Carbenes difluoro

A solid-liquid phase-transfer technique is used to synthesize aryl difluoro-methyl sulfides and selenides thiophenols dissolved in an aromatic solvent are treated with solid sodium hydroxide in the presence of a catalytic amount of tris(3,6-dioxaheptyl)amine (TDA1) [49] This condensation proceeds by a carbene mechanism (equation 44)... 

A trifluoromethyl anion is also difficult to generate because it easily lose a fluoride ion to form difluoro carbene. Shono and Kashimura et al have similarly achieved the generation of such a species from trifiuoromethane using the electrogenerated a-pyrrolidone anion. The efficient trifluoromethylation of aldehydes and ketones in the presence of hexamethyldisilazane (HMDS) can thus be obtained (Scheme 4.3) [32]. 

Miscellaneous. An interesting synthesis of 1,1-difluoro-l-alkenes from ylides and chlorodifluoromethane has been described.47 The ylide acts both as a carbene generator and trapping agent (Scheme 11). 

As carbenes to afford O- and 5-difluoromethyl derivatives and difluoro cyclopropanes. 

However, difluoromethylation occurs when nucleophiles intercept difluoro-carbene generated under basic conditions, providing a route to difluoromethyl-ethers of phenols [33] and thiophenols [34]. The reaction with phosphite anion leads to the corresponding difluoromethyl phosphonate (see Sect. 2.3.2) while nucleophilic carbanions such as alkynes [35] also undergo formal alkylation, as do malonates [36,37]. An -difluoromethylaziridine was reported in a reaction with a glycine imine [38]. The scope of the established chemistry is summarised in Fig. 1. Bromodifluoromethylation occurs with a similar range of nucleophiles [39,40], and also with carbonyl-stabilised carbanions such as malonates [41,42]. 

Figure 2 represents both alkylation reactions mechanistically. More recently, reactive enolates were bromodifluoromethylated successfully via difluoro-carbene formed in situ. [43, 44]. The reaction solvent was critical for the outcome of the reaction (Eq. 11). 

Bis-[trifluoromethyl]-l-meihylen-E10b, 196 (2COOH - 2CF3) 2- ( Bis-[trimelhyl silyl]-amino)-methyl -l-ethoxycarbonyl-1-trifluorometliyl- ElOb, 558 (Carben - R2N — CH2-en) 2-Broino-2-(bromo-difluoro-melhyl)-1,1-difluoro- E10b2, 138 (Eduet)... 

It is abundantly clear from the preceding discussion that dihalocyclopropanes are versatile intermediates in organic synthesis. Although a wealth of chemistry has already been uncovered, prospects remain bright for interesting developments in the future. Areas such as the application of dihalocyclopropanes in heterocyclic synthesis via carbene insertion into C—H bonds adjacent to heteroatoms, reactions of dihalocyclopropanes with organometallics and the synthetic applications of metallated derivatives deserve further exploration. The chemistry of difluoro-, diiodo- and mixed dihalo-cyclopropanes can be expected to attract some attention. Finally, other heteroatom-substituted cyclopropanes derived ftom dihalocyclopropanes will also invoke further investigation. 

The 5,7-diaryl-2-fluoro-4/7-l,3-diazepines have been synthesized from 3-aryl-substituted 277-azirines and difluoro-carbene (Scheme 13). The reaction involves isomerization of azirinium ylide into a 2-aza-l,3-diene, which undergoes [4+2] cycloaddition with the starting azirine, followed by ring expansion and dehydrofluorination <2006TL639>. 

Many of the recent efforts in this area of chemistry have been designed to explore the chemistry of the trifluoromethyl species prepared by these reactions. Among the more interesting results have been the construction of carbene and tetramethylcyclobutadiene ligands affixed to trifluoromethyl platinum cations (78), the synthesis of difluoro-carbene complexes like (Cp)Mo(CO)3CF2+ (79), the formation of (CF3)2CS from CF3Re(CO)5 (38), and the insertion reaction of S02 into CF3-metal bonds (80). 

Grubbs and coworkers used (4a) to perform olefin metathesis with 1,1-difluoroethelyene a metathesis partner that had theretofore been unavailable for reaction consideration. While metathesis did occur, the difluoro carbene Ruthenium complex (4m) (Figure 2) was not an effective catalyst itself thus, little if any turnover was observed, although this did provide a potential convenient pathway for constructing dihalocarbene-metal complexes. 

The production of difluorocarbene fi om a chemically inert precursor allowed a study of carbene reactions with reactive partners like chlorine, iodine, and nitrogen dioxide. Thus, difluorodihalomethanes were obtained with halogens NO2 showed only modest reactivity to form difluoro-dinitromethane, tetrafluoroethylene being formed as a by-product. ° ... 

Generation of difluorocarbene. In an early study1 of the reaction of difluoro-carbene with steroidal double bonds, the methylenation was conducted by portion wise addition of an excess of dry sodium chlorodifluoroacetate to a diglyme solution of the substrate at temperatures of 120-150°. The same laboratory (Syntex)2 now reports that the reaction is improved by addition of a solution of the salt in diglyme to a refluxing diglyme solution of the substrate. The reaction with A4-6- and AI 4 a-3-ketosteroids results mainly in addition to the Afi-double bond to give 6a,7a-difluoromethylene-A4- and A -4-3-ketones, respectively. 

In a search for a photochemical source of difluorocarbene, 4,4-difluoro-pyra-zolidine-3,4-dione (4) was synthesized as a precursor for the corresponding pyrazolinedione (5). The carbene CF2 was expected to be produced by photoelimination of N2 and CO from (5). Upon oxidation of (4), however, the azo compound (5) turned out to be too unstable to be isolated, although it could be trapped as a cycloadduct with cyclopentadiene. 

The photodecompositions of 3,3-bis(l,l-difluorohexyl)diazirine and 3-(l,l-difluoro-octyl)-3//-diazirine have been examined. On irradiation in cyclohexane or methanol, competing photoisomerization to linear diazo-compounds and photofragmentation via carbene intermediates to cyclopropanes and alkenes has been observed and is illustrated for 3,3-bis(l,l-difluorohexyl)diazirine (6) in Scheme 1. The majority of investigations of nitrogen photoelimination in cyclic... 

The derivatives of perfluorodihydrofurans are also prepared from the per-fluorinated olefins. For example, the reaction of vinylketone 76 with difluoro-carbene generated from hexafluoropropene epoxide at 225°C gave 4,5-dihydro-furane 7l7 ... 

I,l-Difluoro-l-alkenes. Alkylidene ylides can function as bases to generate difluorocarbene from chiorodifluoromethane, and also as a trap for the carbene (equation I). Yieids of olefins are in the range of 80-100%. One advantage is... 

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