Hydrogenation oxazolidinones

A solution of 1 equivalent of the oxazolidinone in diethyl ether is cooled to —78 C. To the resultant suspension are added 1.4 equivalents of triethylamine. followed by 1.1 equivalents of dibutylboryl triflate. The cooling bath is removed and the reaction mixture is stirred at 25 °C for 1.5 h. The resultant two-phase mixture is cooled to — 78 "C with vigorous stirring. After 1 equivalent of aldehyde is added, the reaction is stirred at —78 °C Tor 0.5 h, and 0 "C for 1 to 2 h. The solution is diluted with diethyl ether, washed with 1 N aq sodium bisulfate, and concentrated. Following oxidation with 30% aq hydrogen peroxide (10 equivalents, 1 1 methanol/water, 0 C. 1 h), extractive workup and chromatographic purification, the aldol adduct is obtained with >99% diastcrcomeric purity. 

In an indirect amination process, acyl halides are converted to amino acids. Reaction of the acyl halide with a chiral oxazolidinone leads to a chiral amide, which reacts with the N=N unit of a dialkyl azodicarboxylate [R"02C—N=N—CO2R ]. Hydrolysis and catalytic hydrogenation leads to an amino acid with good enantioselectivity. ... 

Entries 4 and 5 are cases in which the oxazolidinone substituent is a 3-ketoacyl group. The a-hydrogen (between the carbonyls) does not react as rapidly as the y-hydrogen, evidently owing to steric restrictions to optimal alignment. The all -syn stereochemistry is consistent with a TS in which the exocyclic carbonyl is chelated to titanium. 

Seebach and Brenner have found that titanium enolates of acyl-oxazolidinones are added to aliphatic and aromatic nitroalkenes in high diastereoselectivity and in good yield. The effect of bases on diastereoselectivity is shown in Eq. 4.59. Hydrogenation of the nitro products yields y-lactams, which can be transformed into y-amino acids. The configuration of the products is assigned by comparison with literature data or X-ray crystal-structure analysis. 

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. 

There are few addition reactions to a,/J-disubstituted enoyl systems 151 that proceed in good yield and are able to control the absolute and relative stereochemistry of both new stereocenters. This is a consequence of problematic A1,3 interactions in either rotamer when traditional templates such as oxazolidinone are used to relieve A1,3 strain the C - C bond of the enoyl group twists, breaking conjugation which results in diminished reactivity and selectivity [111-124], Sibi et al. recently demonstrated that intermolecular radical addition to a,/J-disubstituted substrates followed by hydrogen atom transfer proceeds with high diastereo- and enantioselectivity (151 -> 152 or 153, Scheme 40). 

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. 

With Binaphthol/M(OTf)3 Complexes (M = Yb, Sc) A chiral ytterbium triflate, derived from Yb(OTf)3, (R)-binaphthol, and a tertiary amine, has been applied to the enantioselective Diels-Alder reaction of cyclopentadiene with crotonoy 1 oxazolidinones. Among various tertiary amines, c/s-1,2,6-trimethyl piperidine was found to be highly effective [44] (Eq. 8 A.23). The unique structure of such chiral Yb catalysts is characterized by hydrogen bonding between the phenolic hydrogens of (R)-binaphthol and the nitrogens of tertiary amines. 

We added the acetylene to aldehyde 12 now because this step is not compatible with a protected guanidine. Treatment of 43 with EtMgBr to form the acetylide and addition of aldehyde 12 afforded 54% of 45 and 32% of 44. Under the basic conditions, the secondary amine adds to the carbamate to form the oxazolidinone ring. The decrease in the geminal coupling constant of the methylene hydrogens adjacent to the nitrogen from 11 Hz in 43 to 8 Hz in oxazolidinone 45 is characteristic of the... 

The photoreactions of iV-(trimethylsilyl)methyl- or iV-(tributylstannyl)methyl-substituted a-ketoamides resulted into the formation of complex mixtures including azetidin-2-ones and oxazolidinones with or without the trimethylsilyl or tributylstannyl moiety <2004JOC1215>. It was observed that the reaction of A-(trimethylsilyl)methyl-substituted a-ketoamides proceeded by competitive hydrogen abstraction and sequential single electron transfer (SET)-desilyla-tion pathways, whereas the reaction of iV-(tributylstannyl)methyl-substituted a-ketoamides preferred the sequential SET-destannylation pathway. 

In recent years, a few stereoselective methods for the asymmetric hydrogenation of pyridines and related heterocycles have been developed <20050BC4171>. A chiral auxiliary method starts with an oxazolidinone-substituted pyridine which on reduction with H2/Pd(OH)2 in acetic acid affords the corresponding piperidine in good yield and high enantiopurity. The chiral auxiliary is cleaved during the reaction and can be recovered (Equation 100) <2004AGE2850>. 

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