Catalytic enantioselective phase-transfer

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). 

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.

Hughes, D. L. Dolling, U.-H. Ryan, K. M. Schoenewaldt,E. F. Grabowski, E.J.J., Efficient Catalytic Asymmetric Alkylations. 3. A Kinetic and Mechanistic Study of the Enantioselective Phase-Transfer Methylation of 6,7-Dichloro-5-methoxy-2-phenyl-l-indanone J. Org. Chem. 1987, 52, 4745. 

Scheme 2.86 Enantioselective phase-transfer catalytic Michael addition of p-ketoesters to enones...

Scheme 16.10 Enantioselective phase-transfer catalytic diallq lation using polymer-supported glycine imine esters 15 and 17.

Fukuta Y, Ohshima T, Gnanadesikan V, Shibuguchi T, Nem-oto T, Kisugi T, Okino T, Shibasaki M. Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs application of catalytic asymmetric phase-transfer reaction. PAAS 2004 101 5433-5438. 

Hughes DL, Dolling UH, Ryan KM, Schoenewaldt EE, Grabowski, EJJ. Efficient catalytic asymmetric alkylations. 3. A kinetic and mechanistic study of the enantioselective phase-transfer methylation of 6, 7-dichloro-5-methoxy-2-phenyl-l-indanone. J. Org. Chem. 1987 52(21) 4745 752. 

Kim M, Park Y, Jeong B, Park H, Jew S. Synthesis of ( )-paroxetine via enantioselective phase-transfer catalytic monoalkylation of malonamide ester. Org. Lett. 2010 12 (12) 2826-2829. 

Ohshima, T., Gnanadesikan, V., Shibuguchi, T, Fukuta, Y., Nemoto, T., and Shibasaki, M. (2003) Enantioselective syntheses of aeruginosin 298-A and its analogues using a catalytic asymmetric phase-transfer reaction and epoxidation./. Am. Chem. Soc., 125,11206-11207. 

Some phase-transfer catalytic asymmetric alkylation reactions of glycine imine derivatives have been explored to access natural products and biologically active compounds. For example, by employing an enantioselective phase-transfer catalytic alkylation, Kim et al. accomplished the first asymmetric total synthesis of the naturally occurring phenanthroindolizidine alkaloid (—)-antofine (Scheme 12.2) [102]. The key feature of this synthesis is the creation of the stereogenic center by reacting 65a with electrophile 66 in the presence of the dimeric catalyst 28 under the phase-transfer conditions. 

Early work on the use of chiral phase-transfer catalysis in asymmetric Darzens reactions was conducted independently by the groups of Wynberg [38] and Co-lonna [39], but the observed asymmetric induction was low. More recently Toke s group has used catalytic chiral aza crown ethers in Darzens reactions [40-42], but again only low to moderate enantioselectivities resulted. 

N-Tosylated P-hydroxy alkylamines (which can be easily hydrolyzed to P-hydroxyamines" ) can be prepared " by treatment of alkenes with the trihydrate of Chloramine-T and a catalytic amount of OSO4. In some cases yields can be improved by the use of phase-transfer catalysis." The reaction has been carried out enantioselectively." In another procedure, certain P-hydroxy secondary alkylamines can be prepared by treatment of alkenes with the osmium compounds... 

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... 

An enantioselective synthesis of both (R)- and (5)-a-alkylcysteines 144 and 147 is based on the phase-transfer catalytic alkylation of fert-butyl esters of 2-phenyl-2-thiazoline-4-carboxylic acid and 2-ort/ro-biphenyl-2-thiazoline-4-carboxylic acid, 142 and 145 <06JOC8276>. Treatment of 142 and 145 with alkyl halides and potassium hydroxide in the presence of chiral catalysts 140 and 141 gives the alkylated products, which are hydrolyzed to (R)- and (S)-a-alkylcysteines 144 and 147, respectively, in high enantioselectivity. This method may have potential for the practical synthesis of chiral a-alkylcysteines. 

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°. 

The group of Arai and Nishida investigated the catalytic asymmetric aldol reaction between tert-butyl diazoacetate and various aldehydes under phase-transfer conditions with chiral quaternary ammonium chloride 4c as a catalyst. The reactions were found to proceed smoothly in toluene, even at —40°C, when using 50% RbOH aqueous solution as a base, giving rise to the desired aldol adducts 23 with good enantioselectivities. The resulting 23 can be stereoselectively transformed into the corresponding syn- or anti-P-hydroxy-a-amino acid derivatives (Scheme 2.20) [42],... 

From an evaluation of the catalytic efficiency of 3-5 using standard catalytic phase-transfer benzylation of 1, it was found that all compounds had the ability to catalyze this phase-transfer benzylation, and in all cases the (S)-isomer of the benzylated imine 2a was formed in excess (Scheme 4.3). The 1,3-phenyl-linked dimeric PTC 4 showed the highest enantioselectivity among the three dimeric PTCs. The order of enantioselectivity of the three PTCs, along with the monomeric PTC M, was as follows 1,3-dimeric PTC 4 > 1,4-dimeric PTC 5 = monomeric PTC M 1,2-dimeric... 

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]. 

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