Phase catalytic enantioselective

Our development of the catalytic enantioselective inverse electron-demand cycloaddition reaction [49], which was followed by related papers by Evans et al. [38, 48], focused in the initial phase on the reaction of mainly / , y-unsaturated a-keto esters 53 with ethyl vinyl ether 46a and 2,3-dihydrofuran 50a (Scheme 4.34). 

The similarities of above experimental results inspired us to investigate the role of SE in heterogeneous catalytic enantioselective hydrogenation reactions. In heterogeneous catalytic reaction the SE means that a given template molecule interacts with the prochiral substrate in the liquid phase in such a way that one of the prochiral sites is preferentially shielded. If the substrate is shielded then its adsorption onto the metal can take place with its unshielded site resulting in ED. 

More recently, Maruoka and co-workers have reported several new phase-transfer catalysts one of which incorporates a morpholine ring as part of an azoniaspirocyclic core 161 <2007TL4675>. These were employed in the catalytic enantioselective conjugate addition of a-benzylcyanoacetate to acetylenic methyl ketone under phase transfer conditions. 

Chiral thioureas have been synthesized and used as ligands for the asymmetric hydroformylation of styrene catalyzed by rhodium(I) complexes. The best results were obtained with /V-phenyl-TV -OS )-(l-phenylethyl)thiourea associated with a cationic rhodium(I) precursor, and asymmetric induction of 40% was then achieved.387,388 Chiral polyether-phosphite ligands derived from (5)-binaphthol were prepared and combined with [Rh(cod)2]BF4. These systems showed high activity, chemo- and regio-selectivity for the catalytic enantioselective hydroformylation of styrene in thermoregulated phase-transfer conditions. Ee values of up to 25% were obtained and recycling was possible without loss of enantioselectivity.389... 

E. J. Corey, F. Xu, M. C. Noe, A Rational Approach to Catalytic Enantioselective Enolate Alkylation Using a Structurally Rigidified and Defined Chiral Quaternary Ammonium Salt under Phase Transfer Conditions , J. Am. Chem. Soc, 1997,119,12414-12415. 

There are only a few reports on chiral phase transfer mediated alkylations". This approach, which seems to offer excellent opportunities for simple asymmetric procedures, has been demonstrated in the catalytic, enantioselective alkylation of racemic 6,7-dichloro-5-methoxy-2-phenyl-l-indanone (1) to form ( + )-indacrinone (4)100. /V-[4-(tnfluoromethyl)phenylmethyl]cinchoninium bromide (2) is one of the most effective catalysts for this reaction. The choice of reaction variables is very important and reaction conditions have been selected which afford very high asymmetric induction (92% cc). A transition state model 3 based on ion pairing between the indanone anion and the benzylcinchoninium cation has been proposed 10°. 

Having optimized the catalytic enantioselective phase-transfer alkylation system, the group explored the scope and limitations. A variety of electrophiles were reacted with the benzophenone imine glycine tert-butyl ester 1 catalyzed by 5 mol% of the selected chiral dimeric PTCs, benzene-linked-l,3-dimeric PTC 37, 2 -F-benzene-linked-1,3-dimeric PTC 41, and naphthalene-linked-2,7-dimeric PTC 39, at reaction temperatures of 0°C or — 20 °C (Scheme 4.8). 

In 1999, in consideration of the readily structural modifications and fine-tuning of catalysts to attain sufficient reactivity and selectivity, Maruoka and coworkers designed and prepared the structurally rigid, chiral spiro ammonium salts of type 1 derived from commercially available (S)- or (R)-1,1 -bi-2-naphthol as a new C2-symmetric chiral phase-transfer catalyst, and successfully applied this to the highly efficient, catalytic enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester under mild phase-transfer conditions (Scheme 5.1) [7]. 

Table 5.2 Catalytic enantioselective phase-transfer alkylation of glycine derivative 2 catalyzed by (S)-16Aa, (S)-16Ab, (S)-16Ba, and (S)-16Bb.

Table 5.3 Catalytic enantioselective phase-transfer alkylation of glycine derivative 2.

Table 5.7 Catalytic enantioselective synthesis of a,a-dialkyl-a-amino acids by phase-transfer alkylation.

Although phase-transfer catalytic enantioselective direct aldol reactions of glycine donor with aldehyde acceptors may provide an ideal method for the simultaneous construction of the primary structure and stereochemical integrity of (3-hydroxy-a-amino acids (which are extremely important chiral units, especially from a pharmaceutical viewpoint), the examples reported to date have been very limited [41]. 

All catalytic enantioselective versions of the Darzens condensation are based on the use of chiral phase-transfer agents, e.g. the cations 184a,b derived from ephed-rine, quinine/quinidine-based ammonium ions such as 185a,b, or the crown ether 186. 

Table 4.6 Catalytic enantioselective Michael addition of 28 to a,/ -unsaturated carbonyl compounds under phase-transfer conditions. (For experimental details see Chapter 14.9.11).

An excellent extension to these processes is the enantioselective, molecular oxygen mediated a hy-droxylation reported by Shioii. Oxidation in a two-phase system using a chiral phase transfer catalyst (19) allowed prqMiration of a-hydroxy ketones, for example (19a), in high yield and with good enanti-oselectivity. This is the only currently available catalytic enantioselective a-hydioxylation process. 

