CuBr/QUINAP system

CuBr/QUINAP System The CuBr/QUlNAP system was initially used in the enan-tioselective synthesis of proparyl amines via the reaction of alkynes and enamines (Scheme 5.5). It was rationalized that the enamines reacted with protons in terminal alkynes in the presence of copper catalyst to form zwitterionic intermediates in which both the generated iminiums and alkyne anions coordinate to the copper metal center. After an intermolecular transfer of the alkyne moiety to the iminium ion, the desired products were released and the catalyst was regenerated. The combination of CuBr as catalyst and the chiral ligand QUEMAP is crucial for the good reactivities and enantioselectivities seen in the reaction. Another potential... 

Similar to the CuOTf/PyBox system, the CuBr/QUINAP system also gave high enantioselectivities of the three component reactions to construct propargyl amines from aldehydes, amines, and alkynes (Scheme 5.6). In this system various aldehydes including aromatic aldehydes and aliphatic aldehydes could be used and a wide range of chiral propargyl amines were prepared in good yields and enantioselectivities. Mechanistic studies showed that the dimeric Cu/QUINAP complex is the catalytically active species that differs from the previous reaction. 

The asymmetric alkynylation of isoquinoline iminium ion was reported in the presence of CuBr/QUINAP system (Scheme 5.7). ° Various alkynyl tetrahydroiso-quinolines were obtained in excellent yields and enantiomeric excesses. A natural product, homolaudanosine, was synthesized by the reduction of the obtained propargyl tetrahydroisoquinoline. 

Although the CuBr/QUINAP system is an effective chiral catalyst in alkynylation of imines or iminiums, one drawback is that enantiopure QUINAP is quite expensive. An analog of QUINAP, PINAP (Figure 5.2), was readily synthesized and found as a very effective chiral ligand in the direct addition of alkynes to iminiums generated from aldehydes and secondary amines in situ (Scheme 5.8). ... 

Other systems different from oxazolidinones have been successfully applied as ligand of Cu(I) salts for this transformation. The use of QUINAP (L in Scheme 11.15), combined with CuBr gave excellent results in the total synthesis of (S)-(-l-)-coniine, a highly toxic alkaloid inducing curare-type paralysis, in 45% overall yield and 90%... 

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See also in sourсe #XX -- [ , ]

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