Oxazolidinones Diels-Alder reaction

A quinoline-phosphine ligand has been developed by Buono et ah, and its complex 29 with Cu(OTf)2 found to be an effective catalyst for the Diels-Alder reaction between acryloyl-oxazolidinone and cyclopentadiene, affording the cycloadduct... 

The Diels-Alder reaction catalyzed by this chiral titanium catalyst 31 has wide generality (Scheme 1.53, 1.54, Table 1.22, 1.23). Acryloyl- and fumaroyl-oxazolidinones react with isoprene giving cycloadducts in high optical purity. 2-Ethylthio-l,3-buta-diene can also be successfully employed as the diene [42]. 

The complexation procedure included addition of an equimolar amount of R,R-DBFOX/Ph to a suspension of a metal salt in dichloromethane. A clear solution resulted after stirring for a few hours at room temperature, indicating that formation of the complex was complete. The resulting solution containing the catalyst complex was used to promote asymmetric Diels-Alder reactions between cyclopen-tadiene and 3-acryloyl-2-oxazolidinone. Both the catalytic activity of the catalysts and levels of chirality induction were evaluated on the basis of the enantio-selectivities observed for the endo cycloadduct. 

Although the aqua nickel(II) complex A was confirmed to be the active catalyst in the Diels-Alder reaction, no information was available about the structure of complex catalyst in solution because of the paramagnetic character of the nickel(II) ion. Either isolation or characterization of the substrate complex, formed by the further complexation of 3-acryloyl-2-oxazolidinone on to the l ,J -DBFOX/ Ph-Ni(C104)2 complex catalyst, was unsuccessful. One possible solution to this problem could be the NMR study by use of the J ,J -DBFOX/Ph-zinc(II) complex (G and H, Scheme 7.9) [57]. 

Absolute configurations of the isoxazolidines obtained in the nitrone cydoaddition reactions described in Schemes 7.21 and 7.22 were determined to be 3S,41 ,5S structure by comparison of the optical rotations as well as retention times in a chiral HPLC analysis with those of the authentic samples. Selection of the si face at C/ position of 3-crotonoyl-2-oxazolidinone in nitrone cydoadditions was the same as that observed in the Diels-Alder reactions of cyclopentadiene with 3-croto-noyl-2-oxazolidinone in the presence of the J ,J -DBF0X/Ph-Ni(C104)2-3H20 complex (Scheme 7.7), and this indicates that the s-cis conformation of the dipolaro-phile has participated in the reaction. 

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

Kanemasa et al.63 reported that cationic aqua complexes prepared from the /ram-chelating tridentate ligand (i ,f )-dibenzofuran-4,6-diyl-2,2,-Mv(4-phcnyloxazolinc) (DBFOX/Ph) and various metal(II) perchlorates are effective catalysts that induce absolute chiral control in the Diels-Alder reactions of 3-alkenoyl-2-oxazolidinone dienophiles (Eq. 12.20). The nickel(II), cobalt(II), copper(II), and zinc(II) complexes are effective in the presence of six equivalents of water for cobalt and nickel and three equivalents of water for copper and zinc. 

ENANTIOSELECTIVE, CATALYTIC DIELS-ALDER REACTION (1S-end0)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL). 2-OXAZOLIDINONE... 

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... 

Asymmetric Diels-Alder reactions. Unlike methyl crotonate, which is a weak dienophile, chiral (E)-crotonyl oxazolidinones when activated by a dialkylaluminum chloride (1 equiv.) are highly reactive and diastereoselective dienophiles. For this purpose, the unsaturated imides formed from oxazolidinones (Xp) derived from (S)-phenylalanol show consistently higher diastereoselectivity than those derived from (S)-valinol or (IS, 2R)-norephedrine. The effect of the phenyl group is attributed in part at least to an electronic interaction of the aromatic ring. The reactions of the unsaturated imide 1 shown in equation (I) are typical of reactions of unsaturated N-acyloxazolidinones with cyclic and acyclic dienes. All the Diels-Alder reactions show almost complete endo-selectivity and high diastereoselectivity. Oxazolidinones are useful chiral auxiliaries for intramolecular Diels-Alder... 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted much interest for their various applications in different synthetic transformations.2 Such simple structures, directly related to far better known chiral oxazolidinones,11,12,57 have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations, but mainly in condensation of their /V-acyl derivatives with aldehydes. Chiral OZTs have shown interesting characteristics in anti-selective aldol reactions58 or combined asymmetric addition. 

