Endocyclic cleavage in glycosides with 2,3-trans cyclic protecting groups
Hiroko Satoh1, Shino Manabe, Yukishige Ito
1National Institute of Informatics (NII), Tokyo 101-8430, Japan. hsatoh@nii.ac.jp
Journal of the American Chemical Society
|March 23, 2011
Summary
An endocyclic pathway explains glycoside anomerization with cyclic protecting groups under weak acid catalysis. Inner ring strain, not protecting group conformation, primarily drives this endocleavage reaction.
Area of Science:
- Carbohydrate Chemistry
- Organic Reaction Mechanisms
- Computational Chemistry
Background:
- Anomerization of glycosides typically involves exocyclic cleavage, but compounds with 2,3-trans cyclic protecting groups exhibit an endocyclic pathway.
- This endocyclic cleavage (endocleavage) is observed under milder conditions (weak Lewis or Brønsted acids) compared to typical glycosides.
Purpose of the Study:
- To investigate the reaction mechanism and promoting factors of endocleavage in glycosides with 2,3-trans cyclic protecting groups.
- To rationalize the observed anomerization from β (1,2-trans) to α (1,2-cis) configurations under specific conditions.
Main Methods:
- Quantum-mechanical (QM) calculations were employed to study reaction pathways and transition state (TS) energies.
- Experimental studies, including anomerization reactions of thioglycosides with boron trifluoride etherate (BF(3)·OEt(2)), were conducted.
Main Results:
- A simple model accurately predicted TS energies based on fused ring strain, correlating well with QM calculations and experimental reactivity.
- Excellent agreement was found between predicted and calculated TS energies, supporting the proposed endocyclic mechanism.
Conclusions:
- The study strongly supports the predominance of the endocyclic mechanism over the exocyclic pathway for this class of glycosides.
- Inner ring strain is identified as the primary factor enhancing endocleavage, with the conformation of the protecting group playing a secondary role.
Related Concept Videos
01:13Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization
Dieckmann cyclization is an intramolecular Claisen condensation of diesters. The reaction occurs in the presence of a base and generates a cyclic β-ketoester as the final product. Commonly, 1, 6 and 1, 7-diesters are preferred substrates for the reaction since the generated five, and six-membered cyclic β-keto esters are particularly more stable.
01:16Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
01:23Protecting Groups for Aldehydes and Ketones: Introduction
Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired chemical reactions. These compounds can selectively bind to particular functional groups and advance chemoselective reactions in polyfunctional systems (Figure 1). After the functional group has served its purpose, it is removed by reacting it with specific compounds.
00:57C–C Bond Cleavage: Retro-Aldol Reaction
The reverse of the aldol addition reaction is called the retro-aldol reaction. Here, the carbon–carbon bond in the aldol product is cleaved under acidic or basic conditions to form two molecules of carbonyl compounds. The mechanism of the reaction consists of three steps.
In the first step, as depicted in Figure 1, the base deprotonates the β-hydroxy ketone at the hydroxyl group to form an alkoxide ion.
In the first step, as depicted in Figure 1, the base deprotonates the β-hydroxy ketone at the hydroxyl group to form an alkoxide ion.
03:00Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
01:29Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.