Oxazolidinone, as chiral auxiliary

Table 1.7 2-Oxazolidinones as chiral auxiliaries in Darzens reactions.

The literature presents a large number of examples concerning the use of known oxazolidinones as chiral auxiliaries in many kinds of reactions. Rare is the use of A-amino derivatives of oxazolidinones, which were used to synthesise new A-acylhydrazones 207. Radical addition reactions occurred with high diastereoselectivity <00JA8329>. The use of glycolate oxazolidinones 210 proved to be efficient for the enantioselective preparation of a-alkoxy carboxylic acid derivatives . Photochemical reaction of vinyl... 

The unavoidable loss of 50% of material intrinsic in both these routes, clearly called for the development of stereoselective syntheses of diltiazem. One of these [52] is based on the use of an oxazolidinone as chiral auxiliary, and is reported in Fig. 13. 

Li and co-workers developed a novel asymmetric halo aldol reaction using Evans oxazolidinones as chiral auxiliaries for tandem I-C/C-C bond formations. This reaction provides a practical approach to a variety of halo aldols of a non-Evans type that cannot be easily prepared by other methods. Excellent diastereoselectivity (> 95% de) and yields (80-93%) have been obtained. This reaction can be considered as a Lewis acid (Et2Al-I)-promoted Morita-Baylis-Hillman (MBH) process. 

Several reports gave account of the successful employment of chiral oxazolidinones as chiral auxiliaries. For example, they were used to direct, with a proper stereocontrol, the synthesis of modified amino acids (13BJ02009) and iso-fatty acids (13BJO1807) in one case, they were used to control a torquoselective Nazarov cyclization that yielded a precursor of the natural compound (+)-pauci lorol F (130L4118). 

The applications of primary and secondary amine-ureas and -thioureas in asymmetric organocatalysis have been reviewed (138 references), as has the use of oxazolidinones as chiral auxiliaries in asymmetric aldols employed in total synthesis (193 references). 

Several other oxazolidinones have been developed for use as chiral auxiliaries. The 4-isopropyl-5,5-dimethyl derivative gives excellent enantioselectivity.91 5,5-Diaryl derivatives are also quite promising.92... 

Optically active 2-oxazolidinones and 2-thiazolidinones are versatile compounds as chiral auxiliaries. 5a b (4R,5S)-4,5-Diphenyl-2-oxazolidinone has been used for the synthesis of optically active amines6 because of its high stereoselectivity and easy deprotection by hydrogenolysis after the reaction. Compared with several preparations73-0 of (4R,5S)-4,5-diphenyl-2-oxazolidinone reported so far, this method,... 

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. 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

A wide variety of chiral auxiliaries are available to prepare amino acids (Chapter 23). The most popular are oxazolidinones, a-amino acids, aminoindanol (Chapter 24), imidazolidones, and pseu-doephedrine.7 Oxazolidinones 5 have found widespread usage as chiral auxiliaries. A wide range of reactions is available and well documented7 and includes the following aldol alkylations ... 

Many chiral auxiliaries are derived from 1,2-amino alcohols.7 These include oxazolidinones (l),7-9 oxazolines (2),10 11 bis-oxazolines (3),1213 oxazinones (4),14 and oxazaborolidines (5).15-17 Even the 1,2-amino alcohol itself can be used as a chiral auxiliary.18-22 Other chiral auxiliaries examples include camphorsultams (6),23 piperazinediones (7),24 SAMP [(S)-l-amino-2-methoxy-methylpyrrolidine] (8) and RAMP (ent-8),25 chiral boranes such as isopinocampheylborane (9),26 and tartaric acid esters (10). For examples of terpenes as chiral auxiliaries, see Chapter 5. Some of these auxiliaries have been used as ligands in reagents (e.g., Chapters 17 and 24), such as 3 and 5, whereas others have only been used at laboratory scale (e.g., 6 and 7). It should be noted that some auxiliaries may be used to synthesize starting materials, such as an unnatural amino acid, for a drug synthesis, and these may not have been reported in the primary literature. 

Dianion aldol condensation reactions with Evans oxazolidinones or Oppolzer sultams as chiral auxiliaries have been demonstrated to be a useful method to generate the core skeleton of furofurans with diastereoselectivities of 5 1-20 1. Stereoselective total syntheses of the furofuran lignans (-l-)-eudesmin, (+)-yangambin, (—)-eudesmin, and (-)-yangambin according to this procedure have been reported (Equation 102) <2006TL6433>. 

Synthesis of Enantiomerically pure 2-Oxazolidinones and Tetrahydro-2//-l,3-oxazin-2-ones Using (5)-l-Phenylethylamine as Chiral Auxiliary... 

Bicyclic oxazolidinones derived from carbohydrates have been used as chiral auxiliaries in conjugate addition reactions [147]. After deprotonation with MeMgBr, the D-galacto-oxazolidin-2-one 178 and the D-g/wc6>-oxazolidin-2-one 179 (Figure 10.17) were A-acylated with... 

The preferred auxiliaries in chemistry at NSC Technologies are oxazolidinones. Oxazolidinones have found widespread use as chiral auxiliaries. A wide range of reactions is available and well documented [5], including aldol alkylations oc-substitution with a heteroatom such as halogenation, aminations, hydroxyla-tions, and sulphenylations Diels-Alder cycloadditions and conjugate additions. 

