Double Claisen

This double Claisen-Schmidt reaction takes place under the influence of ethano-lic potassium hydroxide (Expt 7.7) and presumably proceeds in the stepwise manner (cf. formulation in Section 6.12.2, p. 1032). The four aryl groups in tetra-cyclopentadienone effectively stabilise the cyclopentadienone system, which otherwise has only a transient existence and readily undergoes dimerisation by way of a diene-dienophile interaction (Diels-Alder reaction, Section 7.6). The use of tetracyclone as a dienophile for the preparation of 3,4,5,6-tetraphenyl-dihydrophthalic anhydride is noted on p. 1121. 

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. 

The unsaturated angelate ester (7) has been isolated from Brichellia guate-maliensis Complete details of the double Claisen-Cope rearrangement... 

A number of syntheses of hydroxyphthalate, isophthalate and terephthalate systems have been devised. The double Claisen condensation of malondialdehyde with diethyl 3-oxoglutarate which results in 2,6-diethoxycarbonylphenol, represents the simplest approach to this type of structure although the moderate yield of 41% is the lowest of a series with different substituents based on this methodology (ref.48). 

Double Claisen condensation Intermolecular follovs eil by iniramoleeiilar Clai-.sen conclensulion, giving cyclic products. 

A few solvent-free examples of Claisen rearrangement reactions under the action of microwave irradiation have been described. One involves the double Claisen rearrangement of bis(4-allyloxyphenyl)sulfone into bis(3-allyl-4-hydroxy-phenyl)sulfone (Scheme 8.43) [111]. Similarly, 3 -allyl-2 -hydroxyacetophenone has been obtained in quantitative yield from 2 -allyloxyacetophenone by Bennett et al. [112]. 

P.S., and Tilve, S.G. (2009) Cascade wittig reaction-double claisen and cope rearrangements one-pot synthesis of diprenylated coumarins gravelliferone, balsamiferone, and 6,8-diphenylumbelliferone. Tetrahedron Lett, 50,6488-6490. 

Using the approach illustrated in (a), we can analyze this target retrosynthetically in the context of ring-formation by double Claisen condensation ... 

Hexane-1,3,4,6-tetraones 207, easily available from the double Claisen condensation of methyl ketones and diethyl oxalate (MeONa in ether) (Waring et al. 2002), react with 1,2-DABs 155a, n and (1 ,1 )-1,2-DACH 171b in refluxing EtOH in the same way as a-diketones, resulting in symmetrically substituted quinoxalines 208, 209 and a dissymmetrically substituted quinoxaline 210, all bearing two ketonic arms (Scheme 2.15) (Waring et al. 2002). 

Each of the following pairs of compounds undergoes a double Claisen condensation in methanol and sodium methoxide to form a structure containing a second fused ring. Draw the structure of the product of each reaction. 

SCHEME 21.6. Double Claisen cascade for the synthesis of artochamin F. 

---