Oxazolidine opening

Diastereomeric oxazolidines 88 and 89 (Scheme 8.4.27) were available via 1,4-reduction and cyclization of Zincke product 87, with 88 being the kinetic product under the reaction conditions and 89 (X-ray) the thermodynamically favored isomer in CDCI3 solution. Iterative reductive oxazolidine opening provided 3-aryl piperidine 91, which was readily advanced to (-)-PPP (92), a selective dopaminergic receptor antagonist. ... 

Apparently, cyclization involves the formation of open-chain intermediates 342, 343, further closing up to imidazolidines 344 and oxazolidines 345 which eliminate the secondary amine, thus leading to imidazolines 346 and oxazolines 347. The latter exist in the solution exclusively in the enolic forms 348, 349 which are stabilized by conjugation and intramolecular hydrogen bonds. 

Recently, Lee and co-workers reported an efficient method for the preparation of enantiomerically pure oxazolidin-2-ones from aziridine-2-carboxylates 186 (Scheme 3.68) [128]. This one-pot aziridine ring-opening and subsequent intramolecular cyclization process was highly regio- and stereoselective, affording 187 in high yield. 

An entry to. yyrt-2-methoxy-3-hydroxycarboxylic acids is also opened using similar methodology. Thus the norephedrine derived (4/ ,5S)-3-(2-methoxy-l-oxoethyl)-4-methyl-5-phenyl-1,3-oxazolidine-2-one 23105a, as well as the phenylalanine derived (4S)-4-benzyl-3-(2-methoxy-l-oxoethyl)-l,3-oxazolidin-2-one 25105b, can be added to aldehydes via the boron enolates to give, after oxidative workup, the adducts in a stereoselective manner (d.r. 96 4, main product/sum of all others). Subsequent methanolysis affords the methyl esters. 

A way to anh-configurated a-amino-/ -hydroxycarboxylic acids is opened by the aldol addition of oxazolidine amides 7a and 7b. The method1061 is illustrated by a synthesis of (2R,3R)-p-hydroxyleucine (9) which is available from the major diastereomeric adduct 8 (d.r. 92 8) upon successive treatment with 1 N HC1 (30 min). 5 N HCl (100 C, 12 h), and propylene oxide (reflux in ethanol, 30 min). 

Certain reagents promote ring opening and subsequent cyclization to give other heterocycles. For example, di-tert-butyl dicarbonate induces the stereoselective ring transformation of N-alkyl aziridines 159 into oxazolidin-2-ones 160 <96TET2097>. 

On reacting nitromethane and acrylonitrile in the presence of TCS 14/triethylamine in benzene (cf. also Scheme 7.42) the oxazolidine 1076, which is obtained in 85% yield, eliminates trimethylsilanol 4 in the presence of TsOH to give 40% d -oxazoline 1077 [104]. Heating of 1076, however, or treatment of 1076 with solid KF leads, via ring opening, elimination of HCN, and rearrangement to d-iso-oxazolidine 1078 in 82% yield this is converted by TsOH, with elimination of 4, into 83% isooxazole 1079 [104]. In contrast with 1076 the isooxazolidine 1080 de-... 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

The palladium-catalyzed opening of an oxazolidine ring followed by the hydrogenolysis of a benzylic OH group was performed over 5% Pd/C in ethanol at 140 atm H2 in 45 hours (Scheme 4.17).35... 

Inclusion of the amide in oxazolidinone functionality can be used to overcome diene statial disposition issues, for example in the conversion of 19 into 20 yields of 20 were generally high (Table 2). Ring opening of the oxazolidine moiety with or without loss of the mandelic acid moiety then afforded the corresponding azepin-2-ones <06TL3625>. 

Oxazolines can be obtained by the Lewis acid catalyzed epoxide ring opening of glycidic esters or amides (e.g., 118) with acetonitrile . Oxazolidines are available from the palladium-catalyzed cycloaddition of vinyl epoxides with imines <00H885> or the samarium-promoted reaction of ketimines (e.g., 120) with unfunctionalized... 

