The mechanism of the insitu generation is given in the file attached along with

REFERENCE:

JOURNAL OF BACTERIOLOGY, Apr., 1966 Vol. 91, No. 4; PP-1537-1542

Toxicity of Copper and Ascorbic Acid toSerratia marcescens

LEONARD ZIMMERMAN

In order to protect the copper(I) ions from disproportionation to Cu(0) and Cu(II) and from re-oxidation to Cu(II) by air, to enhance their catalytic activity and to improve the reaction’s applicability with a variety of substrates, the search for suitable ligands started immediately after Sharpless’ and Meldal’s initial reports.

THPTA (3 [tris(3-hydroxypropyltriazolylmethyl)amine) ] is found to be best ligand.

Its structure is also contained in the file. ZOOM150.

Reaction conditions:

A solution of sodium ascorbate (0.178 g, 0.90 mmol) and CuSO4•5H2O (0.112 g, 0.45 mmol) in DMF/H2O 2:1 (30 mL). The Cu 1+ ion either generates in situ from sodium ascorbate and one of Cu2+ salts like copper sulfate pentahydarte, cooper acetate,…etc. or using one of the Cu1+ salts like CuI, CuCl,...etc. with base. The Cu(I) catalyst is typically generated by the chemical reduction of Cu(II) to Cu(I).

Sources of copper (I) catalyst can be produced in situ by reduction of copper (II)

Salts or obtained through disproportionation of Cu (0) and Cu (II) salts. Cu (I) can also be introduced as copper (I) salts such as CuI or obtained from oxidation of Cu (0) salt. The optimal reaction conditions are the most commonly employed system, namely CuSO4·5H2O and sodium ascorbate as source of copper (I) in tert-BuOH/H2O.

The most important factor is maintaining the [Cu(I)] at a high level at all times during reaction. This is why the use of a Cu(II) source with addition of a reducing agent in a large excess has been one of the preferred methods. The presence of reducing agent renders the reaction much less susceptible to oxygen, and such reactions have often been carried out under open-air conditions. Nevertheless, this is not always without problems, due to potential oxidative side reactions.

Most frequently, the reaction has been performed with CuI in THF, CH3CN, or DMSO or with CuSO4/ascorbate in water/alcohol mixtures.

In some cases, the CuSO4 is preferred due to ease of workup and purity of products, while, in other reactions, the Cu(1) halides are superior, particularly in rate of reaction.

The protection from oxidation of the catalyst is of course important to maintain a good concentration of the catalytically active complexes throughout reaction. However, the

direct effects on catalysis is due to a straight influence on the catalytic complex involved in the reaction; namely the ligand is coordinated to Cu(1) during the catalytic process.