Methyl glyoxylate

Chiral boron(III) complexes can catalyze the cycloaddition reaction of glyoxy-lates with Danishefsky s diene (Scheme 4.18) [27]. Two classes of chiral boron catalyst were tested, the / -amino alcohol-derived complex 18 and bis-sulfonamide complexes. The former catalyst gave the best results for the reaction of methyl glyoxylate 4b with diene 2a the cycloaddition product 6b was isolated in 69% yield and 94% ee, while the chiral bis-sulfonamide boron complex resulted in only... 

The interest in chiral titanium(IV) complexes as catalysts for reactions of carbonyl compounds has, e.g., been the application of BINOL-titanium(IV) complexes for ene reactions [8, 19]. In the field of catalytic enantioselective cycloaddition reactions, methyl glyoxylate 4b reacts with isoprene 5b catalyzed by BINOL-TiX2 20 to give the cycloaddition product 6c and the ene product 7b in 1 4 ratio enantio-selectivity is excellent - 97% ee for the cycloaddition product (Scheme 4.19) [28]. 

Several groups have reported the use of rare earth complexes as catalysts for asymmetric Diels-Alder reaction. Qian and Wang described thus the preparation and use of Yb complexes chelated by Pr-PyBOx to successfully achieve the hetero-Diels-Alder reaction of methyl glyoxylate with Danishefsky s diene in 77% ee and 73% yield (Scheme 37) [98]. 

Fig. 10.1. Minimum-energy transition structures for ene reactions (a) propene and ethene (b) propene and formaldehyde (c) butene and methyl glyoxylate-SnCl4 (d) butene and methyl glyoxylate-AlCl3. Reproduced from Helv. Chim. Acta, 85, 4264 (2002), by permission of Wiley-VCH.

Methyl glyoxylate can be prepared following a literature procedure.3 The checkers used commercial material supplied by Hoechst Celanese, Specialty Chemicals. Immediately before use, the material is depolymerized by vacuum distillation from phosphorus pentoxide (P2O5) (10% weight) bp 62°C/60 mm. 

A related catalyst 20 was used in the diastereoselective carbonyl-ene reaction between ethylidenecyclohexane, ethylidenecycloheptane, or 2-methyl-2-butene and trifluoroacetaldehyde (21, R = CF3, Equation (ll))19 or methyl glyoxylate (R = C02Me).20 The best results were obtained when X = Br 63-85% yields are obtained with syn/anti ratios of 95 5 or better, and ee s of the. qw-isomer of 74-89%. 

Protonated imines are effective dienophiles. Thus in the reaction of methyl glyoxylate with the hydrochloride 127 of alanine methyl ester in the presence of cyclopentadiene, a mixture of hydrochlorides of the exo- and ewrfo-adducts 128-131 was formed (equation 69). The diastereomeric ratio of the exo-compounds was 83 1761. 

Mukaiyama et al. developed a rather general and versatile method for the preparation of optically active a-hydroxyaldehydes by using the diamine (99) as chiral adjuvant. Thus, one Grignard reagent (R MgX) is reacted with the aminal (102) of methyl glyoxylate. In the next step a second kind of Grignard reagent (R2-MgX) is diastereoselectively added to the ketoaminal, and the desired chiral a-hydroxy-aldehyde (103) is obtained by hydrolysis 117-1I8). 

Methyl 2-methoxy-5,6-dihydro-2H-pyran-6-carboxylate (2 R = Me) can be obtained in optically active form by condensation of diene 1 with methyl glyoxylate in the presence of dichlorotitanium (R)-binaphthol catalyst (3) [45]. 

A similar nonlinearity is seen in the ene reaction of methyl glyoxylate and a-methylstyrene (Scheme 43) (69). Thus, the reaction catalyzed by a complex in situ formed from dibromo(diisopropoxy)titanium(IV) and (/ )-binaphthol in 33% ee affords the chiral adduct in 91% ee with the same enantioselectivity as would have been obtained had enantiomerically pure binaphthol been used. Molecular weight measurements suggest the catalyst is a dinuclear titanium compound, although the structure has not been elucidated. This nonlinear effect is interpreted by the difference in the dissociation constant of the diastereomeric dimers as... 

Enantiotopos discrimination, 93, 128, 142, 234, 235, 331 Ene reactions asymmetric, 223 binaphthol, 222 chiral metal complexes, 222 intramolecular, 226 methyl glyoxylate, 290 Enol silyl ether substrates, 128, 228, 230 Enol substrates, 28 Enolates ... 

