Birch Reduction of Arenes as an Easy Entry to γ‐Spirolactones

Abstract

In memory of Klaus HafnerA convenient method for the synthesis of γ-spirolactones in only 2-3 steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of ethylene oxide affords hydroxy acids, which undergo direct lactonization during work-up. Suitable precursors are methyl-substituted benzoic acids, naphthoic, and dicarboxylic acids. Subsequent hydrogenation proceeds smoothly with Pd/C as catalyst and saturated γ-spirolactones are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation with Raney nickel or Wilkinson's catalyst to obtain products with 1 double bond. Overall, more than 30 new γ-spirolactones have been synthesized in analytically pure form.

Photochemistry of β-γ-Unsaturated Spirolactones

“…The dihedral angle between the two double bonds fits well for metal coordination, which is not possible with 1,4-cyclohexadiene (1), as it prefers a more planar geometry [1]. During our studies on Birch reductions of aromatic carboxylic acids (9) [13][14][15][16], we developed an easy entry to γ-spirolactones 11 in the presence of ethylene oxide (10) (Scheme 2) [17]. The reactions can be performed on a large scale and the yields are high.…”

“…During our studies on Birch reductions of aromatic carboxylic acids (9) [13][14][15][16], we developed an easy entry to γ-spirolactones 11 in the presence of ethylene oxide (10) (Scheme 2) [17]. The reactions can be performed on a large scale and the yields are high.…”

“…After optimization of the reaction conditions, we became interested in the photochemistry of other β-γ-unsaturated spirolactones 11. We investigated dimethyl 11b and naphthyl 11c derivatives, both easily available through Birch reduction of the corresponding aromatic carboxylic acids in the presence of ethylene oxide [17], and compared it with lactone 11a (Scheme 5). Again, we observe only the oxa-di-π-methane rearrangement, apart from the formation of higher molecular weight material, and it was advantageous to stop the reactions at lower conversions.…”