Three-Carbon Dowd−Beckwith Ring Expansion Reaction versus Intramolecular 1,5-Hydrogen Transfer Reaction:  A Theoretical Study

• Published in: Journal of organic chemistry Vol. 70; no. 23; pp. 9417 - 9423
• Main Authors: Ardura, Diego, Sordo, Tomás L
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.11.2005; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Chemistry, Organic; Exact sciences and technology; Free radicals chemistry; Organic chemistry; Physical Sciences; Preparations and properties; Reactivity and mechanisms; Science & Technology; DENSITY; REARRANGEMENT; EXCHANGE; Solvent effect; Intramolecular reaction; Chemical rearrangement; Theoretical study; Ketone; Energy barrier; Ring expansion; Transfer reaction; Solvation; Steric effect; Organic free radical; Density functional method; Carboxylic acid esters; Cyclopentane derivatives; Conformation
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo051551g

The evolution of the primary radicals formed by addition of AIBN/HSnBu3 to methyl 1-(3-iodopropyl)-5-oxocyclopentanecarboxylate, methyl (1R*,2R*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate, and methyl (1R*,2S*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate in benzene has been theoretically investigated by ROMP2/6-311++G(2d,2p)//UB3LYP/6-31G(d,p) calculations taking into account the effect of solvent through a PCM−UAHF model. According to the theoretical results, for methyl 1-(3-iodopropyl)-5-oxocyclopentanecarboxylate and methyl (1R*,2S*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate the major product is the cyclooctane derivative from the three-carbon ring expansion, whereas for methyl (1R*,2R*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate the major product is that corresponding to the 1,5-H transposition in agreement with the experimental findings. This different behavior is a consequence of several factors determining the relative energy barriers. The methyl substituent destabilizes the ring expansion process for methyl (1R*,2R*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate because of steric repulsion but favors it in the case of the β-trans-substituted substrate because it makes possible the evolution of the system along more favorable conformations. The methyl group also favors the 1,5-H transposition rendering the transposed product a tertiary radical. The second stage of the ring expansion process is stabilized by resonance.