Gem-dichlorocyclopropanes

The treatment of the bromoacetal (255) with catalytic amounts ( 10%) of a Co(I) species, generated by the electroreduction of cobaloxime (232) in an Me0H-LiCl04 system at —1.8 V, produces the cis-fused adduct (256) in 60 70% yield (Scheme 96) [392]. Cathodic reduction is used for the synthesis of a [Co(CO)3PBu3] complex in a methanol-methyl formate medium, which catalyzes the alkoxycarbonylation of dichloromethane to dimethyl mal-onate in up to 75% yield [393]. The Co(II) complexes are found to be effective for the homogeneous reduction of gem-dichlorocyclopropanes in the presence of anthracene [394]. The formation of the C—C double bond of (258) may be ascribed to the a-elimination of the Co-H species. Thus, benzalchloride (257) can be converted to a mixture consisting primarily of ds- and trans-stilbenes (258) by the action of electrogenerated Co(I)(salen) (Scheme 97) [395-398]. 

Finally, Tanabe and coworkers reported that treatment of gem-dichlorocyclopropanes with methylmagnesium bromide in the presence of 5% Fe(dbm)3 and 4-methoxytolnene (1 equiv.) affords the dimethylated product (Scheme 52). 

The intramolecular nitrogen-trapping protocol used by Banwell has also been successfully exploited in the assembly of spirocyclic frameworks relating to the aromatic erythrina alkaloids.24 However, when it was applied to the synthesis of nonaromatic spirocycles, as found in histrionicotoxin, the flexible alkyl tether proved to be problematic.25 In this study, gem-dichlorocyclopropane substrate 37 was initially subjected to silver(I) salts under a variety of conditions only to provide solvolysis and elimination products without any indication of trapping by the pendent... 

To further expand the scope of this new silver(I)-mediated reaction sequence, interrupted Nazarov cyclizations were explored using the halocyclopropane chemistry, an investigation that was prompted by the discovery of an intriguing result. It was found that treatment of the phenethyl-substituted compound 76 with 1.5 equiv of silver tetrafluoroborate in dichloromethane provided benzohydrindenone 77 as the sole product, with no apparent formation of the simple a-chlorocyclopentenone (Scheme 4.24). This prompted an examination of appropriately substituted gem-dichlorocyclopropane substrates in analogous interrupted Nazarov processes to ascertain the scope of this new cascade reaction sequence. 

In an effort to provide experimental evidence for the formation of a second oxyallyl cationic intermediate, a gem-dichlorocyclopropane substrate was envisaged with two internal nucleophiles one to participate in the initial interrupted Nazarov reaction, and the other to capture the second cationic species. Surprisingly, when the carefully designed substrate 80 was subjected to the optimized reaction conditions, an alternate mode of trapping occurred to generate the intriguing bridged bicyclic product 81 (Scheme 4.25). 

The cascade sequences presented herein demonstrate unprecedented modes of reactivity in Nazarov chemistry that are initiated by the silver(I)-promoted ring opening of halocyclopropanes. The ease with which the gem-dichlorocyclopropanes can be prepared, the relatively mild reaction conditions, and the efficiency of these processes make these substrates attractive intermediates for an application in natural product synthesis. 

Other means of improving sulfide yields in the reaction of halides with thiolates are (1) the use of thiols and platinum(II) complex catalysts287, (2) the generation of thiolate anions by electrochemical means288 and (3) the use of phase-transfer conditions237. The first method has been used for the synthesis of thioketals from geminal diiodides and the third has been used for the conversion of gem-dichlorocyclopropanes into cyclopropane thioketals, which are effectively masked cyclopropane moieties. 

VmybdkyHJeiiecyelopropanes. Vinylalkylidenecyclopropancs can be prepared from gem-dichlorocyclopropanes by dehydrochlorination with potassium r-buloxide in DMSO. The simplest example is the formation of vinylmethylenecyclopropane (2)... 

The oxirane rings in 3,4-epoxychromanes and 1,2-epoxytetrahydronaphthalenes have been converted into ethoxycarbonylcyclopropanes by reaction with ethyl malonate anion These transformations, however, appear to lack generality, gem-Dichlorocyclopropanes have been obtained from oxiranes under dichlorocarbene-generating PTC conditions Oxiranes can also be transformed into cyclopropanes in their reaction with active methylene compounds (Section III.C.l). 

