Kinetic Resolution of Amines

KR of epoxides through ring opening with carbamates 

---

Kinetic resolution of racemic allylic acetates has been accomplished via asymmetric dihydroxylation (p. 1051), and 2-oxoimidazolidine-4-carboxy-lates have been developed as new chiral auxiliaries for the kinetic resolution of amines. Reactions catalyzed by enzymes can be utilized for this kind of resolution. ... 

Aral S, Bellemin-Laponaz S, Fu GC (2001) Kinetic resolution of amines by a nonenzymatic acylation catalyst. Angew Chem Int Ed 40 234-236... 

Dynamic Kinetic Resolution of Amines Involving Biocatalysis and In Situ Free-radical-mediated Racemization... 

Gastaldi, S., Escoubet, S., Vanthuyne, N., Gil, G. and Bertrand, M.P., Dynamic kinetic resolution of amines involving biocatalysis and in situ free radical mediated racemization. Org. Lett., 2007, 9, 837-839. 

Enzymatic kinetic resolution of amines Faber K (2000) Biotransformations in organic chemistry, 4th edn. Springer, Berlin Heidelberg New York, Sect. 3.1.3... 

Catalytic kinetic resolution of amines has been a typical domain of enzymatic transformations. Attempts to use low-molecular-weight catalysts have notoriously been frustrated by the rapid uncatalyzed background reaction of the amine substrate with the acyl donor [40]. The first solution to this problem was recently developed by Fu, who used the planar chiral catalyst 21d and O-acyl azlactone 40 as the acyl donor (Scheme 12.19) [41]. In this process, the acyl transfer from the azlactone 40 to the nucleophilic catalyst 21d is rapid relative to both direct transfer to the substrate and to the transfer from the acylated catalyst to the substrate amine. Under these conditions, which implies use of low reaction temperatures, selectivity factors as high as 27 were achieved (Scheme 12.19) [41]. 

For a stoichiometric kinetic resolution of amines, using preformed N-acyl derivatives of ferrocenyl DMAP derivatives see Y. Ie, G. C. Fu,... 

In general the hydrolysis of amides is performed as a kinetic resolution and not as a dynamic kinetic resolution. It is applied industrially [96] but in most cases the industrial kinetic resolution of amines, as performed for instance by BASF, is an acylation of racemic amines [38], rather than the hydrolysis of racemic amides. For the acylation of amines many different acyl donors [27] and enzymes can be used, including lipases (or a review see [97]). 

Acylases have also been applied to the kinetic resolution of amines. Aminoacylase I from Aspergillus melleus was used for the resolution of a range of arylalkylamines and amino alcohols via acylation with methyl 2 methoxyacetate (Figure 14.13) [19]. Excellent chemoselectivity was also observed in all cases, as the amino group was preferentially acylated in the presence of a primary alcohol functionality. However, poor to moderate enantioselectivity was observed, with values <10. The best result (E = 9.3) was obtained with 1 aminoindane 10 during the conversion to ester 38. 

Compare and contrast the dynamic kinetic resolution of amines with dera cemization. For each approach, outline the basic principle ofthe method and then suggest suitable biocatalyst/chemocatalyst combinations necessary for each process. 

In the late 1990s, several research groups worked on the development of chiral DMAP analogs. The works of Fu [23], Vedejs [24], and Fuji [25] led to the synthesis of powerful catalysts and the development of enantioselective organocatalytic reactions such as Steghch rearrangements, kinetic resolutions of secondary alcohols, kinetic resolution of amines, and so on (Scheme 1.8). 

The most intriguing aspect, however, lies in the enantioselective formation of amides, where the center of chirality is located on the amine (chiral R ) [271]. Thus, kinetic resolution of amines may be achieved [272-274]. 

Kim, Y.-W., Park, ).-W., and Kim, M.-J. (2011) Dynamic kinetic resolution of amines and amino acids by enzyme-metal Co-catalysis. ChemCatChem, 3, 271-277. 

Synthesis of amides through the dynamic kinetic resolution of amines. 

Arseniyadis, S. Valleix, A. Wagner, A. Mioskowski, C. Kinetic resolution of amines A highly enantioselective and chemoselective acetylating agent with a unique solvent-induced reversal of stereoselectivity. Angew. Chem. 

A simple nucleophilic catalyst such as 4-(dimethylamino)pyridine (DMAP, 23) has been found to be the ideal catalyst in the kinetic resolution of amines when it was used in combination with a chiral hydrogen-bonding (HB) catalyst [13]. The combined catalyst system formed from DMAP and HB catalyst exhibited excellent enanhoselective induction in the kinetic resoluhon of benzylic [13a], propargyHc [13b], and aUylic amines [13c] as well as in the desymmetrization of meso-1,2-diamines (Scheme 43.4) [13d]. 

The synthesis of chiral amines using co-TA can be performed by three different pathways (Scheme 2.2) [19] (i) kinetic resolution of amines by oxidative deamination, (ii) stereoselective synthesis via amination of prochiral ketones, and (iii) deracemization combining (i) kinetic resolution and (ii) stereoselective synthesis [19]. 

The kinetic resolution of amines was exploited first with co-TAs since the reaction is thermodynamically favored using pyruvate as acceptor [21]. Unfortunately, the inherent maximum 50% yield limits the practical applications of this approach and, therefore, will nof be considered in fhis confribufion. Thus, the other methodologies (stereoselective synthesis and deracemization) are preferred since a theoretical yield of 100% is possible. The asymmefric amination allows fhe preparation of enantiomer-ically pure amines at the expense of an amine donor, usually an amine or an AA (Scheme 2.2b). On the other hand, the combination of two stereocomplementary co-TAs enables to establish a deracemization process (Scheme 2.2c). Deracemization strategies are recommended when amines are readily available or the corresponding carbonyl compounds lack stability. 

DYNAMIC KINETIC RESOLUTION OF AMINES AND AMINO ACIDS... 

---