Oxazolidinone, chiral auxiliary

The interesting structures of the Lasioderma compounds have been the subject of many syntheses, serving as models for stereocontrolled approaches. More recent syntheses of serricornin form two groups those using chiral auxiliaries (oxazolidinone [250],boronic esters [251],and SAMP/RAMP [252]) and those involving chemoenzymatic steps ([253-255]). 

A stereocontrolled synthesis of the biologically active neolignan (+)-dehydrodiconiferyl alcohol, which was isolated from several Taxus species, was achieved via Evans asymmetric aldol condensation [58] using ferulic acid amide derived from D-phenylalanine. The reaction steps are shown in Fig. 9. This stereocontrolled reaction is also useful for preparing the enantiomer of (+)-dehydroconiferyl alcohol using chiral auxiliary oxazolidinone prepared from L-phenylalanine. This reaction also enables the syntheses of other natural products that possess the same phenylcoumaran framework. 

Scheme 12. Lewis acid and chiral auxiliary oxazolidinones. Atom transfer radical addition and radical polymerization reactions...

Atom-transfer addition of primary and secondary bromide oxazolidinones to alkenes in the presence of Lewis acids has been investigated and the effects of solvent, temperature, and catalyst were determined. The best Lewis acids were found to be Sc(OTf)3 and Yb(OTf)3 and control was possible using chiral auxiliary oxazolidinones. Tertiary bromides did not react (Scheme 37). Stereochemistry of reduction of the cw-mesityl-alkene (53) with BusSnH proceeds to give the ( )-alkene (54) as the major product ( Z = 9 1). Theoretical calculations at the BLYP/6-31G level were undertaken to rationalize the stereochemistry. Asymmetric hydroxylation of the benzylic position of a range of substrates can be achieved by using a chiral dioxomthenium(VI) porphyrin (55). The oxidation proceeds via a rate-limiting H-abstraction to produce a benzylic radical intermediate. ... 

Table 1.7 2-Oxazolidinones as chiral auxiliaries in Darzens reactions.

Several other oxazolidinones have been developed for use as chiral auxiliaries. The 4-isopropyl-5,5-dimethyl derivative gives excellent enantioselectivity.91 5,5-Diaryl derivatives are also quite promising.92... 

As with the acyl oxazolidinone auxiliaries, each of these systems permits hydrolytic removal and recovery of the chiral auxiliary. 

Stereochemical Control Through Chiral Auxiliaries. Another approach to control of stereochemistry is installation of a chiral auxiliary, which can achieve a high degree of facial selectivity.124 A very useful method for enantioselective aldol reactions is based on the oxazolidinones 10,11, and 12. These compounds are available in enantiomerically pure form and can be used to obtain either enantiomer of the desired product. 

In Entry 5, the aldehyde is also chiral and double stereodifferentiation comes into play. Entry 6 illustrates the use of an oxazolidinone auxiliary with another highly substituted aldehyde. Entry 7 employs conditions that were found effective for a-alkoxyacyl oxazolidinones. Entries 8 and 9 are examples of the application of the thiazolidine-2-thione auxiliary and provide the 2,3-syn isomers with diastereofacial control by the chiral auxiliary. 

As is the case for aldol addition, chiral auxiliaries and catalysts can be used to control stereoselectivity in conjugate addition reactions. Oxazolidinone chiral auxiliaries have been used in both the nucleophilic and electrophilic components under Lewis acid-catalyzed conditions. (V-Acyloxazolidinones can be converted to nucleophilic titanium enolates with TiCl3(0-/-Pr).320... 

Enantioselective Reactions of Organocopper Reagents. Several methods have been developed for achieving enantioselectivity with organocopper reagents. Chiral auxiliaries can be used for example, oxazolidinone auxiliaries have been utilized in conjugate additions. The outcome of these reactions can be predicted on the basis of steric control of reactant approach, as for other applications of the oxazolidinone auxiliaries. 