Tamariz et al. reported the synthesis of mukonine (11) based on a regioselective Diels-Alder reaction of N-phenyl-4,5-dimethylidene-2-oxazolidinone (634) with methyl propiolate (635). The diene 634 was prepared in moderate yield from the condensation reaction of 2,3-butanedione (632) with phenyl isocyanate (633). In an optimized reaction procedure using drastic basic hydrolytic conditions (KOH/ MeOH), followed by methylation with dimethyl sulfate, the adduct 636, was... 

An important catalyst-substrate intermediate that applies to both the TiCl2-TADDOLate catalyzed 1,3-dipolar cycloadditions and Diels-Alder reactions has been isolated and characterized (353). The crystalline compound 248 has been characterized by X-ray analysis, showing that the oxazolidinone is coordinated to the titanium center in a bidentate fashion (Scheme 12.75). The four oxygen atoms. 

The 3-acyl-2(3F/)-oxazolones function as good dienophiles in cycloaddition reactions with cyclic 2,4-dienes such as cyclopentadienes and anthracenes. Thus, the thermal reaction of 3-acetyl-2(37/)-oxazolone with cyclopentadiene and the hexachloro and hexamethyl derivatives gives endo-cycloadducts exclusively. In particular, the chiral cycloadducts 221 and 223 derived from the diastereoselective Diels-Alder reactions of 3-(2-exo-alkoxy-l-apocamphanecarbonyl)-2(3/7)-oxazo-lones with hexamethylcyclopentadiene and 9,10-dimethylanthracene, respectively, are highly useful as chiral 2-oxazolidinone auxiliaries. The conformationally rigid roofed structures play a crucial role in affording excellent chiral induction (Fig. 5.54). 

The ene-reaction, which is mechanistically related to the Diels-Alder reaction, has also been reported. The thermal addition of 3-ferf-butoxycarbonyl-2(3//)-oxazolone 236 to 2,2 -biindole 235 affords 4-(2,2 -biindol-3-yl)-2-oxazolidinone 237, probably via the indoline derivative. The product is further converted to the fused aromatic compound 238 by bromination with NBS and AIBN, followed by dehydrobromination (Fig. 5.58). ... 

The oxazoline ring acts as an electron-withdrawing group for a substituent at the 2-position. Thus, the ot-protons of a 2-alkyloxazoline exhibit some acidity and can be abstracted by a base. A 2-alkenyloxazoline can be viewed as a masked acrylic acid derivative and is capable of undergoing Michael addition and Diels-Alder reactions. These reactions can often be carried out stereoselectively using a chiral oxazoline. Other types of chiral auxilliaries, most notably oxazolidinones, are also very effective for these types of applications. However, they are outside the scope of this chapter. The discussion in this section will focus on the new developments with oxazolines. 

Metal complexes of bis(oxazoline) ligands are excellent catalysts for the enantioselective Diels-Alder reaction of cyclopentadiene and 3-acryloyl-l,3-oxa-zolidin-2-one. This reaction was most commonly utilized for initial investigation of the catalytic system. The selectivity in this reaction can be twofold. Approach of the dienophile (in this case, 3-acryloyl-l,3-oxazolidin-2-one) can be from the endo or exo face and the orientation of the oxazolidinone ring can lead to formation of either enantiomer R or S) on each face. The ideal catalyst would offer control over both of these factors leading to reaction at exclusively one face (endo or exo) and yielding exclusively one enantiomer. Corey and co-workers first experimented with the use of bis(oxazoline)-metal complexes as catalysts in the Diels-Alder reaction between cyclopentadiene 68 and 3-acryloyl-l,3-oxazolidin-2-one 69 the results are summarized in Table 9.7 (Fig. 9.20). For this reaction, 10 mol% of various iron(III)-phe-box 6 complexes were utilized at a reaction temperature of —50 °C for 2-15 h. The yields of cycloadducts were 85%. The best selectivities were observed when iron(III) chloride was used as the metal source and the reaction was stirred at —50 °C for 15 h. Under these conditions the facial selectivity was determined to be 99 1 (endo/exo) with an endo ee of 84%. 

