Brpnsted Acid-Catalyzed Cascade Reactions

Brpnsted acid-catalyzed cascade reactions in natural product synthesis... 

Rueping M, Antonchick AP, Theissmann T. A highly enantioselective Brpnsted acid catalyzed cascade reaction organocatalytic transfer hydrogenation of quinolines and their application in the synthesis of alkaloids. Angew. Chem. Int. Ed. 2006 45 3683-3686. 

In the same year, Enders and coworkers reported an asymmetric one-pot, two-step synthesis of substituted isoindolines 159 in the presence of chiral A-triflyl phosphoramide (R)-Ae (10 mol%, R = d-NO -C H ) (Scheme 67) [87]. The cascade was triggered by a Brpnsted acid-catalyzed aza-Friedel-Crafts reaction of indoles 29 and A-tosyliminoenoates 160 followed by a DBU-mediated aza-Michael cyclization of intermediates 161 to afford the isoindolines 159 in high yields (71-99%) and short reaction times (10 min to 4 h) along with good enantioselectivities (52-90% ee). Longer reaction times (16 h to 10 days) caused increasing formation of the bisindole byproduct 162 (Scheme 68) along with amplified optical purity of isoindolines 159. 

In a related process, Dixon and co-woricers reported a cascade process with the same chiral phosphoric acid in the reaction between tryptamine 134 and enol lactone 133 (Scheme 1.33) [43]. In this reaction, it is postulated that the primary amine of the tryptamine ring-opens the lactone which is then followed by chiral Brpnsted acid catalyzed dehydrative cyclization to give an N-acyliminium ion intermediate 136. Presumably as with the other reactions of this class described above, there is an association between the conjugate base of the chiral acid and the acyl iminium species, allowing the subsequent cyclization onto the indole to be asymmetrically controlled and generate enanliopure product 137. 

To conclude, the mie-pot conversion of cellulose-to-lactic acid (or lactate ester in alcoholic media) thus follows a complex cascade reaction network involving at least six reactions. These reactions have different catalytic needs, but, in general, the presence of both Lewis and Brpnsted acidity are paramount for catalytic success. Br0nsted acidity is key to the hydrolysis of cellulose (step 1) at mild temperatures (<200°C), and to some extent to the dehydration of triose (step 4), whereas Lewis acid sites play a vital role in the isomerization reaction of glucose-to-fructose (step 2), the retro-aldol (step 3), and the 1,2-hydride shift (step 6). Steps 4 and 5 are relatively less demanding they are catalyzed by both acid types. 

In this context. Rueping s group envisioned the asymmetric organocatalytic multiple-reaction cascade version of the abovementioned process in which a six-step sequence was catalyzed by the chiral Brpnsted acid catalyst 21 providing direct access to a broad scope of valuable tetrahydropyridines 26 and azadecalinones 35 with high enantioselectivities (Scheme 11) [99]. 

The Prins cyclization involves the acid-catalyzed addition of olefins to aldehydes and the commonly accepted mechanism involves both carboxonium and carbocationic intermediates. A computational approach was used to examine the role of Lewis and Brpnsted acids in these transformations. Another development of the Prins cyclization involves the use of a reaction cascade with an allylsilyl alcohol and internal trapping of the car-bocation intermediate (Scheme 35). Thus, the allylsilyl alcohol (167) reacts with two... 

In 2010, Wang et al. applied the gold(I)/chiral Brpnsted acid relay catalysis to a novel three-component cascade reaction, providing direct access to structurally diverse julolidine derivatives 374 in high optical purity (Scheme 2.99). The phosphoric acid (Se)-catalyzed asymmetric Povarov reaction of 2-(2-propynyl)anihnes 365, (V-vinylcarbamate 8, and aldehydes 3 provided enantioenriched tetrahydroquinoline intermediates 372, which then underwent a hydroamination reaction under the catalysis of a gold complex to give julolidine derivatives with up to >99% ee [133]. 

In 2012, a further evaluation of the gold(I)/chiral Brpnsted acid binary catalytic systems was carried out by the same research group [134]. In this report, the well-designed enynes 375 can be efficiently converted into 1,3-silyloxydienes 378 via Au(I) 377-catalyzed hydrosiloxylation, thus enabling subsequent asymmetric Diels-Alder reaction in the promotion of a phosphoramide 70b, affording polycyclic compounds 379 in high optical purties (Scheme 2.100). This relay catalytic cascade intramolecular hydrosiloxylation/asymmetric Diels-Alder reaction provides an unprecedented alternative to traditional Diels-Alder reactions. 

More recently, Patil et al. reported a cascade reaction of 2-aminobenzaldehydes and 2-amino benzamides by combining chiral Brpnsted acid and achiral gold catalysis [76]. The attractive optically pure 1,2-dihydroisoquinolines were prepared by chiral phosphoric acid-catalyzed asymmetric condensation of alkyne-tethered aldehydes with 2-aminobenzamides to give rise to the chiral aminal 136, which was followed... 

The first three chapters focus on organocatalytic cascade reactions, including amines, and Brpnsted acids, and the use of organocatalytic cascade reactions in natural product synthesis and drug discovery. Subsequent chapters introduce new developments and progress in transition metal cascade catalysis. Gold- and platinum-catalyzed... 

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