Glycolate aldolization

A new phase-transfer catalyzed asymmetric glycolate aldol reaction was reported that provides diols in low to good yields, high de, and moderate to good ee as illustrated in Scheme 37. The recystalhzation of diol products could enrich the ee to 95%, additionally, the authors used 128 (R = Ph) to synthesize a known (S TJydiol methyl ester to show utility of this new method <05OL3861>. 

SYNTHESIS OF GELDANAMYCIN USING GLYCOLATE ALDOL REACTIONS... 

Development of Anti-Selective Glycolate Aldol Methodology Based on the 2,3-Diaryl t,4-Dioxan-5-one Template 47... 

Key to this synthetic effort is the development of two new asymmetric glycolate aldol methods, used to set the syn C6-7 and anti C11 -12 hydroxy-methoxy functionality. Problems associated with the methoxyquinone formation will also be discussed along with a general solution using a 1,4-diprotected precursor. 

The f.Z-diene of the seco acid 2 would result from Horner-Emmons and Wittig reactions from aldehyde 3 (Scheme 2). The trimethoxyaniline functionality is carried along as a stable nitrobenzene that would be unmasked at a late stage prior to macrolactam formation. The syn methoxy-hydroxy functionality at C6-7 in 3 is installed using the newly developed glycolate aldol reaction with enal 4 and norephedrine glycolate ester auxiliary 5. This new method is an application of Masamune s recent work with propionate norephedrine aldol reactions.The CIO methyl is installed using the aforementioned hydroboration reaction,... 

The new auxiliary developed for the syn glycolate aldol, needed for the C6,7 functionality, was based on Masamune s norephedrine... 

Denmark SE, Chung W-J (2008) Lewis base activatimi of lewis acids catalytic enantioselective glycolate aldol reactions. Angew Chem Int Ed 47 1890-1892... 

M.T. Critnrnins, J. She, Enantioselective total synthesis of (+)-gigantecin exploiting the asymmetric glycolate aldol reaction, J. Am. Chem. Soc. 126 (2004) 12790-12791. 

The synthetic utility of this process was enhanced by the development of the glycolate aldol reaction as illustrated in Scheme 7.6. An important feature was that both syn- and anti-1,2-diols could be obtained under identical conditions by appropriately modulating the steric size of the substituents on the silyl ketene acetals [8]. 

Furthermore, N-silyl oxyketene imines derived from protected cyanohydrins were found to serve as acyl anion equivalents in a similar reaction manifold, enabling the efficient preparation of cross-benzoin and glycolate-aldol products in an almost stereochemically pure form (Scheme 7.11) [18]. 

N-proteded ester 611 -Schiff bases 367,369 glycolate aldol reaction 164 glycolysis 795... 

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