4- Oxazolin-2-ones, preparation reactions

The preparation of 3,5-diphenyl-4-oxazolin-2-one by reaction of phenacylaniline with phosgene was described by McCombie and Scarborough, who also showed that the 3,4,5-triphenyl analog was an extremely stable compound which failed to react with a variety of... 

The power of chiral C2-symmetric bis(oxazolines) in cyclopropanation reactions has also been exhibited in total synthesis. One example is Corey and co-workers synthesis of sirenin 63 using bis(oxazoline) ligand 8 (Fig. 9.19). They showed that the intramolecular cyclopropanation of diazo derivative 61 proceeded in 77% yield and with 90% ee. Shibasaki and co-workers constructed prostratin 67 through the intermediate cyclopropane 66, also shown in Figure 9.19. Using bis(oxazoline) ligand 64 and copper(I) triflate-derived catalyst, compound 66 was prepared in 70% yield and 92% ee from diazo derivative 65. ... 

Enantioselective Diels-Alder reaction. Highly stereoselective Diels-Alder reactions can be achieved by use of the 4,4 -diphenylbis(oxazoline) 2b, prepared from (+)-phenylglycinol, as a chiral, bidentate ligand for iron salts. Thus reaction of Fel3 with 2b and I2 in CH3CN forms a complex presumed to be I-Fel3, which can catalyze reaction of 3-acryloyl-l,3-oxazolidin-2-one with cyclopentadiene at —50° to give the endo-adduct in 95% yield. The product is the 2R-enantiomer (82% ee). 

Enantioselective Diels-Alder catalyst. The chiral bis(oxazoline) 1, prepared from (S)-phenylglycine, in combination with Mgl2 or magnesium tetraphenylborate (2) serves as a highly enantioselective catalyst for the Diels-Alder reaction of cyclopentadiene with 3-acryloyloxazolidine-2-one (equation I). 

Fujisawa et al. [Ill] have reported that the magnesiiun complex prepared from chiral 2-[2-[(tolylsulfonyl)amino]phenyl]-4-phenyl-l,3-oxazoline 81 and methyl-magnesium iodide was efficient, in a stoechiometric amount, for promoting the enantioselective Diels-Alder reaction of 3-alkenoyl-l,3-oxazohdin-2-one with cyclopentadiene (Scheme 45) leading exclusively to the endo adducts in up to 92% ee. The use of 10 mol% of the complex led to an important decrease in enantioselectivity of the product (51% ee). 

The more difficult problem of protecting the carbonyl group can be accomplished by conversion to a oxazoline derivative. One example is the 4,4-dimethyl derivative, which can be prepared from the acid by reaction with 2-amino-2-methylpropanol or with 2,2-dimethylaziridine.269... 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

It was shown previously that saturated 5(4//)-oxazolones or 2-oxazolm-5-ones with only one substituent at C-4 can be considered as the tautomeric form of saturated 5(2//)-oxazolones or 3-oxazolin-5-ones. These compounds can also be considered as amino acid derivatives and, indeed, cyclization procedures are the most commonly used to prepare these compounds. The cyclization reaction employs a variety of cyclodehydrating agents and the general method is shown in Scheme 7.23, with an A-acyl-a-amino acid being the most typical starting material used. In this way, 5(4//)-oxazolones derived from most natural amino acids 99 (R3 = H) have been obtained by heating the corresponding A-acyl derivatives in the presence of acetic anhydride. 

Oxazoline-directed conjugate addition of nucleophiles to a naphthalene nucleus is one of the most useful methods to prepare dihydronaphthalenes. Since Meyers last comprehensive review, the focus has been directed to stereoselective synthesis of these important compounds. Meyers laboratory has continued their preeminence in this field and has expanded the scope and applications of this reaction. 

Two further preparations of 3-nitropropanal 1 have been claimed in the literature by treatment of 1-chloro-3-nitro-2-propanol with potassium hydroxide,5 and by reaction of the 4-isopropyl-2-oxazolin-5-one anion with nitroethene.6 These alternate methods are less suited and less economic for the preparation of 3-nitropropanal 1 on a multigram scale. 

Oxazolin-5-ones have also proven to be important intermediates in the homologation of carboxylic acids (71AG(E)655). The IV-acyl-DL-valine derivative (402), prepared from the acid chloride of the carboxylic acid and DL-valine by the Schotten-Baumann procedure, was treated with excess acetic anhydride to afford (403). Reaction of (403) with acrylonitrile and triethylamine led to (404) in good yield. Hydrolysis of (404) with dilute alkali or acid gave the y-keto nitrile or y-keto acid (Scheme 89). 

Tetrahydro-7H-oxazolo[3,2-a]pyrimidin-7-ones (275) can be prepared from 2-amino-2-oxazolines and a,/8-unsaturated carboxylic esters. The orientation of the substituents in the reaction product corresponds to Michael addition of the oxazoline nitrogen as the first step (74LA593). 

Chiral chelating ligands that contain only one phosphine and another donor atom have been successful in recent years. A readily synthesized example is the phosphino-oxazoline ligand 87 shown in Scheme 31. These types of ligand can be prepared in two steps from an amino alcohol, a substituted benzonitrile and either a electrophillic or nucleophilic phosphorus reagent. They have been used in a number of asymmetric reactions. 

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