Dihalocyclopropanation alkenes

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... 

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

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

Although the gem-dihalocyclopropanes are fairly stable compounds, they can participate — as has been shown in the above sections — in quite a number of chemical transformations. Several reactions between dihalocarbenes and alkenes have been described in which no dihalocyclopropane formation could be observed that these intermediates might have been produced was only inferred from the type of products finally isolated. A typical process of this type is the e/ufo-addition of dihalocarbenes to norbomene and norbomadiene as discussed above. Comparable rearrangements have been observed, when dichlorocarbene additions either lead to aromatic products or when they cycloadd to rather inert aromatic systems. In the latter case a ring-enlargement takes place. A reaction related to the concerted opening of two cyclopropane rings in a bicyclopropyl system as discussed above takes place when dichlorocarbene is added to spiro[2.4]hepta-4,6-diene [227]. 

Dihalocyclopropanes are generally prepared by the addition of dihalocarbenes to alkenic substrates. As indicated in the introduction, the first synthesis of a dihalocyclopropane was accomplished by Doering and Hoffmann by the addition of dichlorocarbene, generated from chloroform and potassium r-butoxide (Bu OK), to cyclohexene giving dichloronorcarane (1), as shown in equation (l).s... 

Interestingly, the alkene to allene conversion can be carried out directly without isolation of the intermediate dihalocyclopropane. This process involves the treatment of the alkene with 1 equiv. of carbon tetrabromide and 2 equiv. of methyllithium in ether at -65 °C.163 Ultrasonic irradiation facilitates the formation of cyclopropylidenes, and therefore the allenes, from dihalocyclopropanes under the influence of Li, Na or Mg.1 The reactions are usually complete in 5-15 min. A report165 on the use of n-butyllithium complexed with the chiral tertiary amine (-)-sparteine, leading to optically active allenes, seems to be of questionable value. 

Because 1,1-dihalocyclopropanes are so readily available by carbene addition to alkenes, their dehydrohalogenation to 1-halocyclopropenes provides, in principle, one of the most attractive routes to functionalised cyclopropenes. However, most early studies of the reaction did not lead to the cyclopropenes themselves, but to products of their further reaction. The main problems arise when the 1-halocyclopropene (9) can undergo prototropic shifts by removal of a proton from C 2 or C3, or when the base used is also a good nucleophile and addition to the cyclopropene can occur ... 

The reaction between CHCI3 and HO- 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 Ph(Cl)C is formed instead. The reaction of iodoform and CrCl2 leads to iodocyclopropanes upon reaction with alkenes. Dihalocyclopropanes are very useful compounds that can be reduced to cyclopropanes, treated with magnesium or sodium to give allenes (18-3), or converted to a number of other products. 

The cyclopropyl group has enough special characteristics to distinguish it from other alkyl and cycloalkyl groups and we believe it deserves a special volume dealing with its chemistry. Two chapters related to this group appeared in previous volumes of the series. The similarities between cyclopropanes and olefins were discussed in a chapter on the Olefinic properties of Cyclopropanes in The Chemistry of Alkenes, Vol. 2 (1970) and Dihalocyclopropanes were described in Supplement D (1983) which deals with the carbon-halogen bond. 

Aithough some reactions, such as the transformation of -hydroxyalkyi selenides to 3-haloalkyl selenides (Scheme 161, b) or to vinyl selenides, enones (Scheme 161, a,a-dihalocyclopropanes (Scheme 162, f) or 3-hydroxya]kyl halides (Scheme 161, h Scheme 162, g), - have bera occasionally described or found oniy with specific types of -hydroxyalkyi seienides, especialiy those having a strained ring [e.g. their transformation to aliyi selenides (Scheme 163, b), - 1-selenocyclobutenes (Scheme 163, c) - and cyclobutanones (Scheme 163, f),i2.is9.i ).i63] others are far more general. This is particulariy the case of their reductions to alcohols (Scheme 161, a Scheme 162, a Scheme 163, a Scheme 164, a Scheme 165, ay.tss,i89,246 alkenes (Scheme 161, c Scheme 162, c Scheme 163, d Scheme 164, c Scheme 165, a Scheme 166, their transformation to allyi alcohols... 

In general, allenes are prepared by the same types of reactions which lead to alkenes elimination of hydrogen halides, halogens and water from adjacent carbon atoms. However, some methods are characteristic of allene synthesis, e.g. the dehalogenation of gem-dihalocyclopropanes, rearrangement of alkynes and the 1,4-addition to vinylalkynes. 

The starting materials are best prepared by the method of Makosza U3) (for dihalocyclopropanes) or via halocarbene addition to alkenes 114°. 

Reaction of dihalocarbenes with alkenes, [1 +2] cycloaddition, is the method of choice for the preparation of 1,1-dihalocyclopropanes. The reaction proceeds stereospecifically preserving the configuration of the alkene in the products. These observations allow the conclusion to be made that the dihalocarbene reacts in the singlet state with alkenes. Experimental data (relative activities of alkenes, selectivity indices as well as theoretical calculations indicate that dihalocarbenes are electrophilic species. This means that they react readily with electron-rich (nucleophilic) alkenes. Dihalocarbenes may also react with electron-poor alkenes, but at a much slower rate. In the case of alkenes with a fairly unreactive double bond, dihalocarbene may also attack other sites of the alkene molecule, e.g. insert into a C-H bond. The selectivity (reactivity) of dihalocarbenes depends on the temperature at 20 C typical dihalocarbenes can be arranged in the order given, with respect to their selectivities versus reactivities (Houben-Weyl, Vol. El9b, p 1598). 

A reaction of haloforms with a base, which generates dihalocarbenes (a-elimination) and their addition to alkenes is an efficient method for the preparation of 1,1-dihalocyclopropanes, with the exception of 1,1-difluoro derivatives (Houben-Weyl, Vol.E19b, pp 1464-1466). When chlorodifluoromethane and an alkene are treated with methyllithium, potassium tcrt-butox-ide, powdered sodium hydroxide in tetraglyme or a concentrated aqueous solution of alkali metal hydroxide and a phase-transfer catalyst, the expected 1,1-difluorocyclopropanes are formed in low yields. Comparable low yields of these products result, if dichlorodi-fluoromethane and an alkene are treated with methyllithium. " The main products formed are those that result from reaction of difluorocarbene (carbenoid), and its precursor, with the base or the solvent present in the system (for examples, see refs 10-12). Therefore, the reaction of chlorodifluoromethane with base and an alkene lacks preparative value. The difficulties mentioned above are circumvented in the method using chlorodifluoromethane, oxirane (or chloromethyloxirane), with tetraalkylammonium halide as a catalyst and an alkene (Houben-eyl, Vol. 4/3, p 380 and Vol. E19b, pp 1468-1469). 

Three dihalocarbenes generated from dibromochloromethane yield, with alkenes, three 1,1-dihalocyclopropanes which are difficult to separate. Therefore, these reactions are not prepa-ratively useful. 

Alkenes of low reactivity such as hex-l-ene, hept-l-ene " and oct-l-ene, give 1-bromo-l-chlorocyclopropanes exclusively (selectivity 100%) with dibenzo-18-crown-6 catalyst, yet a mixture of all dihalocyclopropanes was formed in low yield in the case of 3,3-dimethylbut-l-ene. 1-Bromo-l-chlorocyclopropanes 1 were prepared via the reaction of dibromochloromethane with oxirane, a catalytic amount of tetraethylammonium bromide and an alkene. 

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