On the Formation of 2‐Sulfonylbenzo[a]heptalene‐1,3‐diols as Precursors for the Synthesis of Colchicinoids

The benzoa]heptalene formation from 4‐(R‐sulfonyl)acetyl]heptalene‐5‐carboxylates 15 and 5‐(R‐sulfonyl)acetyl]heptalene‐4‐carboxylates 16 (R=Ph or morpholino) in the presence of R′SO₂CH₂Li and BuLi has been investigated (Scheme 6). Only the sulfonyl moiety linked to the C?O group at C(4) of the heptalene skeleton is found at C(3) of the formed benzoa]heptalene‐2,4‐diols 3 in accordance with the general mechanism of their formation (Scheme 3). Intermediates that might rearrange to corresponding 2‐sulfonylbenzoa]heptalene‐1,3‐diols lose HO^? under the reaction conditions to yield the corresponding cyclopentad]heptalenones of type 11 (Schemes 6 and 7). However, the presence of an additional Me group at C(α) of the lithioalkyl sulfones suppresses the loss of HO^?, and 4‐methyl‐2‐sulfonylbenzoa]heptalene‐1,3‐diols of type 4c have been isolated and characterized for the first time (Schemes 8 and 10). A number of X‐ray crystal‐structure analyses of starting materials and of the new benzoa]heptalenes have been performed. Finally, benzoa]heptalene 4c has been transformed into its 1,2,3‐trimethoxy derivative 23 , a benzoa]heptalene with the colchicinoid substitution pattern at ring A (Scheme 11).