.1-57 PAC can be used to examine the rates and energetics of the reverse reactions, the complexation of halides with carbenes (Fig. 5).58 Plots of A//com versus the proton affinities (PA) of the halides are linear for the two carbenes studied. Although the slopes of the plots are similar, complexation of the halides with phenylchlorocarbene is more exothermic than phenylfluorocarbene. This indicates that fluoro substitution stabilizes the carbene relative to the carbanion more than chloro substitution. The rate of complexation of carbenes with salts has also been examined by nanosecond absorption spectroscopy.59... 

Chloro(phenyl)carbene or carbenoid generated from benzal chloride reacts with potassium salts of benzylic, allylic, and other alkoxides to produce phenyl-substituted oxiranes 9 in high yields, as an approximately 1 1 mixture of cis... 

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

Metal-based nucleophiles may react with activated haloarenechromium complexes leading to substitution of the halides. The reaction of Collmarfs reagent Na2[Fe(CO)4] with chloro-arenetricarbonylchromium complexes in THF/N-methylpyrrolidinone produces the yellow anionic dinuclear complexes 91a in 45 % yield (Scheme 40) as a result of an ipso SNAr [64]. Spectroscopic data suggest that complex 91a adopts the rj6 structure as opposed to the alternative //5 -cyclohexadieny 1 carbene structure 92. Similarly, it has been reported by the same group that the potassium salt of [CpFe(CO)2] participates in ipso nucleophilic attack on chloroarenechromium substrates, producing dinuclear complexes 91b in 92 % yield (Scheme 40) [65]. 

Earlier studies [11,12] have shown that photo excitation of aqueous 2-chloro-phenol or 2-bromophenol leads to contraction of the aromatic cycle to give cyclopentadienic acids (an example of a Wolff rearrangement [13]), and to substitution of the halogen by OH (photohydrolysis), with moderate quantum yields (< = 0.01-0.04). A carbene (2-oxocyclohexa-3,5-dienylidene) was suggested as a possible intermediate in the ring contraction pathway [11]. 

The first two derivatives in the series, monuron and metobromuron, are related to the 4-haloanilines. Their primary photochemistry has been studied by Boulkamh and Richard by means of nanosecond absorption spectroscopy [80]. The transients detected from both compounds in aqueous solution could be assigned to the N-substituted 4-iminocarbene, imino-p-benzoquinone-O-oxide and anilino radical from a complete analogy of their spectral and reactive behavior with that of the species obtained from 4-chloroaniline [55,57]. The quantum yields of carbene formation were determined to be = 0.051 for monuron and

halogen-substituted phenylurea derivatives underwent the same heterolytic dehalogenation process as the 4-haloanilines, which could be understood with reference to the protonability of the amine nitrogen, as in the case of 4-chloro-N,N-dimethylanilinc [55]. 

When imidazole, or 1- and 2-substituted imidazoles react with chloroform at 550 °C the products include 5-chloro- (138) and 4-chloro-pyrimidines, and 2-chloropyrazines. Carbene insertion from the chloroform into either a C—C or C—N bond accounts for the products among which (138) predominates (Scheme 67). With hexachloroacetone at room temperature 2-methylimidazole gives a 5-7% yield of (138 R = Me) (80JCS(P1)1427). 

In a related reaction, addition of chloro-, chloromethyl-, chlorophenyl or chlorofluoro-carbene to ketene alkylsilyl acetals and subsequent ring-opening (MeOH-NEt3 reflux) leads to the corresponding 2-substituted-2-alkenoic esters in high yields (equation 66) ... 

Photolysis of 5-chloro-2-hydroxybenzonitrile (70) in aqueous solution gives the triplet carbene (71), which can be detected by transient absorption spectroscopy (X,max at 368 and 385 nm). The carbene was recognized by its reactions, e.g. with O2, to produce the corresponding carbonyl O-oxide (A ax at 470 nm), and with propan-2-ol to give 2-cyanophenoxyl radical. In deoxygenated solutions the main stable products are 2,5-dihydroxybenzonitriIe and two substituted biphenyls. 

The cyclopropanols 13 were separated from the ketone by column chromatography and rearranged to eucarvone. In a closely related process, the addition of chloro(methyl)carbene to ketene alkyl silyl acetals afforded adducts 14 which were transformed without isolation into esters of 2-methyl-substituted a,/i-unsaturated acids 15. ... 

Chloro(phenyl)carbene adds to ring-substituted styrenes to give cyclopropanes 3 in very low yield together with (Z)-l,2-dichloro-l,2-diphenylethene. ... 

Enamines derived from cyclohexanone and and a-tetralones react with chloro-(phenyl)carbene [generated from dichloro(phenyl)methane and potassium tert-butoxide] to give either 1-chloro-l-phenyl-substituted cyclopropanes, or other products.The type of products formed depends on the structure of the amine moiety in the starting enamines (Table 7). 

During the preparation of l-chloro-l-(2-furyl)cyclopropanes a small amount (up to 12%) of 5-tert-butoxy-2-chloromethylene-2,5-dihydrofuran, the addition product of potassium tert-butoxide to the bipolar structure of chloro(2-furyl)carbene, was formed.Cyclopropanes substituted at C 3 in the thiophene ring are sometimes unstable to column chromatography. The sterically more crowded chloro(3-phenyl-2-thienyl)carbene failed to undergo addition to 2,3-dimethylbut-2-ene. ... 

The reaction of 3-chloro-3-(2-thienyl)-3//-diazirine with alkyl-substituted alkenes gave predominantly the trans-isomer of 5 while with acrylates, crotonates and styrene, the c/s-isomer predominated. The reaction of chloro(2-thienyl)carbene with (Z)- and ( )-but-2-ene proceeded with the retention of alkene stereochemistry. 

Chloro(2,2,2-trifluoroethoxy)carbene was also generated photolytically from the corresponding diazirine and added to alkenes affording substituted cyclopropanes in 18 - 37 % isolated yields. 

Benzyloxy(cyano)carbene would be expected to be electrophilic by virtue of the calculated selectivity index, Wp -HjOccN 111- This has not yet been experimentally proved as 3-bcnzyloxy-3-cyano-3//-diazirine is rather labile and cannot be isolated if it is synthesized by the substitution of chlorine by a cyano group in 3-benzyloxy-3-chloro-3if-diazirine consequently, this substitution reaction is carried out in the presence of an alkene, hence, preparing 1-benzyloxy-cyclopropane-l-carbonitrile derivatives. However, the cyanide ion present in the system induces the polymerization of electrophilic alkenes, such as acrylonitrile or methyl acrylate. 

Ring expansion of the substituted bicyclo[4.1.0]heptanes 8, formed by addition of chloromethyl-carbene to silyl enol ethers, was accomplished almost equally effectively by refluxing in toluene, or by heating in methanol containing triethylamine. In each case, the crude mixture of cis- and /rani-7-chloro-7-methylbicyclo[4.1. Ojheptanes 8 was used, although it was observed that the traui-isomers, with the chlorine and trimethylsiloxy substituents tram to each other, rearranged more rapidly. 

Chloro-l-methyl-2-siloxycyclopropanes are interesting synthetic intermediates as they are easily cleaved to 2-methyl-substituted a,/8-unsaturated aldehydes or ketones. Addition of chloro(methyl)carbene (carbenoid) to trimethylsilyl enol ethers gives l-chloro-l-methyl-2-tri-methylsiloxycyclopropanes 11,70-72 which are usually rearranged without purification, due to their restricted stability. A few examples are given in Table 5 (see also Houben-Weyl, Vol. E19b, p 1516). 

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