Diels-Alder reactions copper-catalysed

Probably the largest catalytic potential lies in the metal complexes of concave reagents. Two sub-structures are well established as metal ligands 1,10-phenanthroline and NHC. Numerous transition metal complexes have been synthesized and some of them have been investigated in metal catalysed reactions such as Lewis-acid catalysed Diels-Alder reactions, palladium-catalysed aUylations, and copper(l)-catalysed cyclopropa-nations. " In the latter reaction, the full potential of concave reagents and the importance of the tine structure of the concave shielding has become obvious. With two different types of concave ligands, two complementary stereoselectivities have been found. 

Copper is clearly the most selective metal-ion catalyst. Interestingly, proton catalysis also leads to high selectivities. This is a strong indication that selectivity in this catalysed Diels-Alder reaction does not result from steric interactions. 

Evans and co-workers investigated the effect of a number of -symmetric bis(oxazoline) ligands on the copper(II)-catalysed Diels-Alder reaction of an N-acyloxazolidinone with cyclopentadiene. Enantiomeric excesses of up to 99% have been reported (Scheme 3.4). Evans et al." suggested transition state assembly 3.7, with a square planar coordination environment around the central copper ion. In this scheme the dienophile should be coordinated predominantly in an cisoid fashion in... 

Interestingly, the rate constants for Diels-Alder reaction of the ternary complexes with 3.9 are remarkably similar. Only with 2,2 -bipyridine and 1,10-phenanthroline as ligands, a significant change in reactivity is observed. It might well be that the inability of these complexes to adopt a planar geometry hampers the interaction between the copper ion and the dienophile, resulting in a decrease of the rate of the catalysed Diels-Alder reaction. 

In contrast, investigation of the effect of ligands on the endo-exo selectivity of the Diels-Alder reaction of 3.8c with 3.9 demonstrated that this selectivity is not significantly influenced by the presence of ligands. The effects of ethylenediamine, 2,2 -bipyridine, 1,10-phenanthroline, glycine, L-tryptophan and L-abrine have been studied. The endo-exo ratio observed for the copper(II)-catalysed reaction in the presence of these ligands never deviated more than 2% from the endo-exo ratio of 93-7 obtained for catalysis by copper aquo ion. 

Likewise, the influence of the ligand catalyst ratio has been investigated. Increase of this ratio up to 1.75 1 resulted in a slight improvement of the enantioselectivity of the copper(L-tryptophan)-catalysed Diels-Alder reaction. Interestingly, reducing the ligand catalyst ratio from 1 1 to 0.5 1 resulted in a drop of the enantiomeric excess from 25 to 18 % instead of the expected 12.5 %. Hence, as anticipated, ligand accelerated catalysis is operative. 

Table 3.4. Enantiomeric excess and reaction times of the copper(L-abrine)-catalysed Diels-Alder reaction of3.8cwith3.9in different solvents at 0 C.

In this section the catalytic efficiency of Co(DS)2, Ni(DS)2, Cu(DS)2 andZn(DS)2 micelles as well as the effect of CTAB and C12E7 on the copper-ion catalysed Diels-Alder reaction between 5.1 and 5.2 is described... 

Table 5.5. Influence of micelles of Cu(DS)2, CTAB and C12E7 on the apparent second-order rate constants (M s" ) for the copper(II) catalysed Diels-Alder reaction of 5.1c, 5.If and 5.1 g with 5.2 at 25 C .

Table 5.6. Hammett -values for the copper(II)-catalysed Diels-Alder reaction of 5.1a-e with 5.2 in different media.

In contrast to SDS, CTAB and C12E7, CufDSjz micelles catalyse the Diels-Alder reaction between 1 and 2 with enzyme-like efficiency, leading to rate enhancements up to 1.8-10 compared to the reaction in acetonitrile. This results primarily from the essentially complete complexation off to the copper ions at the micellar surface. Comparison of the partition coefficients of 2 over the water phase and the micellar pseudophase, as derived from kinetic analysis using the pseudophase model, reveals a higher affinity of 2 for Cu(DS)2 than for SDS and CTAB. The inhibitory effect resulting from spatial separation of la-g and 2 is likely to be at least less pronoimced for Cu(DS)2 than for the other surfactants. 

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. 

