Electron-rich aryl iodides

One of the challenges in the Suzuki-type cross-coupling is to extend this reaction from electron-rich aryl iodides, bromides, and triflates to less reactive aryl sulfonates and aryl chlorides, which show poor reactivity in terms of oxidative addition in the catalytic cycle. Aryl mesylates, benzenesulfonates, and tosylates are much less expensive than triflates, and are unreactive toward palladium catalysts. The Ni(0)-catalyzed Suzuki-type cross-coupling reaction of aryl sulfonates, including mesylates, with arylboronic acids in the presence of K3P04 has been reported [123]. 

A different domino reaction yet involving rather similar steps, i.e. car-bopalladation of an allene and nucleophilic attack of a phenol, was elaborated by the same group and leads to isoxazolidines 138 after intramolecular cycloaddition in the intermediates 137 [81] (Scheme 21). This transformation was performed with several aryl and hetaryl iodides 48 and gave the highest yields with electron-rich aryl iodides while only traces of products were obtained starting from electron-deficient aryl iodides. 

The best results were obtained with n-propylamide, isopropylamide, and cyclohexylamide derivatives. The reactions proceed well with electron-poor aryl iodides. Electron-rich aryl iodides react faster but are more susceptible to side reactions. Thus, more optimization is needed if electron-rich aryl iodides are used. Arylation products can be further elaborated to fluorenones and nitriles in a one-pot reaction with trifluoroacetic anhydride [58],... 

While this ligand-free copper-catalysed Mizoroki-Heck-type reaction required relatively high temperatures of 150 °C [19], the use of DABCO (9) as ligand allowed for significantly milder reaction conditions [20]. Thereby, satisfying isolated yields were even achieved for orf/jo-substituted electron-rich aryl iodides and alkenyl bromides (Scheme 10.4). However, aryl bromides, particularly electron-rich ones, were converted only sluggishly. 

Another example involves the reaction of iodophenol with allenes, where a closely related mechanism can be proposed (Scheme 11). This reaction gives usually high yields of pyran derivatives for electron-rich aryl iodides. 

Shao and coworkers synthesized prolme-derived complex 30 (Figure 4.9), which was active for Heck reactions of aryl iodides and bromides in water [41]. Better results were obtained when electron-rich aryl iodides were used as substrates. 

The carbonylative coupling of an alkynyl zinc reagent 4.18 with a highly substituted, electron-rich aryl iodide 4.17 was used in a short synthesis of luteolin 4.20, a flavanoid natural product (Scheme 4.11). After the coupling, employing the PEPPSI catalyst, selective crr/tc-deprotection and 6-endo cyclization yielded the natural product."... 

Other heterocycles, such as benzoxazole and oxazoline, could be efficiently arylated (eq 16). Benzoxazole produced the highest yield (79%). Nonaromatic heterocycles, such as 6-dihydroquinazoline, were viable substrates however, quinazoline was unreactive. Electron-rich aryl iodides performed superiorly to electron-deficient aryl iodides (73% for p-OMe vs. 30% for /p-CFs). 

The first successful a-atylation of 2-lithio-N-Boc pyrrolidine, one of the most crucial extensions of the field due to its application to biologically active compounds, was reported by Dieter and Li. ° They showed that the reaction of 2-lithio-N-carbamates with aryl iodides in the presence of catalytic CuCN (10 mol%) and a Pd catalyst (5 mol%) afforded 2-aryl pyrrolidines initially in modest to good yields (Scheme 11.28). Although the use of ligands like dppf was shown to increase yields, this later method was limited to electron-rich aryl iodides. ... 

Palladium-catalysed Heck addition of Ar-I to terminal olefins RCH=CH2 has been reported to proceed under ligand-free conditions, with just (AcO)2Pd and AcOAg in AcOH at 110°C, and shown to afford double arylation products RCH=CAr2. Both electron-poor and electron-rich aryl iodides react efficiently. ... 

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