Question

Using protecting groups, show how estrone can be converted to ethynylestradiol, a widely used oral contraceptive.

Short answer

Answer

Estrone can be converted to ethynylestradiol by the following method:

Step-by-step solution

Step-by-Step Solution Step 1: Definition of protecting and deprotecting groups

Protecting groups are reagents added to a compound whose functional group doesn’t interfere with another for undergoing a chemical reaction;for example, TBDMS-Cl.

Deprotecting groups are reagents that cause deprotection of the functional group that is protected;for example, Bu₄N^-F⁺.

Use of protecting and deprotecting groups

When both carbonyl and alcoholic groups are present, then on the addition of the organolithium, an acid-base reaction occurs where organolithium acts as a base which abstracts a proton from the alcohol group, rather than acting as a nucleophile and attacking the carbonyl carbon center. So, TBDMS-Cl is used here to protect the alcohol group from causing interference.

TBDMS-Cl has a leaving group Cl, so alcoholic oxygen can easily attack the Si center of TBDMS-Cl when any nitrogenous base like imidazole and pyridine is used. This causes protection of the alcoholic group.

When TBDMS-Cl is used as a protecting group, Bu₄N^-F⁺ is used for the deprotection. Bu₄N^-F⁺ has a fluoride component with a high affinity for Si and hence attacks the Si center of OTBMS to form TBMS-F.

The following reaction is provided to show the utility of the protecting and deprotecting groups:

Representation of protecting and deprotecting techniques to obtain products