Olefin oxazolidinone

Vinyl epoxides are highly useful synthetic intermediates. The epoxidation of dienes using Mn-salen type catalysts typically occurs at the civ-olefin. Epoxidations of dienes with sugar-derived dioxiranes have previously been reported to react at the trans-olefin of a diene. A new oxazolidinone-sugar dioxirane, 9, has been shown to epoxidize the civ-olefin of a diene <06AG(I)4475>. A variety of substitution on the diene is tolerated in the epoxidation, including aryl, alkyl and even an additional olefin. All of these substitutions provided moderate yields of the mono-epoxide with good enantioselectivity. 

Several new syntheses of the oxazolidinone ring have been published. Treatment of spoxyurethane 184 with a strong base induced the cyclisation to oxazolidinone 185 which, trough an olefine methathesis afforded 186 . Treatment with iron salt of acyl azide 187 afforded an aziridine, which, upon nucleophilic attack of a chloride ion, was transformed in the final oxazolidinone 188 <00CC287>. 

The oxazolidinone-substituted olefin Ic (Scheme 3) constitutes another fortunate substrate for the diastereoselective synthesis of a chiral dioxetane , which is of preparative value for the enantiomeric synthesis of 1,2 diols . For example, the photooxygenation of the enecarbamate Ic produces the asymmetric dioxetane 2c in >95% jt-facial diastereoselectivity. The attack of the O2 occurs from the jt face anti to the isopropyl... 

AN OXAZOLIDINONE KETONE CATALYST FOR THE ASYMMETRIC EPOXIDATION OF cis-OLEFINS... 

In contrast to what we observed in our experiments using 7, the starting oxazolidinone was not recovered. The products of the reaction were not identified, but did not correspond to the expected adducts. It is likely that the oxidative work up, necessary for cleaving B-O and B-C bonds is not compatible with the selenide function. However, we could not find evidence of the (desired) olefinic elimination products that could have been expected. 

The initial synthesis of aprepitant (1), which relies on a Tebbe olefination and reduction to install a methyl group on the benzyl ether side chain, is shown in Scheme 3.8,19 The initial steps are from a literature-precedented synthesis of p-fluorophenyl glycine based on conversion of chiral oxazolidinone 33 to azide 34. Formation of morpholinone intermediate 36 proceeds via benzylation and reaction with 1,2-dibromoethane. 

It is remarkable and impressive to find that stereochemistry in the conjugate addition of a radical species to an activated olefin is controlled by the chiral bisox-azoline ligand 98 to give a conjugate addition product 100 from 99 in quite high ee and diastereoselectivity (Scheme 12) [58]. Radical trapping by hydrogen abstraction was also shown to be possible in the reaction of 99 to 103, which was controlled by the combination of a chiral alcohol 101 and achiral oxazolidinone 102 [59]. 

A-Aminophthalimide (118) can also be added to olefins in an asymmetric fashion. Thus, reaction of A -enoyl oxazolidinone 122 with 118 and lead tetraacetate in the presence of the camphor-derived chiral ligand 120 provides aziridine 123 in 83% yield and with 95% ee <020L1107>. Other useful chiral ligands include imine 121, derived from the condensation of 2,2 -diamino-6,6 -dimethylbiphenyl with 2,6-dichlorobenzaldehyde. The corresponding monometallic Cu(I) complex was found to be very efficient in chiral nitrogen transfer onto chromene derivative 124 using (Ar-(p-toluenesulfonyl)imino)phenyliodinane (PhI=NTs) to provide aziridine 125 in 87% yield and 99% ee <02JOC3450>. 

Precursor of Useful Chiral Ligands. OPEN is widely used for the preparation of chiral ligands. Organometallic compounds with these ligands act as useful reagents or catalysts in asymmetric induction reactions such as dihydroxylation of olefins, transfer hydrogenation of ketones and imines, Diels-Alder and aldol reactions, desymmetrization of meso-diols to produce chiral oxazolidinones, epoxidation of simple olefins, benzylic hydroxylation, and borohydride reduction of ketones, imines, and a,p-unsaturated carboxylates. ... 

