Oxazolidinones Lewis acids

No single examples have been reported so far for the catalyzed asymmetric diazoalkane cydoadditions. Based on the kinetic data on the relative reaction rates observed by Huisgen in the competitive diazomethane cydoadditions between 1-alkene and acrylic ester (Scheme 7.32), it is found that diazomethane is most nu-deophilic of all the 1,3-dipoles examined (kaciyiate/fci-aikene = 250000) [78]. Accordingly, the cydoadditions of diazoalkanes to electron-defident alkenes must be most efficient when catalyzed by a Lewis acid catalyst. The author s group has become aware of this possibility and started to study the catalyzed enantioselective diazoalkane cydoadditions of 3-(2-alkenoyl)-2-oxazolidinones. 

Lewis acid induced alkylation of 4-alkoxy-3,5-dialkyl-2-oxazolidinones with allylsilanes gives the 4-allyl derivatives with complete irons stereoselectivity114,115. Cleavage of the oxazolidi-none ring with aqueous sodium hydroxide in ethanol leads to vicinal twP -aminoalkanols. 

Once again, excellent selectivity for formation of the j3-methyl isomer is observed in the case of the Lewis acid catalyzed reaction of the boron enolate of (4S )-4-isopropyl-3-(l-oxopropyl)-2-oxazolidinone 4177 (see Appendix). 

Lewis-acid-catalyzed asymmetric hetero-Diels-Alder cycloaddition of a 1-thiabuta-1,3-diene with chiral A/-acryloyl and A/-crotonyl oxazolidinone dienophile [105]... 

With titanium enolates it was found that use of excess (3 equiv.) of the titanium reagent reversed facial selectivity of oxazolidinone enolates.140 This was attributed to generation of a chelated TS in the presence of the excess Lewis acid. The chelation rotates the oxazolidinone ring and reverses the facial preference, while retaining the Z-configuration syn diastereoselectivity. 

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... 

High levels of asymmetric induction (97-74% ee) along with high diastereoselectivity (>99 1-64 36) were reported for asymmetric 1,3-dipolar cycloaddition reactions of fused azomethine imines 315 and 3-acryloyl-2-oxazolidinone 709 leading to 711 using a chiral BINIM-Ni(n) complex 710 as a chiral Lewis acid catalyst (Equation 100) <20070L97>. 

This procedure describes the preparation and application of an effective chiral catalyst for the enantioselective Diels-Alder reaction.11 The catalyst is derived from optically active 1,2-diphenylethylenediamine, the preparation of which (either antipode) was described in the preceding procedure. The aluminum-based Lewis acid also catalyzes the cycloaddition of crotonoyl oxazolidinones with cyclopentadiene,11 and acryloyl derivatives with benzyloxymethylene-cyclopentadiene. The latter reaction leads to optically pure intermediates for synthesis of prostaglandins.11... 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

A very reactive Lewis acid is obtained when the complex [(EBTHI)Zr(Me)2] is converted in situ to a dicationic species by protonation with the acid H-BARF (BARF = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) in the presence of the Diels—Alder substrate oxazolidi-none [88] (Scheme 8.48). The dicationic species is stabilized through coordination by the oxazolidinone and by diethyl ether (derived from the acid etherate employed). The catalyst loading in the Diels—Alder reaction could be lowered to 1 mol% (Zr) and the reaction still... 

Chiral Lewis acid promoted atom transfer reaction (Kharasch reaction) of a-halo oxazolidinone imide 90 and 1-octene 92 has been reported by Porter et al. (Scheme 23) [78]. The enantioselective atom transfer utilizing Zn(OTf)2 and phenyl bisoxazoline ligand 93 as a chiral Lewis acid. The yields of the products, however, were quite low ranging from 5-15% and only moderate enantioselectivities were achieved (up to 40%). 

The templates used in these reactions have a significant impact on the reaction outcome and in determining product enantioselectivity. Sibi et al. also showed that changing the oxazolidinone template as in 119 to a 3,5-dimethylpyrazole in 131 resulted in a reversal of stereochemistry using the same chiral Lewis acid (Scheme 34) [91]. Additions in the presence of stoichiometric amounts of zinc triflate and ligand 19 gave good yields and moderate selectivities of 132. These acylated pyrazoles 131 form 5-membered... 

Due to the presence of an electron-withdrawing group on the dipolarophile, these processes are classified as type 1 reactions. The process involves the transference of charge from the dipole to the dipolarophile. When catalyzed by metallic compounds, coordination of the dipolarophile is highly desired. Usually, coordination of a nitrone to the Lewis acid is more feasible than coordination of a carbonyl compound. For this reason, alkenes that enable a bidentate coordination to the Lewis acid, such as 3-alkenoyl-oxazolidinones (Scheme 5), have been frequently employed as a model system to smdy the metal-catalyzed 1,3-dipolar cycloaddition... 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

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... 

One of the problems related to the LA induced activation of a,p-unsaturated carbonyl compounds for the reaction with a nitrone is the competitive coordination of the nitrone and the a,(3-unsaturated carbonyl compound to the Lewis acid (Scheme 12.65). Calculations have shown that coordination of the nitrone to the LA is more feasible than a monodentate coordination of a carbonyl compound. However, this problem can be circumvented by the application of alkenes such as 3-alkenoyl-oxazolidinones, enabling abidentate coordination to the LA, which is favored over the monodentate coordination to the nitrone. 

Alkoxy-2(3/f)-oxazolones 47 react with aliphatic and aromatic aldehydes in the presence of Lewis acid catalysts to produce alkyl 2-oxazolidinone-4-carbox-ylates 291 ° by successive ring opening and reclosure. 

Dialkoxy-2-oxazolidinones 295, which are prepared by reaction of 5-alkoxy-2(3//)-oxazolones 47 with acetals in the presence of Lewis acid catalysts, are hydrolyzed in the presence of a protonic acid to produce a-amino acid esters 296 (Fig. 5.70 Table 5.11, Fig. 5.71 Table 5.12, Fig. 5.72 Table 5.13, Fig. 5.73 Table 5.14, Fig. 5.74). ... 

The first effective enantioselective 1,3-dipolar cycloaddition of diazoalkanes catalyzed by chiral Lewis acids was reported in the year 2000 (139). Under catalysis using zinc or magnesium complexes and the chiral ligand (/ ,/ )-DBFOX/Ph, the reaction of diazo(trimethylsilyl)methane with 3-alkenoyl-2-oxazolidin-2-one 75 (R2 = H) gave the desilylated A2-pyrazolines (4S,5R)-76 (R =Me 87% yield, 99% ee at —40°C) (Scheme 8.18). Simple replacement of the oxazolidinone with the 4,4-dimethyloxazolidinone ring resulted in the formation of (4/ ,5S)-77 (R1 = Me 75% yield, 97% ee at -78 °C). 

With Chiral Bis(oxazoline)/metal Complexes Several research groups have developed chiral Lewis acids by using chiral 1,3-bis(oxazoline) ligands for asymmetric Diels-AIder reactions. Evans designed C2-symmetric bis(oxazoline)/Cu(II) complexes derived from chiral bis(oxa-zoline)and Cu(OTf)2, and applied them to asymmetric cycloadditions of acryloyl oxazolidinones and thiazolidine-2-thione analogues. Attractive features of this catalyst system include a clearly interpretable geometry for the catalyst-dienophile complex, which rationalizes the sense of asymmetric induction for the cycloaddition process [26] (Eq. 8A.14). 

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