Synthesis of novel alkaloids using squaric acid esters

Abstract

A novel route to cyclopenta[b]quinoline-1-ones and-ols has been developed. Substituted cyclopenta[b]quinolin-1-ones were prepared by thermal ringexpansion of substituted N-BOC protected 4-(2-aminophenylethynyl)-4-hydroxy-2-cyclobuten-1-ones forming the corresponding 2-aminophenylmethylidene substituted 4-cyclopentene-1,3-diones. Deprotection of the amine resulted in spontaneous condensation to give cyclopenta[b]quinolin-1-ones. Sodium borohydride reduction of these products produced cyclopenta[b]quinolin-1-ols. The key step in the sequence is a thermally induced ring-expansion of 4-(2aminophenylethynyl)-4-hydroxy-2-cyclobuten-1-ones. Changing the amino protecting group had no effect on the ring size selectivity of the thermal ring expansion. The thermal ring expansion of the corresponding nitro derivative suggests that electron withdrawing substituents may alter the selectivity of the ring formation. The attempted base mediated, copper mediated, copper catalyzed and palladium catalyzed indolization reaction were not further examined since the desired products were not obtained. The N-iodosuccinimide, N-chlorosuccinimide mediated and palladium catalyzed ring expansion reactions Part I A Novel Entry to Cyclopenta[b]quinolines via Thermal Ring-Expansion of (2-Aminophenyl)-Ethynyl-Substituted Cyclobutenone Derivatives