Dienes asymmetric hetero-Diels-Alder reactions, copper

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

Asymmetric Hetero-Diels-Alder Reactions. By using stoichiometric amounts of the bis(oxazoline)-copper(II) triflate system as catalyst, asymmetric hetero-Diels-Alder (HDA) cycloaddition reactions were performed with cyclic and acyclic 1,3-dienes. The reported enantioselectivity (70-98% ee) and... 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

The choice of solvent has had little, if any, influence on the majority of Diels-Alder reactions.210,211 Although the addition of a Lewis acid might be expected to show more solvent dependence, generally there appears to be little effect on asymmetric induction.118129 However, a dramatic effect of solvent polarity has been observed for chiral metallocene triflate complexes.212 The use of polar solvents, such as nitromethane and nitropropane, leads to a significant improvement in the catalytic properties of a copper Lewis acid complex in the hetero Diels-Alder reaction of glyoxylate esters with dienes.213... 

Copper complexes of the bisoxazoline ligands have been shown to be excellent asymmetric catalysts not only for the formation of carbocyclic systems, but also for the hetero-Diels-Alder reaction. Chelation of the two carbonyl groups of a 1,2-dicarbonyl compound to the metal atom of the catalyst sets up the substrate for cycloaddition with a diene. Thus, the activated diene 20 reacts with methyl pyruvate in the presence of only 0.05 mol% of the catalyst 66 to give the adduct 138 with very high enantiomeric excess (3.99). 

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