Chiral oxazolidinone anions

The utility of -phenyl camphor-derived oxazolidinones as chiral formyl anion syn-thons has been demonstrated by Gawley and coworkers (Scheme 42). Deprotonation yields a dipole-stabihzed organolithium intermediate and the absolute configuration of the lithium-bearing carbon is presumed to be R. Additions to benzaldehyde and cyclohexane carboxaldehyde are 86% and 76% diastereoselective, respectively, but recrystallization affords a single diastereomer in the yields shown. Addition is postulated to proceed via the pre-complex shown in the inset, in which the aldehyde is coordinated to the R epimer... 

Nonbranched amino acids substituted by a fluoroalkyl chain on a carbon distant at least one methylene from the amino acid function have been prepared as racemates by various methods." Under nonracemic form, co-perfluoroalkyl norvaline and norleucine (Rf = C2F5 or more) have been prepared by bromination of an anion of a fluorinated chiral oxazolidinone (derived from RfCH2CH2C02H). Substitution of the bromine atom by an azide and subsequent reduction yield the desired amino acids (Figure 5.10)." ... 

H. Reactions with Anions of Chiral Oxazolidinones and Derivatives with... 

Related Reagents. The synthesis of chiral diazenedicarboxylates as potential chiral electrophilic aminating agents has received little attention. A series of chiral bomyl, isobomyl and menthyl diazenedicarboxylates has been reported and their reaction with achiral enolates of esters and N,N-dimethyl amides afforded a-hydrazino acid derivatives with little or no selectivity. Incorporation of a chiral azodicarboxamide unit into a chiral bridging binaphthyl moiety afforded a-hydrazino acid derivatives with high stereoselectivity in reactions with achiral oxazolidinone anions. ... 

Another type of substitution reaction is increasing in popularity—the use of an allylic substrate, such as an allyl acetate where the nucleophile is introduced with stereochemical control in the presence of a palladium catalyst and a chiral ligand. Reactions where a chiral anion, be it derived from a chiral heteroatom group, such as a sulfoxide, or an auxiliary, such as Evans s oxazolidinones, are not included in this chapter because the alkyl halide is usually relatively simple and the stereochemical selectivity is derived from the system itself. 

Finally, in 2006, Xu and Lin reported an asymmetric reduction of 2-acyl-arylcarboxylates using Sml2 and a catalytic amount of a chiral proton source.19 For example, reduction of 17 gave chelated anion 18 that was protonated by enantiomerically pure oxazolidinone 19. A stoichiometric, achiral proton source, 2,2,6,6-tetramethylpiperidine, then regenerated the chiral proton source. Lactone 20 was obtained in excellent yield and high enantiomeric excess (Scheme 4.11).19... 

Intramolecular asymmetric induction has also been used in electrochemistry as in the reduction of optically active alcohol esters or amides of a-keto [469,470] and unsaturated [471] acids and oximes [472] and in the oxidation of olefins [473]. A maximum asymmetric yield of 81% was obtained in the reduction of (5 )-4-isopropyl-2-oxazolidinone phenyl-glyoxylate [470]. Nonaka and coworkers [474,475] found that amino acid A-carboxy anhydrides were polymerized with various electrogenerated bases as catalyst to give the poly(amino acids) with high chirality in high yields. Conductive chiral poly(thiophenes) prepared by electropolymerization can be used for chiral anion recognition [476]. 

Matsumura and his coworkers [38] have employed the 2-pyrrolidone anion, in DMF solution, to deprotonate arylacetic acid esters with subsequent oxidative dimerization of the corresponding carbanions. This study includes a useful comparison between the electrochemical and chemical generation of the 2-pyrrolidone anion (by fluoride anion displacement in A-trimethylsilyl-2-pyrrolidone). The advantage lies with the electrochemical route, which gave yields of final product of 80%, compared with the 30% obtained with the chemically generated base (Scheme 10). The overall process, formation of dimethyl 2,3-diphenylsuccinates, is not only efficient and convenient but also operates with high diastereoselectivity when under the control of an oxazolidinone chiral auxiliary (Scheme 10). 

Addition of ArLi followed by Et30 to Cr(CO)4(nbd) results in the carbene complexes Cr(CO)3 =C(OEt)Ar nbd. The corresponding carbenes are also formed from W(CO)4(cod).306 it is possible to protect carbene complexes towards nucleophilic attack by the temporary formation of anions either at the position a to the carbene or at the oxygen substituent. Chiral (through deuterium incorporation) glycine is available via oxazolidinone chromium carbene complexes.398... 

Several examples can serve to illustrate the use of chiral auxiliaries. First, the chiral, heterocyclic, amino-add-derived lactam, (5)-4-(phenylmethyl)-2-oxazolidinone, is capable of conversion into an anion on treatment with butyllithium [CH3(CH2)2CH2Li]. Acylation at nitrogen with propanoyl chloride produces chiral propionamide. 

We decided to investigate the E wis aldol reaction (54,55) of the chiral a-hydroxy acetic anion equivalent 47 with the A -Cbz imine of trifluoropyruvate 33. Screening of several enolates and reaction conditions revealed that titanium enolate of the oxazolidinone 47, prepared with 1 equiv. ofTiCU and l.l equiv. of/-Pr2NEt, reacts with excellent stereocontrol affording the "Evans" syn diastereomer 48, in 88% isolated yield, having the correct stereochemistry to be used as intermediate for the synthesis of the targeted 2-Tfm-sphingolipids. 

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