Questions: Conjugate Addition and the Michael Reaction

Question 1

Which reagent adds mainly in a conjugate (1,4) fashion to cyclohex-2-en-1-one?

• A. CH₃MgBr
• B. CH₃Li
• C. (CH₃)₂CuLi
• D. NaBH₄ with CeCl₃

Answer: (C)

Lithium dimethylcuprate, a Gilman reagent, delivers a methyl group to the β carbon, giving 3-methylcyclohexanone. Methyl Grignard and methyllithium mainly add to the carbonyl carbon, and NaBH₄ with CeCl₃ (Luche conditions) reduces the carbonyl 1,2.

Question 2

In a conjugate addition, the nucleophile forms a new bond to the carbonyl carbon.

• T. True
• F. False

Answer: False

In conjugate addition the nucleophile bonds to the β carbon. The electrons move through the C=C and onto oxygen, forming an enolate that is later protonated at the α carbon.

Question 3

The enolate of diethyl malonate adds to methyl vinyl ketone. What relationship do the new product's carbonyl groups have?

• A. 1,2-dicarbonyl
• B. 1,3-dicarbonyl only
• C. 1,5-dicarbonyl
• D. No carbonyl survives

Answer: (C)

The donor's α carbon bonds to the acceptor's β carbon. Counting from an ester carbonyl through the new bond to the ketone carbonyl gives a 1,5 relationship, the signature of a Michael product.

Question 4

Describe the two steps of a Robinson annulation and the type of product it forms.

Model answer: First, a ketone enolate adds to an α,β-unsaturated ketone such as methyl vinyl ketone in a Michael reaction, giving a 1,5-diketone. Second, an intramolecular aldol condensation closes a ring and dehydrates, giving a cyclohexenone.

The annulation combines two known reactions to build a new six-membered ring. Robert Robinson developed it, and it has been widely used in steroid and terpene synthesis.