Oxazolines conjugate additions

Unsaturated chiral oxazolines have been employed in conjugate addition reactions... 

The sesquiterpenoid hydrocarbons (5)-a-curcumene (59) and (5)-xanthorrhizol (60) were prepared by asymmetric conjugate addition of the appropriate aryllithium reagent to unsaturated oxazoline 56 to afford alcohols 57 (66% yield, 96% ee) and 58 (57% yield, 96% ee) upon hydrolysis and reduction. The chiral alcohols were subsequently converted to the desired natural products. ... 

Chiral Cu(ll)-complexes ofbis-oxazolines as Lewis acids for catalyzed cycloaddition, carbonyl addition, and conjugate addition reactions 99PAC1407. 

Conjugate addition of chiral amines to allenic and acetylenic sulfones has been reported73. The reaction 112 with (—)-ephedrine gives only one of the two possible diastereomeric oxazolines in high yield (equation 89). 

Whereas the mono- and the S/S-dithioether moieties have been used to date, the 1,3-dithianyl motif was used for the first time in 2005 by Ricci et al. as a new hybrid ligand in asymmetric catalysis. Hence, a series of new chiral oxazoline-1,3-dithianes have been successfully applied to the copper-catalysed conjugate addition of ZnEt2 to enones (Scheme 2.16). The expected products were obtained in almost quantitative yields and enantioselectivities of up to 69% ee. 

Diethylaluminum cyanide mediates conjugate addition of cyanide to a, (3-unsaturated oxazolines. With a chiral oxazoline, 30-50% diastereomeric excess can be achieved. Hydrolysis gives partially resolved a-substituted succinic acids. The rather low enantioselectivity presumably reflects the small size of the cyanide ion. 

Recently, very effective asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes has been reported, as shown in Scheme 4.10. The reaction of ethyl acetoacetate with nitrostyrene is carried out in the presence of 5 mol% of the preformed complex of magnesium triflate and chiral bis(oxazoline) ligands and a small amount ofW-methylmorpholine (NMM) to give the adduct with selectivity of 91%. The selectivity depends on ligands. The effect of ligands is presented in Scheme 4.10.63... 

When trimethylaluminum reacted with 3-methyl-cyclohexa-2,5-dienone in the presence of chiral oxazoline ligands 86, the conjugate addition proceeded efficiently at the less-substituted double bond with up to 68% ee (Scheme 43).129,129a tw0 0 0-substituents on the phenyl ring of ligands 86 were considered to be important for selectivity. 

In addition to the reactions discussed above, a,//-unsaturated oxazolines can also act as chiral electrophiles to undergo conjugated addition of organolithium reagent to give optically active / ,/ -disubstituted carboxylic acids.52 The vinyl oxazolines 48 are prepared using the two methods outlined in Scheme 2-27. 

Organoaluminum reagents have been used in the copper-catalyzed conjugate addition to enones with some success. Iwata and co-workers (182) demonstrated that dimethoxyphenyl oxazoline (247) provides modest selectivities in the copper-catalyzed conjugate addition of trimethylaluminum to 3,4,4-trimethylcyclohexadi-enone to provide the adduct in 68% ee, Eq. 145. The use of TBSOTf is crucial to attain high conversion and selectivity in this process. Woodward and co-workers (183) subsequently reported that a Cu(I) complex of thiocarbamate 248 provides modest facial discrimination in the addition of trimethylaluminum to a linear enone to afford 245b in 51% ee, Eq. 146. The authors note that this catalyst system decomposes under the reaction conditions at ambient temperature. 

In 1975 Meyers and coworkers, having studied reactions of Uthiated chiral oxazolines with various electrophiles, applied the chiral oxazoline method to conjugate addition of... 

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

Hydroxylation of 711 at C-2 can be achieved by an intramolecular conjugate addition of the benzamide to the enone system. The reaction takes place in high yield in the presence of a Lewis acid and affords direct hydroxylation with a syn relationship to the amide group via an intermediate 1,3-oxazoline (Scheme 7.223). " ... 

Phosphorous oxychloride (POCI3) can also be used without further activation. For the synthesis of the antidepressant (/ )-(—)-rolipram 24, cyclization of the (3-hydroxy amide 21 with POCI3 gave the oxazoline intermediate 22. Diastereo-selective conjugate addition of cyanide gave the cyano derivative 23, which was further transformed to (/ )-( )-rolipram (Scheme 8.11). 

Oxazoline-directed conjugate addition of nucleophiles to a naphthalene nucleus is one of the most useful methods to prepare dihydronaphthalenes. Since Meyers last comprehensive review, the focus has been directed to stereoselective synthesis of these important compounds. Meyers laboratory has continued their preeminence in this field and has expanded the scope and applications of this reaction. 

Another type of conjugate addition reaction in which bis(oxazoline)-metal complexes have been used is the Michael addition reaction. Early work in this... 

The absolute configuration of 1 was set by conjugate addition to the oxazoline 3 followed by trapping of the product anion, following the precedent of Meyers. Reduction of the oxazoline to the alcohol, followed by thionocarbonate formation then set the stage for the key aryl transfer reaction. 

A. Barco, S. Benetti, C. De Risi, G. P. Pollini, G. Spalluto, and V. Zanirato, 4-Isopropyl-2-oxazolin-5-one anion as a new convenient formyl anion equivalent for conjugate addition and aldol reactions. Tetrahedron Lett. 34 3907 (1993). 

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