Stereoselective Aldol Additions of Glycolic Acid and Its Derivatives

Abstract

This review gives a comprehensive overview of aldol additions of glycolic acid derivatives to achiral aldehydes and acetals affording α,β-dihydroxycarboxylic acids or derivatives thereof. The focus is on simple diastereoselectivity. A selection of related aldol additions is also presented: aldol additions of glycolic acid derivatives to ketones with two different substituents and aldol additions of α-substituted glycolic acid derivatives.1 Introduction1.1 Organization of this Review1.2 Outside the Scope of this Review: Aldol Additions Giving α,β-Dihydroxyaldehydes and α,β-Dihydroxyketones Diastereoselectively1.3 Non-Aldol Routes to Diastereomerically Pure α,β-Dihydroxycarboxylic Acid Derivatives2 Aldol Additions of Glycolic Acid (Derivative) Enolates to Aldehydes2.1 Aldol Additions of Glycolate Enolates (‘Glycolic Acid Dianions’)2.2 Aldol Additions of Glycolic Ester Enolates2.3 Aldol Additions of Glycolic Thioester Enolates2.4 Aldol Additions of Glycolimide Enolates2.5 Aldol Additions of Glycolamide Enolates2.6 Mukaiyama Aldol Additions of Silyl Ketene Acetals of Glycolic Esters­ and Thioesters2.7 Aldol Additions of Glycoloyl Chlorides via Acyl Ammonium Enolates3 Aldol-Providing Substitutions of Glycolimide Enolates in Acetals4 Additions Related to Aldol Additions of Glycolic Acid Derivative Enolates to Aldehydes4.1 Selected Simply Diastereoselective Aldol Additions of Enolates of Glycolic Acid Derivatives to Ketones with Two Different Substituents4.2 Simply Diastereoselective Aldol Additions of Enolates of Glycolic Acid Derivatives with a Methyl Substituent at C-α (Lactic Acid Derivatives)5 Conclusion

Stereocontrolled Aldol-Like Reactions Involving Oxocarbenium Intermediates

“…Remarkably, the method tolerated the introduction of an oxygenated substituent at the Cα position of the acyl group (Eq 3 in Scheme 15 ). 34 35 As a result of a thorough scrutiny of the Cα alcohol protecting group, we found that α-pivaloyloxy thioimide 62 was particularly suitable for such a glycolate aldol reaction. As shown in Scheme 15 , dimethyl acetals of aromatic and α,β-unsaturated aldehydes reacted with the titanium enolate of 62 in the presence of BF 3 ·OEt 2 at –78 °C, whereas dialkyl acetals from aliphatic aldehydes, less likely to generate the necessary oxocarbenium intermediate, required SnCl 4 and a higher temperature (Scheme 15 ).…”

Diastereoselective and Enantioselective Synthesis of α-p-Methoxyphenoxy-β-Lactones: Dependence on the Stereoelectronic Properties of the β-Hydroxy-α-p-Methoxyphenoxycarboxylic Acid Precursors

“…Koreeda and Luengo applied a similar strategy in the pursuit of the formation of diastereomerically pure ( Z )- and ( E )-1-alkoxy-1,3-butadienes using a glycolate aldol addition strategy . This strategy was successful but was limited by low diastereoselectivities (d.r.…”