Esters chiral catalyst

The Mikolajczyk group36 has developed use of natural alkaloids as chiral catalysts in conversion of symmetrical dialkyl sulfites into alkyl t-butylsulfinate esters in 40-70% enantiomeric purity (equation 6). 

By homogeneous reaction of the conjugated double bond system selectively the C=C double bond is hydrogenated [63-66] the ester function is not affected. Moreover, by action of the chiral catalyst, a chiral hydrogenated product is created with good enantioselectivity. 

The directive effect of allylic hydroxy groups can be used in conjunction with chiral catalysts to achieve enantioselective cyclopropanation. The chiral ligand used is a boronate ester derived from the (VjA jA N -tetramethyl amide of tartaric acid.186 Similar results are obtained using the potassium alkoxide, again indicating the Lewis base character of the directive effect. 

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. 

The preparation of this type of catalyst is quite simple. HPAs such as phos-photungstic acid were adsorbed onto inorganic supports such as clays, alumina, and active carbon. Subsequently, the metal complex was added to form the immobilized catalyst. If necessary, the catalyst can be pre-reduced. These types of catalysts were developed mainly for enantioselective hydrogenations. For instance, a supported chiral catalyst that was based on a cationic Rh(DIPAMP) complex, phosphotungstic acid and alumina showed an ee-value of 93% with a TOF of about 100 IT1 in the hydrogenation of 2-acetamidoacrylic acid methyl ester (Fig. 42.4 Table 42.2). 

Jorgensen s group reported the aza Diels-Alder reactions in the presence of several chiral catalysts.52 They found that chiral bis(oxazoline) ligands 81, 83, 103, 104, and 105, which were effective in asymmetric oxo hetero Diels-Alder reactions, induced the aza Diels-Alder reaction of a-imino ester with Danishefsky s diene with only poor to moderate enantioselectivity. Selected results are listed in Scheme 5-40. 

Cyanohydrins are starting materials of widespread interest for preparing important compounds such as a-hydroxy acids/esters, a-amino acids, / -amino alcohols, a-hydroxy aldehydes, vicinal diols, and a-hydroxy ketones. Cyanohydrin compounds can be synthesized using various chiral catalysts such as cyclic... 

This has become something of a standard reaction, since several authors have successfully used different chiral catalysts to effect the conversion in very high chemical and enantiomeric yield. Bergson and Langstrom (41) were the first to show that acrolein and a-isopropylacrolein added to 2-carbomethoxy-l-indanone (A in eq. [6]) in benzene in the presence of the strongly basic tertiary amine (/ )-( + )-2-(hydroxymethyl)quinuclidine to yield optically active ketoesters. Unfortunately, the quinuclidine catalyst was not enantiomerically pure, and neither the chemical nor the optical yields of the aldehydo ester analogous to B (eq. [6]) were reported. 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

The stereochemical control of the Gabriel reaction by chiral catalysts can be further enhanced in the synthesis of optically active a-amino acids when optically pure (-)-bornyl a-bromo esters are used (Table 12.8) [4]. 

It was apparent from the beginning (Scheme 16.7) that there were four potentially independent aspects of reactivity 1) the rate of bimolecular transfer of the diazo ester to the rhodium-complex [10a, 22] 2) the ratio [21] of C-H insertion to /9-H elimination [(34-1-35 -h 36 -h 37)/33] 3) the chemoselectivity [(34-i-35)/(36-i-37)] [4] and 4) the diastereoselectivity [9] of the insertion (34/35 or 36/37). As a prelude to the development of an effectively chiral catalyst, we felt that it was important to experimentally explore these aspects of reactivity. 

It has recently been demonstrated that a stereoselective synthesis of dipeptides by hydrogenation of the corresponding monodehydropeptides (N-protected free acids or methyl esters) is possible. In this reaction, chiral catalysts, for example BPPM (13), in the form of a Wilkinson complex have been used. These are superior to the corresponding DIOP complexes (DIOP = P,P -[2,2-dimethyl-l,3-dioxolane-4,5-bis(methylene)]bis(diphenylphosphane). A d.s. value of 90—99% was generally obtained 49 ... 

The main product is always the (R)-enantiomer of (28) 64). Employing other chiral catalysts, e.g. Schiff bases prepared from (S)-alaninemethyl ester or (S)-valinemethyl ester and 2-pyridinecarboxaldehyde in form of their rhodium complexes, in the same reaction, no or only very low asymmetric induction was observed. 

In conclusion, we have found a convenient and practical method for the selective reduction of C=0 bond of a wide spectrum of a-keto-)S, -unsaturated esters with Ru(p-cymene)(TsDPEN) as catalyst. The transition metal catalyzed transfer hydrogenation reaction with good selectivity and high efficiency offers possibilities to provide the optically active a-hydroxy-/l, y-unsaturated esters with chiral catalysts. Table 3.8 gives different substrates that can be reduced with Ru(p-cymene) (TsDPEN) complex in isopropyl alcohol. 

Compared with aldehydes, ketones and esters are less reactive electrophiles in the addition of dialkylzincs. This makes it possible to perform a unique reaction that cannot be done with alkyllithium or Grignard reagents, which are too reactive nucleophiles. For example, Watanabe and Soai reported enantio- and chemoselective addition of dialkylzincs to ketoaldehydes and formylesters using chiral catalysts, affording enantiomerically enriched hydroxyketones 30 (equation 12)43 and hydroxyesters 31 in 91-96% , respectively (equation 13). The latter are readily transformed into chiral lactones 3244. 

As lipases are proteins, they are able to act as chiral catalysts, and for example to hydrolyse specifically one of the isomers in a racemic mixture of esters. 

A full account5 describes the enantioselective carbonyl-ene reaction of glyoxylate esters catalyzed by a binaphthol-derived chiral titanium complex that is potentially useful for the asymmetric synthesis of a-hydroxy esters of biological and synthetic importance.6 The present procedure is applicable to a variety of 1,1-disubstituted olefins to provide ene products in extremely high enantiomeric purity by the judicious choice of the dichloro or dibromo chiral catalyst (see Table). In certain glyoxylate-ene reactions involving removal of a methyl hydrogen, the dichloro catalyst... 

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