It is noteworthy that the ene product 227 is obtained exclusively when allylsilane 226 is treated with butynone in the presence of Znl2 catalyst and molecular sieve (ms) 4A(equation 185)331. Methyl vinyl ketone behaves similarly. High enantioselectivity has been observed in product 228 when triphenylallylsilane is coupled with methyl glyoxylate in the presence of (R)-(BINOL)TiCl2 catalyst (equation 186)332. In addition to [2 + 2] cycloaddition, TCNE undergoes a regiospecific ene reaction with y-alkyl substituted allylsilanes to yield the substituted olefins 229 (equation 187)333. 

Methyl glyoxylate adducts of N-BOC-protected allylic amines 321 have been utilized to construct a new C—O bond by an intramolecular, Pd(II)-catalysed reaction436. In analogy, lactones 324a437 and cyclic ethers 324b438 can be prepared by the Pd(II)-catalysed cyclization of the suitable precursors 322a and 322b, respectively. 

Formaldehyde, -acetaldehyde, propionaldehyde, methyl glyoxylic acid, pymvic acid Converted to benzyl esters, then GLC [598]... 

Reaction of the amine 471 with methyl glyoxylate produced electrophilic attack on the activated aromatic ring to yield 472 as a single stereoisomer in good yield <2001TL543, 20030L2095>. 

The ene reaction between 1-methylstyrene and methyl glyoxylate, catalyzed by a BINOL-titanium complex, gives a considerable amplification, as reported by Nakai and Mikami (Scheme 9).33 Many reports of asymmetric amplifications have subsequently been published for a wide range of reactions (vide infra). 

Glyoxylate ene reactions. The diastereoselectivity of the ene reaction of methyl glyoxylate (1) with 2-butene (2) can be controlled by the choice of the Lewis acid catalyst. Reactions catalyzed by SnCl4 with either (E)- or (Z)-2 proceed in quan-tative yield and fairly high syn-selectivity. The reaction catalyzed by (CH,)2A1C1 proceeds in low yield (5%) but with high onh-selectivity, particularly in the reaction... 

Cycloaddition of the diene 2-54 obtained from 2,4-benzylidene-erythrose by a Wittig reaction with sodium glyoxylate 2-55 in water for 2.5 days at reflux provided a mixture of four adducts in good yield, but in low diastereoselectivity. Interestingly, for the reaction of methyl glyoxylate with the acetylated diene in an organic solvent higher temperature was needed (4 h, 140 °C) with decreased yield (25%) (Fig. 2-16) [102]. 

The outstanding properties of binaphthol (BINOL) as a ligand in chiral Lewis acidic metal complexes were also demonstrated highly successfully by Mikami [108, 109] using a binol-titanium complex 2-69a. Even in the cycloaddition of methyl glyoxylate 2-66 to 1 -methoxy-1,3-butadiene 2-65 which usually shows only a low selectivity, a reasonable cis/trans-selectivity and an excellent enantioselectivity could be obtained in the presence of catalytic amounts of this complex. 

Methyl glyoxylate dithioacetal 292, after lithiation, reacted with a protected D-mannitol triflate in the presence of HMPA. This methodology has been applied to the synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO)462. A related ethyl glyoxylate dithioacetal 293 gave conjugate addition to different Michael acceptors, such as a,fi-unsaturated esters, lactones and lactams463,464. 

OL-Keto esters. The cyanohydrin silyl ether < 1) of methyl glyoxylate (4, 542-543 5, 720) can be converted by alkylation of the anion into the enol acetate (2) of a-keto esters. 

The selenium-sihcon linker 1.46 (104), obtained from hydroxy PS resin and methyl glyoxylate through a simple five-step scheme, was coupled with a steroid scaffold to give an acetal then transformed on SP and finally cleaved with TB AF/tetramethyl urea, 1 h, 100 °C to give decorated alcohols via unstable hemiacetals with good yields and purities. 

A chiral Lewis acid prepared in situ from magnesium iodide and (/ ,f )-DPEN efficiently catalyzes asymmetric aza-Diels-Alder reaction of a methyl glyoxylate/p-anisidine derived imine with the Danishefsky diene to give the cyclic adduct in 97% ee (eq 11). ... 

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