Deuterium Labelling to Extract Local Stereochemical Information by VCD Spectroscopy in C-D Stretching Region: A Case Study of Sugars

Stereochemical elucidation of molecules with multiple chiral centers is difficult. Even with VCD spectroscopy, excluding all but one diastereomeric structural candidates is challenging because stereochemical inversion of one chiral center...

Synthesis of 2-C-Branched Sugars

<p>A range of unnatural carbohydrates (sugars) with an unusual 2-C-bromomethylene branch have been synthesised by reaction of the 1,2-cyclopropanated carbohydrate 52 with different nucleophiles. Initial work to optimise the cyclopropane ring opening in the presence of sodium allyloxide/allyl alcohol provided anomers 140 and 141 in up to 75% yield. Use of sodium thiophenolate/thiophenol provided anomeric thioglycosides 181 and 182 (76% yield, 7:2 ratio), while sodium diethylamide/ diethylamine provided anomeric glycosylamines 183 and 184 (50% yield, 1:1 ratio). Further functionalisation of the 2-C-branch of 141 was performed using various palladium-catalysed cross-coupling reactions, providing a series of products. Reaction of 140 and 141 under acidic conditions caused E-Z isomerisation of the bromoalkene forming a single anomer, 194. Efforts to obtain mechanistic information about the cyclopropane ring opening were made through attempted trapping of a cyclopropene intermediate, deuterium labelling experiments, synthesis of possible stable intermediates and reactions with internal nucleophiles.</p>

Synthesis of 2-C-Branched Sugars

<p>A range of unnatural carbohydrates (sugars) with an unusual 2-C-bromomethylene branch have been synthesised by reaction of the 1,2-cyclopropanated carbohydrate 52 with different nucleophiles. Initial work to optimise the cyclopropane ring opening in the presence of sodium allyloxide/allyl alcohol provided anomers 140 and 141 in up to 75% yield. Use of sodium thiophenolate/thiophenol provided anomeric thioglycosides 181 and 182 (76% yield, 7:2 ratio), while sodium diethylamide/ diethylamine provided anomeric glycosylamines 183 and 184 (50% yield, 1:1 ratio). Further functionalisation of the 2-C-branch of 141 was performed using various palladium-catalysed cross-coupling reactions, providing a series of products. Reaction of 140 and 141 under acidic conditions caused E-Z isomerisation of the bromoalkene forming a single anomer, 194. Efforts to obtain mechanistic information about the cyclopropane ring opening were made through attempted trapping of a cyclopropene intermediate, deuterium labelling experiments, synthesis of possible stable intermediates and reactions with internal nucleophiles.</p>

Selective Manganese-Catalyzed Semihydrogenation of Alkynes with in-situ Generated H2 from KBH4 and Methanol

The selective semihydrogenation of alkynes with the Mn(I) alkyl catalyst fac-[Mn(dippe)(CO)3(CH2CH2CH3)] (dippe = 1,2-bis(di-iso-propylphosphino)ethane) as pre-catalyst is described. Hydrogen gas required for the hydrogenation is generated in situ upon alcoholysis of KBH4 with methanol. A series of aryl-aryl, aryl-alkyl, alkyl-alkyl and terminal alkynes were readily hydrogenated to yield E-alkenes in good to excellent isolated yields. The reaction proceeds at 90°C with catalyst loadings of 0.5 -2 mol%. The implemented protocol tolerates a variety of electron donating and electron withdrawing functional groups including halides, phenols, nitriles, unprotected amines and heterocycles. The reaction can be upscaled to the gram scale. Mechanistic investigations including deuterium labelling studies and DFT calculations were undertaken to provide a reasonable reaction mechanism showing that initially formed Z-isomer undergoes fast isomerization to afford the thermodynamically more stable E-isomer.

Photochemical methods for deuterium labelling of organic molecules

This tutorial review is intended as a foundation for the further development of novel photocatalytic strategies to achieve deuterium incorporation using mild and sustainable conditions.

Geminal Difunctionalization of Vinylarenes: Concise Synthesis of 1,3-Dioxolan-4-ones

We report a straightforward method for the synthesis of five-membered 1,3-dioxolan-4-ones by an unprecedented oxidative alkene geminal difunctionalization strategy using α-hydroxy carboxylic acids. Under the geminal oxidative addition conditions, various substituted α-hydroxy carboxylic acids and styrenes containing a variety of substituents, including β-substituted styrenes, were effectively coupled regioselectively (anti-Markovnikov) with an isobutyl-substituted chiral α-hydroxy carboxylic acid, providing an annulation with excellent dia­­stereoselectivity. An aryl migration in the semipinacol rearrangement leading to geminal oxidative addition of the α-hydroxy carboxylic acids was confirmed by deuterium-labelling and control studies.

Manganese PNP-pincer catalyzed isomerization of allylic/homo-allylic alcohols to ketones – activity, selectivity, efficiency

Manganese PNP pincer complexes are excellent catalysts for the isomerization of allylic alcohols to the ketones. The reaction proceeds via a dehydrogenation/hydrogenation mechanism as shown by DFT calculations and deuterium labelling.