Catalyzed Aryl Transfer Reactions

The synthesis of optically active diaryl methanols 27 is of particular synthetic value, since their core structure represents a molecular scaffold which is relevant to numerous biologically active compounds and pharmaceuticals possessing an-tihistaminic, anticholinergic, local-anesthetic, and laxative properties. Examples include neobenodine 28, orphenadrine 29, and carbinoxamine 30 [31]. 

Increasing the catalyst loading to 10 mol% and performing the reaction at — 20 °C raised the ee of 27a to 90%. Of particular note is the observation that ferrocene carbaldehyde gave the best enantioselectivity in such addition reactions ( 96% ee). 

An important issue was the fact that isolated diphenylzinc had to be used in this protocol and that samples of this arylzinc reagent prepared in situ (and presumably still containing lithium or magnesium salts) led to products with lower enantioselectivities. Thus, although pure diphenylzinc was commercially available, its high price was expected to hamper large-scale applications of this catalyzed asymmetric phenyl transfer process [36, 37]. 

It is important to mention that the catalysis with this modified arylzinc reagent not only leads to improved enantioselectivity (at high product yield), but also that in this process swfestoichiometric quantities of diphenylzinc could be applied. This also meant that now both of the phenyl groups could be activated and transferred to the aldehydes. A reaction profile obtained by FT-IR studies revealed that the modification of the zinc reagent had a significant effect on its reactivity [41]. 

Representative results are shown in Fig. 2.1.2.1. Both reactions with mixtures of diphenylzinc and diethylzinc and those with pure diphenylzinc are catalyzed by ferrocene 9 as indicated by the comparisons between curves A and C as well as B and D, respectively. Apparently the reaction becomes slower when the mixture of the zinc reagents is applied (curve A versus curve B). We presume that this effect is - as hoped - due to a less pronounced background reaction as well as to a modification of the aryl source (potentially PhZnEt or complexes thereof). Consequently, a better control of the enantioselectivity at the expense of the reaction rate is observed. 

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Later, the oxazolines 25 were examined to study the effects of matched/mismatched combinations of stereogenic centers on catalyzed aryl transfer reactions to aldehydes. Of these mandelic acid-derived catalysts, 25b gave the best results in terms of enantioselectivity (up to 35% ee), while diastereomer (l ,S)-25b proved to be superior to (S,S)-25b with respect to catalyst activity [29]. With both compounds, the absolute configuration of the product was determined by the oxazo-line moiety. 

With the aim of improving understanding of the mechanism of the ferrocene-catalyzed aryl transfer reactions from organozincs to aldehydes, DPT calculations were performed in close collaboration with Norrby [64]. As a result, the experimentally observed higher reactivity of the phenyl transfer to aldehydes compared... 

Although the precise reason for the MPEG-effect [50] is still unknown, we assume that catalytically active achiral metal species are inactivated by trapping with the polyether and that the catalyzed asymmetric reaction path thereby becomes more dominant. This phenomenon had already been observed in aryl transfer reactions catalyzed by MPEG-bound ferrocene 39 [44], and it can be used to perform catalyses with lower catalyst loadings [50]. 

For a general review of catalyzed asymmetric aryl transfer reactions, see C. Bolm, J. P. Hildebrand, K. Muniz, N. Hermanns, Angew. Chem. 2001, 113, 3382 Angew. Chem. Int. Ed. 2001, 40, 3284. 

Ducept and Marsden described a general synthesis of 5-ethoxy-2-substituted 4-(triethylsilyl)oxazoles 176 from the rhodium(II)octanoate-catalyzed diazo-transfer reaction of ethyl (triethylsilyl)diazoacetate 175 and nitriles (Scheme 1.48). The reaction conditions tolerate a wide variety of functional groups on the nitrile, including alkyl, aryl, heteroaryl, vinyl, carbonyl, sUyloxy, and dialkylamino. Desilylation of 176 with TBAF afforded the corresponding 2-alkyl(aryl)-5-ethoxy-oxazoles 177, which are normally inaccessible from diazoesters using conventional rhodium-carbene methodology. The authors noted that carbonyl groups in the 2 position of 176 are not compatible with TBAF deprotection. 

Scheme 7.45 Use of arylboronic acids in the Fe-catalyzed asymmetric aryl transfer reaction, as reported by Bolm and Rudolph [74].

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

Cyclic triarylbismuth(III) compounds also undergo the Pd-catalyzed cross-coupling reaction with benzoyl chloride (Scheme 27) [42]. The exocyclic aryl group was selectively transferred to form 4-methylbenzophenone in good yield. Bismuth-containing products could not be isolated except for the cyclic bismuth compound possessing a SO2 moiety, for which cyclic bismuth chloride was isolated in 86% yield. 

Bromo- and iodoimidazoles are useful intermediates for further functionalization. 4(5)-Aryl- I //-imidazoles 57 can be efficiently and selectively prepared by palladium-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-l//-imidazole 56 with arylboronic acids under phase-transfer conditions, which then underwent highly selective palladium-catalyzed and copper(I) iodide mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-l//-imidazoles 58 in modest to good yields <07JOC8543>. A new procedure for the synthesis of a series of substituted 2-phenylhistamines 60 utilizing a microwave-promoted Suzuki... 

One cannot distinguish between the analogous copper intermediates involved in oxidative electron-transfer and ligand-transfer reactions. In each the ionization of the ligand to copper(II) has an important role in the formation of carbonium ion intermediates. A reaction analogous to the copper-catalyzed decomposition of peroxides is the copper-promoted decomposition of diazonium salts (178). The diazonium ion and copper(I) afford aryl radicals which can undergo ligand-transfer oxidation with copper(II) halides (Sandmeyer reaction) or add to olefins (Meerwein reaction). 

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