Evans chiral oxazolidine

Oxazolidin-2-ones, a well-known class of organic compounds, have many chemical and biological uses they are, in fact, utilized as chiral auxiliaries (Evans chiral auxiliaries) [31] in asymmetric synthesis and some oxazolidin-2-ones have been found to have activity as immunosuppressant [32] and as antimicrobial. [33]... 

Chiral 3-alkenoyl-l,3-oxazolidin-2-ones have been developed and used in highly diastereoselective Diels-Alder reactions by Evans et al. [26] (Scheme 1.34). In this reaction these dienophiles are highly reactive compared with the corresponding... 

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

Imide Systems. Imide compounds 22 and 23, or Evans reagents, derived from the corresponding oxazolidines are chiral auxiliaries for effective asymmetric alkylation or aldol condensation and have been widely used in the synthesis of a variety of substances. 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted important interest thanks to there various applications in different synthetic transformations. These simple structures, directly related to the well-documented Evans oxazolidinones, have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations (7V-enoyl derivatives), but mainly in condensation of their 7V-acyl derivatives on aldehydes. Those have shown interesting characteristics in anti-selective aldol reactions or combined asymmetric addition. Normally, the use of chiral auxiliaries which can accomplish chirality transfer with a predictable stereochemistry on new generated stereogenic centers, are indispensable in asymmetric synthesis. The use of OZTs as chiral copula has proven efficient and especially useful for a large number of stereoselective reactions. In addition, OZT heterocycles are helpful synthons that can be specifically functionalized. 

The fluorination of enolates of ketone, amide, or hydrazone bearing a chiral auxiliary (SAMP, Evans oxazolidine) with nonchiral fluorination reagent (A-fluoro sulfonimides, A-fluoropyridine) occurs with excellent diastereoselectivities. ... 

A polymer-supported oxazolidine aldehyde 226 was developed for asymmetric chemistry <02JOC6646> as well as a soluble polymer-bound Evan s chiral auxiliary <02TA333> and 3,5-disubstituted oxazolidin-2-one 227 anchored on a solid phase <02TL8327>. 

D.L Boger et al. reported the total synthesis of bleomycin A2. They devised an efficient synthesis for the construction of the tripeptide S, tetrapeptide S, and pentapeptide S subunits of the natural product." " " In their strategy, they utilized an Evans aidoi reaction between the (Z)-enolate derived from (S)-4-isopropyl-3-propionyl-oxazolidin-2-one and A/-Boc-D-alaninal. In order to synthesize one of the diastereomers of the pentapeptide S subunit, they carried out an Evans aidoi reaction between the same aldehyde and the (Z)-enolate of (R)-4-isopropyl-3-propionyl-oxazolidin-2-one. The formation of the diastereomeric syn aldol product in this reaction clearly shows that the stereochemical outcome of the transformation is determined by the chiral auxiliary. 

Boron-mediated asymmetric aldol condensation methodology developed by Evans [90] served as an inspiration for preparation of daunosamine starting from chiral oxazoUdinones. It appeared that the choice of chiral auxiUary is quite important for the stereochemical outcome of planned reactions [91]. A successful series of reactions started from N -succinoylation of (R)-3-(l-oxo-3-carbomethoxypropyl)-4-diphenylmethyl)oxazolidin-2-one as a novel chiral auxihary. The chain extension was achieved in aldol condensation with protected lactaldehyde and the key intermediate 132 was converted into the target aminosugar 135, via Curtius rearrangement of carboxyhc acid azide, and reduction of lactone to lactol, as depicted in Scheme 24 [58]. Unexpectedly, boron catalysts were rather ineffective in the aldol condensation step and had to be replaced with more reactive lithiiun enolates (which proved to be non-Evans syn selective). 

The stannous enolates of Evans (/ )- and (5)-4-benzyl-3-(isothiocyanoacetyl)oxazolidin-2-ones 223 (Figure 11.76) react with aliphatic and aromatic aldehydes to afford 5-substituted 2-thioxo-oxazolidine-4-carboxylates, which are readily hydrolyzed to give syn-(2S,3R)- and (2R,35)-/3-hydroxy-a-amino acids, respectively, in fairly good yields (50-70%) and excellent stereoselectivities (90-99% d.e.) . Although 223 is readily accessible from the respective chloroacetyl precursor through treatment with sodium azide and transformation of the resultant azide with PhsP and CS2, the less commonly used ethyl (lR,2R,5/ )-((2-hydroxypinan-3-ylene)amino)acetate 12241 and its (-l-)-antipode are the only linear chiral glycinate exploited so far in aldol reactions in isotope chemistry. ... 

---