Reduction of Alkyl, Alkenyl, and Aryl Halides

REDUCTION OF ALKYL, ALKENYL, AND ARYL HALIDES I. Dehalogenation and Reductions at Cartran 

In the reduction of alkyl, alkenyl, and aryl halides, the halogen (X = F, Cl, Br, or I) rarely leaves without one or more of the electrons in the bond accompanying it (i.e., it rarely leaves as X+). Thus, even though the halogen generally leaves as an anion or a radical, there are four major reductive pathways that will be considered here. The first three differ from the fourth since, in them, the halogen is directly replaced by hydrogen. The fourth method is more circuitous there is electron transfer from a metal to the alkyl, alkenyl, or aryl halide and then, in a true second step, hydrolysis of the metal-carbon bond. 

catalytic reduction (frequently referred to as hydrogenolysis) can be used. Depending on the conditions, the unsaturation in alkenes, alkynes, and even arenes (if they are present) can be effected since the reduction follows the same general path of adsorption on the surface of the catalyst and then transfer of hydrogen seen in the reduction of those unsaturated groups (Chapter 6). 

Second, substitution by hydride (H ) for halide (X ) can be carried out. Although substitution reactions will be discussed subsequently in this chapter, when many more nucleophiles will be introduced, the replacement of halogen by the nucleophile hydride (H ) can also be thought of as a reduction, and it is thus briefly considered here too. 

there are a few radical processes in which a hydrogen atom (H) enters a site previously occupied by halogen. Presumably, the halogen (X) was abstracted by some radical or atomic species first and a chain reaction similar to that aheady discussed (Chapter 6) for halogenation results. This time, the reaction is a dehaloge-nation and hydrogen replaces halogen (i.e., it is the reverse of that discussed in Chapter 5).  

---

The Reactions of Alkyl, Alkenyl, and Aryl Halides Oxidation, Reduction, Substitution, Addition, Elimination, and Rearrangement... 

The more selective methods of reduction, which also minimize rearrangement reactions of the reacting alkyl halide (substrate), generally involve isolation (and thus at least partial purification) of an organometallic intermediate. Using one or more of these methods has enabled alkyl, alkenyl, and aryl halides, in the presence of an appropriate (usualy ethereal or hydrocarbon) solvent, to react with a variety of metals to produce organometallic compounds. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

Three transmetallation reactions are known. The reaction starts by the oxidative addition of halides to transition metal complexes to form 206. (In this scheme, all ligands are omitted.) (i) The C—C bonds 208 are formed by transmetallation of 206 with 207 and reductive elimination. Mainly Pd and Ni complexes are used as efficient catalysts. Aryl aryl, aryl alkenyl, alkenyl-alkenyl bonds, and some alkenyl alkyl and aryl-alkyl bonds, are formed by the cross-coupling, (ii) Metal hydrides 209 are another partner of the transmetallation, and hydrogenolysis of halides occurs to give 210. This reaction is discussed in Section 3.8. (iii) C—M bonds 212 are formed by the reaction of dimetallic compounds 211 with 206. These reactions are summarized in Schemes 3.3-3.6. 

---