Dr. Eoghan McGarrigle

Dr. Eoghan McGarrigle will give the 4^th Liebig-College seminar and lectures on 

"Adventures with Sulfur in Organic Chemistry"

"Stereoselective Glycosylations"

Abstract:

Chiral Sulfides

The chiral sulfide, isothiocineole, has been synthesized in one step from elemental sulfur, γ-terpinene, and limonene in good yield. A mechanism involving radical intermediates for this reaction is proposed. The application of isothiocineole to the asymmetric epoxidation of aldehydes and the aziridination of imines will be described. Excellent enantioselectivities and diastereoselectivities have been obtained over a wide range of aromatic, aliphatic, and α,β-unsaturated aldehydes using simple protocols. In aziridinations, excellent enantioselectivities and good diastereoselectivities were obtained for a wide range of imines. Mechanistic models have been put forward to rationalize the high selectivities observed, which should enable the sulfide to be used with confidence in synthesis. 

 The synthesis of vinylsulfonium salts and their applications in the synthesis of heterocycles will be described. Practical routes to substituted vinylsulfonium salts will be described.

Two general reaction pathways (above) have been used in the synthesis of a range of heterocycles (examples below). Exceptions and mechanistic investigations will be described. Many of these heterocycles are formed with good control of diastereoselectivity – stereochemical models will be proposed to account for the selectivities.

Glysosylation 

The synthesis of oligosaccharides with stereocontrol remains a challenging task in organic synthesis. We previously reported a mild organocatalytic method for the synthesis of 2-deoxygalactosides, with excellent yields and α-selectivity using thiourea 1 as a catalyst. New organocatalysts for the glycosylation of protected glycals will be presented. These new catalysts are cheap and readily available, and they demonstrate an expanded substrate scope both in terms of glycal and the types of alcohol glycosyl acceptor that can be used. The impact of electrostatic interactions on scope will be discussed. 

 These catalysts have been designed based on a significant change in our understanding of the mechanism of how these glycosylations occur. We now propose that the previously described thiourea catalysts do not operate in a double hydrogen bonding manner and will present evidence to support this new hypothesis. The new mechanism brings to mind the mechanisms thought to operate in some glycosidases and has opened the way for the development of this new class of catalysts.

If time permits, I will also discuss our use of the 3,4-disiloxane protecting group which results in excellent α-selectivity in the glycosylations of glucals and rhamnals. Although conformational control strongly influenced stereochemical outcome, the presence of a hydroxy group at the 6-position also influenced the outcome through electrostatic interactions.