Dehalogenation methods

The main drawback to the dehalogenation method is that the haloallyl halides are usually difficult to obtain. Some of the available methods of synthesis of haloallyl halides are the following. 

Reductive dehalogenation is an efficient method of synthesis of cyclopropanes spiroannulated to five- and higher-membered carbocycles (i.e. compounds in which spiroannulation does not result in accumulation of extra strain) . The required gem-(dihalomethyl)cycloalkanes are usually prepared by halogenation of the precursor diols (equation 1). The cyclization is most efficiently accomplished in the Zn-alcohol-water system . For example, spiro[2.5]octane 7 was prepared in 91% yield using this procedure. This method is useful even for a one-step preparation of bis-spirocyclopropyl compounds as exemplified in equation 2. However, the application of the reductive dehalogenation method to the synthesis of more strained SPC (i.e. spirohexane or spiropentane) often leads to rearranged products. For example, methylenecyclopentane was the only product obtained from bis(bromomethyl)cyclobutane (equation 3) ... 

Recently, the dehalogenation method was further modified by using 1,2-dichlorovinyl ethers 62 as starting compounds" ". Loffler and Himbert applied the reaction of 1,2-dichlorovinyl ethers 62 with butyllithium to generate lithium alkoxyacetylides 61, which were subsequently quenched with ketones or arylated by the palladium-catalyzed crosscoupling with aryl halides to yield alkoxyarylacetylenes 63 (equation 37)". ... 

A novel dehalogenation method, e. g. for a-halogenoketones, through pyridinium salts differs from other methods by the remoteness of the reduction site, at the 4-position of the pyridine ring, from the halogenlosing C-atom . 

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

Nevertheless, an anaerobic system may be the method of choice under certain conditions (/) contamination with compounds that degrade only or better under anaerobic conditions, (2) low yield aquifers that make pump and treat methods or oxygen and nutrient distribution impractical, (J) mixed waste contamination where oxidizable compounds drive reductive dehalogenation of chlorinated compounds, or (4) deep aquifers that make oxygen and nutrient distribution mote difficult and cosdy. 

The classic method for controlling stereochemistry is to perform reactions on cyclic substrates. A rather lengthy but nonetheless efficient example in the prostaglandin field uses bicyclic structures for this purpose. Bisacetic acid derivative S is available in five steps from Diels-Alder reaction of trans-piperylene and maleic anhydride followed by side-chain homologation. Bromolactonization locks the molecule as bicyclic intermediate Esterification, reductive dehalogen-... 

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

---