Aiyl, from aryl halides

Alkyl-aiyl ethers can be prepared from a phenoxide salt and an alkyl halide (the Williamson synthesis, Section 11.4A). They cannot be prepared from an aryl halide and alkoxide salt, however, because aryl halides are unreactive under the conditions of Williamson synthesis they do not undergo nucleophilic displacement by either an Sjjl or Sjj2 mechanism. 

Carbopalladation of Arynes by Arylpalladium Complexes Pd-Catalyzed Annulation Reactions of Arynes. Whereas the Pd-catalyzed annulation of alkynes by aiyl halides has proven to be an effective method for the construction of a wide variety of hetero- and carbocycles similar carbopalladation of arynes were unprecedented until Larock and Zhang reported the synthesis of flu-oren-9-ones 115 through the annulation of arynes by o-haloarenecarboxaldehydes (Scheme 12.57) [100]. Larock s group has also developed a Pd-catalyzed annulation of arynes by 2-halobiaryls, affording polycyclic aromatic and hetCToaromatic compounds such as 116 from simple starting materials. Larock and Cheng have independently reported the related double annulation of arynes by simple aryl halides as an efficient route to functionalized triphenylenes (Scheme 12.57) [101]. 

We then examined the reactions of a variety of aiyl halides with aiylboronic acids containing both electron donating and electron attracting substituents, Table VI. As can be seen from the data contained in Table VI, the reaction appears to be insensitive to the substituents on the boronic acid. However, the reaction is most efficient when aryl iodides are used as the co-reactant. In fact the reactivity trend aiyl iodide > aryl bromide > aryl chloride > aryl fluoride parallels the trend observed in Suzuki reactions carried out thermally, both in solution and on alumina. 

This first plan for a decarboxylative cross-coupling carried with it certain weaknesses for potential industrial applications. It was to be expected that the salt metathesis between alkali metal carboxylates and late transition metal halides would be thermodynamically disfavored. We expected the formation of a palladium benzoate complex i from palladium bromide complexes c and potassium benzoate (g) to proceed well only in the presence of a stoichiometric quantity of silver to capture bromide ions [27]. However, we did not like the idea of using stoichiometric quantities of silver salts or of expensive aiyl triflates in the place of aryl halides. Finally, the published substrate scope of the oxidative Heck reactimi led to concerns that palladium catalysts mediate the decarboxylation rally of a narrow range of carboxylates, precluding use of this reaction as a general synthetic strategy. 

We have shown that the direct arylation of acrolein toward the synthesis of cinnamaldehyde derivatives was an efficient procedure. Using the palladacycle 1 as catalyst, substituted aldehydes 3 were prepared with up to 87% isolated yield from condensed aiyl bromides (Scheme 21.1, Route 1) that was extended successfully to heteroaiyl bromides, like bromoquinolines (6). Alternatively, the acrolein diethyl acetal was used as olefin and a selective formation of the saturated ester 4 was attained under the same reaction conditions (Scheme 21.1, Route 2). The expected aldehydes 3 were, however, obtained from most of the aiyl halides used under modified conditions. It was shown that the addition of n-Bu4NOAc in the medium... 

Larock and Dai developed the synthesis of isoquinolines via palladium-catalyzed coupling of organic halides with 2-(l-allqmyl)benzaldimines. Starting from N-tert-butyl-2-(l-alkynyl)benzaldimines and aiyl, allylic, benzylic, alkynyl halides, as well as a vinylic halide, the corresponding 3,4-disubstituted isoquinolines with aryl, allylic, benzylic, 1-alkynyl, and vinylic substituents, respectively, in the 4-position were produced in good yields. The reaetion appears to require an aiyl group on the end of the acetylene furthest from the imine functionality. 

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