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Updated: May 19, 2026

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Substrate-controlled stereoselectivity in the Yamamoto aldol reaction
Nadin Schläger1, Andreas Kirschning
1Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Schneiderberg 1b, 30167 Hannover.
Abstract:
The Yamamoto aldol reaction is a vinylogous aldol reaction that relies on bulky aluminium-based Lewis acids. These activate both the aldehyde as well as become part of the enolate moiety. The report discloses the first detailed study on the substrate-controlled Yamamoto aldol reaction in which 2,3-syn and 2,3-anti disubstituted aldehydes serve as the stereodirecting elements. The "size" of the substituent in the β-position strongly determines the facial selectivity of enolate addition to the aldehyde. Large substituents favour formation of 1,3-syn diols while slim alkynyl groups preferentially lead to 1,3-anti products.
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