Acetonide protection in presence of acid sensitive O-Protection

Acetonide protection in presence of acid sensitive O-protective group is very critical. You have to be very careful during this reaction. Usually acetonide protection has been carried out in presence of catalytic amount of p-TSA in acetone.

But when you have acid sensitive protective group such as TBDMS, TBDPS etc, donot use p-TSA more than 0.001 equivalent otherwise acid sensitive protective group does not stand any more. The best procedure is the use of 2,2'-dimethoxy propane with 0.001 equivalent p-TSA in anhydrous THF. In this procedure your acid labile protective group will be intact in excellent yield and this is the beauty of this procedure.

Reference: Organic Syntheses, Vol. 82, p. 75 (2005); Coll. Vol. 11, p.88 (2009).

Acetonide protection in presence of acid labile O-Protection

Dr RR and Dr US have performed such a reaction few times and they have interesting observations to share, I hope these observations would be useful to many new Chemists and Grad Students in Chemistry: