Enantioselective amination

Figure 11.1 Enzymatic deracemization of racemic amines via a two-step, one-pot process utilizing an enantioselective amine oxidase in combination with ammonia-borane.

Scheme 2.31 Deracemization of amines via combined use of an enantioselective amine oxidase and ammonia borane.

Recently, Turner et al. described the synthesis of the alkaloid (R)-(-t-)-crispine A, which shows cytotoxic activity against HeLa human cancer cell lines, using in the final step a deracemization procedure with the combination of an enantioselective amine oxidase obtained by directed evolution methods and a chemical non-selective reducing agent (Scheme 10.20) [48]. 

Enantioselective amination of enolsilanes has also benehted from the use of bis(oxazoline) lignads. " For example, (Z)-l-phenyl-l-(trimethylsilyloxy)-l-pro-pene, 242 was condensed with 243 using copper(ll) triflate-complex bu-box ligand 3 to afford 244 in 95% yield (99% ee) as shown in Figure 9.72. 

Troc = 2,2,2-trichloroethoxycarbonyl Figure 9.72. Enantioselective amination of enolsilanes. 

The enantioselective amination of iV-acyl oxazolidinones has been studied as part of a general approach to the synthesis of arylglycines. In this case, the enolization is initiated by a chiral magnesium bis(sulfonamide) complex. The oxazolidinone imide enolates are generated using catalytic conditions (10 mol% of magnesium complex) and treated in situ with BocN=NBoc to provide the corresponding hydrazide. 20 mol% of iV-methyl-p-toluensulfonamide are added to accelerate the reaction (equation 117). 

The Zr-catalyzed asymmetric alkylation shown in Eq. (2) [8] illustrates two important principles (1) The catalytic asymmetric protocol can be readily applied to the synthesis of non-aryl imines to generate homochiral amines that cannot be prepared by any of the alternative imine or enamine hydrogenation protocols. (2) The catalytic amine synthesis involves a three-component process that includes the in situ formation of the imine substrate, followed by its asymmetric alkylation. This strategy can also be readily applied to the preparation of arylamines. The three-component enantioselective amine synthesis suggests that such a procedure maybe used to synthesize libraries of homochiral amines in a highly efficient and convenient fashion. 

In 2000, the first highly enantioselective amine-catalyzed Diels-Alder reaction was disclosed [6], in which the addition of a range of a,/ -unsaturated aldehydes (dienophiles) to a variety of dienes (symmetrical and unsymmetrical) in the presence of catalytic amounts of imidazolidinone 1 (5-20 mol%) afforded the corresponding cycloadducts in good yields (72-99%), and high regio- and enantioselec-tivities (Eq. 3). (For experimental details see Chapter 14.18.1). 

A catalytic approach to the synthesis of arylglycines was proposed by Evans and coworkers using enantioselective amination of iV-acy 1 oxazolidinones [54], Metallo-bis(sulfonamide) complexes derived from chiral diamines are potential chiral catalysts. The magnesium-bis(sulfonamide) complex 109 was generated by treating (S,S)-bis(sulfonamide) 108 with dimethylmagnesium in dichloromethane (Scheme 50). 

An easy approach to optically active a-amino phosphonic acid derivatives was achieved in high yields and with up to 98% ee by enantioselective amination of P-keto phosphonates with azodicarboxylates, catalyzed by chiral bis(oxazolines) and Zn(OTf)2 <05JA5772>. 

Only a few examples in this category were found in the literature and azodi-carboxylic esters are the only animating reagents that have been used. The reactivities appear to be similar to those described above for ester enolates and ketene acetals. The catalyzed enantioselective amination of ketone silyl enol ethers described in Eq. 94 has also been applied to ketene thioacetals.252... 

Figure 4.31 Chiral supported palladium catalyst and its use in enantioselective aminations...

Advances in catal)rtic, enantioselective aminations and oxygenations of carbonyl compounds (heterocycles and their complexes as catalysts) 05AG(E)4292. 

The aziridination and amidation reactions of imidoiodanes can be efficiently catalyzed by Rh(II) complexes [810-815]. Dirhodium(II) tetrakis[Al-tetrafluorophthaloyl-(S)-tcrt-leucinate], Rh2(S-TFPTTL)4, has been found to be an exceptionally efficient catalyst for enantioselective aminations of silyl enol ethers 661 with imidoiodane 662 to afford a-amido ketones 663 in high yields and with enantioselectivities of up to 95% ee (Scheme 3.265). The effectiveness of this catalytic protocol has been demonstrated by an asymmetric formal synthesis of (-)-metazocine [810]. This catalyst has also been used for the asymmetric synthesis of phenylglycine derivatives by enantioselective amidation of silylketene acetals with PhINTs [811]. 

