Solvent chiral diamines

Preparation of ligand 31 Originally, chiral ligand 31 was prepared from (1R,2R)-1,2-diaminocydohexane 33 based on the racemic synthesis reported by Barnes et al. in 1978 [15], where picolinic acid 34 was activated with P(OPh)3 and then coupled with trans-l,2-diaminocyclohexane. The reported isolated yield in the case of racemate was only 47%. We optimized the preparation as shown in Scheme 2.8 [16]. Picolinic acid 34 was activated with CDI in THF. After confirmation of activation, chiral diamine 33 was added to the solution. When complete, the reaction was quenched via the addition of a small amount of water (to quench excess CDI). The reaction solvent was then switched from THF to EtOH, when the desired ligand 31 directly crystallized out. Ligand 31 was isolated in 87% yield by simple filtration of the reaction mixture in high purity. With a 22 litter flask, 1.25 kg of 31 was prepared in a single batch. 

Whiting and co-workers (231) reported that the chiral diamine 341Cu(OTf)2 complex is moderately effective in inducing the hetero-Diels-Alder reaction between glyoxylate imine (339) and Danishefsky s diene (334). In acetonitrile as solvent, this reaction provides cycloadduct 340 in 58% yield and 86% ee, Eq. 190. 

Table 9.6 shows the effect of both the addition time and the polarity of the solvent, as well as the nature of the aldehyde, in the catalytic asymmetric aldol condensation promoted by tributyltin fluoride and a chiral diamine coordinated to tin(n) triflate. 

High rates and selectivities are attainable only by the coordination of structurally well-designed catalysts and suitable reaction conditions. The base system employs a [RuCl2(phosphane)2(l,2-diamine)] complex as precatalyst, isopropanol serving both as solvent and hydrogen donor and in the presence of base, typically t-BuOK. Use of chiral diphosphanes, particularly BINAP compounds, and/or chiral diamines... 

The same group subsequently discovered that the loading of the chiral diamine catalyst can be reduced substantially if triethylamine is added in stoichiometric amounts as an achiral proton acceptor [37b]. As shown at the top of Scheme 13.23, as little as 0.5 mol% catalyst 45 was sufficient to achieve yields and ee comparable with the stoichiometric variant (application of the Oriyama catalysts 44 and 45 in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). Oriyama et al. have also reported that 1,3-diols can efficiently be desymme-trized by use of catalysts 44 or 45. For best performance n-butyronitrile was used as solvent and 4-tert-butylbenzoyl chloride as acylating agent (Scheme 13.23, bottom) [38]. 

Current efforts are directed towards (i) mechanistic issues to rationalize the effectiveness of the diamine-modified system in protic solvent in comparison to Zn-hydride catalyst, and (ii) the development of an efficient enantioselective version of this system with chiral diamines. 

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]. 

The aldol reaction of cyclic ketones and acetone with aromatic aldehydes were carried out in combination with triflic acid in water at 25°C [250]. Other chiral primary-tertiary diamine catalyst such as compound 167 (20 mol%) was used in combination with solid polyoxometalate acid support (6.67% mol) in the aldol reaction between dihydroxyacetone (149a) and aromatic aldehydes in NMP as solvent at 25°C to afford mainly iyn-aldol products in good yields (59-97%) and high diastereo- and enantioselectivities (78-99% de, 84-99% ee). The combination of catalyst 167 with triflic acid was used in the reaction of acyclic ketones and a-hydroxyketones 8 with aromatic aldehydes also with good results [251]. Simple chiral diamine 168 (10 mol%) in the presence of Iriflic acid (20 mol%) was applied as catalyst in the reaction between acetone and cyclohexanone with aromatic aldehydes in water at 25°C, giving aldol adducts 4 in low yields (15-58%) and moderate diastereo- and enantioselectivities (50-98% de, 45-93% ee) [252]. 

Bu SnF added to a soln. of Sn(OTf)2 and (S)-l-methyl-2-[(piperidin-l-yl)methyl]pyr-rolidine in dichloromethane at room temp., stirred for 30 min, cooled to —78°, S-ethyl ethanethioate trimethylsilyl enol ether in the same solvent added, followed after 30 min by benzaldehyde in dichloromethane, and stirring continued for 12 h before quenching with aq. NaHC03 S-ethyl 3-hydroxy-3-phenylpropanethioate. Y 78% (e.e. 82% 0% in the absence of BujSnF). F.e. and chiral diamines s. S. Kobayashi, T. Mukaiyama, Chem. Letters 1989, 297-300. 

After screening suitable metal combinations for Schiff base 2, Ga(0-/Pr)3/Yb (OTf)3 afforded promising results. The chiral diamine backbone affected both the reactivity and enantioselectivity, and the best reactivity and selectivity were achieved using Schiff base 2c with an anthracene-derived diamine unit (Table 1, entry 3 94% ee). After optimization of the solvent (CH2Q2) and Ga/Yb ratio (1 0.95), product was obtained in > 95 % conversion and 96% ee after 24 h (entry 4). To confirm the utility of the Ga(0-iPr)3/Yb(0Tf)3 combination, several cmitrol experiments with the best ligand 2c were performed (entries 5-13). Neither Ga-2c alone nor Yb-2c alone efficiently promoted the reaction (entries 5-6). With Ga(0-/Pr)3 and other rare earth metal triflates, the reactivity decreased in correlation with the Lewis acidity of the rare earth metals (Yb > Gd > Nd > La) [17], while good to excellent enantioselectivity... 

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