Oxazolines preparation

It would require a Herculean effort to prepare a complete discussion and review of every report related to the synthesis, reaction, or application of an oxazole while tabulating every oxazole, oxazolone, oxazoline, and chiral bis(oxazoline) prepared and evaluated during the period of 1983-2001. Such an undertaking is beyond the scope of this review. Furthermore, the ease with which electronic databases, including the patent literature, can be searched, the data retrieved, and the information tabulated would render such a project somewhat redundant. 

Tables are included in every chapter. Wherever possible, these contain a variety of selected examples to provide the reader with the scope and hmitations of synthetic methods and reactions. However, in some cases a table will contain only the examples reported. No attempt has been made to provide an exhaustive compilation of every oxazole, oxazolone, or oxazoline prepared since 1983.

Michael reaction. Different example, an oxazoline prepared fn carbohydrate-based thiolhave bei... 

Michael reaction. Different ligands for copper catalysts are available. For example, an oxazoline prepared from valine," a phosphine from proline,"" and a carbohydrate-based thiolhave been tested. 

Selected examples of 2- and 3-oxazolines prepared by this methodology are shown in Table 1.57. 

Poly(iV-alllinear poly(isopropylenimine) (PiPI) back in 1974 based on the hydrolysis of poly(2,5-dimethyl-2-oxazoline), prepared by living CROP of the corresponding 2-oxazoline monomer. The PiPI is of interest as it is the simplest PAI with a chiral main-chain structure. Even though this specific example yielded a racemic PiPI, this synthetic procedure also provides access to a PiPI with controlled stereochemistry if... 

Uemura and coworkers used a carbohydrate-based phosphinite-oxazoline prepared from D-glucosamine as hgand for palladium in the alkylation of l,3-diphenyl-3-acetoxyprop-l-ene in water or in an aqueous/organic biphasic medium. High yields of alkylation products were obtained with up to 85% ee (Scheme 8.23). ... 

One product is poly(2-ethyl-2-oxa2oline) (PEOX). It is prepared by the ring-opening polymerization of 2-ethyl-2-oxazoline (19) with a cationic initiator (48) (eq. 6). 

Methylene thiirane is obtained by thermolysis of several spirothiirane derivatives which are formally Diels-Alder adducts of methylenethiirane and cyclopentadiene or anthracene <78JA7436). They were prepared via lithio-2-(methylthio)-l,3-oxazolines (c/. Scheme 121). A novel synthesis of the allene episulfide derivatives, 2-isopropylidene-3,3- dimethylthiirane (good yield) or its 5-oxide (poor yield), involves irradiation of 2,2,3,3-tetramethyl-cyclopropanethione or its 5-oxide (81AG293). Substituents on the thiirane ring may be modified to give new thiiranes (Section 5.06.3.9). The synthesis of thiirane 1-oxides and thiirane 1,1-dioxides by oxidation is discussed in Section 5.06.3.3.8 and the synthesis of 5-alkylthiiranium salts by alkylation of thiiranes is discussed in Section 5.06.3.3.4. Thiirene 1-oxides and 1,1-dioxides may be obtained by dehydrohalogenation of 2-halothiirane 1-oxides and 1,1-dioxides (Section 5.06.4.1.2). 

A number of 2-acylazetidines have been prepared by reaction of 1,3-dihaloacyl compounds with amino derivatives (Section 5.09.2.3.l(m)). This is illustrated for azetidine 2-carboxylic acid (56), the only known naturally occurring azetidine. Ring expansion of activated aziridines (43) and contraction of 4-oxazolines (55) has also found limited use (Section 5.09.2.3.2(f) and Hi)). 

Alkyl-l,3-oxazolines are prepared to protect both the carbonyl and hydroxyl groups of an acid. They are stable to Grignard reagents and to lithium aluminum hydride (25°, 2 h). ... 

Oxazolines are prepared by the reaction of a fatty acid with ethanolamine Figure 7.11). 

The first synthesis and use of a chiral oxazoline was reported by Meyers in 1974. The chiral oxazoline 1 was prepared in two steps by condensation of (-i-)-l-phenyl-2-amino-1,3-propanediol (6) with the ethyl imidate of propionitrile followed by 0-methylation of the resulting alcohol 7 with NaH/Mel. Meyers demonstrated chiral oxazoline 1 could be... 

The sesquiterpenoid hydrocarbons (5)-a-curcumene (59) and (5)-xanthorrhizol (60) were prepared by asymmetric conjugate addition of the appropriate aryllithium reagent to unsaturated oxazoline 56 to afford alcohols 57 (66% yield, 96% ee) and 58 (57% yield, 96% ee) upon hydrolysis and reduction. The chiral alcohols were subsequently converted to the desired natural products. ... 

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... 

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). 

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). 

Single crystals of 1 1 complex. °1 1 Catalyst obtained by evaporation of CH2CI2. After 3 months in an open air. Ligand (Ff,Ff)-isopropylidene-2,2 -bis(4-phenyl-oxazoline). Anhydrous complex catalyst prepared from NIBr2 and AgSbFg. 

We therefore prepared a new chiral ligand, (l ,J )-isopropylidene-2,2 -bis[4-(o-hy-droxybenzyl)oxazoline)], hereafter designated J ,J -BOX/o-HOBn. To our delight, the copper(II) complex catalyst prepared from J ,J -BOX/o-HOBn ligand and Cu(OTf)2 was quite effective (Scheme 7.45). Especially, the reaction of O-benzylhydroxylamine with l-crotonoyl-3-isopropyl-2-imidazolidinone in dichloromethane (0.15 m) at -40°C in the presence of J ,J -BOX/o-HOBn-Cu(OTf)2 (10 mol%) provided the maximum enantioselectivity of 94% ee. 

A similar influence of the lithium-magnesium exchange is documented for tetrahydroisoquino-lines, derived from chiral oxazolines (see Section 1.3.2.3.3.2 ). The tuning by magnesium bromide also serves well in the carbonyl addition of lithiated tetrahydro-2-isoquinolinecarboxy-late24, prepared by the Katritzky protection/activation method27,28. 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

The search for the racemic form of 15, prepared by allylic cyclopropanation of farnesyl diazoacetate 14, prompted the use of Rh2(OAc)4 for this process. But, instead of 15, addition occurred to the terminal double bond exclusively and in high yield (Eq. 6) [65]. This example initiated studies that have demonstrated the generality of the process [66-68] and its suitability for asymmetric cyclopropanation [69]. Since carbon-hydrogen insertion is in competition with addition, only the most reactive carboxamidate-ligated catalysts effect macrocyclic cyclopropanation [70] (Eq. 7), and CuPF6/bis-oxazoline 28 generally produces the highest level of enantiocontrol. 

A variation of an approach developed by Meyers was used to prepare nifedipine-type 1,4-dihydropyridines 35 from pyridine 34 using an oxazoline-directed aryllithium 1,4-addition reaction <96H(43)2425>. 

Andersson et al. [15,16] (and simultaneously Knight et al. [17]) studied the effect of the length and structure of the bridge between the two oxazoline moieties. They prepared and tested a new class of bis(oxazolines) in which... 

---