Aryl chlorides, reduction

Hydrogenolysis of aryl and alkenyl halides and triflates proceeds by the treatment with various hydride sources. The reaction can be explained by the transmetallation with hydride to form palladium hydride, which undergoes reductive elimination. Several boro hydrides are used for this purpose[680], Deuteration of aromatic rings is possible by the reaction of aryl chlorides with NaBD4681]. 

Palladium(II) complexes provide convenient access into this class of catalysts. Some examples of complexes which have been found to be successful catalysts are shown in Scheme 11. They were able to get reasonable turnover numbers in the Heck reaction of aryl bromides and even aryl chlorides [22,190-195]. Mechanistic studies concentrated on the Heck reaction [195] or separated steps like the oxidative addition and reductive elimination [196-199]. Computational studies by DFT calculations indicated that the mechanism for NHC complexes is most likely the same as that for phosphine ligands [169], but also in this case there is a need for more data before a definitive answer can be given on the mechanism. 

Palladium NHC systems for the hydrodehalogenation of aryl chlorides and bromides and polyhalogenated aromatic substrates originate from about the same time as the first reports on Ni chemistry, and show many similarities. Initial efforts showed that the combination of PdCdba) (2 mol%), one equivalent of imidazolium chloride and KOMe produced an effective system for the reduction of 4-chlorotolu-ene, especially upon use of SIMes HCl 2 (96% yield of toluene after 1 h at 100°C) [7]. Interestingly, higher ligand to metal ratios severely inhibited the catalysis with only 7% yield of toluene achieved in the same time in the presence of two equivalents of SIMes HCl 2. Variation of the metal source (Pd(OAc)2, Pd(CjHjCN)jClj), alkoxide (NaOMe, KO Bu, NaOH/ ec-BuOH) or imidazolium salt (IMes HCl 1, IPr HCl 3, lAd HCl, ICy HCl) all failed to give a more active catalyst. 

As an example, consider the use of PVPy as a solid poison in the study of poly(noibomene)-supported Pd-NHC complexes in Suzuki reactions of aryl chlorides and phenylboroiuc acid in DMF (23). This polymeric piecatalyst is soluble under some of the reaction conditions employed and thus it presents a different situation from the work using porous, insoluble oxide catalysts (12-13). Like past studies, addition of PVPy resulted in a reduction in reaction yield. However, the reaction solution was observed to become noticeably more viscous, and the cause of the reduced yield - catalyst poisoning vs. transport limitations on reaction kinetics - was not immediately obvious. The authors thus added a non-functionalized poly(styrene), which should only affect the reaction via non-specific physical means (e.g., increase in solution viscosity, etc.), and also observed a decrease in reaction yield. They thus demonstrated a drawback in the use of the potentially swellable PVPy with soluble (23) or swellable (20) catalysts in certain solvents. 

Boc-protection needed during reductive hydrogenation of the azide group to prevent reaction medium becoming basic Competitive de-chlorination of the aryl chloride group occurs under basic conditions... 

A study of the a-arylation of diazine mono iV-oxides, under Heck-like conditions, also gave emphasis to pyrazines but a number of examples using pyrimidines and pyridazines were also described (Scheme 1). A wide range of aryl chlorides, bromides and iodides was used and the products were easily deoxygenated by catalytic reduction. An interesting feature was the use of a copper additive, which was only required for the pyrimidine reactions, to give a very substantial improvement in yield <06AG(I)7781>. 

Vinyl and Aryl Halides and Triflates. The organosilane reduction of aryl halides is possible in high yields with triethylsilane and palladium chloride.195 The reaction is equally successful with aryl chlorides, bromides, and iodides. Aryl bromides and iodides, but not chlorides, are reduced with PMHS/Pd(PPh3)4 in moderate to excellent yields.199 This system also reduces vinyl bromides.199 p-Chlorobenzophenone is reduced to benzophenone with yym-tetramethyldisilo-xane and Ni/C in excellent yield (Eq. 59).200 There is a report of the organosilane reduction of aryl and vinyl triflates in very high yields with the combination of Et3SiH/Pd(OAc)2/dppp (l,3-bis(diphenylphosphino)propane) (Eq. 60).201... 

Milstein and colleagues [100] have developed very efficient methods using basic, chelating phosphine ligands. Even aryl chlorides underwent reductive dechlorination to the corresponding arenes with ](dippp)2Pd] as catalyst (dippp,... 

The most abundant rate data concern the reductive cleavage of aryl chlorides and bromides, obtained by either direct or indirect electrochemistry (Section 2.2) or by pulse radiolysis. They show (Figures 3.19 and 3.20), a rough linear... 

Long-lived homogeneous Pd(0)f4 [L = P(Ph)3] catalysts for the cyanation of aryl chlorides (295) (X = Cl) have been developed, which are activated by cathodic reduction (Scheme 113) [433]. A high temperature, 130 °C, and a high-boihng solvent, dimethylformamide, are required because Pd does not insert into the aryl C—Cl bond at lower temperatures. Cat-alytically inactive metal species formed in undesirable side reactions with cyanide are electrochemically restored to a catalytically... 

It has been proposed that in this reaction CO2 reacts as an electrophile with [ArPd (PPh3)2] formed by reduction of the aryl-palladium(II) [102]. Aryl chlorides react too slowly with Pd° to enable an efficient carboxylation reaction. On the other hand aryl triflate and aryl bromide have similar reactivity. The synthesis of aryl carboxylic acids can then be obtained from phenols via the formation of the corresponding aryltriflate (Eq. 15) [29, 30] ... 

The reductive dehalogenation of aryl chlorides in the presence of electron transfer sensitizers is thought to proceed through radical ion pairs. For example, the formation of mono-chloroanthracene from the photolysis of 9,10-dichloroanthracene in the presence of 2,5-dimethyl-2,4-hexadiene, eq. 59 (183),... 

Aromatic acid chlorides are decarbonylated to aryl chlorides when they are heated to 300-360 C with palladium on carbon. The reaction proceeds by way of an aroylpalladium chloride, then to an arylpalla-dium chloride and finally through a reductive elimination to the aryl chloride. If the reaction is conducted in the presence of a reactive alkene under mild conditions the aroylpalladium chloride intermediate will sometimes acylate the alkene, as noted in Section 4.3.5.3.I. More usually, however, decarboxylation is more rapid than acylation, especially at higher temperatures (>100 C), and decarbonylation occurs. The... 

Reductive radical cyclization and tandem radical addition/cyclization reactions catalyzed by Ni(II) complexes, such as Ni(cyclam)(C104)2 98a, were studied starting in the 1990s by Ozaki s group [128]. The reaction conditions are applicable to alkyl and aryl halides bearing suitable positioned olefin units. Iodides and bromides can be used in some cases even aryl chlorides were successfully applied. The field was reviewed recently, and thus only more recent results are summarized here [19, 20]. 

Trimethylsilyl chloride has been employed in some synthetically useful reductions of aryl halides. The electrochemical reductive trimethylsilylation of aryl chlorides is a good... 

---