Leaving groups, Heck reactions

Brase reported an intramolecular asymmetric Heck-intermolecular Heck cascade reaction of l,3-bis(enolnonaflates) 131 to the highly congested bicyclic compound 132 [122] (Scheme 5). Although the level of asymmetric induction is low (up to 52% ee), this result shows that the concept of two leaving groups in the desymmetrization reaction can be applied. 

Other leaving groups are effective in the oxidative addition with Pd , and can lead to efficient Heck reactions. An attractive possibihty is an aniline as starting material, with in situ generation of a diazonium salt. While the oxidation of the amino group can occur with Pd° alone at elevated temperatures, dehberate addition of t-butyl nitrite leads to... 

The radical 36 can react with cupric chloride by two pathways, one of which leads to addition and the other to substitution. Even when the addition pathway is taken, however, the substitution product may still be formed by subsequent ehmination of HCl. Note that radical reactions are presented in Chapter 14, but the coupling of an alkene with an aromatic compound containing a leaving group prompted its placement here. Note also the similarity to the Heck reaction in 13-10. 

Since the Heck reaction tolerates a variety of functionalities, extensive use of protecting groups can be avoided, and thus many highly functionalized target molecules can be assembled in just a few highly efficient steps. The frequently employed elevated reaction temperatures, which may be detrimental to the yield, can be avoided, if necessary, by an appropriate choice of special additives and/or leaving groups (cf. Sections 3.2.4 and 3.2.5). 

Some effects of various leaving groups on the Heck reaction are listed in Table 3-6. 

Choice of leaving group Modified Conjugate Addition The Heck Reaction... 

The Heck reaction can be used to couple alkenyl, aryl, allyl (the intramolecular Heck reaction on aUyUc substrates is called a palladaene reaction),f ° t f benzyl, methyl, alkoxycarbonyhnethyl, alkynyl, certain alkyl, and silyl fragments to a variety of alkenes. The nature of the leaving group greatly affects the reaction rate aryl iodides react faster than bromides, and aryl chlorides are notoriously unreactive unless special catalysts or ligands and elevated temperatures are used to enhance the reaction rate. This has been taken to indicate that the oxidative addition of the haloarene (haloalkene) to pal-ladium(O) is the rate-determining step. " It has been shown that the Heck reaction can be performed with aryldiazonium salts, A -nitroso-Af-arylacetamides, and hy-pervalent iodo compounds " at room temperature. 

Heck reactions of allylalcohols, with the involvanent of neutral intermediates and more strongly coordinating leaving groups, alternatively provided aldehydes or ketones, as a result of H /3-elimination or double bond migration by hydridopalladium leaddition/elimination to give unstable enols (Sect. B.vii). 

True base-free Mizoroki-Heck reactions should not be mistaken with base-free Mizoroki-Heck reactions of such special substrates as acid anhydrides, in which it is the leaving carboxylate group which serves as base [15] this reaction benehts from hahde additives [16]. 

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