Brpnsted acid catalysis catalysts

List and coworkers reasoned that BINOL phosphates (specific Brpnsted acid catalysis) could be suitable catalysts for an asymmetric direct Pictet-Spengler reaction [26], Preliminary experiments revealed that unsubstituted tryptamines do not undergo the desired cyclization. Introduction of two geminal ester groups rendered the substrates more reactive which might be explained by electronic reasons and a Thorpe-Ingold effect. Tryptamines 39 reacted with aldehydes 40 in the presence of phosphoric acid (5)-3o (20 moI%, R = bearing 2,4,6-triisopropyI-... 

Two years later, Terada and coworkers described an asymmetric organocatalytic aza-ene-type reaction (Scheme 28) [50], BINOL phosphate (7 )-3m (0.1 mol%, R = 9-anthryl) bearing 9-anthryl substituents mediated the reaction of A-benzoylated aldimines 32 with enecarbamate 76 derived from acetophenone. Subsequent hydrolysis led to the formation of P-amino ketones 77 in good yields (53-97%) and excellent enantioselectivities (92-98% ee). A substrate/catalyst ratio of 1,000 1 has rarely been achieved in asymmetric Brpnsted acid catalysis before. 

Until 2006, a severe limitation in the field of chiral Brpnsted acid catalysis was the restriction to reactive substrates. The acidity of BINOL-derived chiral phosphoric acids is appropriate to activate various imine compounds through protonation and a broad range of efficient and highly enantioselective, phosphoric acid-catalyzed transformations involving imines have been developed. However, the activation of simple carbonyl compounds by means of Brpnsted acid catalysis proved to be rather challenging since the acid ity of the known BINOL-derived phosphoric acids is mostly insufficient. Carbonyl compounds and other less reactive substrates often require a stronger Brpnsted acid catalyst. 

Specific Brpnsted acid catalysis is a popular field within the domain of asymmetric organocatalysis. Since the introduction of stronger chiral Brpnsted acids as powerful catalysts for enantioselective synthesis in 2004, numerous asymmetric Brpnsted acid-catalyzed transformations have been developed. 

Most chemical reactions proceed via charged intermediates or transition states. In asymmetric Brpnsted acid catalysis the substrate is protonated by the catalyst and a chiral H-bond-assisted ion pair is generated. We reasoned that, in principle, any reaction that proceeds via cationic in-... 

The use of chiral Brpnsted acid catalysis as a mode of asymmetric activation burgeoned dramatically in the early part of the twenty first century [35]. The role of hydrogen in this process is, in essence, similar to that of Lewis acid catalysts - i.e. activation of the C=X bond (X=0, NR, CR ) by decreasing the LUMO energy and ultimately leading to promotion of nucleophilic addition to the C=X bond (Fig. 1.5). 

According to previous reports, under Brpnsted acid catalysis, three classes of products can be expected (Fig. 9.16). Four stereoisomeric products 13 and products 12a-d can be generated as major and minor products, respectively. Additionally, product 14 can be formed from condensation of 13 with 11. Using a coordination cage as a catalyst, 11 can be encapsulated within the hydrophobic interior of the cage, as confirmed by HNMR technique. It was established that, in contrast to cyclization in acidic aqueous solution, the hydrophobic interior of the cage prevents the capture of reactive intermediates by water [29], Cyclization followed by elimination resulted in diastereomeric products (Fig. 9.17) [10]. 

In the failure of the phosphoric acid catalysts, we recognized a much more general issue in current Brpnsted acid catalysis, that is, small aliphatic substrates and loosely bound intermediates such as oxocarbenium ions represent essentially unsolved problems in the area. Instead of focusing on the decoration of the spiroacetalization substrates with bulky or aromatic groups, we turned to the development of a catalyst class that could solve these general problems in asymmetric Brpnsted acid catalysis [57]. 

We believe the concept of confined acids to be very general, even beyond Brpnsted acid catalysis, and these and similar catalysts to be of use in tackling current challenges with reactions that include small volume and/or loosely organized transition states [58]. 

Abstract New reagents and catalysts have unlimited potential for the future of organic synthesis. We have been interested in Lewis and Brpnsted acid catalysis for a number of years. In this chapter, I am going to review on several of these acids and related catalysts from the conceptual aspect of their molecular design and engineering. 

Chiral Brpnsted acid catalysis of organic reactions has become a rapidly growing area of research, as it offers operational simplicity together with mild reaction conditions. However, the first Brpnsted acid-catalyzed 1,3-DC of diaryl nitrones 17 to ethyl vinyl ether 18 was demonstrated by Yamamoto and coworkers in 2008 [16]. Only 5 mol% of chiral phosphoramide catalyst 20 was enough for this transformation. Similar to some Lewis acid-catalyzed 1,3-DC reaction, this protocol provided the endo products as the major diastereomers (Scheme 2.7). 

During the past decade, Brpnsted acid catalysis has been employed successfully to promote versatile cascade processes, efficiently constructing a huge number of structurally diverse chiral architectures with high optical purity. Based on the deep insights in the active modes and reaction mechanisms, new Brpnsted acid catalysts and... 

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