FREE-RADICAL THIOL-ENE AND THIOL-YNE COUPLINGS AS CLICK PROCESSES FOR GLYCOCONJUGATION - Click Chemistry in Glycoscience: New Developments and Strategies - page 42

FREE-RADICAL THIOL-ENE AND
THIOL-YNE COUPLINGS AS CLICK
PROCESSES FOR
GLYCOCONJUGATION

ALESSANDRO DONDONI AND ALBERTO MARRA

3.1 INTRODUCTION

Since the formulation of the click chemistry concept by Sharpless and coworkers
[1] in 2001 and the discovery of the copper-catalyzed azide-alkyne cycloaddition
(CuAAC) as the quintessential click reaction [2] in 2002, there has been an explosive
growth in the number of applications of this reaction in the most disparate fields of
synthetic chemistry, including material and life sciences. No better start of the new
millennium could have been foreseen by synthetic chemists. In fact, the advent of the
click chemistry concept was very likely determined by the need to put some order in
the plethora of new synthetic methods that had been discovered in the second half
of last century. The set of criteria that a process must meet in the context of click
chemistry was defined by Sharpless as follows:

“The reaction must be modular, wide in scope, give very high yields, generate only
inoffensive byproducts that can be removed by nonchromatographic methods, and be
stereospecific (but not necessarily enantioselective). The required process character-
istics include simple reaction conditions (ideally, the process should be insensitive to
oxygen and water), readily available starting materials and reagents, the use of no
solvent or a solvent that is benign (such as water) or easily removed, and simple
product isolation. Purification—if required—must be by nonchromatographic methods,