Oxazolidine ligand

Chiral rhodium284 and ruthenium catalysts285,286 have been reported to catalyze the Diels-Alder reaction of methacrolein with cyclopentadiene. Several bis(oxazolidine) and 2-pyridyl-l,3-oxazolidine ligands were used as chiral ligands. The adducts were obtained with only moderate enantioselectivities. 

Chiral disulfide oxazolidine ligands were developed by Braga et al. more recently. The ligand was prepared from / -cysteine in a few steps (Scheme 21.18). The / ,/ -oxazolidine (2) was efficient in the presence of diethyl zinc to furnish chiral propargyl alcohols with moderate to good selectivity. 

C-C bond formatirm is a major task in synthetic chemistry, and direct C-C bond formation through sp C-H transformation is an ideal method. Up to date, only a few examples were reported via silver catalysts in this field. In 1996, Burgess and coworkers described the earliest work of silver-mediated intramolecular carbene insertion toward C-H bonds (Scheme 2) [14]. They examined 96 potential systems of ligand/metal/solvent combinations to optimize such a C-H insertion reaction. Silver hexafluoroantimonate(V) (AgSbFe) together with bis(oxazolidine) ligand L in THF showed an unexpected activity and gave desired insertion products in moderate yield (44%) and diastereoselectivity (2.7 1). 

Chiral oxazolidinones were used also to determine the stereochemical outcome of aldol and aldol-type reactions (130L1898,13TL2171). In one case, a sy -selective Kobayashi aldol reaction was reported between silyldi-enol ethers and acetals (130L678). The chiral oxazolidine ligand 193 was... 

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

Zeijden [112] used chiral M-functionalized cyclopentadiene ligands to prepare a series of transition metal complexes. The zirconium derivative (82 in Scheme 46), as a moderate Lewis acid, catalyzed the Diels-Alder reaction between methacroleine and cyclopentadiene, with 72% de but no measurable enantiomeric excess. Nakagawa [113] reported l,T-(2,2 -bis-acylamino)binaphthalene (83 in Scheme 46) to be effective in the ytterbium-catalyzed asymmetric Diels-Alder reaction between cyclopentadiene and crotonyl-l,3-oxazolidin-2-one. The adduct was obtained with high yield and enantioselectivity (97% yield, endo/exo = 91/9, > 98% ee for the endo adduct). The addition of diisopropylethylamine was necessary to afford high enantioselectivities, since without this additive, the product was essentially... 

Scheme 1.43 Test reaction with oxazolidine-thioether and thiazolidine-methanol ligands.

In 2001, Braga et al. reported the synthesis of new chiral C2-symmetric oxazolidine disulfide ligands from (R)-cysteine and successfully applied them as catalysts in the asymmetric addition of ZnEt2 to various aldehydes (Scheme 3.23). In the presence of 2mol% of ligand, excellent enantioselectivities of up to >99% ee were obtained even with aliphatic aldehydes such as n-decanal or n-hexanal. These authors proposed that the active catalyst did not maintain its C2-symmetry during the reaction. The disulfide bond was probably cleaved in situ by ZnEt2. 

Scheme 3.23 Oxazolidine disulfide ligands for additions of ZnEt2 to aldehydes.

In addition, other chiral sulfide ligands containing oxazolidines have been tested for the enantioselective addition of ZnEt2 to aldehydes, providing moderate enantioselectivities, as shown in Scheme 3.25. ... 

In 2002, Braga el al. employed a chiral C2-symmetric oxazolidine disulfide as a ligand for the enantioselective synthesis of propargylic alcohols by direct addition of alkynes to aldehydes (Scheme 3.64). Good yields but moderate enantioselectivities (<58% ee) were obtained for the enantioselective alkyny-lation of aldehydes in the presence of ZnEt2. 

Scheme 3.64 Oxazolidine disulfide ligand for alkynylations of aldehydes.

In 2005, Carretero et al. reported a second example of chiral catalysts based on S/P-coordination employed in the catalysis of the enantioselective Diels-Alder reaction, namely palladium complexes of chiral planar l-phosphino-2-sulfenylferrocenes (Fesulphos). This new family of chiral ligands afforded, in the presence of PdCl2, high enantioselectivities of up to 95% ee, in the asymmetric Diels-Alder reaction of cyclopentadiene with A-acryloyl-l,3-oxazolidin-2-one (Scheme 5.17). The S/P-bidentate character of the Fesulphos ligands has been proved by X-ray diffraction analysis of several metal complexes. When the reaction was performed in the presence of the corresponding copper-chelates, a lower and opposite enantioselectivity was obtained. This difference of results was explained by the geometry of the palladium (square-planar) and copper (tetrahedral) complexes. 

The same reaction with acetaldehyde produces carbene complex 34 with a saturated ring, i.e., an oxazolidin-2-ylidene ligand with the tosyl group replaced by methoxide. 

Some reactions in which a preformed 1,3-oxazolidine ring is transformed into another oxazolidine derivative were described. A detailed study of the enantioselective reduction of A-tosyl-4-alkylidene-l,3-oxazolidin-2-ones under the catalysis of Rh salts and chiral ligands, was published <06T9237>. 

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