The syntheses in Schemes 13.45 and 13.46 illustrate the use of oxazolidinone chiral auxiliaries in enantioselective synthesis. Step A in Scheme 13.45 established the configuration at the carbon that becomes C(4) in the product. This is an enolate alkylation in which the steric effect of the oxazolidinone chiral auxiliary directs the approach of the alkylating group. Step C also used the oxazolidinone structure. In this case, the enol borinate is formed and condensed with an aldehyde intermediate. This stereoselective aldol addition established the configuration at C(2) and C(3). The configuration at the final stereocenter at C(6) was established by the hydroboration in Step D. The selectivity for the desired stereoisomer was 85 15. Stereoselectivity in the same sense has been observed for a number of other 2-methylalkenes in which the remainder of the alkene constitutes a relatively bulky group.28 A TS such as 45-A can rationalize this result. 

The synthesis in Scheme 13.47 was also based on use of a chiral auxiliary and provided the TBDMS-protected derivative of P-D lactone in the course of synthesis of the macrolide portion of the antibiotic 10-deoxymethymycin. The relative stereochemistry at C(2)-C(3) was obtained by addition of the dibutylboron enolate of an A-propanoyl oxazolidinone. The addition occurs with syn anti-Felkin stereochemistry. 

The literature presents a large number of examples concerning the use of known oxazolidinones as chiral auxiliaries in many kinds of reactions. Rare is the use of A-amino derivatives of oxazolidinones, which were used to synthesise new A-acylhydrazones 207. Radical addition reactions occurred with high diastereoselectivity <00JA8329>. The use of glycolate oxazolidinones 210 proved to be efficient for the enantioselective preparation of a-alkoxy carboxylic acid derivatives . Photochemical reaction of vinyl... 

S)-4-isopropyl-2-oxazolidinone, 82% Scheme 2-19. Synthesis of Evans chiral auxiliary 25. 

Reagent control This involves the addition of a chiral enolate or allyl metal reagent to an achiral aldehyde. Chiral enolates are most commonly formed through the incorporation of chiral auxiliaries in the form of esters, acyl amides (oxazolines), imides (oxazolidinones) or boron enolates. Chiral allyl metal reagents are also typically joined with chiral ligands. 

Asymmetric Diels-Alder reactions. Unlike methyl crotonate, which is a weak dienophile, chiral (E)-crotonyl oxazolidinones when activated by a dialkylaluminum chloride (1 equiv.) are highly reactive and diastereoselective dienophiles. For this purpose, the unsaturated imides formed from oxazolidinones (Xp) derived from (S)-phenylalanol show consistently higher diastereoselectivity than those derived from (S)-valinol or (IS, 2R)-norephedrine. The effect of the phenyl group is attributed in part at least to an electronic interaction of the aromatic ring. The reactions of the unsaturated imide 1 shown in equation (I) are typical of reactions of unsaturated N-acyloxazolidinones with cyclic and acyclic dienes. All the Diels-Alder reactions show almost complete endo-selectivity and high diastereoselectivity. Oxazolidinones are useful chiral auxiliaries for intramolecular Diels-Alder... 

Chiral active pharmaceutical ingredients, 18 725-726. See also Enantio- entries Chiral additives, 6 75—79 Chiral alcohols, synthesis of, 13 667-668 P-Chiral alcohols, synthesis of, 13 669 Chiral alkanes, synthesis of, 13 668-669 Chiral alkenes, synthesis of, 13 668—669 Chiral alkoxides, 26 929 Chiral alkynes, synthesis of, 13 668-669 Chiral ammonium ions, enantiomer recognition properties for, 16 790 Chiral ansa-metallocenes, 16 90 Chiral auxiliaries, in oxazolidinone formation, 17 738—739... 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted much interest for their various applications in different synthetic transformations.2 Such simple structures, directly related to far better known chiral oxazolidinones,11,12,57 have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations, but mainly in condensation of their /V-acyl derivatives with aldehydes. Chiral OZTs have shown interesting characteristics in anti-selective aldol reactions58 or combined asymmetric addition. 

Optically active 2-oxazolidinones and 2-thiazolidinones are versatile compounds as chiral auxiliaries. 5a b (4R,5S)-4,5-Diphenyl-2-oxazolidinone has been used for the synthesis of optically active amines6 because of its high stereoselectivity and easy deprotection by hydrogenolysis after the reaction. Compared with several preparations73-0 of (4R,5S)-4,5-diphenyl-2-oxazolidinone reported so far, this method,... 

The chiral iV-propionyl-2-oxazolidinones (37 and 38.) play the role of recyclisable chiral auxiliaries, which can be smoothly removed from the aldol adducts 39 and 40 with aqueous potassium hydroxide in methanol to give the... 

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

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