Free radical 5-exo-dig cyclization as the key step in the synthesis of bis-butyrolactone natural products: experimental and theoretical studies

Gangavaram V. M. Sharma, Devoju Harinada Chary, Nagula Chandramouli, Florian Achrainer, Sateesh Patrudu, Hendrik Zipse
2011 Organic and biomolecular chemistry  
Radical cyclization reactions were performed by 5-exo-dig mode to yield cis-fused bicyclic systems, leading to the synthesis of bis-butyrolactone class of natural products. The study was aimed at understanding the impact of alkyl side chains of furanoside ring systems in L-ara configuration on the radical cyclization. It was amply demonstrated by experimental studies that the increase in the length of the alkyl side chain has an effect on the cyclization: while efficient cyclization reactions
more » ... uld be realized with methyl and ethyl side chains, the yields were significantly reduced in the case of n-pentyl side chain. Theoretical studies using DFT and (RO)MP2 methods were carried out to analyze the influence of the substitution pattern on the cyclization barriers. Scheme 1 Retrosynthetic analysis of 1-5 and 9. derivative 11, 9c met with failure and the synthesis of 9 could not be achieved by the above protocol. Results and discussion The successful synthesis of 1-5 (Scheme 1), and failure to attain 9 inferred that: (a) the systems with D-xylo configuration undergo a facile cyclization and (b) the systems with L-ara configuration resisted doing so. The above observations on the resistance of 10 to undergo radical cyclization prompted us to study the impact of the side chain on radical cyclization reactions. Based on the retrosynthetic analysis (Scheme 2), synthesis of cis-fused bicyclic systems 12a-12c and 13a-13c could be achieved through the This journal is Scheme 4 5-Exo-dig cyclizations in selected systems derived from the tetrahydrofuran skeleton. 4080 | Org. Biomol. Chem., 2011, 9, 4079-4084 This journal is
doi:10.1039/c1ob00019e pmid:21494735 fatcat:34o5eijnnjcaji6mfwjmnznfmq