Meso dialdehyde

The meso-dialdehydes 4.43 and 4.46 undergo the HWE reaction with chiral phosphonate 4.44 in the presence of the base KHMDS and 18-crown-6 followed by the treatment with NaBH4 to give major amounts of monoaddition products 4.45 and 4.47, respectively, with good diastereoselectivities and high -selectivities. Similarly, meso-diketone 4.48 reacts with chiral phosphonate 4.49 to give a,(3-unsaturated ester 4.50 in 95% yield with high E-selectivity (98% ee). ... 

The first enantioselective total synthesis of (-)-denticulatin A was accomplished by W. Oppolzer. The key step in their approach was based on enantiotopic group differentiation in a meso dialdehyde by an aldol reaction. In the aldol reaction they utilized a bornanesultam chiral auxiliary. The enolization of A/-propionylbornane-10,2-sultam provided the (Z)-borylenolate derivative, which underwent an aldol reaction with the meso dialdehyde to afford the product with high yield and enantiopurity. In the final stages of the synthesis they utilized a second, double-dlastereoditferentiating aldol reaction. Aldol reaction of the (Z)-titanium enolate gave the anf/-Felkin syn product. The stereochemical outcome of the reaction was determined by the a-chiral center in the aldehyde component. 

De Brabander, J., Oppolzer, W. Enantioselective total synthesis of (-)-denticulatins A and B using a novel group-selective aldolization of a meso dialdehyde as a key step. Tetrahedron 1997, 53, 9169-9202. 

Rein, T., Vares, L., Kawasaki, I., Pedersen, T. M., Norrby, P.-O., Brandt, P., Tanner, D. Asymmetric Horner-Wadsworth-Emmons reactions with meso-dialdehydes scope, mechanism, and synthetic applications. Phosphorus, Suifur Siiicon Reiat. Bern. 1999, 144-146, 169-172. 

The strategy being pursued is guided by knowledge obtained during the structure elucidation that the hemilactal component of (140) (Scheme 34) exists in equilibrium with a-hydroxylactone forms such as (141) 103). One mode of disconnection of the latter (Scheme 34) leads sequentially to the glyoxylate ester (142) and thence to the meso dialdehyde (143). Actually, employment of (143) would yield a racemic product unless the aldehydic centres were differentiated as in the case of dinitro equivalent... 

In an analogous manner to the route to the THF derivatives described above, the chiral THF derivatives 170 and 171 were successfully prepared from the meso-dialdehyde 69b by asymmetric HWE reaction followed by Pd-catalyzed intramolecular cyclization [98]. 

De Brabander et al. have reported a very rapid enantioselective synthesis of the Prelog-Djerassi lactonic acid through an asymmetric aldol reaction [88] (Scheme 44). The Oppolzer sultam-derived A-propionyl derivative 215 was used to desymmetrize meso-dialdehyde 216, and the diastereoselectivity was found to be 80 %. Oxidation of the resulting lactol 217 to lactone 218 was followed by oxidative removal of the chiral auxiliary. The unwanted diastereoisomer resulting from the aldol reaction was removed chromatographically after the oxidation step. 

BouzBouz, S. and Cossy, J. (2004) Stereoselective synthesis of the C15-C24 fragment of discodermolide by desymmetrization of a meso dialdehyde. Synlett, 2034-2036. 

Oppolzer, W., De Brabander, (., Walther, E., and BemardineUi, G. (1995) Asymmetric synthesis of (—)-denticulatins A and B via group-selective aldolization of a meso dialdehyde with a chiral N-propionylsultam. Tetrahedron Lett, 36, 4413-4416. 

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