Oxazolines, chiral, formation

The 1-t-butylphospholane sulfide intermediate to TangPhos was also used to prepare the P,N ligands 48 by reacting the lithium complex with C02 and then oxazoline formation with a range of chiral amino alcohols [69b, 74]. The Ir complexes of these ligands have been successfully used in the reduction of / -methylcinnamic esters (80-99% ee) and methylstilbene derivatives (75-95% ee), a particularly challenging class of unfunctionalized olefins [4 c]. 

The carbanion generated by ot-proton abstraction of a 2-alkyloxazoline is capable of typical enolate chemistry. Thus, the carbanion was found to react with nitriles to give an enamine, with formate esters to give an aldehyde that can be trapped,with chiral sulfinate esters to give chiral sulfoxides,and with alkylating agents. A carbamate-protected aminomethyl chiral oxazoline was deprotonated and alkylated with diastereoselectivities up to 92% de. ... 

Simple alkylation of the chiral chelate complex leads to formation of chiral dialkylacetic acids (Scheme 109).3S5 388 Simpler chiral enamines can also be used. The formation of chiral propanoic acids results from a resolution of racemic alkyl halides by the interaction of a chiral lithiooxazoline, which recognizes and reacts with one enantiomer at the expense of the other (Scheme 110).389 The above aspects of the asymmetric carbon—carbon bond formation from chiral oxazolines have been reviewed by Meyers.390... 

A very useful extension of the de Mayo reaction has been recently introduced by Blechert et al. (Scheme 6.26) [78]. The retro-aldol fragmentation was combined with an intramolecular enantioselective allylation (asymmetric ring-expanding allylation) catalyzed by a chiral Pd complex. Bicycloheptane 68, for example, was accessible by intermolecular [2 + 2]-photocycloaddition of cyclopentenone 67 with allene. Further transformation in the presence of Pd2(dba)3 (dba = dibenzylideneacetone) and the chiral oxazoline ligand 69 (tBu-phox) resulted in the enantioselective formation of cycloheptadione 70. 

Meyers AI (1978) Asymmetric carbon-carbon bond formation from chiral oxazolines. Acc Chem Res 11 375-381... 

Methyl-l-phenylisoquinoline (380) is obtained when the oxazoline (379) is heated with phosphorus pentoxide. An efficient synthesis of alkylated and dialkylated acetic acids consists in the alkylation of 4,5-dihydro-oxazoline bound to polystyrene, followed by hydrolysis." The asymmetric synthesis of a series of a-alkylphenylacetic acids C H2 +i CHPhC02H ( = 1-5) from the chiral oxazoline (381) has been described. Another example of the use of oxazolines for asymmetric synthesis is the preparation of the optically active binaphthyl (383) from 1-lithionaphthalene and compound [382 R = (—)-menthyl]. The stereoselective formation of threo-dXdoX products (385 = Et, Pr, n-pentyl, etc from the chiral boron compound... 

As previously aluded to, Bolm has used Cu with a chiral oxazoline S,S-cat to promote the asymmetric formation of lactones from racemic ketones. This catalyst worked well only on 2-phenylcyclohexanones.32... 

Serrano and co-workers have reported the synthesis of two interesting series of chiral, hexacatenar metal complexes, that is, mono- and dinuclear, derived from chiral oxazoline-based ligands.None of the pure dinuclear compounds (136 X = OAc, Cl) was mesomorphic and most were room-temperature oils or glassy materials. This is likely due to the sterically demanding central chiral unit preventing molecular stacking and, hence, mesophase formation. 

A. I. Meyers, Asymmetric Carbon-Carbon Bond Formation from Chiral Oxazolines , Accounts Chem. Res., 1978,11, 375. 

Corey et al. synthesized a chiral bis(oxazoline)Fe(III) catalyst 30, the ligand of which was prepared from chiral phenylglycine. The catalyst was formed by the reaction of the ligand with Fel3 in the presence of I2.12 greatly enhances the Lewis acidity of the catalyst owing to the formation of a cationic species [39] (Scheme 1.49). 

Other asymmetric syntheses, based on aldol condensation of chiral a-sulfinyl carbanions with carbonyl compounds, are the formation of / -hydroxyketones from /J-sulfinylhydrazones 166211-214, of /3, /l -dihydroxyketones from 3-(p-tolylsulfinyl-methyl)-A2-methylisoxalinones 167215, of /1-hydroxyacids from 2-(p-tolylsulfinylmethyl)oxazolines 168216 and of /J-hydroxyesters from ethyl-p-tolylsulfinyl-W-methoxyacetamide 169217. 

Can a chiral catalyst containing the same ligand/metal components promote the formation of both enantiomers enantioselectively The bis(oxazoline)magnesium perchlorate-catalyzed asymmetric Diels-Alder reaction [103]... 

Here the critical step is the formation of the oxazoline ring. Both the stereochemistry of the two chiral centers and its acid lability had to be considered. Two approaches have been published. They can be modified for other members of this class. 

In a recent modification of the second synthesis (50S) effected for fluvibactin (45) an o-xylene protection group was proposed (reaction of 2,3-dihydroxy-benzoic acid methyl ester with 1,2-di(bromomethyl)benzene) which could be removed later by hydrogenolysis. The formation of the oxazoline ring from protected DHB-L-threonine methyl ester was achieved with Mo(VI) catalysts (e.g. (NH4)2Mo04) without affecting the chiral centers. Derivatization of the primary amino groups of norspermidine with the protected DHB methyl ester was catalyzed by Sb(OC2115)3. 

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