Diels-Alder reaction adduct, resolution

Another example of an enzymatic one-pot multiple Diels-Alder reaction is illustrated in Table 4.20 [83]. Racemic furfuryl alcohols 130 in the presence of ethoxy vinyl methyl fumarate 131 and enzyme TOYOBO-LIP undergo enzymatic acylation followed by kinetic enzymatic resolution to give the acyl derivatives 132 which then affords the adducts 133 and 134 by intramolecular Diels-Alder reaction 3-methyl-furfuryl alcohol 130 (R = Me) in acetone gives the best results. 

The chiral furan 120, prepared from 119, underwent a Diels-Alder reaction with racemic 110b (4equiv.) at -100 °C. Kinetic resolution of the allenic diester efficiently occurred to afford the oxabicydic enamine adduct 121 stereoselectively [100], The adduct was transformed to (+)-cydophellitol. 

Hydrolase-catalyzed domino reactions incorporating a resolution and a subsequent cycloaddition reaction have been described [95-97]. This constitutes an attractive approach to complex synthetic intermediates. For example, the l-(3-methyl-2-furyl)]propanol roc-93 reacts with ethoxyvinyl methyl fumarate (94) catalyzed by Lipase LIP (from Pseudomonas aeruginosa) to furnish a dienophilic fumarate ester, which spontaneously undergoes an intramolecular Diels-Alder reaction with the furan moiety furnishing exclusively the syn-adduct, the oxabicy-clohexene 95 in excellent along with the remaining alcohol S-96 (Scheme 4.31) [95]. A similar approach has been used for a procedure that includes a series of domino reactions that includes dynamic kinetic resolution of the 3-vinylcyclohex-... 

An approach to lactone [12] similar in concept to that just described, but not requiring a resolution, involved asymmetric Diels-Alder reaction of (benzyloxymethyl)cyclopentadiene [21] with the chiral ester of acrylic add and 8-phenylmenthoI (22), The adduct [22] was obtained in undetermined but apparently quite high e.e. Oxidation of the ester enolate of [22], followed by lithium aluminum hydride reduction, gave diol [23] as an... 

A tetrahydropyran that inhibits leukotriene biosynthesis Asymmetric synthesis of2-methyl-tetrahydropyran-4-one by kinetic resolution Part VI - Asymmetric Desymmetrisation of a Diels-Alder Adduct Ifetroban sodium a thromboxane receptor antagonist A laboratory synthesis starting with a Diels-Alder reaction Desymmetrisation of a symmetrical anhydride with a chiral Grignard reagent Laboratory and process routes compared Part VII - Asymmetric Synthesis of A Bicyclic 3-Lactone Lactacystin a naturalproteasome inhibitor... 

The Diels-Alder reaction between furan and maleic anhydride is reversible and gives the more stable exo-adduct 100 (also commercially available). This compound contains the bicyclic ring system of ifetroban but is achiral and the key problem is to disrupt symmetry of the adduct 100 in a controlled way. The original synthesis used to make the drug17 converted the adduct 100 into the menthyl acetal 101 as a single enantiomer in four steps and then into the carboxylic acid 102 in another six steps. This strategy amounts to a resolution as each menthol adduct could be isolated by crystallisation of a diastereoisomeric mixture in only about 30% yield. 

All sixteen of the racemic carba-sugars predicted are known, as well as fifteen of the enantiomers. The most accessible starting-material for the synthesis of racemic carba-sugars is the Diels-Alder adduct of furan and acrylic acid, namely, e i o7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylicacid (29). Furthermore, adduct 29 is readily resolved into the antipodes, (—)-29 and (+)-29, by use of optically active a-methylbenzylamine as the resolution agent. The antipodes were used for the synthesis of enantiomeric carba-sugars by reactions analogous to those adopted in the preparation of the racemates. 

---