Oxazolidinone amides, with

The 3-acyl-2-oxazolidinones are readily deprotonated by strong, sterically hindered amide bases in dry telrahydrofuran at low temperature to afford the. vyn-enolates. Alkylation then provides products with induced chirality in the a-position of the amide with good to excellent di as tereo selectivities. 

The approach for the enantioselective aldol reaction based on oxazolidinones like 22 and 23 is called Evans asymmetric aldol reaction.14 Conversion of an oxazolidinone amide into the corresponding lithium or boron enolates yields the Z-stereoisomers exclusively. Reaction of the Z-enolate 24 and the carbonyl compound 6 proceeds via the cyclic transition state 25, in which the oxazolidinone carbonyl oxygen and both ring oxygens have an anti conformation because of dipole interactions. The back of the enolate is shielded by the benzyl group thus the aldehyde forms the six-membered transition state 25 by approaching from the front with the larger carbonyl substituent in pseudoequatorial position. The... 

An antibacterial agent in the oxazolidinone class, Dup-721 (67) was synthesized via a convergent route using Pd-catalyzed amination of oxazolidinones 66 with arylbromides [144]. The amide of arylated oxazolidinone 67 was deprotected with TFA to provide Dup-721 in 65% yield. 

Copper-promoted aminations have recently been reported as a general strategy for the A-alkynylation of carbamates, sulfonates, and chiral oxazolidinones and imidazolidinones (eq 7). A variety of substituted ynamides can be synthesized via deprotonation of amides with KHMDS followed by reaction with copper(I) iodide and an alkynylbromide or iodide. 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

In a more recent study on 1,3-dipolar cycloaddition reactions the use of succi-nimide instead of the oxazolidinone auxiliary was introduced (Scheme 6.19) [58]. The succinimide derivatives 24a,b are more reactive towards the 1,3-dipolar cycloaddition reaction with nitrone la and the reaction proceeds in the absence of a catalyst. In the presence of TiCl2-TADDOLate catalyst 23a (5 mol%) the reaction of la with 24a proceeds at -20 to -10 °C, and after conversion of the unstable succinimide adduct into the amide derivative, the corresponding product 25 was obtained in an endojexo ratio of <5 >95. Additionally, the enantioselectivity of the reaction of 72% ee is also an improvement compared to the analogous reaction of the oxazolidinone derivative 19. Similar improvements were obtained in reactions of other related nitrones with 24a and b. 

We previously described the cyclocoupling of 2-bromoamides onto the carbonyl group of a variety of amides, including 2-bromoamides themselves (ref. 17). The cyclocoupling with DMF affords 2-dimethylamino-oxazolidinone derivatives 12 (ref. 19). Its mechanism has been recently investigated (refs. 14,15b). 

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. ... 

Palladium acetate in conjunction with a diphosphine ligand, xantphos, is active for arylation of amides, ureas, oxazolidinones and sulfonamides.174... 

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>. 

Reagent control This involves the addition of a chiral enolate or allyl metal reagent to an achiral aldehyde. Chiral enolates are most commonly formed through the incorporation of chiral auxiliaries in the form of esters, acyl amides (oxazolines), imides (oxazolidinones) or boron enolates. Chiral allyl metal reagents are also typically joined with chiral ligands. 

S)-2-Amino-3-methylbutanol [(S)-valinol] derived oxazolidinones, i.e., (S)-3-acyl-4-iso-propyl-2-oxazolidinones 1, have been used extensively for the preparation of a-alkylated acids, aldehydes and alcohols. The enolates are formed by deprotonation with lithium diisopropyl-amide or sodium hexamethyldisilazanide at low temperature in tetrahydrofuran. Subsequent addition of a haloalkane gives alkylation, which occurs from the Si-face2. The diastereoselectivities are usually good (>90 10), and the products are usually purified by flash chromatography and/or recrystallization (see Table 10). Additional examples of alkylation of 1 have been published5 l0 12- 20 22-29 39.44.-47,49.57.70-78... 

The formation of isocyanurates in the presence of polyols occurs via intermediate allophanate formation, i.e, die urethane group acts as a cocatalyst in the dimerization reaction. By combining cyclotrimeiization with polyurethane formation, processibility is improved, and the friability of the derived foams is reduced. Modification of cellular polymers by incorporating amide, imide, oxazolidinone, or carbodiimide groups has been attempted but only the urethane-modified isocyanurate foams are produced in the 1990s. PUIR foams often do not require added fire retardants to meet most regulatory requirements. A typical PUIR foam formulation is shown in Table 2. 

Allylamines may be converted directly to oxazolidinones through condensation with CO2, to form carbamate salts, and treatment with iodine (equation 64 and Table 20).166 High stereoselectivity was obtained only in cases where the a-substituent was hydroxymethyl (entry 5) or the amine was secondary and the substituent was phenoxymethyl (entry 4). The results with primaiy amines are comparable to those for amide cyclizations shown in equation (57). 

Stepwise Selective Amine and Amide Alkylation (Fig. 14) 44 A first alkylation step is performed by suspending (78) in a 2 M solution of a suitable alkyl halide in DMF at 50° for 24-48 h. After thorough washing with DMF (3x), CH2C12 (3x), and THF (3x) intermediate (79) (usually formed with >85% purity) is subjected to the final alkylation. The reaction flask is sealed with a fresh rubber septum and flushed with nitrogen followed by cooling to 0°. In a separate flame-dried 25-ml round-bottom flask 12 equiv. (with respect to 79) of 5-phenylmethyl-2-oxazolidinone is added. To the reaction flask freshly distilled THF is added (the appropriate volume to provide a 0.2 M solution of the 5-phenylmethyl-2-oxazolidi-none). The resulting clear solution is then cooled to —78° and 1.6 M n-butyl... 

The amides are derived from oxazolidinones and yield "Z"-enolates with high stereoselectivity. The alkylating agent reacts in both cases from the side that is opposite to the side of the substituent highlighted in red. Alkaline hydrolysis accelerated by hydrogen peroxide proceeds with retention of configuration and yields enantiomerically pure a-alky-lated carboxylic acids X t and X 2 are the chiral amide groups. 

The alkylations of the oxazolidinone-containing amide enolate of Figure 13.43 occur with diastereoselectivities of 93 7 and > 99 1, respectively. The hydrogen peroxide-accelerated alkaline hydrolysis of these compounds occurs with complete retention of the previously established configuration at the a-stereocenter. To date, the Evans synthesis offers the most versatile access to enantiomerically pure a-alkylated carboxylic acids. 

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