OXYXOR(PO)nOXYXOR(PO)nOR(PO)nhexoseor pentose123
Scheme 1. Retrosynthetic analysis.
According to this, a polyhydroxylated carbocycle-dihydropyran fused ring system 1 could be obtained applying a Knoevenagel condensation of d,e-unsaturated aldehydes 3 with appropriate 1,3-dicarbonyl components to form intermediates 2, followed by an intramolecular hetero Diels- Alder cycloaddition reaction. In turn, aldehydes 3 could be synthesized from an hexose or a pentose.
Results and Discussion
To investigate the feasibility of our plan we chose to perform our reactions with three extensively studied 1,3-dicarbonyl compounds: N,N-dimethylbarbituric acid, 4, Meldrum’s acid, 5, and dimedone, 6, (Figure 1) are readily available symmetrical reagents, which were often employed in DKHDA reactions with good results.7
OOOOOONNOOO654
Figure 1. Structures of selected 1,3-dicarbonyl components for DKHDA reactions.
The required d,e-unsaturated aldehydes 8 (Scheme 2) and 14 (Scheme 3) were prepared from the corresponding iodide 7 and alcohol 13, respectively, and used without isolation in the domino reactions. Precursors 7 and 13 are derivatives of D-glucose and D-ribose; easily accessible following well established procedures.14e
Tietze’s general protocol8d which involves catalysis of ethylenediamine diacetate (EDDA) and the presence of a dehydrating agent was followed using initially the most reactive of the 1,3- dicarbonyl compounds shown in Figure 1, barbituric acid derivative 4. Reactions were found to proceed smoothly under refluxing conditions in acetonitrile with both sugar derived candidates affording the desired cycloadducts in average overall yields from iodide 7 and alcohol 13 (Scheme 2 and Scheme 3).
