Ethyl glyoxalate

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. 

Allenyltrimethylsilanes add to ethyl glyoxalate in the presence of a chiral pybox scandium triflate catalyst to afford highly enantioenriched homopropargylic alcohols or dihydrofurans, depending on the nature of the silyl substituent (Tables 9.39 and 9.40) [62]. The trimethylsilyl-substituted silanes give rise to the alcohol products whereas the bulkier t-butyldiphenylsilyl (DPS)-substituted silanes yield only the [3 + 2] cycloadducts. A bidentate complex of the glyoxalate with the scandium metal center in which the aldehyde carbonyl adopts an axial orientation accounts for the observed facial preference ofboth additions. 

Hulme C, Chenier MP (1999) Novel applications of ethyl glyoxalate with the Ugi MCR. Tetrahedron Lett 40 5295-5299... 

Hulme et al. describes the novel use of ethyl glyoxalate in the Ugi-4CR to create ketopiperazines [31]. iV-alkylated/Boc-protected ethylene diamines 60 reacted with an isocyanide 61, a carboxylic acid 62, and ethyl 2-oxoacetate 63 in stoichiometric ratio of 1/1/1/1.25 in methanol. Deprotection and cyclization is completed using TFA and MP-carbonate (a macroporous polystyrene... 

Scheme 11 3-CR synthesis of ketopiperazines using ethyl glyoxalate and two representative 3D conformations of 65A (cyan) and 65B (blue). Yield shown represents yield over all steps...

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). 

Reagents vinyl acetate, ethyl glyoxalate, 60 °C, 14h bovine serum albumin (BSA), thymine, TMSOTf, MeCN, A, 1 h 3.7% HCl in EtOH, room temperature (rt), 3 h. 

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). 

V-/ -methoxyphenyl protected a-imino ethyl glyoxalate 169 in the presence of L-proline as catalyst resulted in the formation of enantioselective p-formyl a-aminoacid derivatives 170 in excellent yields. 

Typical Experimental Procedure (Scale Up). Stoichiometric amounts (6.2 mL) of 0.1 M methanolic solutions of the three supporting Ugi components and ethyl glyoxalate (7.75 ml) were combined and stirred at reflux overnight. The solvent was evaporated in vacuo and crude Ugi product dried under high vacuum. A 10% solution of AcCl in MeOH (25 mL) or a 10% solution of TFA (trifluoroacetic acid) in dichloroethane (25 mL) was added to the crude material and stirred at room temperature overnight. The solvent was evaporated in vacuo. The crude material was preadsorbed onto flash silica and purified by flash column chromatography (EtOAc hexane, 1 4) to yield the desired product 57 (192 mg, 71%) as a white solid. 

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). 

A 20 ml 50% solution of benzenesulfonyl isocyanate (0.10 mol) in toluene and 50 ml ethyl glyoxalate in toluene were refluxed 24 hours, then treated with 1,3-cyclohexadiene (0.21 mol), and refluxed an additional 10 hours. Upon cooling, a white precipitate was formed, which was recrystallized in EtOAc, and 19.1 g product isolated as a white solid. 

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>. 

An efficient procedure for the preparation of ethyl glyoxalate consists in oxidation of ethyl bromoaeelale in, 3 equivalents of dimethyl sulfoxide at 70° in the presence of 1.2-cpoxy-3-phcnoxypropiinc. a nonalkaline scavenger for hydrogen bromide, and... 

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). 

Table 4.6 D ual Lewis acid-Lewis base activation in the enantioselective [2 + 2] cycloaddition of TMS-ketene and ethyl glyoxalate.

In an alkaline medium, chloroacetic acid converts a diamine into a fused pyrazinone [2191]. Most 1,2-dicarbonyl compounds including ethyl benzoylfor-mate [3776] react with 1,2-phenylenediamines to form quinoxalines. Chloroacetic acid or (A phenylsulphonyl)arylglyoxalamides yield 3-arylquinoxalin-2-ones [2892] ethyl glyoxalate diethylacetal behaves similarly with pyrimidine-... 

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. 

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