The ketones also develop a partial positive charge at the carbonyl carbon, thus helping them to be more effective heterodienophiles (Figure 1). For the first time, it was proven experimentally that a simple ketone could be a starting material for a hetero-Diels-Alder reaction. Huang and Rawal studied hetero-Diels-Alder reactions between various simple ketones and 1-amino-3-siloxybuadiene in polar protic and polar aprotic solvents. After the completion of the hetero-Diels-Alder reaction and successive elimination of the amino group with acetyl chloride, they concluded that the product yield was the highest when a polar protic solvent containing a non-shielded alcohol group was utilized. 2-butanol was found to be the most efficient solvent for this reaction (1).
Figure 1. A simple ketone hydrogen bonded to the polar protic solvent. The carbonyl carbon develops a partial positive charge, thus helping it to be a more effective heterodienophile. The resulting hetero-Diels-Alder reaction is shown which is more effective than a ketone that does not participate in hydrogen bonding.
Several mechanisms could be proposed for this reaction, and two are shown. The first is that of the concerted hetero-Diels-Alder reaction. The concerted mechanism involves the diene and the heterodienophile reacting together in one step to form a product. The amino group on the cyclic product is then protonated by the acetyl chloride. The acetyl chloride then removes the TBS group, thus causing the carbonyl to form and the electrons in the double bond to move to the next carbons, thus pushing out the amine as a leaving group (Figure 2).
Figure 2. The concerted hetero-Diels-Alder mechanism.
A second possible mechanism would be a step-wise hetero-Diels-Alder mechanism. The diene first attacks the carbonyl carbon, forming a carbocation intermediate. The oxyge View More »