Unsubstituted oxazolines

Deprotonation of Oxazolines. New chiral oxazoline-sulfoxide ligands have recently been prepared and utilized as chiral ligands in copper(II)-catalyzed enantioselective Diels-Alder reactions. These new ligands were prepared via sulfinylation of chiral 1,3-oxazoline to lead to unsubstituted oxazoline sulfoxide derivatives. While the first methylation was conducted using LDA and methyl iodide, the introduction of the second methyl was carried out using JCHMDS and methyl iodide to afford the desired chiral ligand (eq 39). 

Thioacetyl derivatives (155) are obtained by direct heterocyclization reactions (365. 378, 563) and by a sulfur-oxygen exchange" reaction involving thioacetic acid and A-2-oxazoline-5-one (154) or A-2-thiazoline-5-one (156) (Scheme 81) (365, 378, 379). Ra-Ni reduction of 155 affords the 5-unsubstituted thiazole (379). 

Since Evans s initial report, several chiral Lewis acids with copper as the central metal have been reported. Davies et al. and Ghosh et al. independently developed a bis(oxazoline) ligand prepared from aminoindanol, and applied the copper complex of this ligand to the asymmetric Diels-Alder reaction. Davies varied the link between the two oxazolines and found that cyclopropyl is the best connector (see catalyst 26), giving the cycloadduct of acryloyloxazolidinone and cyclopentadiene in high optical purity (98.4% ee) [35] (Scheme 1.45). Ghosh et al., on the other hand, obtained the same cycloadduct in 99% ee by the use of unsubstituted ligand (see catalyst 27) [36] (Scheme 1.46, Table 1.19). 

The utility of chiral oxazoline enolates in asymmetric synthesis has elegantly been demonstrated by Myers (106,120). The stereoselective aldol condensations of these enolates have been examined in a hmited number of cases (eq. [107]) (32,121). Assuming that the enolate formed has the geometry indicated in 164 (120b), the diastereoselection observed for both the aldol condensation and the previously reported alkylations favors electrophile attack on the Re face as indicated. In contrast, the unsubstituted enolate 163b exhibits significantly poorer diastereoface selection with a range of aldehydes (eq. [108]) (121). 

Unsubstituted species 114a is prepared from tropone 112 by cyclization with formamide (61BCI312) or with ethoxymethylene acetates and pyrolysis of intermediate oxazolines 115e-g (60NKZ509 61BCJ611). 2-Phenyl derivative 114d is obtained from 2-methoxy-7-(benzoylamino)tropone with... 

Oxazoline and thiazoline derivatives metalated at the 2-position can also be prepared by the combination of acyclic precursors, namely by the reaction of a-metalated isocyanides with ketones or thioketones (Scheme 141) [76LA183 77AG(E)339 79PAC1347]. Although this route is normally used to produce 2-unsubstituted derivatives via protonation, there is presumably no reason why other electrophiles could not also be utilized instead. 

A common and effective direct approach to unsubstituted or multiply substituted oxazolines is the Lewis acid catalyzed reaction of nitriles with amino alcohols in an alcoholic or aromatic solvent (chlorobenzene) at reflux. The most common Lewis acids employed include ZnCl2, ZnBr2, NiBr2, CuCl2, and kaolinitic clay. Microwave irradiation has also been reported to facilitate the transformation. Alternatively, the condensation can be carried out in the presence of catalytic amounts of potassium carbonate. The method works well for both aliphatic and aromatic nitriles, with retention of stereochemistry. Some representative examples from the recent literature are listed in Table 8.16 (Scheme 3 40),2 35.2oi-2i3... 

The DFT study of the 3 + 2-cycloaddition between ketene and TV-silyl-, IV-germyl-, and TV-stannyl-imines shows that the TV-germylimine reaction is a two-step process the TV-stannylimine reaction is a competition between two- and three-step processes whereas the TV-silyl process follows a three-step process44 A new and convenient synthesis of functionalized furans and benzofurans based on 3 + 2-cycloaddition/oxidation has been reported. The cyclization of cyclic 1,3-bis-silyl enol ethers (48) with l-chloro-2,2-dimethoxyethane (49), via a dianion, produced 5,6-bicyclic 2-alkylidenetetrahydrofurans (50), which are readily oxidized with DDQ to 2,3-unsubstituted benzofurans (51) (Scheme 13)45 The Evans bis(oxazoline)-Cu(II) complex catalyses the asymmetric 1,3-dipolar cycloaddition of a -hydroxyenones with nitrones to produce isoxazolidines.46 The... 

