Hydrogenation of aldimines

The transfer hydrogenation of aldimines has not been reported. In our own studies we have tested the simple Schiff base adduct between benzylamine and benzaldehyde and shown this to be reduced in straightforward manner. 

Scheme 6.24 Amines obtained from the transfer hydrogenation of aldimines in the presence of catalyst 9 and Hantzsch ester 19.

A new Ru- 7 -arene complex (45) acts as a C-based Lewis acid catalyst for the hydrogenation of aldimines at ambient temperature via a frustrated Lewis pair mechanism with 102 atm H2 in DCM at 25 °C, 1 mol% catalyst gives up to 99% amine in 8 h. The catalyst and its mechanism have been extensively characterized by X-ray crystallography and NMR, including deuteration experiments with D2 which prove that exchange is occurring ortho- and para- to the boron. 

The combinahon of a stronger Bronsted acid with an electrophile bearing a basic electrophile would result in a Bronsted-acid-catalyzed reaction. Use of aldehyde in place of aldimine with neutral acid would lead to a hydrogen-bond-catalyzed reaction. 

With enamino nitrile 9 intramolecular hydrogen bonding cannot take place so a rapid isomerization occurs between 13a and 13b giving rise to the trans AMCPA as the major isomer after hydrogenation. Isomerization to 13b is reinforced also by the slower rate of hydrogenation of a nitrile group than an aldimine one. 

Aldimines are generally more easily hydrogenated than ketimines, due to the steric hindrance arising with the latter compounds444. The rate of hydrogenation of imines and the product composition are determined by the structure of the imine448. 

It appears probable that the aldimine II, initially formed by hydrogenation of the nitrile group, is itself in the stabilized, cyclic-hemiacetal form as a 1,2-diamino-l, 2-dideoxy derivative (III), the 1-amino group of which is subsequently hydrolyzed to yield the cyclic 2-amino-2-deoxy sugar (IV) directly.10 10a... 

Over the past half-dozen years, many laboratories have focused their efforts on the development of chiral hydrogen bond donors that function as catalysts for enantioselective organic reactions. One of the earliest successes in this area came from Jacobsen and co-workers, who reported the use of peptide-like chiral urea-based catalysts for the hydrocyanation of aldimines and ketoimines [40, 41]. Several other laboratories have also reported highly enantioselective transformations catalyzed by a chiral hydrogen bond donor. The following sections provide a summary of the many developments in hydrogen bond-catalyzed enantioselective reactions, along with a discussion of mechanisms and selectivity models. 

The N-hydroxy structure (26) was preferred123 to an iV-oxide representation on account of the amphoteric nature of the product and because the derived acetate formed a well-defined hydrochloride salt. Hydrogenation of these N-hydroxyimidazoles over Raney nickel gives imidazoles in 60-94% yields.122 The reaction has been adapted for the preparation of 4-mercaptoimidazoles, using an a-ketothionamide (27) with an aldimine.124... 

Hydrogenation of a mixture of amines and aldehydes or ketones results in the formation of unsymme-trical secondary amines. The hydrogenation of the intermediate aldimine or ketimine can be carried out by heterogeneous catalytic hydrogenation over metal catalysts such as platinum, palladium, nickel or Raney nickel. The overall reaction can be regarded as an alkylation of the amino compounds, and also as a reductive amination of the aldehyde or ketone (Scheme 3). 

Hydrogenation of a nitrile under ordinary conditions suffers from the dilflculty Unit the primary amine formed condenses with the Intermediate aldimine to form the secondary amine, (iould. Johnson, and Ferris" eliminated this side reaction by... 

Formation of an aldimine intermediate is the first step in the catalytic hydrogenation of nitriles. When hydrogenation is carried out in aqueous acidic media, aldehydes may form by hydrolysis of the aldimine. Selective hydrogenation of aromatic nitriles to ben-zaldehydes over finely divided Ni (Raney Ni) is best obtained with an equimolecular amount of H2SO4 in a 10 1 mixture of tetrahydrofuran-water ... 

A titanium chelate of dihydroxylamine 87 helps organization of the addends so that a-amino nitriles of the (/J)-conliguration ate generated. Thiourea 88 with a proximal salen unit offers multiple hydrogen bonding sites for an analogous purpose of acetylcyana-tion of aldimines. ... 

The strategies presented in Table 8.1 can be generalized in the following manner (1) carbanion addition to aldimine or ketimine derivatives (2) sequential amination-alkylation of aldehydes (carbanion addition to in situ formed aldimine derivatives) (3) transfer hydrogenation or hydrogenation of imines (4) reductive amination of ketones and (5) N-acetylenamide reduction. Because of the difficulty of their synthesis, a-alkyl,-alkyl substituted amines are highlighted whenever possible. 

These dihydride complexes readily catalyze the hydrogenation of neat ketones to the alcohols under 1 atm of H2 gas at 20°. For example neat acetophenone (4.1 g, 34 mmol) was quantitatively hydrogenated to 5-phenethyl alcohol (60% e.e.) in less than 8 h by use of catalyst containing the chiral diamine (5 mg, 0.0068 mmol). Benzene was used as the solvent for the a,p-unsaturated ketone, benzal-acetone, and the product was exclusively the allylalcohol. The hydrogenation of an aldimine and a ketimine in benzene also proceeded under notably mild conditions [111]. 

Recognizing that FLP activation of H2 requires a bulky base and acid combination, we probed the question of whether a bulky imine could act both as the base component of an FLP and as the substrate for catalytic reduction. Indeed, a number of aldimines and ketimines could be hydrogenated with a catalytic amount of B(QF5)3 under H2 in a facile manner (Table 11.2, Scheme 11.13) [47]. As with the phosphino-borane catalyst, dx-triphenylaziridine is also reduced under these conditions to N-(l,2-diphenylethyl)aniline (Table 11.2) [47]. 

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