In addition, the same group has used copper complexes of these ligands as efficient catalysts for enantioselective Cu-catalysed aza-Diels-Alder reactions of A-sulfonyl imines with Danishefsky s dienes, providing the corresponding six-membered heterocycles with enantioselectivities of up to 80% ee. ... 

The reverse reaction is catalysed by copper sulphate in an ethanol/water (50 50) mixture297 298. Indium(III) chloride catalysis of Diels-Alder reactions was also reported, but the effects were poor and comparison to uncatalysed reactions was made only in a few cases299,300. A very versatile Lewis acid catalyst for such reactions is methylrhenium trioxide (MTO)300. This catalyst can be used without a solvent, in pure organic solvents like chloroform and even in pure water. While the catalyst is active in the latter two solvents (Table 22), it gives the best results in water (Table 23). 

Erraan and Stonehave devised a new method for the construction of the tricyclic skeleton associated with such sesquiterpenes as a-patchoulene (438) and cyperene (439). The route they employed was the formation of the acid-ester (440 R = OH) by a Diels-Alder reaction of 3-ethoxycarbonyl-2,4-dimethyl-penta-1,3-diene with acrylic acid. The corresponding diazo-ketone (440 R = CHN2), on treatment with boron trifluoride etherate, gave the keto-esters (441) and (442) directly. This direct acid-catalysed cyclization proved to be more efficient than the conventional copper-catalysed thermal decomposition of (440 ... 

Owens, T.D., Souers, A.J. and Ellman, J.A. (2003) The preparation and utility of bis(sulfinyl) imidoamidine ligands for the copper-catalysed Diels-Alder reaction. The Journal of Organic Chemistry, 68, 3-10 Kochi, T. and Ellman, J.A. (2004) Asymmetric a-alkylation of N -tert-butanesulfinyl amidines. Application to the total synthesis of (6R,75)-7-amino-7,8-dihydro-a-bisabolene. Journal of the American Chemical Society, 126, 15652-15653. 

The bis-oxazoline-catalysed Diels-Alder reaction is not restricted to the use of oxazolidinone-based dienophiles. For instance the a-sulfenylacrylate (8.74) and oi-hydroxyenones such as (8.75) undergo enantioselective Diels-Alder reaction with cyclopentadiene in the presence of the copper complex of (8.67) and (8.68) respectively. 

The magnesium and copper bis-oxazoline catalysts used in the asymmetric Diels-Alder reaction (see Section 8.1) display high levels of selectivity in the nitrone cyclo addition with bidentate, electron-deficient dipolarophiles. The magnesium bis-oxazoline catalysts effect moderate to good ee in the cycloaddition with oxazolidines such as (8.51), while copper bis-oxazoline complexes show good selectivity in the addition to bidentate pyrazolidinones rather than oxazo-lidinones and also a-hydroxyenones such as (8.75) used as substrates in the copper bis-oxazoline-catalysed Diels-Alder reaction. ... 

The Au(I)- or Ag(I)-catalysed intermolecular hetero-Diels—Alder cycloaddition of push-pull l,3-dien-5-ynes (76) with aldimines or silylaldimines (77) produced 5,6-dihydropyridin-2-ones (78) with high diastereo- and regio-selectivities (Scheme 24). A copper-catalysed intramolecular aza-Diels—Alder reaction has been used to produce dihydrochromeno[4,3-Mpyrrolo[3,2-/ quinolmes in good yields. The cinchonidine-derived quaternary ammonium catalyst, A-2, 3, 4 -trifluorobenzyl-0-benzylcinchonidinum bromide (79), catalysed the aza-Diels—Alder reactions between... 

The second example of enantiodiveregent hetero-Diels-Alder reaction is shown in Scheme 6.28. Thus, racemic cyclohexadiene 132 was reacted with 2-nitrosopyridine 133 in the presence of a copper(I) source and the chiral phosphine ligand 134 to afford regioisomeric hetero-Diels-Alder products 135 (48% and 97% ee) and 136 (52% and 92% ee) [49b]. The Cu(I) complex of 134 functions as a chiral Lewis acid that catalyses the 2-1-4 cycloaddition. 

In 2012, Christmann et al. developed an enantioselective tandem oxidation-Diels-Alder reaction of a trienol which constituted the key step in the synthesis of the key decalin subunit of UCS1025A. The first step of this one-pot process was a copper-catalysed oxidation of this trienol into... 

Scheme 7.69 Tandem oxidation-Diels-Alder reaction catalysed by copper catalysis...

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