Dynamic kinetic asymmetric amines

Trost s dynamic kinetic asymmetric amine aiiyiation appiied to the synthesis of 3,5-dideoxy-2,5-imino-D-manni-toi and (-)-buigecinine... 

In 2015, Zhao and co-workers described the first dynamic kinetic asymmetric amination of alcohols via borrowing hydrogen methodology under the cooperative catalysis of iridium complex 25 and chiral phosphoric acid 27 (Schemes 31, 32) [179]. The authors proposed that, initially, the two stereocenters in the alcohols were both racemized to ketone by the first oxidation, followed by tautomerization of the iminium intermediates 28 and 30 through enamine intermediate 29. Then, the... 

Rong Z-Q, Zhang Y, Zhao Y et al (2015) Dynamic kinetic asymmetric amination of alcohols from a mixture of four isomers to diastereo- and enantiopure (x-lnanched amines. J Am Chem Soc... 

The Gabriel synthesis represents another indirect but highly valuable approach to amines. Trost has demonstrated a method for the asymmetric ring-opening of butadiene monoepoxide by use of one equivalent of phthalimide, 7t-allylpalladium chloride dimer, and the chiral bisphosphine 22 (Scheme 7.37). The dynamic kinetic asymmetric transformation proceeded through a putative achiral intermedi-... 

Notable were highly enantioselective additions of N-phosphonyl imines with dialkyl zinc or hydroxyketones and a one-pot reaction of alkynylzirconocenes with alkynyl phosphazenes and zinc carbenoids to give single isomer cyclopropylphosphonamides. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. Other interesting reports cover the use of phosphoramidates for the synthesis of allylic amines as well as the first example of C-P cleavage of a-aminophosphono acids using periodate. 

By analogy to the DYKAT reactions with vinyl epoxides, Trost et al. have developed the Pd-eatalysed asymmetric dynamic kinetic allylic amination and acyl migration of vinyl aziridines with benzoyl imido carboxylates. As shown in Scheme 2.51, the process afforded the corresponding protected vicinal diamines in high yields and enantioselectivities of up to 93% ee. This methodology was demonstrated to be a platform for the formal synthesis of (-I- )-balanol and analogues. 

Recently, Lin et al. demonstrated that the propargyl alcohol could participate in such a transformation for the synthesis of chiral dihydrofurans [53]. The reaction began with a challenging oxa-Michael addition to cinnamaldehyde derivatives, which was followed by a secondary amine/Pd complex-catalyzed nucleophilic addition/ isomerization of the alkyne moiety in excellent yields and enantioseleclivities (Scheme 9.58). Since the oxa-Michael addition of propargyl alcohol to 0[,P-unsaturated aldehydes was a slow process, this cascade reaction proceeded through a dynamic kinetic asymmetric transformation (DYKAT) process, whereby it made the overall reaction proceed efficiently and with high stereocontrol using the second reaction with precise stereocontrol to shift the first reversible oxa-Michael addition selectively. 

Considering the rapid growth of asymmetric construction of oxindoles, Sun et al. recently reported their assembly of chiral spirooxindoles by combining secondary amine and palladium catalysis in a cascade reaction [55]. The reaction was initiated by the reversible Michael addition of 3-substituted oxindole to enal, which was followed by a metal/organic-cocatalyzed carbocyclization of the aUcyne tether (Scheme 9.60). Similar to the aforementioned dynamic kinetic asymmetric transformations, this chemistry highlighted the cooperative effects of the two catalysts in the same reaction vessel, while either catalyst could not solely promote the overall reaction, and unsatisfactory results were observed when this reaction was conducted in a two-step mode. 

The complete transformation of a racemic mixture into a single enantiomer is one of the challenging goals in asymmetric synthesis. We have developed metal-enzyme combinations for the dynamic kinetic resolution (DKR) of racemic primary amines. This procedure employs a heterogeneous palladium catalyst, Pd/A10(0H), as the racemization catalyst, Candida antarctica lipase B immobilized on acrylic resin (CAL-B) as the resolution catalyst and ethyl acetate or methoxymethylacetate as the acyl donor. Benzylic and aliphatic primary amines and one amino acid amide have been efficiently resolved with good yields (85—99 %) and high optical purities (97—99 %). The racemization catalyst was recyclable and could be reused for the DKR without activity loss at least 10 times. 

List later reported the asymmetric reductive amination of a wide spectrum of aromatic and aliphatic a-branched aldehydes via dynamic kinetic resolution (Scheme 5.27) [49]. The initial imine condensation product is believed to undergo fast racemization in the presence of the acid catalyst Ih through an imine/enamine tautomerization pathway. Preferential reductive amination of one of the imine enantiomers furnishes the optically pure P-branched amine. 

