Diels-Alder reaction hgands

Lassaletta et al. designed new hgands for the copper-catalyzed Diels-Alder reaction by introduction of C2-symmetric dialkylamino substructures in gly-oxal bis-hydrazones [104] (73 in Scheme 40). This hgand can advantageously be prepared in its both enantiomeric forms on a multigram scale from 1,4-diphenylbutanedione. 

Bolm et al. [108] prepared a C2-symmetric bis (sulfoximine) as ligand for the copper-catalyzed hetero-Diels-Alder reaction. The stereogenic sulfur atom being located near the AT-coordinating atom, these structures were assumed to be promising for asymmetric catalysis. Their Hgand (79 in Scheme 43) was synthesized by palladium-catalyzed N-aryl imination from 1,2-dibromobenzene and (S)-S-methyl-S-phenylsulfoximine with Pd2dba3 in 70% yield. 

During this study, the authors noted that aging of the catalyst in the absence of substrate resulted in a decrease in the enantioselectivity in the Diels-Alder reaction. Aging the catalyst in the presence of the substrate, however, provided the most enantioselective catalyst. These results suggested that the substrate stabilized the catalyst. The authors then examined the abihty of various substrate-like additives to stabilize the catalyst. It was found that some additives not only stabilized the catalyst, but also impacted the catalyst enantioselectivity. When 3-acetyl-l,3-oxazolidin-2-one was used as additive the endo (25,3f )-product was formed with 93% ee. In contrast, acetylacetone derivatives led to a reversal of the facial selectivity. Using the additive 3-phenylacetylacetone as the additive resulted in formation of the (27 ,3i9)-product in 81% enantioselectivity. In both instances, the configuration of the chiral hgand was the same (f )-BINOL. A similar reversal of enantioselectivity with these additives was observed when other substrates were employed. 

The enantiopure phosphinooxazolinidines (POZ)s were a type of N—P chiral ligand developed by Nakano and used for asymmetric Pd-catalyzed allylic alkylations [133] and Diels-Alder reactions [59]. A PS-supported version of this type of chiral hgand 210 was prepared and apphed to the asymmetric aUylic alkylation of acetate 201 with dialkyhnalonates [134], affording the product in exceUent yield (99%) with 99% ee, as shown in Scheme 3.69. 

Promising results have been reported by Corey using cationic oxazaborinane complex 16 as an aldehyde-diene cycloaddition catalyst (Scheme 20) [70]. a-Substituted aldehydes and four dienes are reported to undergo low-temperature (-94 °C) Diels-Alder reaction to give adducts in high exo selectivity and excellent enantioselection. The catalyst is prepared in seven steps and hgand recovery after the reaction is 85% catalyst decomposition occurs above -60 °C. 

A bis(oxazoline)Fe(III) complex has also been shown to function as an effective catalyst for an enantioselective Diels-Alder reaction between cyclopentadi-ene and acryloyl imide (Scheme 33) [96]. Recovery of the chiral hgand proceeded in >85% yield. The scope of this catalyst has not been evaluated against less reactive dienes and dienophiles that require higher reaction temperatures. 

Mikami and coworkers conducted the Diels-Alder reaction with a catalyst prepared by mixing enantiomerically pure R)-56 and racemic 56 and observed a positive nonlinear effect however, they found no asymmetric amplification when they prepared the catalyst by mixing enantiomerically pure R)-56 and enantiomerically pure (S)-56 (i.e., linear correlation between catalyst and product ee). Introduction of molecular sieves restores the asymmetric amplification in the latter case, apparently by equilibration of R) R) and (S)(S) dimers into catalytically less active R) S) dimers. As expected, the reaction rate was faster for R)-56 than for ( )-56 derived from racemic binaphthol hgand ca. 5-fold faster). 

Mikami and coworkers also reported the development of lanthanide bis(trif-luoromethanesulfonyl)amides (bistrifylamides) as a new type of asymmetric catalysts for the hetero-Diels-Alder reaction of Danishefsky s diene, wherein the significant effect of water as an additive is observed in increasing not only the enan-tioselectivity but also the chemical yield. Bistrifylamides can be used as effective bidentate Hgands to increase the Lewis acidity of their chiral metal complexes on account of the higher acidity of the conjugated acids than those of afiphatic and aromatic diols, which are commonly used as chiral bidentate hgands [33]. 

Note added in proof. O Brien has now obtained bispidine ligand 38 (Fig. 3) from (-)-cytisine in 3 steps and demonstrated that it function as a readily accessible (+)-sparteine surrogate in most processes, the stereoselectivity of reactions with ligand 38 are comparable to those with (-)-sparteine as a hgand [92]. Imino Diels-Alder reactions have been investigated as a new route to sparteine analogs, and diamines 38 and epi-38 prepared by this methodology have been examined in the lithiation on hf-Boc-pyrrolidine [93]. 

Another type of reaction that has been developed in order to resolve nitrogen-containing compounds is the Diels-Alder cycloaddition. As a rare example, Sibi et al. [235] have recently reported the KR of pyrazohdinones that could not be obtained in high enantioselectivities from direct methods on the basis of a Diels-Alder cycloaddition with cyclopentadiene catalysed by a combination of Cu(OTf)2 with a chiral aminoindanol-derived bisoxazohne hgand. The recovered almost enantiopure (98% ee) substrate was isolated with a selectivity factor of 34. Excellent results were also reported by Fu et al. [236] for the KR of azomethine imines via copper-catalysed [3-1-2] cycloadditions with aUcynes performed in the presence of a chiral phosphaferrocene-oxazoline ligand, which furnished the chiral recovered substrates with high selectivity factors of up to 76, as shown in Scheme 3.15. 

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