Question

Question. Grignard reactions are often limited by steric hindrance. While Grignard reagents react in high yield with ethylene oxide and monosubstituted epoxides, yields are often lower with disubstituted epoxides. Tri- and tetrasubstituted epoxides react with difficulty, if at all.

(a) Show how to make these alcohols by a Grignard reacting with an epoxide.

(b) These alcohols cannot be made by a Grignard plus an epoxide. Show the reagents that would be required and why that reaction would be unlikely to succeed.

Short answer

(a)

(b)

In each case, the epoxide is derived from a tetrasubstituted double bond, far too hindered for the Grignard reagent to approach.

Step-by-step solution

Step-1. Explanation of part (a):

In reaction (i), benzyl magnesium bromide on reaction with 2,2-diethyloxirane, involves the attack of carbanion on less hindered carbon of the epoxide as a result of which, epoxide ring opens and on further hydrolysis, we get our required alcohol.

In reaction (ii), the attack of Grignard reagent or carbanion occurs at less hindered carbon of the epoxide to avoid steric repulsions, and as a result, the epoxide opens up, and on further hydrolysis, we get our required alcohol.

Formation of alcohol products

In each case, the new bond is shown in bold.

Step-2. Explanation of part (b):

If the epoxide is derived from a tetrasubstituted double bond, then Grignard reagent will not be able to approach the epoxide due to steric hindrance that will be caused by groups which are attached to the epoxide. As a result, the products will not be formed.

The approach of the Grignard reagent is difficult if epoxide is hindered.