Ester, amide Intermolecular alkylation

With respect to the substrate scope, ketones are the most efficient nucleophiles although the intermolecular reaction works also well for esters, amides and Weinreb amides (Fig. 2.7). Regarding the Michael acceptor, enones are the best electrophiles with a wide range of substituents tolerated (alkyl, aryl and heteroaryl ketones). a,p-Unsaturated esters, in the case of the intermolecular cyclopropanation, and a,p-unsaturated diimides for the intramolecular reaction, extends the substrate scope of the process (Fig. 2.7). A transition state model for the intramolecular cyclopropanation reaction has been proposed as depicted in Scheme 2.38 for catalyst 65 [106d]. In this model the ammonium salt adopts a conformation that gives the Z-enolate of the nucleophile on deprotonation with the base. The intramolecular conjugate addition of the enolate then takes place through a boat-type transition state. 

In intermolecular cyclopropanations [100], it was found better to use a-bromoesters and amides as ylide precursors and a,/ -unsaturated ketones and esters as electron-deficient alkenes - rather than using a-haloketones as the ylide precursor. (For experimental details see Chapter 14.11.4). The reaction gives access to a range of 1,2-dicarbonyl-substituted cyclopropanes (see Fig. 10.5). The al-kene could have an aryl-, alkyl- or indole-substituted ketone, and a-substitution was also tolerated. Notably, Weinreb amides could be used as the ylide precursor and the product subsequently transformed into a diketocyclopropane. Both enan-... 

Caddick [19] has reported the use of a novel polymer-supported tetra-fluorophenol-Unked acrylate as an activated acceptor for intermolecular radical reactions. Treatment of immobiUzed acrylate 132 with a variety of alkyl iodides in the presence of tributyltin hydride and AIBN gave the corresponding esters 133 (Scheme 29). NucleophiUc cleavage using amines gave amides 134 in good overall yield whilst regenerating phenol resin 131. 

Ester- and amide-substituted radicals bearing an adjacent stereocenter abstract hydrogen with high diastereoselectivity1. The radicals are generated via intra- or intermolecular radical addition to alkenes, halogen abstraction from alkyl halides or reductive cleavage of alkylmercury compounds. Some examples are shown in Table 1. 

Ester and Thioester Formation. These reactions occur through the same O-acylurea or anhydride active intermediate as in the amide coupling reactions, and the discussion of associated problems applies here as well. In general, alkyl and (particularly) aryl thiols can be efficiently coupled to carboxylic acids using DCC. Reactions of primary and secondary alcohols proceed reliably, but require the presence of an acylation catalyst. This is usually 4-Dimethylaminopyridine (DMAP), " (see also 1,3-Dicyclohexylcarbodiimide—4-Dimethylaminopyridine), but others have been used including 4-pyrrolidinopyridine and pyridine (.solvent) with catalytic p-Toluenesulfonic Acid The acylation of more hindered alcohols often re.sults in reduced yields however, even f-butanol can be acylated, providing a useful route to t-butyl esters. Various other carbodiimide derivatives have also been used in the preparation of esters. As with amides, which are not limited to intermolecular reactions, a wide variety of lactones can also be synthesized. ... 

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