2-substituted 2-oxazolines

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>. 

An alternative procedure for the synthesis of aliphatic 2-substituted oxazoline hydroxamates was described by Pirrung and colleagues in the context of preparing inhibitors of E. coli LpxC zinc amidase [378], As shown in Scheme 6.210 a, the protocol involved the cyclization of suitable amides, formed in situ by acylation of a serine-derived 0-2,4-dimethoxybenzyl (DMB)-protected hydroxamate. The cyclization... 

First of all a 2-substituted oxazoline (1) is formed by cyclocondensation of a carboxylic acid ester with 2-aminoethanol and a small amount of (1) is converted with an alkylating agent (e.g., methyl tosylate) to the activated, ionic form (2). 

S-Ethenylsulfimines 287 react with amides to yield 2-substituted-oxazolines 28 9 304 reaction proceeds via initial Michael addition of an amide anion to 287 to give 288 that collapses to the oxazoline. The reaction is typically carried out at room temperature or 50 °C in THF, 1,2-dimethoxyethane (DME), or even MeCN using NaH as the base. Aryl, heteroaryl, and aliphatic amides can be used and the yields of 289 are modest to excellent (Scheme 8.82). 

Yokozawa reported that the 2-substituent strongly affects the reactivity of a 2-substituted-oxazoline 360 with dimethyl 2,2-dicyano-3-ethoxy-l,l-dicarboxylate as shown in Scheme 8.115. Thus, oxazoline itself, 360 (R = H), gave the annulated bicyclic product 361 that resulted from collapse of the zwitterionic intermediate 362, whereas simple 2-alkyloxazolines, 360 (R = Me, Et), gave an alternating (1 1) copolymer. 2-Phenyloxazoline, 360 (R = Ph), was unreactive under the reaction conditions. The zwitterionic intermediate 362 (R = Me) was trapped by acetic acid to give the open-chain adduct 363 that resulted from nucleophilic ring opening at the 5-position of the oxazolinium zwitterion. 

Achiral 2-stannyloxazolines are known to undergo Shlle coupling with aromahc halides. However, Stille couplings with chiral 2-halooxazolines were not reported until Meyers and Novachek prepared the requisite 2-bromooxazoline 365 (see Scheme 8.116) and successfully coupled 365 with a variety of alkynyl and alkenylstannanes to afford chiral 2-substituted oxazolines 635 in reasonable yields (Scheme 8.200). ... 

Substituted oxazoline-4-carboxamides 134, present in several families of bioactive natural products, have been prepared in an efficient and general one-pot, four-component Ugi condensation of (1-keto mesylates 132, ammonia, carboxylic acids, and isonitriles, leading to intermediate diamides 133. 

A major interest, early foreseen [178] of poly(N-acylethyleneimine)s obtained by the cationic polymerization of 2-substituted oxazolines, was their ability to lead to linear polyethyleneimines by hydrolysis reaction. An almost complete basic hydrolysis was performed on polymers prepared using BF3-Et20 catalyst [179]. 

The selenium dioxide promoted oxidative rearrangement of 2-substituted oxazolines 72 unexpectedly gave [31] 3-substituted 5,6-dihydro-2ff-l,4-oxa-zin-2-ones 73, useful chiral synthons for the synthesis of amino acid derivatives [32] (Eq. 14). 

The reaction between benzene-1,2-diamine and 2-trifluoromethyloxazol-5-ones is similar. Condensation of benzene-1,2-diamine with 4-arylidene-2-substituted oxazolin-5-ones in acetic acid also results in the formation of 3-(l-aryl)alkylquinoxalin-2(1 A/)-ones. - ... 

Shafer, C. M., Molinski, T. F. Oxidative Rearrangement of 2-Substituted Oxazolines. A Novel Entry to 5,6-Dihydro-2H-1,4-oxazin-2-ones... 

A new method for the preparation of 2-substituted oxazolines 173 by rhodium-catalyzed coupling of alkenes 172 with 4,4-dimethyl-2-oxazoline 171 has been reported. Compounds 173 were obtained in good yields and excellent selectivity for the linear product <04OL1685>. 

Lateral Metallation of 2-Substituted Oxazolines, Thiazolines, Dihydrooxazines, Thiazoles 129... 

Treatment of 2-substituted oxazolines (367) with sodium hypochlorite, followed... 

Cwik, A., Hell, Z., Hegedus, A., Finta, Z., Horvath, Z. 2002. A simple synthesis of 2-substituted oxazolines and oxazines. Tetrahedron letters 43(22) 3985-3987. 

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