Jorgensen et al. described a highly enantioselective amination of a-substituted a-cyanoacetates with di-tert-butyl-azodicarboxylate (DEAD) catalysed by the quinidine-derived constrained alkaloid, p-isocupreidine (p-ICPD). ° Products were isolated in excellent yield and enantioselectivity (up to >98%). The generality of the method was demonstrated by the reaction on both open-chain and cyclic p-ketoesters. Products were again obtained in up to 99% yield, but in somewhat lower ee (up to 90%). Deng... 

Nitrogen-containing reagents electrophilic at the N atom such as azodicarboxylate esters, tosyl and nosyl azides, and nitrosobenzene have been successfiilly applied to a variety of organocatalyzed enantioselective amination reactions of carbonyl compounds and other related pronucleophiles. Early work in this area has been covered in previous reviews [1 ], and here the most representative examples are presented. 

Reviews have also featured transfer processes of nitrenes arising from chloramine-T and iminoindane catalysed by silver,C-H insertion of metallonitrene as an efficient process to perform enantioselective aminations, and silver-catalysed silylene transfers. " ... 

The nickel-iminophosphine-catalysed 4- -2-cycloaddition of enones with allenes formed highly substituted dihydropyrans. The enantioselective amine-catalysed 4-I-2-cycloaddition of allenoates with oxo-dienes produced polysubstituted dihydropyrans in high yields and with high enantioselectivities. Novel enam-ine/metal Lewis acid bifunctional catalysis has been used in the asymmetric inverse-electron-demand hetero-Diels—Alder reactions of cyclic ketones with Q ,j9-unsaturated a-ketoesters. The 4- -2-cycloaddition of acylketenes (80) with 2-unsubstituted and 2-monosubstituted 3-aryl-2//-azirines (81) produced 1 1 (82) or 2 1 (83) adducts, being derivatives of 5-oxa-l-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-l-azabicyclo[4.4.1]undeca-3,8-diene. The formation of the monoadducts proceeds via a stepwise non-pericyclic mechanism (Scheme 25). A-heterocyclic carbene-catalysed 4- -2-cycloaddition of ketenes with 1-azadienes yielded optically active 3,4-dihydropyrimidin-2-ones (93% ee) ... 

In a study aimed at obtaining enantioselective quartz crystal microbalance (QCM) sensors, it was found that bovine serum albumin (BSA) and human serum albumin (HSA) bind enantioselectively amines, alcohols, and esters with a decrease... 

In 2014, by employing the hydrogen autotransfer method, Zhao and co-workers reported the first enantioselective amination of alcohols to chiral secondary arylamines in high yields and high ee up to 97 % (Eq. 56, Scheme 31) [178]. Intramolecular amination could also be achieved to give quinoline 24 with 68 % ee. The authors proposed that the high enantioselectivity might be attributed to the cooperation of the iridium complex 25 and the chiral phosphoric acid 26. 

Zhang Y, Lim CS, Zhao Y et al (2014) Catalytic enantioselective amination of alcohols by the use of borrowing hydrogen methodology cooperative catalysis by iridium and a chiral phosphoric acid. Angew Chem Int Ed 53(5) 1399-1403... 

Tanaka M, Kurosaki Y, Washio T, Anada M, Hashimoto S. Enantioselective amination of silylketene acetals with (N-arylsulfonylimino)phenyliodinanes catalyzed by chiral dirhodium(II) carboxylates asymmetric synthesis of phenylglycine derivatives. Tetrahedron Lett. 2007 48 8799-8802. 

Anada M, Tanaka M, Washio T, Yamawaki M, Abe T, Hashimoto S. Catalytic enantioselective amination of silyl enol ethers nsing chiral dirhodinm(II) carboxylates asymmetric formal synthesis of (—)-Metazocine. Org Lett. 2007 9 4559-4562. 

Amines as nucleophiles in AAA have proven a challenge due to mono- vs. bisalkylation, regioselectivity issues and rate of nucleophilic addition vs allyl equilibration. While no AAA-based total synthesis has been reported utilizing an alkylamine nucleophile, novel ligand systems are being developed which provide unprecedented selectivity. For example, novel P,N-ferrocene ligand 69 mediated a regio- and enantioselective amination of allylic acetates. The product 68 was isolated predominantly as the branched isomer in 90% yield, 98% ee. 

Binaphthyl derivatives. Cooperative catalysis by [Pd(dba)2] and the chiral phosphoric acid (204) in combination with the phos-phoramidite ligand (205) has been applied for efficient enantioselective amination of racemic allylic alcohols (202) with a variety of functionalised amines (203) (Scheme 54). ... 

The acid (223) has also been applied as a cocatalyst together with the iridium complex (224) in enantioselective amination of alcohols (225). The reaction provided access to a wide range of chiral amines (226) with good to excellent enantioselectivity (69-97% ee) (Scheme 60). ... 

Scheme 10.55 Guanidine-catalyzed enantioselective amination of a-ketoesters.

Tandem enantioselective amination/spontaneous annulation as a key step in the preparation of suvorexant. 

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