Intramolecular asymmetric induction has also been used in electrochemistry as in the reduction of optically active alcohol esters or amides of a-keto [469,470] and unsaturated [471] acids and oximes [472] and in the oxidation of olefins [473]. A maximum asymmetric yield of 81% was obtained in the reduction of (5 )-4-isopropyl-2-oxazolidinone phenyl-glyoxylate [470]. Nonaka and coworkers [474,475] found that amino acid A-carboxy anhydrides were polymerized with various electrogenerated bases as catalyst to give the poly(amino acids) with high chirality in high yields. Conductive chiral poly(thiophenes) prepared by electropolymerization can be used for chiral anion recognition [476]. 

Phenylalanine-derived oxazolidinone has heen used in O Scheme 52 as a chiral auxiliary for as)rmmetric cross-aldolization (Evans-aldol reactions [277,278,279,280,281,282,283,284, 285]). The 6-deoxy-L-glucose derivative 155 has heen prepared by Crimmins and Long [286] starting with the condensation of acetaldehyde with the chlorotitanium enolate of O-methyl glycolyloxazohdinethione 150. A 5 1 mixture is obtained from which pure 151 is isolated by a single crystallization. After alcohol silylation and subsequent reductive removal of the amide, alcohol 152 is obtained. Swem oxidation of 152 and subsequent Homer-Wadsworth-Emmons olefination provides ene-ester 153. Sharpless asymmetric dihydroxylation provides diol 154 which was then converted into 155 (O Scheme 60) (see also [287]). 

The thermal decarboxylation of a P-lactone has been widely used for preparation of an olefin. See [51, 52]. Recent examples of the thermal decarboxylation of P-lactones are described in [53-57], 301efins have been prepared by elimination reactions, in which oxazolidinone functioned as a leaving group. See [59-61],... 

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). 

Ozonolysis of the mixture of 35 and 36 followed by sodium borohydride reduction afforded 39 (86%) and 40 (6%) (Scheme 3)7 Detrityladon of 39 followed by Swem oxidation and Wittig olefination of the resulting aldehyde with Ph3P=CH(CH2)9CH3 furnished the Z-olefin 41 (49%) and the fi-olefin 42 (3%). The Z-olefin was hydrogenated and the oxazolidinone ring was saponified to produce (-)-desoxoprosopinine (4). 

Figure 6.12g-l illustrates auxiliaries that may chelate the metal of the Lewis acid catalyst. In these cases, the metal is coordinated anti to the olefin and the preferred conformation of the C1-C2 bond is 5-cis, as shown in Figure 6.13b. Again, the preferred approach of the diene is from the direction of the viewer, but because of the different conformation of the enone, it is now the C2 Si face. The example is Evans s oxazolidinone [178]. In this example, the Lewis acid is Et2AlCl, but more than one molar equivalent is required for optimum results [178]. Castellino has shown by NMR that Et2AlCl initially binds in a monodentate fashion, but excess acid creates a bidentate dione-AlEt2 complex having a Cl2AlEt2 gegenion [180].

Oxazolidinones have proven to be useful auxiliaries in reactions of radicals substituted a to carboxiimides bearing this group. The use of this auxiliary requires a Lewis acid to control the conformation of the oxazolidinone relative to the reactive radical center, and the complexation of the Lewis acid to the radical makes the radical very electrophilic, promoting reactions to unactivated olefins. The equilibrium between radical and Lewis acid is shown for structures 29A and B. The con-... 

The stage was now set for the final push forward towards oxazolidinone 77 (Scheme 23). This commenced with our implementation of a Vasella reductive ring-opening on 90 with zinc dust in aqueous THF. Aldehyde 89 was then olefinated under Kocienski s conditions with the carbanion derived from 5-methanesulfonyl-l-phenyl-If/-tetrazole. It was not usually possible to remove all of the oxytetrazole byproduct from diene 88 on large scale. However, this impurity did not adversely affect the Grubbs-Hoveyda ring-closing metathesis reaction " ... 

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