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

Abstract

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 could 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.

Efficient Synthesis of (-)-Osmundalactone and Its Epimer from Carbohydrate Precursor

“…As shown in Scheme 2, the synthesis commenced with the readily available PMB ethers 9 [29,30] derived from Larabinose 7. The PMB ether 9 was subjected to hydrolysis with 60% aq.…”

Modular Synthesis of Cyclic β-Difluoroamines

“…The exo-cyclisation has a barrier of 8.3 kcal/mol (Figure 3) which is consistent with related processes. 25 Possible C-H functionalisation products arising from oxidation of either the amine substrate or product were absent. This is due to the negative inductive effect of the β-difluoro group which substantially alters the redox potential of both compounds, thereby preventing C-H functionalisation adjacent to nitrogen.…”

Modular synthesis of cyclic β-difluoroamines

“…3) which is consistent with related processes. 25 Possible C–H functionalisation products arising from oxidation of either the amine substrate or product were absent. This is due to the negative inductive effect of the β-difluoro group which substantially alters the redox potential of both compounds, thereby preventing C–H functionalisation adjacent to nitrogen.…”