Cupreine/cupreidine

Cupreines and cupreidines are pseudoenantiomers of Cinchona alkaloids with the replacement of quinoline C(6 )-OCH3 with an OH-group. The result is availability of an additional hydrogen-bonding moiety. 

The nitroaldol reaction, particularly involving ketones has been relatively unexplored in the field of asymmetric organocatalysis. Employing cupreines and cupreidines as catalysts, Deng [63] presented an enantioselective nitroaldol reaction of a-ketoesters... 

The Deng group identified QN-derived thiourea 121 and QD -derived thiourea 124 to be also efficient promoters of enantio- and diastereoselective Diels-Alder reactions between the 2-pyrone diene 3-hydroxypyran-2-one and the dienophiles fumaronitrile, maleonitrile as well as acrylonitrile, while various C9-hydroxy acylated and alkylated (dihydro)cupreines and (dihydro)cupreidines failed for the same reactions under identical conditions (e.g., 97% yield, 15% ee, 64 36 endoxxo) [289], Catalysts 121 and 124 (5mol% loading), however, produced the corresponding Diels-Alder adducts 1-3 with synthetically useful enantioselectivities (85-... 

Figure 13.2 Structural features of cinchona alkaloid molecules (QN, quinine QD, quinidine CN, cinchonine CD, cinchonidine CPN, cupreine CPD, cupreidine).

Cupreines and cupreidines as bifunctional cinchona organocatalysts 06AG (E)7496. 

Since the scope of the reaction with respect to the electrophile vras limited to trifluoropyruvate, in 2006 Deng and coworkers searched for a more efficient catalyst for the Friedel-Crafts hydro)grallgrlation of indoles. O-Phenanthiyl cupreidine and cupreine derivatives PHNO-CPD and PHNO-CPN were identified as optimal structures, allowing the use of aiyl and allgmyl pyruvates, glyoxalate and (electron-poor) benzaldehydes in this reaction (Scheme 14.18). ... 

Marcelli T, van Maarseveen JH, Hiemstra H (2006) Cupreines and Cupreidines An Emerging Class of Bifunctional Cinchona Organocatalysts. Angew Chem Int Ed 45 7496... 

Figure 6.1 Structures of the natural cinchona alkaloids and of cupreine and cupreidine. The analogs of quinine, quinidine, cinchonidine, and cinchonine with an ethyl at C3 (the dihydro species) are also isolated from natural sources.

The importance of an -OH group at the C6 position for an organocatalytic reaction was noted by Deng and coworkers in a series of studies of C9 ether derivatives of cupreine and cupreidine [34]. Based on the observation that the C9 0-benzyl and O-phenanthryl ether derivatives (10 and 11, respectively. Figure 6.5) gave similar results for the conjugate addition of carbon nucleophiles to nitroalkenes as obtained with 3 (Scheme 6.18) [34], a transition state model was proposed for this reaction. 

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