Lewis acid magnesium complex

The Diels-Alder reaction has been performed with a range of Lewis acids. Copper complexes are the most successfully used, but other metals such as iron, magnesium, palladium, nickel or ytterbium have proved to be efficient to catalyse this reaction. 

Perhaps the most attractive method of introducing enantioselectivity into the Diels-Alder reaction is to use a chiral catalyst in the form of a Lewis acidic metal complex. In recent years, this area has shown the greatest progress, with the introduction of many excellent catalytic processes. Quite a number of ligand-metal combinations have been evaluated for their potential as chiral catalysts in Diels-Alder reactions. The most commonly used metals are boron, titanium, and aluminum. Copper, magnesium, and lanthanides have also been used in asymmetric catalytic Diels-Alder reactions. 

In this cyclic transition state, one Grignard molecule donates its alkyl group to the carbonyl carbon, while the other Grignard molecule activates this carbon by acting as a Lewis acid in complexing to the carbonyl oxygen. The resultant magnesium alkoxide is hydrolysed in the aqueous acidic work-up to yield the alcohol. 

The types of dienophiles which have been studied most are acrylic aldehydes, acrylates and 3-acryloyl-l,3-oxazolidines. The latter have been used predominantly in copper, magnesium, zinc and lanthanide catalyzed reactions in which the chiral Lewis acid binds in an rj2 fashion to the dienophile (complexation to both carbonyls). 

The first effective enantioselective 1,3-dipolar cycloaddition of diazoalkanes catalyzed by chiral Lewis acids was reported in the year 20(X) (139). Under catalysis using zinc or magnesium complexes and the chiral ligand (R,/ )-DBFOX/Ph, the reaction of diazo(trimethylsilyl)methane with 3-alkenoyl-2-oxazolidin-2-one 75 (R = H) gave the desilylated A -pyrazolines (4S,5R)-76 (R =Me 87% yield, 99% ee at 40 °C) (Scheme 8.18). Simple replacement of the oxazohdinone with the 4,4-dimethyloxazolidinone ring resulted in the formation of (4R,5S)-77 (R = Me 75% yield, 97% ee at -78 °C). 

In 1993, Evans and co-workers examined phe-box 6, /-pr-box 45, and bu-box 3 ligands in the Diels-Alder reaction of cyclopentadiene 68 and 3-acryloyl-l,3-oxazolidin-2-one 69 using a weak Lewis acid such as copper(II) triflate." The results are summarized in Table 9.9. The reaction was carried out between —50 and —78 °C for 3-18 h and achieved selectivities of up to 98 2 (endo/exo) with an endo ee of >98% (using bu-box 3). Interestingly, the enantiomer produced in these reactions was the (25) configuration, compared to the (2K) isomer obtained with iron(III) and magnesium(II) as reported by Corey. This observed stereochemistry was explained by the chelation model of the copper(II) complex 74 (Fig. 9.23)... 

Metalloenzymes contain a bound metal ion as part of their structure. This ion can either partidpate directly in the catalysis, or stabilize the active conformation of the enzyme. In Lewis acid catalysis (typically with zinc, vanadium, and magnesium), the M"+ ion is used instead of H+. Many oxidoreductases use metal centers such as V, Mo, Co, and Fe in much the same way as homogeneous catalysis uses ligand-metal complexes. Figure 5.7 shows a simplified mechanism for the halide oxidation readion catalyzed by vanadium chloroperoxidase. The vanadium atom ads as a Lewis add, activating the bound peroxide [30]. 

For a-bromo ketones and related compounds, enhancement of the enantioselectivities has been achieved by the addition of simple Lewis acids (e.g., BF3, Cp2TiCl2, or magnesium salts, which presumably form Lewis acid-Lewis base complexes with the carbonyl functions of the substrates).2627 The stereochemical effect of some Lewis acid additives on the reduction of a racemic a-bromo ester, namely ethyl 2-bromo-2-phenylpropanoate, is summarized in Scheme 27.2. 

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