Additional evidence for the presence of cyclopropene intermediates in the interconversion of aryl and aromatic carbenes comes from the products of dehydrohalogenation of gem-dichlorocyclopropanes For example, treatment of cyclopropane 229 with base gives a ca. 1 2 mixture of the ethers 231 and 233, products which are easily rationalized by the pathways shown in equation 76. Of particular significance here is the observation that products derived from both 230 and 232 are obtained. This represents the first definite evidence that bicycloheptatrienes open to both cycloheptatrienylidenes and arylcarbenes under mild conditions, i.e. at ambient temperatures. 

Despite intense theoretical interest, surprisingly few attempts to prepare the parent hydrocarbon were reported prior to its synthesis in 1984 however, evidence for simple alkyl methylenecyclopropenes can be found in the base-induced elimination-isomerization reactions of gem-dichlorocyclopropanes " " . 

The above conditions allow the synthesis of a large variety of a,a-dialkyl substituted ketones including spiro derivatives and cyclopentanones, cyclohexanones, cycloheptanones and cyclododecanones bearing two alkyl groups at die a-posidon (Scheme 162, e Scheme 165, c Scheme 166, e Scheme 186, a and b Scheme 187 Scheme 188, a Scheme 189, a and The reactions are less selective when the dichlorocarbene is generated from bromodichloromethane and lead to gem-dichlorocyclopropanes if the dichlorocarbene is produced from chloroform and potassium r-butoxide (Scheme 162, f Scheme 188, b Scheme 189, c). ... 

Alkylidenmalonitriles were converted to gem-dichlorocyclopropanes 2 in reasonable yield by reaction with trichloroacetic acid. This reaction is presumed to proceed by a MIRC mechanism. 

The ring opening of unreactive gem-dichlorocyclopropanes can occasionally be improved by using silver(I) tetrafluoroborate supported on alumina as reagent without solvent (dry reaction) under microwave aetivation. " ... 

A synthesis of substituted buta-l,2,3-trienes 168 from the double dehydrohalogenation of gem-dichlorocyclopropanes 167 has been described. This reaction does not involve cyclopropylidene but likely proceeds through the chlorocyclopropene-vinylcarbene-l-chlorobuta-... 

At elevated temperatures, e.g. in a high-boiling solvent, LiAlH can be used to fully reduce gem-dichlorocyclopropanes Kaufmann D, Fick H-H, Schallner O, Sfrielmaim W, Meyer L-U, G51itz P. de Meijere A (1983) Chem. Ber. 116 587... 

Dichlorocarbene. This silane decomposes in the vapor phase at 120-140° to liberate dichlorocarbene and SiF3Cl. Added olefins are converted into gem-dichlorocyclopropanes in 85-95% yields. The reaction is stereospecific with cis- and tra/is-2-butene. ... 

Another piece of experimental evidence against an extraction mechanism for PTC generation and reaction of dichlorocarbene is the observation that attempts to use ion-pair extraction methodology, namely, executing the process in a two-phase system, viz., chloroform and concentrated aqueous NaOH in the presence of an equimolar amount of tetra-butylammonium hydrogen sulfate, which assures transfer of Q" OH into the organic phase, result in dominant, rapid hydrolysis of dichlorocarbene. Its addition to alkene, producing gem-dichlorocyclopropane, was in such an experiment a minor reaction. 

A mechanophore (blue in Fig. 2a) is a strategically designed chemical entity which responds to mechanical force in a predictable and useful manner (Fig. 2d-f). The polymer strand here acts as an actuator to transmit macroscopic force to the target. For a fully extended polymer chain, the maximum tension force is at the middle point of the chain contour. So the mechanophore should be incorporated into the middle of the chain with its active bond along the chain contotu (Fig. 2a) [15, 29, 32]. Examples of mechanochemical reactions include homolytic scission of weak bonds (diazo [33]), electrocyclic ring-opening (benzocyclobutenes [29], spiropyrans [32, 34 5], gem-dichlorocyclopropanes [46-49], ge/n-difluorocyclo-propanes [30, 50], and epoxide [51]), cycloreversion reactions (cyclobutane derivatives [52-56], Diels-Alder adducts [57, 58], 1,3-dipolar adducts [59, 60], and 1,2-dioxetanes [61]), dative bond scission [62-64], and flex-activated reactions [34, 65, 66], as recently reviewed by Bielawski [67]. 

---