Alkenes with Halogen Substituents

Roedig, H. Aman, and E. Fahr, Justus Liebigs Ann. Chem. 675, 47 (1964). 

DABCO in chloroform, the transient 3//-pyrazoIe 44 being identified by H-NMR spectroscopy before rearranging to isomeric 1/f-pyrazoles.90 

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There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Naphthalene dioxygenase from P. putida strain FI is able to oxidize a number of haloge-nated ethenes, propenes, and butenes, and d5 -hept-2-ene and cis-oct-2-ene (Lange and Wackett 1997). Alkenes with halogen and methyl substituents at double bonds form allyl alcohols, whereas those with only alkyl or chloromethyl groups form diols. 

Halogen-substituted carbenes attack olefins from their sterically less hindered face, however, exceptions are known for alkenes with oxygen substituents (vide infra). Two of numerous examples demonstrate the directive power of steric effects. Thus, spiro compound 1 and dichlorocarbene combine to provide the product 2 with the dichloromcthylcnc unit exclusively trans to the phenyl group14. 

When we discussed elimination reactions in Chapter 5, we learned that a Lewis base can react with an alkyl halide to form an alkene. In the present chapter, you will find that the same kinds of reactants can also undergo a different reaction, one in which the Lewis base acts as a nucleophile to substitute for the halogen substituent on carbon. 

An a-halosulfone 1 reacts with a base by deprotonation at the a -position to give a carbanionic species 3. An intramolecular nucleophilic substitution reaction, with the halogen substituent taking the part of the leaving group, then leads to formation of an intermediate episulfone 4 and the halide anion. This mechanism is supported by the fact that the episulfone 4 could be isolated. Subsequent extrusion of sulfur dioxide from 4 yields the alkene 2 ... 

In these reactions (Scheme 3.1), the first electron addition is to the alkene giving a radical-anion. This interacts with the alkyl halide to transfer an electron, in a process driven by simultaneous cleavage of the carbon-halogen bond. The alkyl radical formed in this manner adds an alkene radical-anion [25]. Aluminium ions generated at the anode are essential to the overall process. They coordinate with the intermediate carbanion, which then interacts with the second halogen substituent in an Sn2 process to form the carbocycle. 

Cyclopropenes 2, prepared by treatment of a trihalocyclopropane 1 with alkyllithium (see Section 2.A. 1.1.1 for the generation of cyclopropenes from cyclopropenes by elimination), ring open under appropriate conditions to generate vinylcarbenes 3. Such intermediates bearing halogen substituents on the divalent carbon can be trapped by carbene scavengers such as alkenes. Optimized conditions even permit these transformations of trihalocyclopropanes to be carried out as one-pot procedures. 

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