Ethyl glyoxalate reactions

Garbostyrils. Carbostydls such as (14) [33934-60-0] are prepared by the reaction of 2-alkylainino-4-iiitrotoluene with ethyl glyoxalate in the... 

As already discussed for aldol and Robinson annulation reactions, proline is also a catalyst for enantioselective Mannich reactions. Proline effectively catalyzes the reactions of aldehydes such as 3-methylbutanal and hexanal with /V-arylimines of ethyl glyoxalate.196 These reactions show 2,3-syn selectivity, although the products with small alkyl groups tend to isomerize to the anti isomer. 

Type (ii) cyclizations are more common. Thus, acid derivatives of pyrrolo[l,2-f>]-[l,2,5]benzothiadiazepine 5,5-dioxide 346 and 347 have been prepared from amino sulfonyl pyrrole 345 with acetal (2006JMC5840) or the semiacetal (1994JHC867) of ethyl glyoxalate or ethyl 2,2-diethoxy propionate (1996FES425) in the presence of PTSA catalyst in boiling absolute ethanol by a Pictet-Spengler type of reaction (Scheme 73). 

It is conceivable that a carbonyl compound with an n,n triplet energy lower than that of benzophenone could yield the photocycloaddition product in some of these cases. A reaction which may illustrate this point is the photocycloaddition of ethyl glyoxylate to styrene and 1,1-diphenylethylene.66 Unfortunately, the triplet energy of ethyl glyoxalate has not been measured however, there is adequate reason to believe it is lower than that of benzophenone (see Table VI). 

Trost and coworkers recently reported that these dinuclear zinc complexes catalyze Mannich reactions with unmodified aromatic hydroxy ketones as donors with excellent enantioselectivity [18]. Mannich-type reactions between an N-para-meth-oxyphenyl (PMP)-protected a-ethyl glyoxalate and hydroxyacetophenone in the presence of a catalytic amount of catalyst 5a afford the desired N-PMP protected amino acid derivative in 76 % yield with a dr of 7 1 and 95 % ee (Eq.5). 

Iridium-catalyzed annulation of the precursor 179, which is available by a three-component reaction of 1-hexyne, allylbenzylamine, and ethyl glyoxalate, provided the conceivable intermediate 180, which was trapped with A-phenylmaleimide to provide the tricyclic system 181 in respectable yield (Scheme 21). Variation of the alkyne components gave a set of similar products <2005JA10804>. 

Quite recently, Doyle and coworkers found that dirhodium(II) complexes such as rhodium(II) acetate and Rh2(4S-MEAZ)4 (14) also act as highly active Lewis addcatalysts (1 mol%) for the reaction of trimethylsilylketene and ethyl glyoxalate, affording the P-lactonel5 (Table4.6) [42]. However, theuseofthechiral Rh-complex, Rh2(4S-M EAZ)4, alone afforded almost no asymmetric induction (5% ee for (S)-isomer) (entry 2). The use of quinine (10 mol%) as a cobase catalyst to activate the ketene simultaneously provided exceptional enantiocontrol (99% ee) and enhanced reactivity (entry 5). 

A third basic synthetic approach to L-ascorbic acid involves the combination of C4 and C2 carbon units. An example of this is the benzoin condensation reaction between L-threose and ethyl glyoxalate in the presence of sodium cyanide (Figure 4.6 j. 

The reaction of the (aminophenyl)pyrrolylamine (59) with ethyl glyoxalate ethoxy hemiacetal in ethanol afforded the pyrrolo-l,2,5-benzotriazepine (60) (77% yield) via a Pictet-Spengler type condensation. Treatment of (60) with chloroacetyl chloride, followed by cyclization with methyl-amine, gave the diketopiperazine derivative (61), which was reduced with lithium aluminum hydride to yield the pyrazino[2,l-i/]pyrrolo[l,2-Z>]-l,2,5-benzotriazepine (62) (80% yield) (Scheme 10)... 

In combination with Cu(II) and Cu(I) salts, the polymer-anchored, enantio-merically pure bisoxazoHnes showed only poor enantioselectivity in the Diels-Alder cycloaddition between N-acryloyloxazolidinone and cyclopentadiene (up to 45% ee). Better stereocontrol was found in the cyclopropanations of styrene and 1,1-diphenylethylene with ethyl diazoacetate (up to 93% ee) and in the ene reactions between ethyl glyoxalate and a-methylstyrene or methylenecyclohexane (up to 95% ee), which was comparable to the structurally related, unsupported ligands. Only a slight decrease in activity and in stereocontrol was observed upon recovery and recycling of the catalyst. The catalytic transformations were as efEdent as if performed with the corresponding catalysts supported on insoluble polymers. 

