Ene reaction glyoxylate

ASYMMETRIC CATALYTIC GLYOXYLATE-ENE REACTION METHYL (2R)>2 HYDROXY-4-PHENYL-4 PENTENOATE (Benzenabutanoic acid, a-hydroxy-y-methylene, methyl ester, (R)-)... 

ASYMMETRIC CATALYTIC GLYOXYLATE-ENE REACTIONS WITH 1,1- PISUBSTITUTED OLEFINSa... 

ASYMMETRIC CATALYTIC GLYOXYLATE-ENE REACTION METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTEN0ATE... 

Scheme 8-44. General scheme for Ti-catalyst asymmetric glyoxylate-ene reactions. Reprinted with permission by Wiley-VCH Verlag GmbH, Ref. 89.

Mandoli, A. and Orlandi, S. and Pini, D. and Salvador , P. (2004). Insoluble polystyrene-bound bis(oxazoline) batch and continuous-flow heterogeneous enantioselective glyoxylate-ene reaction. Tetrahedron Asymmetry, 15, 3233-3244. 

Evans, D.A. and Tregay, S. W. and Burgey, C.S. and Paras, N.A. and Vojkovsky, T. (2000). C2-Symmetric Copper(ll) Complexes as Chiral Lewis Acids. Enantioselective Glyoxylate-Ene Reaction with Glyoxylate and Pyruvate Esters. J. Am. Chem. Soc., 122, 7936-7943. 

A full account5 describes the enantioselective carbonyl-ene reaction of glyoxylate esters catalyzed by a binaphthol-derived chiral titanium complex that is potentially useful for the asymmetric synthesis of a-hydroxy esters of biological and synthetic importance.6 The present procedure is applicable to a variety of 1,1-disubstituted olefins to provide ene products in extremely high enantiomeric purity by the judicious choice of the dichloro or dibromo chiral catalyst (see Table). In certain glyoxylate-ene reactions involving removal of a methyl hydrogen, the dichloro catalyst... 

Mikami and Nakai et al. have developed a chiral titanium catalyst for the glyoxylate-ene reaction, which provides the corresponding a-hydroxy esters of biological and synthetic importance [7] in an enantioselective fashion (Scheme 8C.3) [8,9]. Various chiral titanium catalysts were screened [ 10]. The best result was obtained with the titanium catalyst (1) prepared in situ in the presence of MS 4A from diisopropoxytitanium dihalides (X2Ti(OPr,)2 X=Br [11] or Cl [12]) and enantiopure BINOL or 6-Br-BINOL [13], The remarkable levels of enantiose-lectivity and rate acceleration observed with these BINOL-Ti catalysts (1) [14] stem from the... 

TABLE 8C.1. Asymmetric catalytic glyoxylate-ene reaction with various olefins... 

The lanthanide complex-catalyzed asymmetric glyoxylate-ene reaction has also been reported (Scheme 8C.5) [17,18], Although the reaction of glyoxylate and a-methylstyrene... 

Desymmetrization of an achiral, symmetrical molecule through a catalytic process is a potentially powerful but relatively unexplored concept for asymmetric synthesis. Whereas the ability of enzymes to differentiate enantiotopic functional groups is well-known [27], little has been explored on a similar ability of non-enzymatic catalysts, particularly for C-C bond-forming processes. The asymmetric desymmetrization through the catalytic glyoxylate-ene reaction of prochiral ene substrates with planar symmetry provides an efficient access to remote [28] and internal [29] asymmetric induction (Scheme 8C.10) [30]. The (2/ ,5S)-s> i-product is obtained with >99% ee and >99% diastereoselectivity. The diene thus obtained can be transformed to a more functionalized compound in a regioselective and diastereoselective manner. 

A remarkable level of ( +)-NLE has been observed in the catalytic ene reaction. For instance, the glyoxylate-ene reaction with 2-phenylpropene using a catalyst prepared from BINOL with 33.0% ee provides the corresponding ene product with 91.4% ee in 92% chemical yield (Scheme... 

