Enantioselective Lewis base-catalyzed transformations

Such phosphazenes could play a role in enantioselective Lewis base-catalyzed transformations (13JA15306, 14CC4319). The catalytic performances of the phosphazene hase 129-HI have been evaluated in the electrophilic amination of2-alkyltetralones 130 with azodicarboxylate. The best conditions employed the use of 10mol% of phosphazene 129-HI and 20 mol% of NaHMDS. The reaction afforded excellent yields and ee, up to 99% and 97%, respectively. However, the position of methoxy groups on the tetralones 130 has a deep influence on enantioselectivity and yield. The 6- and 8-methoxy substituted tetralones 130 require higher temperatures for sufficient conversion 8-MeO-130 gave only 78% conversion and 10% ee at 25 °C (Scheme 34). 

Denmark utilized chiral base promoted hypervalent silicon Lewis acids for several highly enantioselective carbon-carbon bond forming reactions [92-98]. In these reactions, a stoichiometric quantity of silicon tetrachloride as achiral weak Lewis acid component and only catalytic amount of chiral Lewis base were used. The chiral Lewis acid species desired for the transformations was generated in situ. The phosphoramide 35 catalyzed the cross aldolization of aromatic aldehydes as well as aliphatic aldehydes with a silyl ketene acetal (Scheme 26) [93] with good yield and high enantioselectivity and diastereoselectivity. 

Cook reported that a 3,3 bis(trifluoromethyl) BINOL catalyzed asymmetric addition of allylindium to hydrazones proceeds in modest to good enantioselec tivities (10 92% ee) [90]. The stoichiometric version of this reaction yields much higher enantioselectivities (84 97% ee). Jacobsen later found that a chiral urea catalyst is effective in catalyzing a similar transformation [96]. The bifunctional catalyst 55 bearing a hydrogen bond donor and a Lewis base that are properly... 

Denmark and Fan developed a chiral Lewis base (138)-catalyzed asymmetric a-addition of isocyanides to aldehydes with good to excellent enantioselectivity (Scheme 5.41) [84]. The protocol is applicable to non-chelating aldehydes, but it is a bimolecular transformation since the carboxylic acid is excluded from the reaction. 

This review covers the catalytic literature on condensation reactions to form ketones, by various routes. The focus is on newer developments from the past 15 years, although some older references are included to put the new work in context. Decarboxylative condensations of carboxylic acids and aldehydes, multistep aldol transformations, and condensations based on other functional groups such as boronic acids are considered. The composition of successful catalysts and the important process considerations are discussed. The treatment excludes enantioselective aldehyde and ketone additions requiring stoichiometric amounts of enol silyl ethers (Mukaiyama reaction) or other silyl enolates, and aldol condensations catalyzed by enzymes (aldolases) or catalytic antibodies with aldolase activity. It also excludes condensations catalyzed at ambient conditions or below by aqueous base. Recent reviews on these topics are those of Machajewski and Wong, Shibasaki and Sasai, and Lawrence. " The enzymatic condensations produce mainly polyhydroxyketones. The Mukaiyama and similar reactions require a Lewis acid or Lewis base as catalyst, and the protecting silyl ether or other group must be subsequently removed. However, in some recent work the silane concentrations have been reduced to catalytic amounts (or even zero) this work is discussed. 

More recently, it has been reported that primary amines derived from cinchona alkaloids [75] as well as proline derivatives [76], combined with achiral Brpnsted or Lewis acids, may also efficiently catalyze the enantioselective Biginelli reaction. Alternatively, a carbohydrate-based bifnnctional primary amine-thiourea catalyst was developed for this transformation, with similar enantiocontrol [77]. 

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