Alkyl substituted 2-oxazolines, for instance 2-methyl-2-oxazoline9), or 2-ethyl-2-oxazoline 10) can be used in the place of unsubstituted 2-oxazoline. In all cases, the molecular weight of the resulting PEI is relatively low, usually in the order of a few thousands. 

Unsubstituted and substituted oxazolines are easily polymerized with cationic initiators. The polymerization reaction is a ring-opening reaction with isomerization and it has been studied and reviewed extensively [176,177]. 

Imidazoles can also be made by heating 4-tosyloxazolines in saturated methanolic ammonia or monoalkylamines. These reactions proceed through intermolecular condensation of a-aminoketones and amidines and intramolecular cyclization of a-ainidinoketones, respectively [49] (see Section 4.2). When A -unsubstituted 4-oxazolin-2-ones are added to isocyanates, the 2-oxo-4-oxazoline-3-carboxamide products cleave under the influence of strong acids and heat. Subsequent ring closure gives 4-imidazolin-... 

Iso-nicotinic acid 103 must also react at C-3 but nicotinic acid 105, R = H shows the regio-selectivity expected from the relative acidity of C-l and C-4 and gives substitution at C-4 whether C-l is substituted 105, R = Cl, or unsubstituted 105, R = H. The same result is found for amides or oxazolines as ortho-directors.10... 

Saegusa T, Ikeda H, Fujii H. Isomerization polymerization of 2-Oxazoline. I. Preparation of unsubstituted 2-Oxazoline polymer. Polym J 1972 3 35-39. 

Djafri et al. have determined by DNMR the barriers to rotation of aryl groups (unsubstituted in the ortho positions) in position 3 of 4,5-dimethyl-oxazoline-2-thiones (53), -imidazoline-2-thiones (54), and -thiazo-line-2-thiones (55) (85JCS(P2)273) the barriers were 38.9, 51.5, and 74.0 kJ mol respectively. They conclude that the ring element X (O, NCH3, S) affects the barriers mainly by its influence on the geometry of the ring. 

Poly ethylene imines) are polymers with two carbon atoms between each nitrogen atom in the main chain, that is, they are actually secondary amines. Unbranched poly(ethylene imines) are obtained by the isomerization polymerization of unsubstituted 2-oxazolines initiated by C2H5[BF30C2Hs] with subsequent saponification of the products ... 

Unbranched poly(ethylene imines) can be produced by the isomerization polymerization of unsubstituted 2-oxazolines ... 

Ring-opening polymerization evidently constitutes another method for the synthesis of regular internal structures [8]. In order to obtain a strictly linear polyampholyte with a repeating unit as small as possible, A -alkyl substituted ethylenimines have to be used, since conventional unsubstituted polyethylenimine has a highly branched structure. The synthesis of strictly linear polyethylenimine has, however, been described recently by Saegusa and coworkers by isomerization polymerization of 2-oxazoline [9]. 

The ligand was prepared in a straightforward manner. Aminoindanol and diethyl malonimidate dihydrochloride are heated together in THF (eq 5) (9). On cooling, the unsubstituted bis(oxazoline) is precipitated in 81% yield by the addition of 0.5 N NaHCOa. The cyclopropane bridge is installed in 85% yield with 1,2-dibromoethane, employing LiHMDS as the base (10). 

The use of phenyl vinyl sulphoxide, PhSOCH=CH2, as an acetylene equivalent in Diels-Alder cycloadditions has been developed/ an example being the synthesis of 3,6-diphenylpyridazine (191 Ar = Ph R = H) in 97% yield (Scheme 44 path a). 4-Amino-pyridazines are available also by cycloaddition reactions, in this case between lV-acetyl-4-oxazolin-2-ones, or (better) the unsubstituted oxazolinone, and 1,2,5,6-tetrazines, as illustrated in Scheme 44 (path... 

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