Claisen reactions intramolecular

Crossed Claisen reactions with two different esters, each of which has a-H atoms, are seldom useful synthetically as there are, of course, four possible products. Crossed Claisen reactions are, however, often useful when one of the two esters has no a-H atoms, e.g. HCOzEt, ArC02Et, (C02Et)2, etc., as this can act only as a carbanion acceptor. Such species are in fact good acceptors, and the side reaction of the self-condensation of the other, e.g. RCH2C02Et, ester is not normally a problem. Intramolecular Claisen reactions, where both C02Et groups are part of the same molecule [e.g. (123)], are referred to as Dieckmann cyclisations. These work best, under simple conditions, for the formation of the anions of 5-, 6- or 7-membered cyclic / -ketoesters... 

Should there be two ester functions in the same molecule, then it is possible to achieve an intramolecular Claisen reaction, particularly if this results in a favourable five- or six-membered ring. This reaction is usually given a separate name, a Dieckmann reaction, but should be thought of as merely an intramolecular extension of the... 

Claisen reaction. As we have seen previously (see Section 7.9.1), intramolecular reactions are favoured over intermolecular reactions when the reaction is carried out at high dilution, conditions that minimize the interaction of two separate molecules. A simple example involving the transformation of diethyl adipate into a cyclic P-ketoester is shown. 

The intramolecular carbon-carbon bond-forming reactions considered in this section are based on the aldol condensation (see Section 5.18.2, p. 799), the Claisen-Schmidt reaction (see Section 6.12.2, p. 1032), the Claisen ester condensation (see Section 5.14.3, p. 736), and the Claisen reaction (see Section 6.12.2, p. 1032). Since these carbonyl addition reactions are reversible, the methods of synthesis are most successful for the formation of the thermodynamically stable five- and six-membered ring systems. The preparation of the starting materials for some of these cyclisation reactions further illustrates the utility of the Michael reaction (see Section, 5.11.6, p. 681). 

Scheme 32 Sequential Claisen rearrangement-intramolecular Heck reaction [84]...

Fused acenaphthylene derivative was prepared (52%) by Westphal condensation (89H2369). The reaction of l-ethoxycarbonylmethyl-2,6-di-methypyridinium salt and acenaphthenequinone in the presence of dibut-ylamine gave quinolizinium salt 241. Intramolecular Claisen reaction of 241 occurred under the reaction conditions to afford cyclazinone 242, which was treated with HBr to yield 243. 

Intramolecular Claisen reactions of dlesters form five- and six-membered rings. The enolate of one ester is the nucleophile, and the carbonyl carbon of the other is the electrophile. An intramolecular Claisen reaction is called a Dieckmann reaction. Two types of diesters give good yields of cyclic products. 

Dieckmann reaction (Section 24.7) An intramolecular Claisen reaction of a diester to form a ring, typieally a five- or six-membered ring. 

The Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a /3-keto ester product. Mixed Claisen condensations between two different esters are successful only when one of the two partners has no acidic a hydrogens (ethyl benzoate and ethyl formate, for instance) and thus can function only as the acceptor partner. Intramolecular Claisen condensations, called Dieckmann cyclization reactions, provide excellent syntheses of five- and six-membered cyclic /3-keto esters starting from 1,6- and 1,7-diesters. 

In K.C. Nicolaou s biomimetic synthesis of 1-O-methylforbesione, the construction of the 4-oxatricyclo[4.3.1.0]decan-2-one framework was achieved by using a double Claisen rearrangement that was followed by an intramolecular Diels-Alder reactionJ This one-pot biomimetic double Claisen rearrangement/intramolecular Diels-Alder reaction cascade afforded the natural product in 63% yield. 

Intramolecular Claisen reactions are known as Dieckmann reactions, and these work well to give 5- or 6-membered rings. A 1,6-diester forms a 5-membered ring, while a 6-membered ring is formed by the condensation of a 1,7-diester. 

Thermolysis of the cyanophosphorane (104.11) at about 265 °C under reduced pressure resulted in tandem intramolecular Wittig and Claisen reactions in... 

Similarly, the substitution pattern determines the rcgioselectivity in the tandem Claisen rearrangement-intramolecular Diels-Alder reaction 283. The double-bond geometry, however, is still E. 

The initial radical addition reactions can also be sequenced with a second, nucleophilic reaction. Thus radical conjugate addition and subsequent reduction leads to an enolate. Enolates thus generated can undergo a variety of reactions [8] including aldol reactions [9], Claisen condensations, intramolecular Michael reactions, and intermolecular Tischenko redox processes (Eqs. 7, 8). 

---