Cyclobutenones electrocyclic ring opening

An unusual synthesis of ( )-septicine (866) from dimethyl squarate (878) exploits rearrangement of a 4-(l-pyrrolo)cyclobutenone 879 to the indolizine-5,8-dione 880, presumably via a ketene intermediate formed by electrocyclic ring opening of 879 (Scheme 113) (584). Partial reduction of 880 yielded the 4-hydroxypyridone 881, the triflate ester of which was deoxygenated with a palladium(II)-formic acid system to yield the l,2,3,5-tetrahyi oindolizin-5-one 882. Mild reduction with aluminum hydride completed the synthesis of ( )-866 in an excellent overall yield of 27% from 878. 

As a matter of fact, the above preparative reaction to obtain the framework of bicyclo[ 3.2.0 ]heptenone is already in hand. Indeed, the ring closure step after electrocyclic ring opening of 4-hydroxy-2-cyclobutenone is not limited to fully conjugated systems synthetic variants are realizable with other prox-imally placed ketenophUes. When an allyl group was located at C-4, the ketene underwent an intramolecular [2 + 2] cycloaddition reaction with this double bond to give the bicyclo[3.2.0]heptenone derivatives [111, 112[. 

An analogous vinylketene intermediate (127, see Schemes 57 and 59) as proposed for the Dotz reaction has been assumed in the so-called cyclobutenedione methodology [161]. The key intermediate is a 4-aryl or 4-alkenyl substituted 2-cyclobutenone (128) that can be obtained e.g. by the reaction of the 3-cyclo-butene-1,2-dione (129) with the appropriate lithium reagent or Stille coupling with 4-chloro-3-cyclobutenone. Thermal cyclobutenone ring opening to the vinylketene 130 followed by electrocyclization furnishes the highly substituted aromatic compound 131 (see Scheme 59). 

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