New Silyl Ether Reagents for the Absolute Stereochemical Determination of Secondary Alcohols

Abstract

[reaction: see text] Herein we report a new set of silyl ether reagents for determining the enantiomeric purity and absolute stereochemistry of secondary alcohols. These derivatives are easily synthesized, provide straightforward spectroscopic results, and allow for facile recovery of the original chiral alcohol.

Synthesis of Chiral Bridled Porphyrins in their Two Enantiomeric Forms

“…These two compounds were easily separated by column chromatography on basic alumina. The absolute configuration of the enantioenriched alcohol was established by a published NMR procedure [9] and is in agreement with the enantioselectivity of Amano PS lipase established by Kazlauskas. [8] The NMR method enabled quantification of the ee value, which was found to be 80 % for (S,S)-3. Next, (R,R)-3 was obtained with a 92 % ee by hydrolysis of (R,R)-enantioenriched 4, which was also catalysed by Amano PS lipase in a THF/pH 7 buffer mixture.…”

Using NMR to identify and characterize natural products

“…121 Subsequently, a number of other chiral derivatizing agents have been proposed for this purpose. 122 One advantage of this approach is that, by determining the absolute conguration at one chiral center in a molecule, it may be possible to determine the absolute conguration of the entire molecule, if the relative congurations of this and other chiral centers are known from other NMR data. 121…”

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery—Building chiral technology toolboxes

“…[198][199][200][201][202][203] These and structurally-related acids as well as several types of optically-active alcohols have found great utility to determine the absolute stereochemistry of enantiomerically pure or enriched secondary alcohols [353][354][355][356][357][358] and diols, 359,360 b-chiral alcohols, 361,362 a-chiral amines, [363][364][365][366][367] mixed chiral amines and alcohols, 368,369 chiral carboxylic acids, [370][371][372] and chiral 3-hydroxy b-lactams. 373 These reagents have also found combined utility in enantiomeric separation, including LC-NMR, plus determination of absolute stereochemistry of various types of compounds such as diastereomeric alcohols [374][375][376][377] and 2-hydroxypyrrolizidinones.…”

“…10). 353 This silane derivative can be removed easily by treatment with tetrabutylammonium fluoroborate (TBAF) should recovery of the alcohol be desirable or necessary. In general, the caveats in the (modified) Mosher's or Trost NMR approach are that the chiral compound must be amenable to derivatization and effectively derivatized, the reaction mixture in some cases must be purified, and the solution conformations of the respective optically active diastereomers that are produced must be known in order to assign the configuration of the asymmetric center correctly.…”