Thermal Concerted Process

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].

Especially, directed synthesis of heterocycles is feasible by placing heteroatoms such as nitrogen and oxygen at the appropriate position. When hetero double bonds are located at the 4-position, tandem 4n-6n electro-cyclic reactions (Fig. 3) can afford six-membered heterocycles. This is the case for a C = O bond to give a-pyrone. Thus, treatment of cyclobutenedione [e.g., 5 (R = i-Pr)] at - 78 °C with O-TBDMS-cyanohydrin/LiHMDS followed by low-temperature quench and workup directly gave a-pyrone 41, which is often found in bioactive compounds [37,78]. A particularly interesting aspect is the ability of the intermediate 4-acylcyclobutenone 40 to rearrange to 41 at or below room temperature as most ring expansions of 4-aryl or 4-vinylcyclobutenones require heating at higher than 100 °C. This is attributed to greater polarization of the C = O bond (Scheme 7).

0 0

Post a comment