LACDAC

The Lewis acid catalyzed diene-aldehyde cyclocondensation (LACDAC) reaction is a fast procedure to obtain dihydropyrones such as 28.4... 

LACDAC Lewis acid catalyzed diene-aldehyde cyclocondensation... 

A particularly elegant example is the application of Danishefsky s diene [107] to the total synthesis of carbohydrates and carbohydrate derivatives. While it was known that activated aldehydes undergo cycloaddition with electron-rich dienes, the process was not efficient with typical aldehydes under thermal conditions. A major breakthrough was realized [108] with the development of the Lewis acid-catalyzed diene-aldehyde cyclocondensation (LACDAC) reaction, which provided a new strategy for the synthesis of carbohydrates and other polyoxygenated natural products (Scheme 1.4) [109],... 

Initially, the de novo synthesis of enantiomerically pure carbohydrates [110] and glycolipids [111] using transition metal complexes and chiral auxiliaries afforded only modest success. Ultimately, it was the use of enantiomerically pure aldehydes, such as the R and S enantiomers of 2-(phenylseleno)propionaldehyde, to convey facial selectivity upon the LACDAC reaction that enabled the synthesis of optically pure glycals. Syntheses of several complex monosaccharides such as the main sialic acid-type N-acetylneuraminic acid (Neu5Ac) and rac-3-deoxy-ma o-2-octulosonic acid (KDO) were accomplished with this technology [112, 113], The LACDAC... 

SCHEME 1.4 Enantioselective synthesis of L-glucose via the LACDAC reaction, hfc, 3-(heptafluoropropylhydroxymethylene)-D-camphorato TBS, ferf-butyldimethylsilyl. 

SCHEME 1.5 LACDAC reaction in the total synthesis of Neu5Ac. Bz, benzoyl TMS, trimethylsilyl. 

The 6,6-spiroketal system of the northern segment was constructed via their developed LACDAC reaction and oxidative cyclization at C21 (Scheme 63). 

The first total synthesis of epothilone A (5a) was accomplished by Danishefsky et al. [142a,c,d] based on macroaldol reaction for the construction of the macro-cyclic ring (Fig. 9). The synthetic feature includes stereoselective synthesis of the C3-C11 segment based on their LACDAC reaction, Suzuki coupling with the C12-C21 segment, and unique intramolecular macroaldolization at the C2 and C3 positons. 

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