Key steps, as shown in Scheme 4-15, involve the formation of a urethane intermediate 37 by treating epoxide 36 with methyl isocyanate in the presence of sodium hydride. Intramolecular A-nucleophilic ring opening of oxirane affords oxazolidine 38. Subsequent treatment furnishes product 34. 

Perhydrooxazolo[3,2- ]pyridines 338 are excellent precursors of iminium ions 339 obtained after treatment of the oxazolidine with either a Bronsted or Lewis acid. Trapping of these intermediate iminium ions with nucleophiles then allows for substitution at the C-8a position together with ring opening, yielding functionalized piperidines 340 (Scheme 93). 

This transformation opens a new access to enantiomerically pure l,3-oxazolidin-2-ones, a class of compounds which has been extensively studied either in medicinal chemistry85 87 or in stereocontrolled synthesis.11,12... 

The dimethyl ester of adipic acid, rather than adipic acid, was used as a transesterification substrate. Reaction rate studies had shown that the transesterification would be much faster than the esterification reaction. It was considered that the rate of attack on the oxazolidine ring by methanol would be slower than the rate of attack by water and that the ring opening would not be catalysed by the enzyme, whereas the rate of the transesterification would be increased significantly, particularly at the low temperature of the enzymatic esterification. 

Lactol 128 has been converted into a variety of racemic C-nucleosides. The unstable aldehyde 130 was prepared from 128 by way of oxazolidine 129. Lactone 131 was also derived from 128 and used as starting material in the synthesis of racemic C-nucleosides. Adducts 77 + 77 were transformed into epoxide 132. Opening of the epoxide, followed by ozonolysis and reduction allowed one to... 

Upon warming, these oxazolinyl-stabilized lithiooxiranes undergo an electrocyclic a-ring opening to give a-oxo-2-oxazolines after hydrolysis (Scheme 87). However, all attempts to quench the presumed oxazolidine enolate intermediates through reaction with electrophiles failed. 

By the addition of 2-sulfanylacetic acid to the open tautomeric form of tetrahydro-l,3-oxazines, 3-(3-hydroxypro-pyl)thiazolidin-4-ones were obtained in moderate to good yields. The process proved to be slower than the analogous reactions of oxazolidines <2006RJ01101>. 

As shown in Scheme 8, in acidic aqueous solution oxazolidine-4-carboxylic acid (47, R1 = H) exists in equilibrium with the protonated open-ring form 48. 173 174 ... 

The acid lability of oxazolidine-4-carboxylic acids strongly depends on the C2 substituents. Whilst dilute trifluoroacetic acid is sufficient to open the ring of 2,2-dimethyloxazolidine-4-carboxylic acids, strong acids such as trifluoromethanesulfonic acid require longer periods of time to open the unsubstituted ring. 139 Since in neutral or alkaline solutions oxazolidine-4-... 

This method 1011 includes the isolation of the oxazolidinones 9 before reductive ring opening. A one-pot method without isolation of the oxazolidin-5-ones has also been developed11061 and mainly used to prepare a variety of 7V-Fmoc-7V-methyl co-carboxylic adds. 

Few solid-phase syntheses of oxazoles have been reported (Table 15.17). The most general strategy is the dehydration of a-(acylamino) ketones (Entry 2, Table 15.17) or 2-(acylamino)phenols (Entry 1, Table 15.17). Oxazolidin-2-ones have been prepared by intramolecular nucleophilic cleavage of carbamates from insoluble supports (Entries 5 and 6, Table 15.17). Resin-bound 2-aminoethanols, which are accessible by nucleophilic ring-opening of oxiranes with amines, undergo cyclocondensation with aldehydes to yield oxazolidines [220,221]. These compounds are unstable towards acids, and can be released from the support only under neutral or basic reaction conditions. 

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