Dihalocyclopropanation

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

The process in which a dihalocarbene is formed from a tnhalomethane is an ehmi nation m which a proton and a halide are lost from the same carbon It is an a elimination When generated m the presence of an alkene dihalocarbenes undergo cycloaddi tion to the double bond to give dihalocyclopropanes... 

SKATTEB0L DihalocydapropaneRearrangemant Rearrangement of gem-ditialocyclopropanes to ailenes or of vinyt dihalocyclopropanes to eyciopentadienes and fulvenes by MeU... 

Parham and co-workers have studied the addition of dichloro- and dibro-mocarbene to cyclic enol ethers and the transformations of the resulting dihalocyclopropanes. ... 

Reaction of dibromocyclopropane (39) with hot quinoline gives 1-ethoxy-cyclohepta-l,3,5-triene (37) in 32% yield. Dihalocyclopropanes prepai ed from larger ring enol ethers do not react with hot pyridine but afford products with hot quinoline formed by transannular reactions. 

When generated in the presence of an alkene, dihalocaibenes undergo cycloaddition to the double bond to give dihalocyclopropanes. 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

Haloforms react with potassium /-butoxide to form dihalocarbenes, which add smoothly to olefins giving 1,1-dihalocyclopropanes (2). The reaction does not appear... 

Seyferth (7) discovered that phenyl(trihalomethyl)mercury compounds decompose when heated in a solvent giving dihalocarbenes. When the solvent contains a suitable olefin, carbene addition occurs giving 1,1-dihalocyclopropane derivatives. The reaction has the advantage that strong base is not required in the reaction mixture, and base-... 

The treatment of 1,1-dihalocyclopropanes by methyllithium appears to be a general route to allenes, providing the product is not highly strained. An example is shown in the reaction (13). The procedure given below employs the reaction for the preparation... 

CHAIN ELONGATION OF ALKENES via gem-DIHALOCYCLOPROPANES l,l-DIPHENYL-2-BROMO-3-ACETOXY-l-PROPENE... 

The reaction between CHCI3 and OH is often carried out under phase-transfer conditions. It has been shown that the reaction between PhCHCl2 and t-BuOK produces a carbenoid, but when the reaction is run in the presence of a crown ether, the free PhCCl is formed instead.Dihalocyclopropanes are very useful compoundsthat can be reduced to cyclopropanes, treated with magnesium or sodium to give allenes (18-3), or converted to a number of other products. 

An important synthetic application of this reaction is in dehalogenation of dichloro- and dibromocyclopropanes. The dihalocyclopropanes are accessible via carbene addition reactions (see Section 10.2.3). Reductive dehalogenation can also be used to introduce deuterium at a specific site. The mechanism of the reaction involves electron transfer to form a radical anion, which then fragments with loss of a halide ion. The resulting radical is reduced to a carbanion by a second electron transfer and subsequently protonated. 

Much of the literature regarding dihalocarbenes is concerned with reactions of CX2 with olefinic substrates to give 1,1-dihalocyclopropane derivatives. These reactions occur with retention of stereospecificity, as expected for singlet carbenes. Dihalocarbenes also exhibit strong electrophilic behavior towards olefins, and will often not react with weakly nucleophilic species if stronger nucleophiles are present. 

Experimental work in this area is notably lacking. Hence, a systematic study of the relative stabilities of dihalocyclopropanes would be most welcome. 

Di-iodocyclopropanes are unstable and cannot be isolated readily [133]. Other dihalocyclopropanes rearrange thermally during work up, or in the presence of the base, to produce ring-opened allylic dihalides or vinyl halides [e.g. 15, 81, 87, 96, 100, 103, 152, 157] (Scheme 7.4). Thermal rearrangement of the dihalocarbene adducts from halocycloalkenes leads to ring expanded products or methylene derivatives [e.g. 87], whereas 1, l-dichlorocyclopent-3-enes produce halobenzenes in high yield [96]. 

Predictably, the reaction of A V-disubstituted enamines [26-29] and non-conju-gated unsaturated amines with dihalocarbenes results in the exclusive formation of the dihalocyclopropane derivatives (see Section 7.3). Dichlorocarbene inserts into the a-CH bond of Af-alkyldibenzo[6,/]azepines [16], in addition to the expected electrophilic addition to the C=C bond (see Sections 7.2 and 7.3). 

Bicyclic gem-dihalocyclopropanes lead predominantly to the corresponding endo-monohalocyclopropanes, which are formed by reduction of the exo-halogen, whose approach to the cathode is less hindered [356, 357]. 

A 1 1 mixture of (Z)- and ( )-tetramethylbicyclopropylidenes 24b,c was obtained by dihalocyclopropanation of dimethyl(dimethylethenylidene)cyclopro-pane 27 [45,46] followed by reduction of the adducts with sodium in methanol (Scheme 6). Addition of monochlorocarbene onto 2-(trimethylsilyl)-l-ethenyl-idenecyclopropane (29) proceeds with low diastereo- and regioselectivity to give a mixture of bicyclopropylidene and methylenespiropentane derivatives 30, 31 in poor yield [47]. Upon treatment of l,l-dibromo-2-methylpropene (36) with butyllithium at -110°C the unique diisopropylidenetetramethylbicyclo-propylidene 37 was formed by addition of isobutylidene to in situ generated tetramethylbutatriene (32), albeit in very low yield [48] (Scheme 7). 

Cyclopropyl iodides like 70 and bromides are good substrates for the exchange reaction (equation 44)77,82,83 reaction is stereoselective and sufficiently fast at low temperatures, thus allowing the preparation of functionalized compounds. If a coordinating group like an ester is present in a. gem-dihalocyclopropane like 71, the cA-halogen substituent is exchanged selectively in ether (equation 45). ... 

The elimination reactions involving dehalogenation, dehydrohalogenation, and dehydration are often laborious compared to the more recent techniques involving dehalogenation of gem-dihalocyclopropanes [10a, b]. However, the availability of the starting materials is the deciding factor. 

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