Effect of high pressure on Biginelli reactions. Steric hindrance and mechanistic considerations

The effect of high pressure is examined in 3-CC Biginelli reactions. This effect is small when moderately hindered aldehydes or ureas are involved. However, particularly in the case of bulky aldehydes, the sensitivity of the reaction to pressure increases with increasing steric congestion in line with earlier studies described in the reference list. The results also provide insights into the mechanism. Such a result highlights the synthetic utility of high pressure activation for the preparation of hindered Biginelli products.