Oxazolidinones amination

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. 

The alkylurea 576 and oxamide 577 are formed by oxidative carbonylation of amines under CO pressure using Pd/C as a catalyst[518]. The urea formation proceeds under atmospheric pressure using PdCh and CuCl2[519]. The mono-and double carbonylations of / -aminoethanol (578 and 579) afford the cyclic carbamate (oxazolidinones) 580 and oxamide (morpholinediones) 581 [520,521]. 

Pentafluorobenzyl bromide has been used in the derivatization of mercaptans [55] and phenols [36], m the analysis of prostaglandins [37], and in quantitative GC-MS [5S] 1,3 Dichlorotetrafluoroacetone is used for the derivatization of amino acids to the corresponding cyclic oxazolidinones and allows the rapid analysis of all 20 protein ammo acids [d] Pentafluorophenyldialkylchlorosilane derivatives have facilitated the gas chromatographic analysis of a wide range of functionally substituted organic compounds, including steroids, alcohols, phenols, amines, carboxylic acids, and chlorohydrms [4]... 

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. ... 

Oxidative carbonylation generates a number of important compounds and materials such as ureas, carbamates, 2-oxazolidinones, and aromatic polycarbonates. The [CuX(IPr)] complexes 38-X (X = Cl, Br, I) were tested as catalysts for the oxidative carbonylation of amino alcohols by Xia and co-workers [43]. Complex 38-1 is the first catalyst to selectively prepare ureas, carbamates, and 2-oxazolidinones without any additives. The important findings were the identity of the counterion and that the presence of the NHC ligand influenced the conversions. 2-Oxazohdinones were formed from primary amino alcohols in 86-96% yield. Complex 38-1 also catalysed the oxidative carbonylation of primary amines to ureas and carbamates. n-Propylamine, n-butylamine, and t-butylamine were transformed into the... 

These oxazolidinones can be acylated and converted to the lithium, boron, tin, or titanium enolates by the same methods applicable to ketones and esters. For example, when they are converted to boron enolates using di-n-butylboron triflate and triethyl-amine, the enolates are the Z-stereoisomers.125... 

To create the free secondary amine group (N-H) fulleropyrrolidine, an amine-protected starting material can be used in the reaction (Cai et al., 2006). For instance, a trityl-oxazolidinone (using either triphenylmethyl- or better, 4-methoxytriphenylmethyl-protecting groups) can be reacted with C60 to yield the trityl-protected pyrrolidine (Figure 15.5). 

Figure 15.5 A trityl-protected pyrrolidine derivative of Cgg can be prepared by the reaction of N-trityl-oxazolidinone with a fullerene. Deprotection of the trityl group using methanesulfonic acid gives the secondary amine, which can be used in further conjugation reactions.

Combs and coworkers have presented a study on the solid-phase synthesis of oxa-zolidinone antimicrobials by microwave-mediated Suzuki coupling [38], A valuable oxazolidinone scaffold was coupled to Bal resin (PS-PEG resin with a 4-formyl-3,5-dimethoxyphenoxy linker) to afford the corresponding resin-bound secondary amine (Scheme 7.18). After subsequent acylation, the resulting intermediate was transformed to the corresponding biaryl compound by microwave-assisted Suzuki coupling. Cleavage with trifluoroacetic acid/dichloromethane yielded the desired target structures. 

Chloriminovanadium trichloride, 4165 A-Chloroacetamide, 0789 A-Chloroallylamine, 1202 A -Chloro-3 -aminopropyne, 1129 A -Chloro-3 -aminopropyne, 1129 1-Chloroaziridine, 0786 1-Chlorobenzotriazole, 2150 A -Chloro-bis(2-chloroethyl)amine, 1590 A-Chlorobis(trilluoromethanesulfonyl)imide, 0596 A-Chlorocinnamaldimine, 3126 A -Chlorodimethylamine, 0895 A -Chloro-4,5-dimethyltriazole, 1490 A -Chloro-4-methyl-2-imidazolinone, 1554 A -Chloro-5-methyl-2-oxazolidinone, 1488 A -Chloro-3 -morpholinone, 1489 A-Chloro-4-nitroaniline, 2231 A-Chloro-5-phenyltetrazole, 2674 A-Chloropiperidine, 1948 A -Chloropy rrolidine, 1584... 

