Glyoxylate esters Diels-Alder reaction

Similar transformations have been performed with Danishefsky s diene and glyoxylate esters [85] catalyzed by bis (oxazoHne)-metal complexes to afford the hetero Diels-Alder product in 70% isolated yield and up to 72% ee. Jorgensen [86,87] reported a highly enantioselective, catalytic hetero Diels-Alder reaction of ketones and similar chiral copper(II) complexes leading to enantiomeric excesses up to 99% (Scheme 31, reaction 2). They also described [88] a highly diastereo- and enantioselective catalytic hetero Diels-Alder reaction of /I, y-imsaturated a-ketoesters with electron-rich alkenes... 

TABLE 9.18. HETERO-DIELS-ALDER REACTION OE DANISHEFSKY S DIENE WITH GLYOXYLATE ESTERS"... 

TABLE 9.18 HETERO DIELS-ALDER REACTION OF DANISHEFSKY S DIENE WITH GLYOXYLATE ESTERS, 558... 

The choice of solvent has had little, if any, influence on the majority of Diels-Alder reactions.210,211 Although the addition of a Lewis acid might be expected to show more solvent dependence, generally there appears to be little effect on asymmetric induction.118129 However, a dramatic effect of solvent polarity has been observed for chiral metallocene triflate complexes.212 The use of polar solvents, such as nitromethane and nitropropane, leads to a significant improvement in the catalytic properties of a copper Lewis acid complex in the hetero Diels-Alder reaction of glyoxylate esters with dienes.213... 

Diels-Alder reactions have been very successfully subjected to asymmetric catalysis by binaphthyl complexes. Accordingly, the synthesis of tetrahydropyranes 41 and 42 can be realized by reaction of glyoxylic esters 39 with methoxy-dienes 38 (Scheme 8) [20]. Some of these reactions take place with excellent endo-conxro and... 

Ene Reactions. Bis(triflate) complex 2 catalyzes the ene reaction of glyoxylate esters (eq 15). Catalyst turnover was not observed at low temperature. As is the case with Diels-Alder reactions, the related bis(hexafluoroantimonate) complex is a more efficient catalyst for this transformation. 

A mechanism has been proposed for the enantioselective Mikami ene reaction of a terminal alkene with a glyoxylic aldehyde using a chiral binaphthol as Lewis acid. Stereoselective synthesis of 5-amino esters via asymmetric aldol-type and aza-Diels-Alder reactions has been reviewed. Siliranes react cleanly with benzaldehyde to produce oxasilacyclopentanes—with inversion— under conditions of Bu OK catalysis enolizable aldehydes yield sdyl enol ethers. ... 

A cost effective and easily scaled-up process has been developed for the synthesis of (S)-3-[2- (methylsulfonyl)oxy ethoxy]-4-(triphenylmethoxy)-1 -butanol methanesulfonate, a key intermediate used in the synthesis of a protein kinase C inhibitor drug through a combination of hetero-Diels-Alder and biocatalytic reactions. The Diels-Alder reaction between ethyl glyoxylate and butadiene was used to make racemic 2-ethoxycarbonyl-3,6-dihydro-2H-pyran. Treatment of the racemic ester with Bacillus lentus protease resulted in the selective hydrolysis of the (R)-enantiomer and yielded (S)-2-ethoxycarbonyl-3,6-dihydro-2H-pyran in excellent optical purity, which was reduced to (S)-3,6-dihydro-2H-pyran-2-yl methanol. Tritylation of this alcohol, followed by reductive ozonolysis and mesylation afforded the product in 10-15% overall yield with excellent optical and chemical purity. Details of the process development work done on each step are given. 

Two groups have investigated N-sulfonyl imines of glyoxylate esters, derived from scalemic alcohols, in Diels-Alder reactions [67b, 73]. Prato and coworkers reported that glyoxylate N-sulfonyl imines bearing (-)-menthyl, (-)-bornyl and (-)-8-phenylmethyl auxiliaries reacted with cydopentadiene either thermally or using Lewis acids to give only very modest diastereomeric product ratios (56 44, 53 47,60 40, respectively) [67b]. 

In an extensive study Jurczak et al. examined asymmetric induction in the Diels-Alder reactions of a number of achiral dienes with several optically active esters of glyoxylic acid. Cycloadditions were run both at atmospheric pressure and at high pressures (6-10 kbar). To summarize these studies, asymmetric induction using glyoxylate esters of... 

This means that this substituent has to be arranged by a kinetically controlled stereo selective method, which in our case was a Hetero-Diels Alder reaction between a diene 164 and a glyoxylate 165. Ketone 166 is the precursor of 164 and tartaric ester 167 that of 165. The methyl ether 164 could not been made by deprotona-tion/methylation of 166 (Scheme 27). 

The stereochemical outcome of the hetero Diels-Alder reaction of the erythrose based diene with sodium glyoxylate was further rationalized by preparing the same compounds via decarboxylation of 2-carboethoxy-2-deoxy-2-ulosonic acid esters, obtained by cycloaddition with diethyl ketomalonate [146], A range of 2-nonulosonic acid derivatives - KDN analogues - were prepared including protected form of 2-deoxy-KDN,... 

Hetero Diels-Alder reactions. Methylaluminura BINOLoxide catalyzes cycloadditions such as those involving glyoxylic esters. Products with excellent ee values of up to 97% are routinely obtained. 

Furthermore, Pd(Il) eomplexes catalyze asymmetric ene and Diels-Alder reactions. Mikami and co-workers reported enantioselective synthesis of a-hydroxy esters by the ene reaction of glyoxylate 27 using a chiral Pd catalyst. They obtained the (/ )-hydroxy ester 28 with 88% ee in 97 % yield by the reaetion of methylenecyelohexane (26) with ethyl glyoxylate (27) at 60 °C using the eadonic Pd(II) eonqilex of (5)-Tol-BINAP [7]. 

Asymmetric hetero-Diels-Alder reactions of glyoxylate esters and Danishefsky s diene catalyzed by various chiral bis(oxazoline)-lanthanide complexes afforded the corresponding aldol adducts, which upon treatment with... 

Aminals and hemiaminals of glyoxylic acid esters were employed in Diels-Alder-reactions with cyclohexa-1,3-diene (491, 492), the intermediate imino acid derivative acting as dienophile. Several authors dealt with asymmetric hydrogenation of optically active Schiff bases of a-keto acids (532—535). For prior publications in this field these papers should be consulted. 

Using a diene, the reaction can proceed through the ene pathway as above, or through the hetero-Diels-Alder pathway. For example, the condensation of 2,3-dimethyl-1,3-butadiene 103 with glyoxylate esters 99, 104, and 105 can proceed to form either a hetero Diels-Alder cycloadduct 106 or an ene product 107 (Fig. 9.35). 

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