Cuprate 1,4- vs Grignard 1,2-addition template

Lithium dimethylcuprate adds to the β-carbon of cyclohex-2-enone (conjugate addition) and work-up gives 3-methylcyclohexanone; methylmagnesium bromide adds directly to C=O to give 1-methylcyclohex-2-en-1-ol.

Mechanism step by step

Soft Me₂CuLi adds to the β-carbon of an enone; hard MeMgBr adds to the C=O carbon

1. Cuprate: 1,4-addition – Simplified: Me goes to the β-carbon, giving the enolate (accepted path: π-complex, then Cu(III), then reductive elimination); Li⁺ not drawn
2. Work-up – The enolate takes H⁺ at carbon: 3-methylcyclohexanone
3. Grignard: 1,2-addition – The hard C–Mg nucleophile attacks the C=O carbon directly
4. Work-up – The alkoxide is protonated: an allylic tertiary alcohol

Key points

• Grignard and organolithium reagents are hard: fast, irreversible attack at the carbonyl carbon, which carries the most positive charge (1,2-addition).
• Cuprates are soft and add at the β-carbon (1,4- or conjugate addition); a few mol% CuI turns RMgX into a 1,4-reagent too.
• Me₂CuLi (from 2 MeLi + CuI) transfers only one methyl group; MeCu is thrown away. Accepted mechanism: Cu(I) forms a π-complex with the C=C, oxidative addition gives a Cu(III) enolate, and reductive elimination forms the C–C bond.
• The enolate from conjugate addition can be trapped by an electrophile (e.g. CH₃I) before work-up, adding two groups across the C=C.

Drawn with 93 atoms, 15 arrows, 9 shapes – every one editable in MolDraw.

Sources

• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 22 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 15 Textbook