Mukaiyama aldol reaction template

TiCl₄ binds benzaldehyde; the silyl enol ether of cyclohexanone attacks the activated carbonyl, chloride takes the silyl group and aqueous work-up releases the β-hydroxy ketone.

Mechanism step by step

A silyl enol ether adds to an aldehyde activated by TiCl₄: a crossed aldol with no base

1. Lewis acid activation – The aldehyde oxygen donates to titanium: a very electrophilic carbonyl
2. C–C bond formation – The silyl enol ether (an enol equivalent) attacks: a silyloxocarbenium ion and a titanium alkoxide
3. Desilylation and work-up – Chloride from titanium takes the silyl group (Me₃SiCl); water then frees the β-hydroxy ketone

Key points

• A crossed (directed) aldol: the silyl enol ether is a neutral, isolable enol equivalent, so neither partner self-condenses.
• The Lewis acid (TiCl₄, BF₃·OEt₂, SnCl₄) activates the aldehyde; no base or metal enolate is involved.
• Open (acyclic) transition state: the syn/anti ratio depends on the substrates and Lewis acid, not on the enol ether geometry (unlike the Zimmerman–Traxler chair).
• Chiral Lewis acids make catalytic asymmetric versions; the silyl enol ether is made regioselectively (kinetic: LDA then Me₃SiCl; thermodynamic: Et₃N, Me₃SiCl).

Drawn with 128 atoms, 8 arrows, 7 shapes – every one editable in MolDraw.

Sources

• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 26 Textbook
• Kürti & Czakó, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier 2005 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 16 Textbook