The integration of a catalyzed kinetic enantiomer resolution and concurrent racemization is known as a dynamic kinetic resolution (DKR). This asymmetric transformation can provide a theoretical 100% yield without any requirement for enantiomer separation. Enzymes have been used most commonly as the resolving catalysts and precious metals as the racemizing catalysts. Most examples involve racemic secondary alcohols, but an increasing number of chiral amine enzyme DKRs are being reported. Reetz, in 1996, first reported the DKR of rac-2-methylbenzylamine using Candida antarctica lipase B and vinyl acetate with palladium on carbon as the racemization catalyst [20]. The reaction was carried out at 50°C over 8 days to give the (S)-amide in 99% ee and 64% yield. Rather surpris-... 

A dynamic kinetic resolution has been employed to achieve a catalytic asymmetric reductive amination of aldehydes.332 Reductive amination of ketones and aldehydes by sodium triacetoxyborohydride has been reviewed, highlighting its advantage over other reagents.333... 

It was mentioned at the beginning of this chapter that alkaloids were among the first catalysts to be used for asymmetric hydrocyanation of aldehydes. More recent work by Tian and Deng has shown that the pseudo-enantiomeric alkaloid derivatives 5/6 and 7/8 catalyze the asymmetric addition of ethyl cyanoformate to aliphatic ketones (Scheme 6.6) [50]. It is believed that the catalytic cycle is initiated by the alkaloid tertiary amine reacting with ethyl cyanoformate to form a chiral cyanide/acylammonium ion pair, followed by addition of cyanide to the ketone and acylation of the resulting cyanoalkoxide. Potentially, the latter reaction step occurs with dynamic kinetic resolution of the cyano alkoxide intermediate... 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

The first example of the asymmetric synthesis of P-chiral trialkyl phosphates (12) via trialkyl phosphite, in which the keystone is dynamic kinetic resolution in the condensation of a dialkyl phosphorochloridite (13) and an alcohol by the catalytic assistance of a chiral amine has been reported (Figure 2)." 2,4-Dinitrophenol (DNP) was employed as an activating reagent with ben-zyloxy-bis-(diisopropylamino) phosphite to synthesize the cyclic phosphate derivatives (14) from a series of alkane diols HO-(CH2)n-OH (n=2-6). Included was a cyclic phosphate derivative of carbohydrate (15). The mechanism of activation by 2,4-DNP and cyclization was also described (Figure 3). ... 

The product class of enantiomerically pure amines is of considerable importance in both pharmaceutical and agrochemical applications. For instance, enantiopure aryl-alkyl amines are utilized for the synthesis of intermediates for pharmaceutically active compounds such as amphetamines and antihistamines. Several chemical as well as biotransformation methods for the asymmetric synthesis/dynamic kinetic resolution [29] or separation of enantiomers of chiral amines have been described. These are illustrated in Scheme 4.5 for (S)-a-methylbenzylamine [30]. 

The first example of the asymmetric synthesis of P-chiral trialkyl phosphates (12) via trialkyl phosphite, in which the keystone is dynamic kinetic resolution in the condensation of a dialkyl phosphorochloridite (13) and an alcohol by the catalytic assistance of a chiral amine has been reported (Figure 2). ... 

Only a limited number of examples of the biocatalytic oxidation of tertiary amines have been reported. Colonna et td. used bovine serrmi albumin (BSA) as a biocatalyst for the asymmetric oxidation of tertiary amines to N-oxides [127]. Oxone, NaI04, H2O2, and MCPBA were tested as oxidants, and the best results were obtained with NaI04 and H2O2 (Eq. (8.30)). Thus, BSA-catalyzed N-oxidation of 36 with these oxidants afforded N-oxide 37 in high yield in 64—67% ee. The reaction is formally a dynamic kinetic resolution, since the enantiomers of the starting material are in rapid equilibrium. 

TABLE 29.2 A Variety of Chiral Amines and Amino Alcohols Produced with Asymmetric Synthesis (AS) and Dynamic Kinetic Resolution (DKR)/Deracemization (DE)... 

Hoffmann S, Nicoletti M, List B. Catalytic asymmetric reductive amination of aldehydes via dynamic kinetic resolution. J. Am. Chem. Soc. 2006 128 13074-13075. 

Stereoselective Reductive Amination Using Chiral Ketones as Auxiliary The first report of asymmetric reductive amination using chiral ketone was published by Nugent and co-workers in 2004. The current methodology includes dynamic kinetic resolution of a racemic ketone 128 producing a chiral ketone 129,... 

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