Squaric acid 4-hydroxy-2-cyclobutenone

Derivatization of Squaric Acid to 4-Hydroxy-2-Cyclobutenone Skeleton. . 3... 

There are several approaches for derivatization of squaric acid (1). The traditional major route relies on the nucleophihc reaction of the eligible esters 5 with organolithium and organomagnesium reagents their addition to 5 is known to be sufficiently selective to give 1,2-addition products 6 (4-substituted 4-hydroxy-2-cyclobutenones) from the former and... 

Apart from these methods based on the squaric acid family, direct formation of cyclobutenedione rings by [4 + 2] and [2 -i- 2] cycloaddition reactions is a plausible approach to variably substituted 4-hydroxy-2-cyclobutenone systems [47-54]. 

The intrinsic reactivity of small rings is ascribable to ring strain relief in nature, and in squaric acid chemistry it is accomplished by conversion of rather stable cyclobutene-1,2-dione to the more reactive 4-hydroxy-2-cyclobutenone [55,56] as described in the previous section. At the same time, this conversion step fulfills the regiospecific introduction of substituents required for the targeted heterocychc structure. Thereby, the set-up four-membered ring is now subjected to directed synthesis through variable ring transformation reactions. 

Thermal ring expansion of polysubstituted 4-hydroxy-2-cyclobutenones, which can be prepared from squaric acid ester (see the previous section), has been extensively studied and its synthetic value has now been confirmed. The early works have been reviewed several times for the cases of cyclobutenones that have unsaturated bonds at the 4-position, such as (cyclo)alkenyl, alkynyl, and aromatic groups [19-23]. 

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