Palladium catalysis halogenation

Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

Similar results for the replacement of halogen on an olefinic linkage by phosphorus have been accomplished using dialkyl phosphites with palladium(O) catalysts.4179 Another reaction involving replacement of a vinylic halide by phosphorus utilizes palladium catalysis with a trimethylsilyl-substituted phosphine (Figure 6.19).80... 

The scope of vinyl metals as sources of nucleophilic vinyl groups is very great. As well as the expected electrophiles such as halogens, alkyl and acyl halides, aldehydes and ketones, unsaturated carbonyl compounds and epoxides, they also combine with aryl and alkenyl halides with palladium catalysis. The usual stereochemical course is retention at the vinyl group. It is necessary to decide whether the vinyl metal is reactive enough or whether it must first be transformed into an ate complex. Since most of these vinyl metals can be converted into each other with retention, this is an unusually versatile group of reagents. 

This ring may be built by the formation of a new C—C bond between alkyne and halogen functions, a reaction which is assisted by palladium dichloride-triphenylphosphtne (reviews of palladium catalysis [IMI, 3069, 3505] in the presence of piperidine (as base) and formic acid (to remove hydride ion). The reaction is regio- and stereo-selective. Replacement of the piperidine and formic acid by R-substituted tributyltin enables the R group to be transferred to the indole stereospectfically [3448]. 

Such substitutions follow the same mechanistic route as the displacement of halide from 2- and 4-halo-nitrobenzenes, i.e. the nucleophile first adds and then the halide departs. By analogy with the benzenoid situation, the addition is facilitated by (i) the electron-deficiency at a- and y-carbons, further increased by the halogen substituent, and (ii) the ability of the heteroatom to accommodate negative charge in the intermediate thus produced. A comparison of the three possible intermediates makes it immediately plain that this latter is not available for attack at a p-position, and thus p nucleophilic displacements are very much slower - for practical purposes they do not occur (see, however, reactions with palladium catalysis, 4.2)... 

On the other hand, the direct coupling, under palladium catalysis, of aryUithiums obtained by halogen/lithium exchange with haloarenes was recently reinvestigated. First reported by... 

The palladium-catalyzed intramolecular C-H arylation of aromatic C-H bonds with haloarenes (Ar-H/Ar-X coupling, where X is halogen) is effective for the synthesis of carbazole alkaloids with amine linkers, as reported by Bedford and coworkers in 2006 (Scheme 16.16a) [34]. Buchwald-Hartwig coupling of an aryl bromide and an aniline derivative generated aryl chloride 91 in situ, which was easily cyclized under palladium catalysis to give clausine P in 80% yield. They also... 

It is evident in this case that the velocity of reaction is not dependent on the energy of activation alone. This as we have seen is due to the fact that catalysis is not proceeding over the whole area of the catalyst but only at highly localised patches which in the case of palladium are evidently much more extensive than on duroglass. The energy of activation is calculated from the influence of temperature on the reaction velocity proceeding at an unknown area of surface whilst in the case of the combination of ethylene and the halogens it was tacitly assumed that a surface covered with molten fatty acids or alcohols would in all cases exhibit a... 

The synthesis of unsymmetrical biaryls 8 from two monoaryl species involves the coupling of a metallated aromatic molecule 6 with an aryl halide or triflate 4 under the action of palladium(O) catalysis. The reaction involves a catalytic cycle in which palladium(O) inserts into the C-halogen bond via an oxidative addition to generate an arylpalladium(II) species 5 (Scheme 10.18). This undergoes a trans-metallation with the metallated component, producing a biarylpalladi-um(II) complex 7. The biaryl product is formed by reductive elimination. In the process, Pd(0) is regenerated and this can then react with a second molecule of aryl halide. Pd(0) is therefore a catalyst for the reaction. 

The C—I bond is very unstable and more reactive than C—Br, C—Cl and C—F bonds. Iodine is the most expensive of the common halogens and is much less frequently used in synthesis than bromine, chlorine or fluorine. Organometallic reactions proceed with iodinated aliphatic or aromatic compounds more easily than with the other halogens. Noble metal catalysis with palladium complexes is most effective with iodinated compounds. A useful synthetic procedure is the facile reduction of iodinated derivatives under mild conditions. Replacement of iodine by hydrogen at an sp carbon is an exothermic reaction with A// = -25 kJ mol . ... 

Intramolecular displacement of an orf/to-halogen can be achieved at high temperature or with copper(I)-catalysis. " Palladium-catalysed aminations of halide can be used to form either the N-C-2 or N-C-7a links, or both, for example in the double displacement shown below. ... 

The alkene, allyl, and alkyne complexes of Pd and Pt have been discussed to a large extent in earlier Sections, as have the use of palladium species in catalysis (Chapters 23 and 24). Here we deal mainly with complexes of the type MXHL2 and MXRL2 where X is halogen, R is an alkyl or aryl group and L is usually a tertiary phosphine. 

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