Oxazolidinones electron-deficient

Yamamoto and co-workers (135,135-137) recently reported a new method for stereocontrol in nitrile oxide cycloadditions. Metal ion-catalyzed diastereoselective asymmetric reactions using chiral electron-deficient dipolarophiles have remained unreported except for reactions using a-methylene-p-hydroxy esters, which were described in Section 11.2.2.6. Although synthetically very useful and, hence, attractive as an entry to the asymmetric synthesis of 2-isoxazohnes, the application of Lewis acid catalysis to nitrile oxide cycloadditions with 4-chiral 3-(2-aIkenoyl)-2-oxazolidinones has been unsuccessful, even when > 1 equiv of Lewis acids are employed. However, as shown in the Scheme 11.37, diastereoselectivities in favor of the ffc-cycloadducts are improved (diastereomer ratio = 96 4) when the reactions are performed in dichloromethane in the presence of 1 equiv of MgBr2 at higher than normal concentrations (0.25 vs 0.083 M) (140). The Lewis acid... 

Fig. 3 (a) Lewis acid chelation induces rigidity and electron-deficiency into the iV-acylhydrazone radical acceptor (LA = Lewis acid), (b) Benzyl substituent of 4-benzyl-2-oxazolidinone provides facial differentiation of the C=N bond... 

In 1995, Porter et al. [34] reported the first excellent results for free radical addition to an electron-deficient alkene by use of chiral zinc complexes. Reaction of the oxa-zolidinone 9 with tert-butyl iodide and allyltributylstannane 30 in the presence of Zn(OTf)2 and a chiral bis(oxazoline) ligand 12 gave the adduct 44 in 92 % yield with 90 % ee (Sch. 18). The chiral bis(oxazoline) complexes derived from ZnCl2 or Mg(OTf)2 gave racemic products. In this reaction, lower allyltin/alkene ratios gave substantially more telomeric products, and a [3 + 2] adduct 45 of the oxazolidinone 9 and the allylstannane 30 was obtained at temperatures above 0 °C. 

Minakata and coworkers also reported the asymmetric aziridination reactions of electron-deficient olefins using cinchona-based PTCs 33-37 and N-chloro-N-sodio carbamate as an oxidant [32]. Moderate values of the ee were obtained. Comparative experiments revealed that the electron-deficient olefin bearing both the dimethylpyr-azole and the di-isopropylpyrazole groups turned out to be a better Michael acceptor than that bearing the oxazolidinone substituent. The modification of the R-substit-uent of the cinchona-derived anthracenylmethylated ammonium salts 35-37 did not have any effect on the enantioselectivity (Scheme 5.26). 

Oxazolidinone-substituted siloxydiene 105b also is applicable in DA reactions with electron-deficient alkenes under slightly vigorous conditions (Scheme 10.108)... 

A small number of enantiomerically pure Lewis acid catalysts have been investigated in an effort to develop a catalytic asymmetric process. Initial work in this area was carried out by Narasaka and coworkers using the titanium complex derived from diol (8.216) in the cycloaddition of electron-deficient oxazolidinones such as (8.217) with ketene dithioacetal (8.218), alkenyl sulfides and alkynyl sulfides. Cyclic alkenes can be used in this reaction and up to 73% ee has been obtained in the [2- -2] cycloaddition ofthioacetylene (8.220) and derivatives with2-methoxycarbonyl-2-cyclopenten-l-one (8.221) usingthe copper catalyst generated with bis-pyridine (8.222). Furthermore, up to 99% ee has been obtained in the [2-1-2] cycloaddition of norbornene with alkynyl esters using rhodium/Hs-BINAP catalysts. This reaction is not restricted to the use of transition metal-based Lewis... 

SCHEME 2.6. Proline deactivation by oxazolidinone formation from electron-deficient aldehydes. 

Sibi et al. reported that substoichiometric chiral Mg(II) complexes catalyzed regio- and enantioselective nitrile oxide cycloadditions to electron-deficient alkenes (Scheme 4.8) [6]. For an achiral template, bulky pyrazolidinone (20) was essential for high regio- and enantioselectivity in (22) and (23), while oxazolidinone crotonate and 3,5-dimethylpyrazole gave the adducts, but with poor results. In particular, mesityl nitrile oxide (21), a stable dipole, was chosen as the reagent due to steric interactions of that group with either a bulky achiral template and/or a bulky Lewis acid center. Aliphatic (t-Bu and i-Bu) nitrile oxides also provided cycloaddition... 

To circumvent this problem, asymmetric 1,3-dipolar cycloaddition catalyzed by a metallic Lewis acid catalyst was designed to use electron-deficient alkene as a dipolarophile that has a chelating ligand structure, such as A-acyl oxazolidinone (Figure 11.2). The incorporation of a Lewis acid was expected to be equilibrating between 1,3-dipole and dipolarophile in the reaction and the reaction rate acceleration of cycloaddition occurs only in the Lewis acid/dipolarophile complex [4]. 

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