Ghosh s " and Kanemasa s groups" examined their ligands 9, ent-9 and 14, respectively, in the Diels-Alder reactions of oxazolidinones 80a-d and cyclopen-tadiene 68. Their results are summarized in Table 9.14 (Fig. 9.29). 

Evans has utilized Cu(ll)-bis(oxazoline)-mediated Diels-Alder reactions as the key step in several total syntheses. In 1996, Evans and co-workers used bu-box ligand 3 in the intramolecular Diels-Alder reaction of oxazolidinone 87 to form cycloadduct 88 enantioselectively, as shown in Figure 9.31. Compound 88 was subsequently converted to (-)-isopulo upone 89. 

Ghosez and co-workers also presented a hetero-Diels-Alder reaction using a hetero-atom-containing diene 121 and the oxazolidinone 80a in the presence of bu-box 3 complexed with copper(II) triflate to afford the cycloadduct 122 in 80% yield (>99 1 exo/endo, 95% ee) as shown in Figure 9.38Z . ... 

TABLE 9.14 DIELS-ALDER REACTIONS OE A-ACYL OXAZOLIDINONES, 553 TABLE 9.15 DIELS-ALDER REACTIONS WITH VARIOUS DIENOPHILES, 553 TABLE 9.16 ENANTIOSELECTIVE ENE REACTIONS OF ETHYL GLYOXYLATE, 556... 

Diels-Alder reactions of benzo[fc]furan-43-diones and benzo[b]furan-4,7-diones have been reported <99H(50)1137>. The activation of a C-0 bond in a Mn(C0>3 complexed benzo[i>]furan was examined <99AG2343>. The enzyme-catalyzed dealkylation of (+)-marmesin to the phototoxic psoralene (and acetone) has been investigated <99AG413>. A hi yielding synthesis of bidentate bisoxazoline DBFOX/Ph [(R,R)-4,6-dibenzofutandiyl-2 2 -bis(4-phenyloxazoline)] was developed. DBFOX/Ph was subsequently tested in enantio-selective conjugate radical additions onto 3-(3-phenyl-2-propenoyl)-2-oxazolidinone <99TA2417>. 

Diels-Alder reactions have featured heavily during the period of review. Ar-Vinyl-2-oxazolidinone has been reported as a dienophile for the first time, including the preparation of various tetrahydro-277,77/-pyrano[4,3-. ]pyrans <2002SL952>. The heterodiene cycloaddition reaction of 3-formylchromone with a series of ketene acetals formed from C2-symmetric l,2-diarylethane-l,2-diols is completely diastereoselective (Scheme 40) <1995J(P1)2293>. 

Some enantiomerically pure substituted 2-oxazolidinones are excellent as chiral auxiliaries. From the pioneering studies 2 conducted in the early 1980 s of the uses of such auxiliaries has emerged what is perhaps the most widely used method today for the preparation of enantiomerically highly enriched a-alkylalkanoic acids, alcohols and aldehydes, that is, the alkylation of enolates from chiral 3-acylated 2-oxazolidinones followed by auxiliary removal2 59. The early work has been reviewed60-62. These enantiomerically pure cyclic imide auxiliaries have been used not only for alkylations but also in a plethora of a-functionalization reactions, such as diastereoselective aldol, a-hydroxylation, a-amination and Diels-Alder reactions and these are discussed elsewhere in this volume. 

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. 

The alkylation of enolates from some recently developed 2-oxazolidinone auxiliaries will be briefly discussed. The Diels-Alder reaction of the enantiomerically pure 3-(apocamphane-carbonyl)-2(3//)-oxazolone 13 with anthracene gives, diastereoselectively, a 97 3 ratio of diastereomeric adducts63. Recrystallization followed by removal of the apocamphanecarbonyl auxiliary and acylation gives the diastereomerically pure enantiomer 14 in good yield. Subsequent enolate formation and alkylation gives highly diastereoselective reactions and easily purified products due to the fact that the major product is readily crystallized. Thus alkylation... 

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