A current limitation of the amination methodology is encountered with carbamate esters derived from 2° alcohols (that is, 22 and 24 in Scheme 17.14). With some notable exceptions, substrates in this class often give only small amounts ( 0-20%) of oxazolidinone, and instead afford the corresponding ketones in variable yields. A similar observation has been made by Doyle for C-H insertion reactions with 1-indanol diazo-... 

Padwa has shown that rhodium-catalyzed oxidation of indolyl carbamate 67 employing either Phl(OAc)2 or Phl=0 follows a path similar to that of the D-aUal carbamate (Scheme 17.26) [95]. In principle, indole attack of the putative rhodium-nitrene generates zwitterion 68, which is trapped subsequently by an exogenous nucleophile. Spiro-oxazolidinone products (for example, 69) are isolated as single diastereomers in yields ranging from 50 to 85%. As an intriguing aside, Padwa has found that certain carbamates react with Phl=0 in the absence of any metal catalyst to furnish oxazoHdinone products. This result may have implications for the mechanism of the rhodium-catalyzed process, although it should be noted that control experiments by Espino and Du Bois confirm the essential role of the metal catalyst for C-H amination [57]. 

Treatment with amines of the type 279 generated the intermediate oxazolidinone 280, which underwent thermal decarboxylative formation of the azomethine yhde. Subsequent in situ intramolecular cycloaddition formed the products 281 and 282 in 63% yield and in a 1 1.2 ratio for n=l. Replacing toluene for acetonitrile, for n = 2, gave comparable yields and an improved ratio of 1 2.1 in favor of 281 (Scheme 3.93). 

The addition of hydrazine to diphenylvinylene carbonate 92 quantitatively affords a 1 1 mixture of perhydro-l,3,4-oxadiazin-2-one 93 and 2-oxazolidinone 94 derivatives, both of which are smoothly dehydrated with P2O5 to afford 1,3,4-oxadiazin-2-one 95 and 3-amino-2(3//)-oxazolone 96 (Fig. 5.24), respectively. Addition of primary amines to diphenylvinylene carbonate results in exclusive formation of 3-aIkyl-2(3//)-oxazolones, previously investigated as amino protecting groups in peptide synthesis. 

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 enantioselective amination of iV-acyl oxazolidinones has been studied as part of a general approach to the synthesis of arylglycines. In this case, the enolization is initiated by a chiral magnesium bis(sulfonamide) complex. The oxazolidinone imide enolates are generated using catalytic conditions (10 mol% of magnesium complex) and treated in situ with BocN=NBoc to provide the corresponding hydrazide. 20 mol% of iV-methyl-p-toluensulfonamide are added to accelerate the reaction (equation 117). 

Complexes of maltose with urea, thiourea, imidazole, methanol, 2-oxazolidinone, N,N-dimethylformamide, and hexamethylphosphoric triamide have been described.131 These complexes were noncrystalline and hygroscopic. Such complex-forming reactions could be valuable in the preservation of food flavors during the dehydration process. Sugars have been shown to complex with ethylenediamine.133,133 The nature of the complex has been suggested to be that of a proton-transfer type, in which the carbohydrate moiety is the proton donor and the amine is the proton acceptor. 

The cyclization of carbamate derivatives of unsaturated amines has proven synthetically useful. Cyclizations of carbamates of allylamines containing a terminal vinyl group give oxazolidinone products (equation 60 and Table 17, entries 1 and 2).99,161 Bromocyclizations of systems with a di- or tri-sub-stituted alkene often give mixtures of oxazolidinones and tetrahydrooxazinones,163 while cyclization of an A -cinnamyl carbamate with phenylsulfenyl chloride gave only the oxazolidinone product.163b,163c The stereochemistry of the cyclization of primary carbamates of either allylic or homoallylic amines is low... 

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). 

Table 20 Cyclization to 2-Oxazolidinones from Allylic Amines and Carbon Dioxide (Equation 64)...

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. 

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