Transfer ketimine

The acid-catalyzed reaction of acetophenone with acyclic secondary amines results in the formation of the expected enamine and a rearrangement product. The latter product arises from the transfer of one of the amino N-alkyl groups to the cnamine s carbon to produce a ketimine (53a). 

The first example of an asymmetric reduction of C=N bonds proceeding via DKR was reported in 2005 by Lassaletta et al. In this process, the transfer hydrogenation of 2-substituted bicyclic and monocyclic ketimines could be accomplished via DKR by using a HCO2H/TEA mixture as the hydrogen source and a chiral ruthenium complex including TsDPEN ligand,... 

Ketimines were hydrogenated faster than aldimines, and electron-donating groups accelerated the rate of hydrogenation. The OH and RuH bonds are regenerated by hydrogen transfer to the unsaturated 16-electron Ru complex from isopropanol, generating acetone (Scheme 7.13). 

Various phenyl-substituted ketimines and aldimines react with metallocenes 1 and 2, in a manner that depends on the substituents present [41]. In all cases, elimination of the al-kyne is observed. Complex 2b reacts with PhN=CMePh to give the r 2-complex 64, which is stabilized by an additional pyridine ligand [41a], In the reactions of 1 or 2a with the ketimine HN=CPh2, hydrogen transfer generates complexes 65. Two molecules of the aldimine PhN=CHPh are coupled by 2a to give the cyclic diamido complex 66 [41b]. 

The Br0nsted acid catalyzed enantioselective reduction of several methyl-aryl ketimines affords the corresponding amines in good yields and enantioselectivities (Table 4.1). The mild reaction conditions and generally good chemoselectivity of this transfer hydrogenation render this transformation an attractive and metal-free approach to optically active amines. 

Recently, we established that several proton acids catalyze the metal-free reduction of ketimines under hydrogen-transfer conditions with Hantzsch dihydropyridine as the hydrogen source.Additionally, we were able to demonstrate a catalytic enantioselective procedure of this new transformation by employing a chiral Br0nsted acid as catalyst.(see Chapter 4.1). 

Keywords Asymmetric hydrogenation, Asymmetric transfer hydrogenation, Ketimines, Oxime, Nitrones... 

Epoxidation of both aldimines and ketimines is possible. Most oxaziridines formed are stable compounds, especially aldimines containing aromatic substituents, and 2-sulfonyl-and 2-sulfamyl oxaziridines5. Generally, /V-sulfonyloxaziridines are isolated as stable crystalline solids. Certain compounds are widely used in synthetic organic chemistry as oxygen-transfer reagents (15-17). 

A hindered BINAP-phosphoric acid catalyst allows the enantioselective reduction of ketimines via transfer hydrogenation.307 Imines can be generated in situ from either aliphatic or aromatic ketones, with low catalyst loading. 

In 2005, both Rueping et al. and List et al. reported the first transfer hydrogenation with Hantzsch ester 1 of several N-protected ketimines catalyzed by chiral Bronsted acids derived from l,l -binaphthol [17, 18]. The reaction typically requires 1 to 20 mol% of catalyst, is performed in benzene at 60 °C, and enantio-selectivities of up to 90% are obtained. The chiral Bronsted acid protonates the lcetimine at nitrogen, giving an ion-pair which is reduced by Hantzsch ester 1. (For experimental details see Chapter 14.21.2). A preferred transition state has... 

Table 11.3 Transfer hydrogenation of ketimines catalyzed by chiral Bronsted acids.

The nucleophilic activation of hydrosilanes as HSi(OR)3 offers an opportunity to transfer one hydride on the carbon of ketones or imines [22]. The enantioselective organocatalytic hydrosilylation of ketones was first reported in 1999 by Matsu-mura et al. [23], the catalyst employed being a proline derivative 19 (Scheme 11.7). Amide 20 was also able to catalyze the hydrosilylation of ketimines, as indicated in Scheme 11.7 [24]. Improved results were recently reported by Kocovsky and Maikov [25], who prepared from valine some acyclic analogues of prolina-... 

Silver-catalyzed di-tert-butylsilylene transfer to imines proved general (Scheme 7.49).123 Exposure of alkyl- or arylimines with IV-benzyl or iV-aryl groups to cyclohexene silacyclopropane 58 in the presence of 1 mol% of silver triflate produced silaaziridines 170. Even ketimine 169f was tolerated as a substrate. 

Scheme 7.49. Scope of Ag-catalyzed di-tert-butylsilylene transfer to aldimines and ketimines.

Early examples of intramolecular aryl radical addition reactions to heteroatom containing multiple bonds included cyclizations on N=N and C=S moieties [52, 53]. Recently, cyclizations to imines have been used as part of a new enantio-selective approach to indolines (Scheme 8). In the first step of the sequence, the required ketimines 19 were obtained by phase-transfer catalyzed alkylation of 2-bromobenzyl bromides 20 with glycinyl imines 21 in the presence of a cincho-nidinium salt [54], Due to the favorable substitution pattern on the imine moiety of 19, the tributyltin hydride mediated radical cyclization to 22 occurred exclusively in the 5-exo mode. The indoline synthesis can therefore also be classified as a radical amination. 

The bulky orange-yellow precipitate of the ketimine hydrochloride is separated by decanting the ether and washed twice with 20-cc. portions of dry ether. The solid is transferred to a 2-1. round-bottomed flask with r 1. of hot water. The flask is provided with a reflux condenser, and the yellow solution is boiled vigorously over a wire gauze for two hours. A small quantity (3-4 g.) of decolorizing carbon (Norite) is added, the... 

Biomimetic Reductions Amino Acid Dehydrogenases as the Role Model for the Brpnsted Acid Catalyzed Transfer Hydrogenation of Ketimines... 

Based on the above activation mechanism we wondered whether it would be possible to develop a biomimetic, organocatalytic reductive amination or transfer hydrogenation of ketimines. We reasoned that the activation of the imine by catalytic protonation through the Brpnsted acid should enable the hydrogen transfer from a suitable NADH mimic to yield the corresponding amine (Fig. 2). Hence, initial experiments focused on the examination of various Brpnsted acids in combination with different hydride sources (Rueping et al. 2005a). 

With regard to the mechanism we assume that, similar to the dehydrogenase (Fig. 1), the ketimine 1 will be activated by protonation through Brpnsted acid 5 which results in the formation of a chiral ion-pair, an iminium ion A. Subsequent hydrogen transfer from the dihy-... 

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