Figure 8C 3. Positive non-linear effect in aymmetric glyoxylate-ene reaction.

Catalysis of racemic BINOL-Ti(OPr )2 ( 2) in the glyoxylate-ene reaction with 2-phenyl-propene achieves extremely high enantioselectivity by adding another diol for enantiomer-selective activation (Scheme 8C.15, Table 8C.3) [42], For example, excellent enantioselectivity (90% ee, R) was achieved by adding just a half-molar equiv. (5 mol %) of (/ )-BINOL activator to racemic ( )-BINOL-Ti(OPr )2 complex ( 2) (10 mol %) in this reaction (Table 8C.3, entry 4). 

Mikami et al. reported the first examples of catalytic asymmetric intramolecular carbonyl-ene reactions of types (3,4) and (2,4), using the BINOL-derived titanium complex (1) [46,49], The catalytic 7-(2,4) carbonyl-ene cyclization gives the corresponding oxepane with high enantiopurity, and the gem-dimethyl groups are not required (Scheme 8C.I8). In a similar catalytic 6-(3,4) ene cyclization, tran.v-tetrahydropyran is preferentially obtained with high enantiopurity (Scheme 8C. 19), The sense of asymmetric induction is the same as that observed for the glyoxylate-ene reaction, that is, (R)-BINOL-Ti catalyst provides (R)-alcohol. Therefore, the... 

Mikami reported a highly enantioselective carbonyl-ene reaction where a chiral titanium complex 11 prepared from enantiomerically pure binaphthol (BINOL) and Ti(0-i-Pr)2Br2 catalyzed a glyoxylate-ene reaction with a-methylstyrene to give chiral homoallyl alcohol 12 with 94.6% ee [22]. In this reaction, a remarkable asymmetric amplification was observed and almost the same enantioselectivity (94.4% ee) was achieved by using chiral catalyst prepared... 

Scheme 9. (+)-NLE in the glyoxylate-ene reaction catalyzed by a BINOL-Ti reagent.33...

This was one of the first classes of catalyzed reactions that were shown to give rise to strong asymmetric amplifications (vide supra, Scheme 9).33 Many subsequent studies have been performed with variations in the structure of the chiral catalyst, generated from BINOL and titanium salts.50-52 Asymmetric amplification is frequently observed with these catalysts in the glyoxylate-ene reaction (Table 5). 

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... 

Carbonyl-Ene Reaction. BINOL-TiX2 reagent exhibits a remarkable level of asymmetric catalysis in the carbonyl-ene reaction of prochiral glyoxylates, thereby providing practical access to a-hydroxy esters. These reactions exhibit a remarkable positive nonlinear effect (asymmetric amplification) that is of practical and mechanistic importance (eq 19). The desymmetrization of prochiral ene substrates with planar symmetry by the enantiofacial selective carbonyl-ene reaction provides an efficient solution to remote internal asymmetric induction (eq 20). The kinetic resolution of a racemic allylic ether by the glyoxylate-ene reaction also provides efficient access to remote but relative asymmetric induction (eq 21). Both the dibromide and dichloride catalysts provide the (2R,5S)-syn product with 97% diastereoselectivity and >95% ee. 

The asymmetric glyoxylate-ene reactions have been exploited in the total synthesis of (—)-specionin, which involves asymmetric desymmetrization of a prochiral diene (eq 3), and (—)-xylomollin, which involves an efficient kinetic resolution of a racemic diene (eq4).i - ... 

The synthetic utility of the vinylic sulfide and selenide approach is exemplified by the synthesis of enantio-pure (i )-(-)-ipsdienol, an insect aggregation pheromone (Sch. 13) [54], Kabat and Uskokovic have demonstrated the asymmetric catalytic synthesis of la,25-dihydroxyvitamin D3 (la,25(OH)2D3) A-ring synthon by means of a glyoxylate-ene reaction catalyzed by BINOL-Ti complex (1) (Sch. 14) [55]. 

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