It has been observed that addition of Lewis acids to the free radical allylation improved the chemical yield [101]. When substrates with a chiral auxiliary were subjected to free radical allylation in the presence of a Lewis acid, the desired allylated products were obtained with high stereoselectivity [94 d]. In these reactions the Lewis acid plays a pivotal role in fixing the conformation of radical intermediates. Recently Sibi indicated that an elevated reaction temperature accelerated inversion of the stereochemistry of the radical-centered carbon giving rise to greater diastereoselectivity (Scheme 12.39) [102]. When enantiomerically pure Lewis acids were employed as chiral auxiliaries enantioselective free radical allylation of sulfones [103] and oxazolidinones [104] were realized. In the latter reaction two contiguous chiral centers were generated successfully in a single operation with excellent stereoselectivity via tandem C-C bond formation both enantiomers can be se-... 

Most of the chemistry associated with 2-oxazolidinones employs the heterocycles as chiral auxiliaries and takes place on a nitrogen substituent (see Section 3.04.8). 2-Oxazolidinones unsubstituted in the 4 and 5 position give ring-cleaved products by attack of nucleophiles at C-5, followed by loss of CO2. 3-Aryl-2-oxazolidinones react with sodium alkoxides to afford 7V-(2-alkoxyethyl)anilines (120) (Equation (12)) <88TL5095>. 

Diels-Alder reactions with Oppolzer s chiral sultam Diels-Alder reactions with pantolactone as chiral auxiliary Chiral auxiliaries attached to the diene Improved Oxazolidinones SuperQuats Asymmetric Michael (Conjugate) Additions... 

Other oxazolidinones have been used as chiral auxiliaries in asymmetric aldol reactions. Bomane derivatives 1.121 (X = O or S) and 1.122 are readily transformed into V-acyl derivatives. The reactions of their boron or titanium enolates with aldehydes give the same selectivities as Evans s reagents [426, 428, 429, 431, 436], iV-Acylimidazolidinones 1.131 and 1.132 [449, 1270] lead to similar results, but the selectivities observed are somewhat lower. 

In addition to amino acids, 1,2-amino alcohols can be used as chiral auxiliaries. The synthesis of the amino acid derivative 16 outlined in Scheme 9.15 is a variation of a Strecker reaction. - Evans oxazolidinone chemistry is well documented, which allows for a wide variety of reactions to be performed with a high degree of predictability. In addition to alkylation reactions to introduce the side chain of an amino acid, the nitrogen group can also be introduced in a variety of ways, one of which is illustrated in Scheme 9.16. ... 

Sibi et al. [58] employed a similar approach 4-diphenylmethyl-2-oxazolidinone 61 as was chosen as chiral auxiliary in the asymmetric synthesis of both enantiomers of enterolactone (62), Scheme (11). 

Sibi and co-workers developed two protocols which utilized 4-diphenylmethyl-2-oxazolidinone (170) as chiral auxiliary to enter different classes of lignans. Oxazolidinone 170 was efficiently acylated to... 

The enolates of other carbonyl compounds can be used in mixed aldol condensations. Extensive use has been made of the enolates of esters, thioesters, and amides. Of particular importance are several modified amides, such as those derived from oxazolidinones, that can be used as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, tin, and titanium derivatives have all been used. Because of their usefulness in aldol additions and other synthetic methods (see especially Section 6.4.2.3, Part B), there has been a good deal of interest in the factors that control the stereoselectivity of enolate formation from esters. For simple esters such as ethyl propanoate, the E-enolate is preferred under kinetic conditions using a strong base such as EDA in THE solution. Inclusion of a... 

Enantiomerically pure oxazolines and oxazolidinones have found widespread application in organic synthesis as chiral auxiliaries. They have been mainly used for the synthesis of enantiomerically pure amino acids but also as chiral auxiliaries to produce non-racemic enolates as pioneered by Evans.The reaction types proceeding with high stereocontrol include enolate alkylation, enolate oxidation, enolate halogenation, enolate amination, enolate acylation, aldol reaction and Diels-Alder reactions. 

Chiral iV-acetyloxazolidinones and 3-haloacetyl-2-oxazolidinones have also been employed by Evans and coworkers [93] to synthesize a thienamycin intermediate and monobactam precursors. Thiazolidinethiones have also been used as chiral auxiliaries in the aldol addition to produce optically active monocyclic P-lactams [94]. Miller et al. [95] (Scheme 35), employed such a strategy by using cysteine- and serine-derived thiazolidinethiones 221 and oxazolidinethiones 222 to provide direct access to hydroxamate precursors 224 of bicyclic P-lactams, like 225. 

Oxazolidinones are frequently used as chiral auxiliaries in asymmetric transformations, as ligands for metal catalysts, and as precursors to vicinal amino alcohols. These common structural motifs in natural products and pharmaceuticals have spurred interest in the development of methods for their preparation. Espino and Du Bois reported the synthesis of indane-appended oxazolidinone 215 via Rh-catalyzed C-H insertion of carbamate ester 214. A variety of other carbamates was found to be competent substrates for this reaction. The role of magnesium oxide as additive was presumed to be as scavenger of acetic acid generated from the iodinane oxidant. 

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