Aldol-type reactions oxazolidinones

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

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... 

Section A.5). Indeed, three enantiomeric pairs of 2-oxazolidinones have been commercially available since 1991. Enantiomerically pure 4-phenyl-2-oxazolidinone has likewise been prepared from / -aminobenzeneethanol (phenylglycinol)64. Base-catalyzed acylation of the enantiomerically pure 2-oxazolidinones with an appropriate acyl chloride gives the desired 3-acyl-2-oxazolidinones 3, 6 and 9 which have been used extensively in highly diastereoselective reactions of various types such as alkylations, aldol reactions (see Section D.l.3.4.2.4), hydrox-ylations (see Section D.4.1), aminations (see Section D.7.1) and Diels-Alder reactions (see Section D. 1.6.1.6) alkylation giving products with induced chirality in the a-position. 

Evans type aldolizations using boron or lithium enolates are mechanistically different. Although both reactions lead predominantly to 2,3-syrc-aldols, the enantioselectivities are inverted i.e. whereas in our original strategy (5)-oxazolidinones lead to the desired 2(5), 3(5) aldols, the same result via lithium enolates requires switching to (R)-oxazolidinones. This change of selectivity has been explained by differing... 

The aldol reaction illustrated in eq 2 has been applied to the targeted synthesis of a number of complex molecules including Tylosin, Hapalosin, the antibiotic Sinefungin, and the HIV protease Saquinavir inhibitor. Oxazolidinone-type chiral auxiliaries derived from 1 have also been employed for the control of Diels-Alder reactions of attached acryloyl or crotonyl groups. ... 

The synthesis started with an Evans aldol between the phenylalanine-derived oxazolidinone 110 and the aldehyde 111. Reductive cleavage of the. vvn-aldol 112 gave the diol 113 in excellent yield. This type of aldol reaction is discussed in detail in chapter 27. You may be impressed by the near perfect stereoselectivity but unimpressed that 113 is the wrong diastereoisomer. Look and wonder. 

Enantiomerically pure oxazolines and oxazolidinones have found widespread application in organic synthesis as chiral auxiliaries. They have been mainly used for the synthesis of enantiomerically pure amino acids but also as chiral auxiliaries to produce non-racemic enolates as pioneered by Evans.The reaction types proceeding with high stereocontrol include enolate alkylation, enolate oxidation, enolate halogenation, enolate amination, enolate acylation, aldol reaction and Diels-Alder reactions. 

Two new glucose-derived oxazolidinones have been prepared, and converted to iV-acyl derivatives of type 204 (R = Me or Piv). The dialkylboron enolates derived from 204 underwent aldol reactions to give syn-products 205, with diastereomeric ratios between 8 1 and 16 1. The same group has also made the oxazolidinone 206 from D-xylose. When this was treated with Mukaiyama s reagent (2-chloro-l-methylpyridinium iodide) in the presence of an imine, a Staudinger ketene-imine cyclization occurred to give a p-lactam such as 207, the structure of which was confirmed by X-ray crystallography, in >98% de. ... 

Li and co-workers developed a novel asymmetric halo aldol reaction using Evans oxazolidinones as chiral auxiliaries for tandem I-C/C-C bond formations. This reaction provides a practical approach to a variety of halo aldols of a non-Evans type that cannot be easily prepared by other methods. Excellent diastereoselectivity (> 95% de) and yields (80-93%) have been obtained. This reaction can be considered as a Lewis acid (Et2Al-I)-promoted Morita-Baylis-Hillman (MBH) process. 

OTHER TYPES OF ALDOL REACTIONS USING THE CHIRAL OXAZOLIDINONE 219... 

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