Stereochemistry with hydrogen halides

The order of reactivity of the hydrogen halides is HI > HBr > HCl, and reactions of simple alkenes with HCl are quite slow. The studies that have been applied to determining mechanistic details of hydrogen halide addition to alkenes have focused on the kinetics and stereochemistry of the reaction and on the effect of added nucleophiles. The kinetic studies often reveal complex rate expressions which demonstrate that more than one process contributes to the overall reaction rate. For addition of hydrogen bromide or Itydrogen... 

Anti stereochemistry can be explained by a mechanism in which the alkene interacts simultaneously with the proton-donating hydrogen halide and with a source of halide ion, either a second molecule of hydrogen halide or a free halide ion. The anti stereochemistry is consistent with the expectation that the attack of halide ion would be from the opposite... 

Addition of hydrogen halides to alkenes is not stereospecific. In contrast, addition of Br2 proceeds exclusively with anti stereochemistry. 

As reported in Scheme 1 the process involves a series of steps. The alkylpalladium species 1 forms through oxidative addition of the aromatic iodide to palladium(O) followed by noibomene insertion (4-7). The ready generation of complex 2 (8-11) from 1 is due to the unfavourable stereochemistry preventing P-hydrogen elimination from 1 (12). Complex 2 further reacts with alkyl halides RX to form palladium(IV) complex 3 (13-15). Migration of the R group to the... 

As p-hydride elimination is reversible, hydropalladation with the opposite regiochemistry provides a mechanism for forming regioisomers of the alkene. This allows the most stable alkene that is accessible by the hydropalladation-dehydropalladation sequence to dominate. The only restriction is that all of these processes are syn. The migration can be prevented by the addition of bases like silver carbonate, which effectively removes the hydrogen halide from the palladium complex as soon as it is formed. This synthesis of a complex trans dihydrofuran involves the Heck reaction followed by alkene isomerization and then a Heck reaction without migration to preserve the stereochemistry. 

Rh(TTP) reacts with alkyl halides, acyl halides, aroyl halides, and sulfonyl halides, but it shows no evidence of reaction with molecular hydrogen. These observations further emphasize the fact that Rh(TTP) is essentially a nucleophile and it therefore reacts with those reagents RX that can oxidatively add by nucleophilic attack (34). Rh(TTP) does not react with H2, and H2 seems always to add to (P complexes via a concerted mechanism (35). It appears that Rh(TTP) has very little diradical character, i.e. it is not a good analog of a carbene (35). It is possible that this unreactivity may be associated with the stereochemistry of chelation by the macrocyclic ligand. Earlier studies on the oxidative addition reactions of Rh(I) complex with a tetraaza macrocycle revealed that the Rh(I) had strong nucleophilic properties but the activation of molecular H2 was not reported (36, 37). This possibility is supported by reports that dialkyl sulfide complexes of rhodium chloride catalyze the hydrogenation of olefins (38). 

The elimination reaction, given in Equation 7e, is accompanied by a formal reduction in the oxidation state of the rhodium from (III) to (I). The stereochemistry of this reaction has also attracted substantial interest. If /8-hydrogens are absent, the alkyl halide is eliminated with retention of configuration at the carbon. If /8-hydrogens are present, /8-hydride elimination occurs as shown in Equation 7f, giving an alkene and hydrogen halide. Investigations into the /8-hydride elimination have shown... 

This reaction was first reported by Nenitzescu in 1931. It is the formation of an a,p-unsaturated ketone directly by aluminum chloride-promoted acylation of alkenes with acyl halides. Therefore, it is known as the Darzens-Nenitzescu reaction (or Nenitzescu reductive acylation), or Nenitzescu acylation. Under such reaction conditions, Nenitzescu prepared 2-butenyl methyl ketone from acetyl chloride and 1-butene and dimethylacetylcyclohex-ene from acetyl chloride and cyclooctene. However, in the presence of benzene or hexane, the saturated ketones are often resolved, as supported by the preparation of 4-phenyl cyclohexyl methyl ketone from the reaction of cyclohexene and acetyl chloride in benzene, and the synthesis of 3- or 4-methylcyclohexyl methyl ketone by refluxing the mixture of cycloheptene and acetyl chloride in cyclohexane or isopentane. This is probably caused by the intermolecular hydrogen transfer from the solvent. In addition, owing to its intrinsic strain, cyclopropyl group reacts in a manner similar to an oleflnic functionality so that it can be readily acylated. It should be pointed out that under various reaction conditions, the Darzens-Nenitzescu reaction is often complicated by the formation of -halo ketones, 3,)/-enones, or /3-acyloxy ketones. This complication can be overcome by an aluminum chloride-promoted acylation with vinyl mercuric chloride, resulting in a high purity of stereochemistry. ... 

A significant modification in the stereochemistry is observed when the double bond is conjugated with a group that can stabilize a carbocation intermediate. Most of the specific cases involve an aryl substituent. Examples of alkenes that give primarily syn addition are Z- and -l-phenylpropene, Z- and - -<-butylstyrene, l-phenyl-4-/-butylcyclohex-ene, and indene. The mechanism proposed for these additions features an ion pair as the key intermediate. Because of the greater stability of the carbocations in these molecules, concerted attack by halide ion is not required for complete carbon-hydrogen bond formation. If the ion pair formed by alkene protonation collapses to product faster than reorientation takes place, the result will be syn addition, since the proton and halide ion are initially on the same side of the molecule. 

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