- Draw the products for each of the following reactions for compound A. Indicate which is the kinetic and which is the thermodynamic product (6 points). 1)
2)
1)
2)
The Correct Answer and Explanation is:
Reaction Products
1. Reaction with CH₃MgBr (Methylmagnesium bromide)
The product of this reaction is a tertiary alcohol, formed by the addition of the methyl group directly to the carbonyl carbon.
This is the Kinetic Product.
2. Reaction with (CH₃)₂CuLi (Lithium dimethylcuprate)
The product of this reaction is a ketone, formed by the addition of the methyl group to the beta-carbon of the double bond within the ring.
This is the Thermodynamic Product.
Explanation
The starting material, an α,β-unsaturated ketone, possesses two electron-deficient sites for a nucleophile to attack: the carbonyl carbon (position 2) and the β-carbon of the double bond (position 4). The choice of nucleophile determines which site is attacked.
The first reaction uses a Grignard reagent (CH₃MgBr). The methyl group in a Grignard reagent is a “hard” nucleophile, meaning its charge is concentrated and it is highly reactive. Hard nucleophiles preferentially attack the “harder” electrophilic site, which is the carbonyl carbon due to the large partial positive charge induced by the highly electronegative oxygen atom. This direct attack on the carbonyl is known as 1,2-addition. This reaction pathway has a lower activation energy and proceeds more rapidly. The resulting product is therefore known as the kinetic product, as it is the one that forms the fastest.
The second reaction employs a Gilman reagent, or organocuprate, ((CH₃)₂CuLi). The methyl group in this reagent is a “soft” nucleophile, with a more diffuse and polarizable charge. Soft nucleophiles prefer to attack “softer” electrophilic centers like the β-carbon of the conjugated system. This attack is called 1,4-conjugate addition. While this reaction is slower, it leads to a more stable final product. The stability comes from preserving the very strong carbon-oxygen double bond while breaking the weaker carbon-carbon double bond. Because this pathway yields the most stable, lowest-energy product, it is referred to as the thermodynamic product.