Recently, Jorgensen reported the first example of a catalytic enantioselective vinylic substitution reaction (Scheme 11.14). With a bulky 1-adamantylcarbonyl group modified phase-transfer catalyst lOd as the catalyst, the reaction between alkyl cyclopentanone-2-carboxylates (53a) with (ZJ-P-cholro-l-phenylpropenone (63a) proceeded smoothly, affording the product 64a with Z/f > 95 5 and 94% ee [50]. As for the trisubstituted alkene 64b, the a-iodine atom was tolerated in the catalytic reaction. 

Although the catalytic asymmetric borane reductions mentioned above are a powerful tool to obtain highly enantio-enriched alcohols, these require the use of a rather expensive and potentially dangerous borane complex. Sodium borohydride and its solution are safe to handle and inexpensive compared to borane complexes. Thus sodium borohydride is one of the most common industrial reducing agents. However its use in catalytic enantioselective reductions has been limited. One of the most simple asymmetric catalysts is an enantiopure quaternary armnonium salt that acts as phase-transfer catalyst. For instance, in the presence of the chiral salt 81 (Fig. 9), sodium borohydride reduction of acetophenone gave the secondary alcohol in 39% ee [124]. The polymer-supported chiral phase-transfer catalyst 82 (Fig. 10) was developed for the same reduction to give the alcohol in 56% ee [125]. 

Figure 8.31. Comparison between experimental and calculated according to eq. 8.117 data for three-phase catalytic hydrogenation in a fixed bed reactor (E. Toukoniitty, P. MSki-Arvela, A. Kalantar Neyestanaki, T. Salmi, D. Yu. Murzin, Continuous hydrogenation of l-phenyl-1,2 - propanedione under transient and steady-state conditions, regioselectivity, enantioselectivity and catalyst deactivation, Applied Catalysis A General, 235 (2002) 125).

Breuzard et al. [25] prepared chiral polyether ligands derived from (S)-binaphthol and combined with the [Rh(cod)2]BF4 complex. This system has been used in the catalytic enantioselective hydroformylation of styrene in thermoregulated phase-transfer conditions, but the ee value is less than 25%. 

As good results for the asymmetric HTR of acetophenone were obtained (conversion 100% and 91% ee) with diurea [19], not only copolymerization of diamine 18 has been performed but 1,2-cyclohexyldiamine 19 was also used. Thus pseudo-C2 polyamide 23, polyureas 24, 24 and 26 or polythioureas 27 were prepared by polycondensation with diacid chloride, diisocyanate [20] or dithioisocyanate respectively (Scheme 12) [21]. With rhodium complexes the conversions varied from 22% to 100% and ee from 0% to 60% for HTR with acetophenone at 70°C, in the presence of [Rh(cod)Cl]2 with diamine polymer imit (23-26)/Rh ratio of 10, 2-propanol and KOH. Polyamide 23 proved to be useless (only 22% conversion and 28% ee) contrary to polymea 25 which presents similar ee to those observed with diamine 18 when (Rh(cod)Cl)2 was employed as the catalytic preciu or for HTR (ie 100% conversion for both of them and 55% and 59% ee respectively). Polyureas 24a, 24b, 25 and crosslinked 26 led to better conversions, 80, 50, 97 and 100% with respectively 0, 13, 39 and 60% ee. Moreover, the chiral crosslinked polyurea 26 presented a slight increase in enantioselectivity over the monomer analog 18 (55% ee and 94% conversion under similar conditions) and the reaction rate appeared to be even higher than in the homogeneous phase. Catalytic system from 25 showed a capacity to recycle (Scheme 13) [20]. 

Within the area of PTC, purely synthetic chiral quaternary oninm salts have also been developed. For example, in 1999 Marnoka and co-workers prepared structurally rigid, chiral spiroammoninm salts of type 107 as new C2-symmetric phase-transfer catalysts and successfully applied them to the highly efficient, catalytic enantioselective alkylation of 106 under mild conditions. In general, 1 mol% of 107 promotes efficient alkylation, although the catalyst loading can be reduced to 0.2mol% without a decrease in ee (Scheme 18). 

Cinchona alkaloids comprising quinine, quinidine, cinchonidine, and cinchonine as the major members constitute a unique class of quinoline alkaloids with tremendous impact on human civilization. The odyssey of Cinchona alkaloids began with the discovery of their antimalarial properties followed by the very successful application in stereochemistry and in asymmetric synthesis. Currently, the portfolio of applications of Cinchona alkaloids is much broader, involving chiral stationary phases for enantioselective chromatography, novel biological activities, and several useful transformation converting them into other modular and chiral building blocks, such as, for example, quincorine or quincoridine. Current pressure on a more intense exploration of sustainable products and easy access to diverse molecular architectures make Cinchona alkaloids of primary importance for synthetic catalytic and medicinal chemistry. 

Ooi, T., Takeuchi, M., Kameda, M., Maruoka, K. (2000). Practical catalytic enantioselective synthesis of a,a-dialkyl-a-amino acids by chiral phase-transfer catalysis. Journal of the American Chemical Society, 122, 5228-5229. 

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