Achiral transfer hydrogenation

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

A nice analysis of non-linear effects in Rh-chiral diamine-catalysed transfer hydrogenation has been performed that reinforces the need to consider the kinetics of all of the steps in reaction manifolds (e.g. reversible formation of diastereomeric precursors and their subsequent interaction with achiral reactants). ... 

A new catalyst salt (20) that consists of an achiral ammonium ion and a chiral phosphate anion and which catalyses highly enantioselective transfer hydrogenations of ,/J-unsaturated aldehydes to the corresponding saturated derivatives has been developed. The underlying principle, namely asymmetric counteranion-directed catalysis, is claimed to be a new strategy for highly enantioselective synthesis.357... 

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. 

The reaction actually produces a mixture of the primary amine and the correspond ing formyl derivative, but the amine product is exclusively isolated after the crude product is treated with H Cl (Scheme 7.3). As of this writing, the method provides low yields and ee for cyclic aromatic substrates, for example, 1 indanone (6% yield, no ee reported, chiral Ru catalyst) [11b]. Regarding aliphatic ketones, for example, 2 octanone (44% yield, 24% ee, chiral Ru catalyst [lla[ or 37% yield with an achiral Rh catalyst [11b]). The same authors have recently made inroads concerning the use of aromatic ketones and molecular hydrogen [12], although the transfer hydrogenation method presented here appears to be superior as of now. 

An alternative enzyme/transition metal combination employs transfer hydrogenation catalysts that are capable of racemizing secondary alcohols. The racemization procedure temporarily converts the alcohol into an achiral ketone, which is reduced back to the racemic alcohol. Coupling this racemization procedure to an enzyme-catalyzed acylation reaction affords a dynamic resolution process (Fig. 9-12). Several enzyme/transition metal combinations have been shown to be effective for these reactions, although ruthenium complexes 1-3 appear to be especially effective for the in situ racemization of the alcohol. The product esters are not prone to racemization under the reaction conditions. Early results employing transfer hydrogenation catalysts to effect the racemization of alcohols required the use of added ketone 21, 22. However, it was subsequently shown that added ketone was not required when appropriate transition metal complexes were used as catalysts. Furthermore, the use of 4-chlorophenyl acetate as the acyl donor afforded improved results. 

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... 

Gong and co-workers developed the first step-economical synthesis of the previously described process. The approach involves a Friedlander condensation [88, 89] followed by a transfer hydrogenation catalyzed by a combination of an achiral Lewis acid and a chiral Brpnsted acid. This affords the direct conversion of 2-aminobenzaldehyde derivatives 19 and ketones 23 into highly optically active 1,2,3,4-tetrahydroquinoline derivatives 22 and 24, with enolizable dicarbonyl compounds 20 (Scheme 7) [90]. 

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). 

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). 

Recently hydroamination of alkyne along with transfer hydrogenation employing achiral Au-complex, Hantzsch ester 7, and chiral Brpnsted acid 8 has been found to be useful for the synthesis of chiral tetrahydroquinolines 9 (Scheme 39.6). ... 

Han Z-Y, Xiao H, Chen X-H, Gong L-Z. Consecutive intramolecular hydroamination/asymmetric transfer hydrogenation under relay catalysis of an achiral gold complex/chiral brpnsted acid binary system. J. Am. Chem. Soc. 2009 131 9182-9183. 

Hydrogen atom transfer implies the transfer of hydrogen atoms from the chain carrier, which is the stereo-determining step in enantioselective hydrogen atom transfer reactions. These reactions are often employed as a functional group interconversion step in the synthesis of many natural products wherein an alkyl iodide or alkyl bromide is converted into an alkane, which, in simple terms, is defined as reduction [ 19,20 ]. Most of these reactions can be classified as diastereoselective in that the selectivity arises from the substrate. Enantioselective H-atom transfer reactions can be performed in two distinct ways (1) by H-atom transfer from an achiral reductant to a radical complexed to a chiral source or alternatively (2) by H-atom transfer from a chiral reductant to a radical. 

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