Organocatalytic Asymmetric Synthesis of Si-Stereogenic Siloxanols.

We report the organocatalytic synthesis of Si-stereogenic compounds via desymmetrization of a prochiral silanediol with a chiral imidazole-containing catalyst. This metal-free silylation method affords high yields with enantioselectivity up to 98:2 for various silanediol and silyl chloride substrate combinations (including secondary alkyl, vinyl, and H groups), accessing products with potential for further elaboration. NMR and X-ray studies reveal insight into the H-bonding interactions between the imidazole organocatalyst and the silanediol and the dual activating role of the Lewis basic imidazole to account for the high enantioselectivity.

Selected Ion Monitoring Using Low-Cost Mass Spectrum Detectors Provides a Rapid, General, and Accurate Method for Enantiomeric Excess Determination in High-Throughput Experimentation.

High-Throughput Experimentation (HTE) workflows are efficient means of surveying a broad array of chiral catalysts in the development of catalytic asymmetric reactions. However, use of traditional HPLC-UV/vis methodology to determine enantiomeric excess (ee) from the resulting reactions is often hampered by co-elution of other reaction components, resulting in erroneous ee determination when crude samples are used, and ultimately requiring product isolation prior to ee analysis. In this study, using four published reactions selected as model systems, we demonstrate that the use of LC-MS, SFC-MS, and selected ion monitoring (SIM) mass chromatography provides a highly accurate means to determine ee of products in crude reaction samples using commonplace, low-cost MS detectors. By using ion selection, co-eluting signals can be deconvoluted to provide accurate integrations of the target analytes. We also show that this method is effective for samples lacking UV/vis chromophores, making it ideal for HTE workflows in asymmetric catalysis.

Metal-Free Synthesis of 1,3-Disiloxanediols and Aryl Siloxanols.

The first example of metal-free oxidative hydrolysis of hydrido-siloxanes is reported. Both base-catalyzed and organocatalytic hydrolysis methods are demonstrated to transform 1,3-dihydrido-disiloxanes into 1,3-disiloxanediols. The first example of a chemoselective silane hydrolysis is demonstrated.