As the intermediate enamine reacts faster with imines than aldehydes, a one-pot three component coupling of the donor ketone, aldehyde and amine is possible. List and coworkers have achieved high ees in this reaction utilising L-proline (7.66) and some aliphatic aldehydes and aromatic aldehydes such as (7.136) in combination with p-anisidene (7.137). This catalyst system is also effective for the coupling of a-hydroxyketones. Use of the tetrazole-substituted proline (7.80) allows the reaction to be performed in dichloromethane rather than DMSO and high ees in the Mannich reaction between aliphatic ketones and imines derived from ethyl glyoxalate have been obtained imder these reaction conditions. 

The Evans copper(ll) bis-oxazoline (BOX) catalysts (7.193) and (7.194) (see Section 7.1) have also been used effectively for glyoxalate ene reactions. Even monosubstituted alkenes can be used as the ene component, where the alkene (7.195) reacts with ethyl glyoxalate (7.196) to give the a-hydroxy ester (7.197) with very high enantioselectivity. Other alkenes were also effective, providing enantiomeric excesses of over 90%, including alkene (7.198), which is converted into the ene-product (7.199). 

N-Phenylsulfonylprolinamide 15a was first used as organocatalyst in the reaction of cyclohexanone with the highly reactive N-PMP-protected a-imino ethyl glyoxalate (eqn. (1) in Scheme 6.5). Dodecylphenylsulfonamide-hased... 

An iodine-catalyzed three-component reaction of quinazoline-2,5-diones with either paraformaldehyde or ethyl glyoxalate and styrenes in dioxane at 110 °C, reported by Zhang and collaborators, fmnished the corresponding allylamine derivatives with high regioselectivity in moderate-to-good yields (Scheme 43) (14T9093). 

A four-component tandem reaction is proposed by Zhenjun et al., by treating pyridine (or quinoline) with phenacyl bromides (or bromoacetophenones), ethyl glyoxalate, and Na2C03 in refluxing acetonitrile. The resulting polysubstituted indoUzines are obtained after 16 h of reaction time in moderate-to-good yields [22]. 

A few years later [69] the reaction of propargyl bromide with zinc in the presence of ethyl glyoxalate was reported to yield the propargylic derivative exclusively ... 

Highly reactive ene components, which allow the reaction to occur at lower temperature, have also been reported. Ene 125 generated by Kishner reduction of the 2-furylhydrazone proved to be a very powerful ene component reacting separately with ethyl glyoxalate at 0 °C without Lewis acid and with Eschenmoser s salt at rt providing 126 and 127, respectively, in high yield. ... 

Imino-Diels-Alder reaction [49] containing the coupling of imine and electron-rich alkene gradually became a powerful tool for the synthesis of quinazohne derivatives [50], In Povarov imino-Diels-Alder reaction, aniline and ethyl glyoxalate were chosen as substrates. And two molecules of a-iminoesters, which were obtained from the condensation of aniline and ethyl glyoxalate, were hypothesized to form the direct additive product. Cascade imino-Diels-Alder reaction conducted by Chenetal. [51] (Scheme 13.11) was extended from the Povarov imino-Diels-Alder reaction. In this research, researchers chose the same substrates as in the Povarov imino-Diels-Alder reaction, adopted various kinds of Lewis acids as catalysts, and finally produced quinazoline derivatives. Iron powder was determined as the optimized catalyst with highest yields. 

Sc(OTf)3 also catalyzed the three-component condensation of dihydropyridines, ethyl glyoxalate, and primary amines (Scheme 12.29) [64]. Depending on the reaction conditions, a bicyclic amine or rearranged tetrahydropyridines was obtained in moderate yield. 

Similar substituted quinolines can be efficiently obtained starting from N-alltylaniline (including glycine) derivatives by reaction with alkenes in the presence of FeCls (10 mol%) and TEMPO oxoammonium tetrafluoroborate salt (2 equiv.) as the oxidant in dichloromethane (DCM) at 60 °C. Interestingly, the same quinolines can be obtained starting from anilines, ethyl glyoxalate and alkenes, in a one-pot multi-component reaction, under similar conditions. ... 

There is at least one multicomponent reaction that uses four different components that lead to formation of four of the five bonds within a 3-pyrrolin-2-one ring. Zeng, Ye, and coworkers developed a Pd-catalyzed type acde multicomponent approach to amine-substituted 3-pyrrolin-2-ones (Scheme 112 20120L5640). Mixing three equivalents of ethyl glyoxalate (423) and two equivalents of p-anisidine (405) with a Pd catalyst led to formation of the 3-arylamino-3-pyrrolin-2-one 426. A suggested mechanism includes the Pd-mediated formation of imine 424 and enamine 425 and subsequent cyclocondensation leading to 426. 

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