Ethyl glyoxylates

The mechanism of the reaction of ethyl glyoxylate 4 with 2,3-dimethyl-l,3-hutadiene 5 leading to the ene product 7 is shown in Scheme 4.5. This brief introduction to the reaction mechanism for cycloaddition reactions of carhonyl compounds activated hy Lewis acids indicates that many factors influence the course of the reaction. 

The cycloaddition reaction between ethyl glyoxylate 4a and Danishefsky s diene 2a has been investigated by Ghosh et al. applying catalyst systems derived from Cu(OTf)2 and ligands (S)-Ph-BOX (S)-21a, (S)-t-Bu-BOX (S)-21b, and the confer-... 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

The copper complexes of these ligands were tested in the cyclopropanation of styrene with ethyl diazoacetate (Scheme 7) and the ene reaction between a-methylstyrene and ethyl glyoxylate (Scheme 8). hi both cases moderate enantioselectivities were obtained but these were lower than those foimd with the parent hgand. 

Table 12 Results of reactions of ethyl glyoxylate with different alkenes, catalyzed by several bis(oxazoline)-copper complexes immobilized on Y zeolite...

Condensation of Hydroxy Aldehydes with Ethyl Glyoxylate or Ethyl... 

Condensation of hydroxy aldehydes with ethyl glyoxylate or ethyl mesoxalate. 

This retention of reagents by the graphite support has been shown in a series of experiments involving volatile dienes such as 2,3-dimethylbutadiene (12) and iso-prene (13) (Tab. 7.2) [30, 31]. The reaction of 12 with diethyl mesoxalate gave 14 in 75% yield after SMW irradiation at low power (30 W) for 20 x 1 min only (Tab. 7.2, entry 1). When conventional heating was used a satisfactory yield was obtained after 4 h at 135 °C in a sealed tube [32]. Ethyl glyoxylate is a weaker carbonyl dienophile... 

Examples of the use of heterodienophiles under the action of microwave irradiation are not common. Soufiaoui [84] and Garrigues [37] used carbonyl compounds as die-nophiles. The first example employed solvent-free conditions the second is an example of the use of graphite as a susceptor. Cycloaddition of a carbonyl compound provided a 5,6-dihydro-2H-pyran derivative. These types of reaction proceed poorly with aliphatic and aromatic aldehydes and ketones unless highly reactive dienes and/or Lewis acid catalysts are used. Reaction of 2,3-dimethyl-l,3-butadiene (31) with ethyl glyoxylate (112) occurred in 75% yield in 20 min under the action of microwave irradiation. When conventional heating is used it is necessary to heat the mixture at 150 °C for 4 h in a sealed tube to obtain a satisfactory yield (Scheme 9.33). 

Li et al.39 reported the hetero Diels-Alder reaction of alkyl-3-(t-butyldimethylsilyl) oxy-1,3-butadiene 95 with ethyl glyoxylate 96 in the presence of a salen-Co(II) catalyst 94 (2 mol%). Product 97 was obtained in 75% isolated yield with an endo. exo ratio >99 1. The enantiomeric excess of the endo-iorm was up to 52% (Scheme 5-30). 

The same, understandable bias towards the preferred use of man-made catalysts, rather than biocatalysts, continues in the area of hetero-Diels-Alder reactions1141-1. For example, in the presence of 5mol% of copper complexes of the type (47), cyclohexadiene and ethyl glyoxylate produce the oxabicyclooc-tene (58) (66% yield, 97% ee)[142]. 

The solvent was removed from the filtrate using a rotary evaporator to afford the corresponding ethyl glyoxylate (9.7 g, 95 mmol)... 

In the 250 mL round-bottomed flask equipped with a magnetic stirrer bar, the resulting ethyl glyoxylate (9.7 g) was placed under nitrogen. Dry methylene chloride (125 mL) was added followed by activated molecular sieves (10 g). The mixture was then cooled at 0 °C under nitrogen. 

The considerable Lewis acidity of bis(oxazoline)-copper(II) complexes held promise for catalyzing the ene reaction, a process that usually requires strong Lewis acids. Indeed, these catalysts effect a highly selective ene reaction between a variety of alkene partners and glyoxylate esters to produce a-hydroxy esters in good yield, Eq. 210 (245). The ene reaction between cyclohexene and ethyl glyoxylate proceeds in excellent diastereoselectivity and enantioselectivity, Eq. 211. As a testament to the Lewis acidity of these complexes, it is noteworthy that... 

Figure 31. Proposed stereochemical model for 271c mediated ene reaction of various alkenes with ethyl glyoxylate.

The benzotriazole derivatives 111, obtained from benzotriazole, ethyl glyoxylate and secondary amines (diethylamine, pyrrolidine, piperidine or morpholine), furnish the amino esters 112 by the action of organozinc reagents R2ZnX (R2 = Me, Bu, PhCH2 or Ph)120. 

In recent years, much work has been done on catalyzed and asymmetric cycloaddition reactions. In the presence of 5 mol% bismuth trichloride, the simple dienes 10 (R1 = R" = H R1 = H, R2 = Me or R1 = Me, R2 = H) react with diethyl mesoxalate to afford mixtures of the cycloadducts 11 and the products 12 of an ene-reaction (equation 13)11 12. 1,3-Cyclohexadiene and ethyl glyoxylate give solely the endo adduct 13 in 50% yield (equation 14)12. 

Under the influence of 20 mol% of the chiral aluminum complex (S)-26, 2,3-dimethyl-1,3-butadiene adds to ethyl glyoxylate in dichloromethane at —78 °C to room temperature during 20 h to produce a mixture of the cycloadduct 23 (R2 = Et) (73% yield, 97% ee) and the ene product 24 (R2 = Et) (9% yield, 88% ee)17. The analogous aluminum complexes (R)-27 and (S)-27 (Ar = Ph or 3,5-xylyl) (10 mol% in toluene) catalyze the Diels-Alder reaction of benzaldehyde with the diene 28 to give, after the addition of trifluoroacetic acid, the dihydropyrone 29 in 95% ee, accompanied by a small amount of the corresponding fraws-isomer (equation 19)18. 

The sulfonylimine 72 reacts with cyclopentadiene in benzene at 0°C to afford solely the exo-adduct 73 in 84% yield (equation 48)42. The unstable inline 75, formed from the phosphorus compound 74 and ethyl glyoxylate by an aza-Witig reaction, adds to dienes... 

The metal complexes even with tropos ligands can thus be used as asymmetric catalysts for carbon-carbon bond-forming reactions in the same manner as atropos catalysts. The single diastereomer (7 )-32/(/ )-DABN can be employed as an activated asymmetric catalyst for the Diels-Alder reaction at room temperature (Table 8.11). The high chemical yield and enantioselectivity (62%, 94% ee) in the Diels-Alder reaction of ethyl glyoxylate with 1,3-cyclohexadiene are obtained... 

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