Phosphoric acid catalysis transfer hydrogenation

Soon after these initial reports, the groups of Antilla [92] and You [93] indepen dently applied the chiral phosphoric acid catalysis to the enantioselective hydro genation of a imino esters. The method provides an alternative route to the enantioselective synthesis of a amino esters. Antilla and coworkers employed a new type of axially chiral phosphoric acid (9) derived from VAPOL originally developed by his research group (Scheme 3.42), whereas lg was used in You s case. In both cases, excellent enantioselectivities were achieved. You and coworkers further applied the method to the enantioselective reduction of a imino esters having an alkynyl substituent at the a position (Scheme 3.43) [94]. Both alkyne and imine moieties were reduced under transfer hydrogenation conditions with an excess amount of... 

Scheme 7.22 Domino addition-cycloisomerisation-transfer hydrogenation reaction catalysed by chiral phosphoric acid catalysis, amine catalysis,...

Almost at the same time, Liu and Che published a cascade intermolecular hydroamination/asymmetric reduction sequence, which included achiral Au complex-catalyzed hydroamination of aryl amines and chiral phosphoric acid-promoted Hantzsch ester reduction to afford secondary aryl amines [70], More recently, the same group reported a tandem one-pot assembly of functionalized tetrahydroquino-lines from amino aldehyde and alkynes by combining Au and chiral phosphoric acid catalysis [71], The reaction was initiated by Au-promotedquinololine 210 generation, followed by an enantioselective HEH-incorporated transfer hydrogenation process (Scheme 9.67). 

The enantioselective version of the relay transformation by organic and metallic catalyses was successfully demonstrated by Gong and coworkers (Scheme 3.39) [83]. They accomplished the direct transformation of o propargylaniline derivatives into tetrahydroquinolines in a highly enantioselective manner through the hydroamina tion of alkynes/isomerization/enantioselective transfer hydrogenation (see Sec tion 3.3 for details) sequence under the relay catalysis of an achiral Au complex/ chhal phosphoric acid binary system. 

A novel protocol described the direct conversion of 2-(2-propynyl)aniline derivatives (128) into tetrahydroquinolines (129) in high enantioselectivities, in one operation, through a consecutive hydroamination of alkynes/asym-metric transfer hydrogenation reactions under the catalysis of an achiral Au complex and the chiral phosphoric acid (124) binary system (Scheme 31). ... 

On the other hand, the use of chiral anions in conjunction achiral or chiral ammonium ion catalysts has been pioneered by List and co-workers. In 2006, Mayer and List [ 166] hypothesized that catalytic salts of achiral amines and chiral phosphoric acids could induce asymmetry in the transfer hydrogenation of p,p-disubstituted-a,p-unsaturated aldehydes, in a process that would be complementary to the previously developed chiral iminium catalysis (see Section 2.2.1.4) of this process [68,167]. The experimental verification of this hypothesis demonstrated that excellent yields and enantioselectivities (90-98% ee) could be achieved in these hydrogenations. The fact that with an achiral secondary amine such as morpholine the process was highly stereoselective led the authors to postulate that ion-pairing and not Brpnsted acid... 

The use of iminium-catalysis to facilitate highly asymmetric transfer hydrogenations has already been covered in some detail previously (Sect. 3.2.1) (203-205, 210) and the interested reader is referred to the original literature cited therein. Besides iminium activation in combination with Hantzsch dihydropyridines as hydride donors, the use of chiral phosphoric acids in... 

Scheme 7.67 Tandem hydroamination-hydroarylation-transfer hydrogenation reaction catalysed by gold catalysis and chiral phosphoric acid...

Recently, Chen et al. reported a novel hydrogenation of quinoxalines 357 via the convergent disproportionation reaction of dihydroquinoxalines 359 under a ruthe-nium/Br0nsted acid relay catalysis system (Scheme 2.95) [130a]. This transformation was initiated by the reduction of quinoxalines to dihydroquinoxalines 359 under the catalysis of [Rul/i-cymene) ] 360 the active intermediate then underwent phosphoric acid-catalyzed self-transfer hydrogenation to afford primary starting material 357... 

Au(l)/Br0nsted Acid System Han et al. developed an unprecedented protocol to synthesize tetrahydroquinolines 332 directly from 2-(2-propynyl)aniline derivatives 365 in one pot under relay catalysis of an achiral Au complex 368 and a chiral phosphoric acid 5j [131]. The Au -catalyzed intramolecular hydroamination of 2-(2-propynyl)aniline provided the 1,4-dihydroquinolines 366, followed by isomerization into imine-like 3,4-dihydroquinoliniums 367 with 5j. This active intermediate then underwent asymmetric transfer hydrogenation with Hantzsch ester to produce enantioenriched tetrahydroquinoUne products (Scheme 2.97). 

Asymmetric hydride reduction using Hantzsch ester has recently been extensively explored in organocatalysis using iminium-based catalysts or Brpnsted acid catalysts [72a-c], As an advance to their asymmetric conterion-directed catalysis (ACDC), List and coworkers found that the combination of simple primary amino acids such as L-valine with a chiral phosphoric acid led to an effective primary aminocatalyst for asymmetric transfer hydrogenation of a,P-unsaturated ketones (Scheme 5.43) [72d]. The catalysis could be applied to a range of substrates with good yields and excellent enantioselectivity. 

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