2-Oxazolines allyl amides

In contrast to the above additions A-allyl- and substituted A-allyl-amides, -urethanes, -ureas and -thioureas undergo intramolecular cyclization only in 6(3-96% sulfuric acid to give the corresponding oxazolinium and thiazolinium salts. Treatment of these cations with base yields 2-oxazolines and 2-thiazolines in moderate to good yields. The reaction is illustrated by the conversion of A-2-phenylallylacetamide (342) into 2,5-dimethyl-5-phenyl-2-oxazoline (343) in 70% yield 70JOC3768) (see also Chapter 4.19). 

Allyl amides (enamides), for example, 225, 228, and 230 cyclize to oxazolines, for example, 226, 229, and 231 when the double bond is activated by an electrophile. The double bond can also be conjugated to a ketone, or present as an allylic epoxide. Reagents commonly used to promote the cyclization include acids,iodine,selenium reagents,and trimethylsilyl triflate (Scheme 8.63). ... 

Nitrene transfer to selenide is also possible. Catalytic asymmetric induction in this process has been studied with Cu(OTf)/bis(oxazoline) catalyst (Scheme 22). When prochiral selenide 206 and TsN=IPh are allowed to react in the presence of Cu(OTf)/chiral bis(oxazoline) 122b, selenimide 207 is obtained with enantioselectivity of 20-36% ee. When arylcinnamyl selenide 208 is applied to this reaction, corresponding selenimide 209 is produced which undergoes [2,3]-sigmatropic rearrangement to afford chiral allylic amides 211 in up to 30% ee. 

Intramolecular cyclization of allylic amide 772 in the presence of strong acid gives oxazoline 773 in high yield. Hydrolysis of 773 in aqueous acid leads to the formation of 774 (Scheme 189) <20000L3443>. 

Overman and co-workers carried out extensive studies on Pd(II)-catalyzed asymmetric allylic rearrangement of allylic imidates to form enantioenriched allylic amides. They achieved 97 % ee as the best result by the reaction of the allylic imidate 612 using the cyclopalladated ferrocenyl oxazoline 613 having elements of planar chirality as a catalyst precursor, and discussed the mechanism of the reaction [220]. 

A cyclopalladated ferrocenyl oxazoline 3-methoxy-3-pentyl derivative 8.12 was activated in CH2CI2 by deiodination with CFjCOOAg, for example, to give rearranged allylic amide 8.11 in a high yield and a high enantioselectivity from -allylic imidate 8.10, as shown in Eq. (8.1) [16]. 

The size of the oxazoline substituent in the catalysts (8.30-8.32) was increased to 3-methoxy-3-pentyl (8.32), and an iodide-bridged dimer was activated in CH2CI2 by deiodination with Ag(OOCCF3). These in iitw-generated species catalyzed the rearrangement of -allylic imidate to allylic amide with moderate to good yields with enantioselectivities of 72-79 % ee (Nos. 8-10). 

Several related compounds, in which either the isopropyl group of the oxazoline moiety has been modified or this latter fragment was replaced by chiral imidazole units, have been obtained following a similar procedure. These and related compounds were found to be the most active catalysts for the rearrangement of prochiral allylic imidates to allylic amides with high enantioselectivities. " ... 

Reagent control This involves the addition of a chiral enolate or allyl metal reagent to an achiral aldehyde. Chiral enolates are most commonly formed through the incorporation of chiral auxiliaries in the form of esters, acyl amides (oxazolines), imides (oxazolidinones) or boron enolates. Chiral allyl metal reagents are also typically joined with chiral ligands. 

Kang and co-workers prepared the (3-halo amide arrangement required for oxazoline formation from allylic alcohols via a two-step process. For example, treatment of the allylic alcohol 122 with trichloroacetonitrile and base followed by activation of the double bond with iodine monochloride, provides 123. Hydrolysis of 123 gave 124 from which cyclization provided the oxazoline 18a used for paclitaxel synthesis (Scheme 8.36). 

Allyl alcohols readily react with trichloroacetonitrile to give the corresponding trichloroacetimidates 145. Activation of the double bond with electrophilic reagents results in ring closure to yield oxazolines 146. The most commonly employed electrophiles include iodine, iodine monochloride, phenylselenyl chloride, and mercuric trifluoroacetate. Other nitriles including cyanogen bromide and N,N-dimethylcyanamide can also be used. Since oxazolines readily hydrolyze to amides, the net effect of this reaction sequence is to produce p-amino alcohols 147 from an allyl alcohol. This strategy has been employed in numerous total syntheses of natural products. Examples are listed in Table 8.18 (Fig. 8.7 Scheme 8.43). ° ... 

Planar chiral phosphaferrocene-oxazolines (379) constitute another family of complexes that are usefiil as ligands in asymmetric catalysis. Preparation of these takes advantage of a modified Friedel-Crafts acylation of (373) and an unusual conversion of the resulting trifluoromethyl ketone into an amide that is then cyclized to an oxazoline. The diastereomeric complexes thus formed are chromatographically separable and are used in a palladium-catalyzed asymmetric allylic substitution. Modification of this complex by using the anion derived from 3,4-dimethyl-2-phenylphosphole gives more... 

Vinyl oxazolidinone 148 has been shown to be a good precursor to rra r-oxazolines (Scheme 38). Under palladium(O) catalysis, an intermediate 7t-allyl complex is formed with the loss of CO2. Intramolecular attack by the amide oxygen forms the thermodynamically favored /ra r-oxazoline 149. This oxazoline was then converted to the natural product balanol <19990L615>. 

As mentioned earlier, oxazolines can be hydrolyzed in the presence of strong bases to the corresponding N-(2-hydroxyethyl)amides, and also can react with weak electrophiles like benzyl bromide or allyl chloride to give poly(N-acylethyleneimines). Therefore, if the etherification reaction is... 

A wide number of chiral palladium complexes have been used in the context of DKR. In 1999, Cook et al. reported the palladium-mediated synthesis of chiral vicinal diamines from chiral oxazolidinones. The process involved successive oxidative insertion, loss of CO2 and subsequent cyclisation at the amide oxygen atom. The intermediate re-allyl palladium complexes underwent a rapid equilibration. Moreover, the intermediate oxazoline was also ionised by the palladium catalyst and was in equilibrium with the 7t-allylpalladium complexes, giving rise to thermodynamically controlled product ratios. These dynamic intermediates could be trapped with phthalimide under kinetic control to afford enantio- and diastereoselectively the corresponding syn-ch x 1,2-diamines (Scheme 2.46). 

During the course of their pioneering work on the copper-catalyzed cyclopropanation reaction of alkenes [25], the copper-catalyzed aziridination of alkenes using PhI=NTs was also discovered by Evans et al. in 1991 [26], A wide range of alkenes can be smoothly converted to the corresponding aziridines in the presence of Cu(I) and Cu(II) salts, such as Cu(MeCN)4C104 and Cu (acac)2, respectively (Scheme 2.16). Notably, aliphatic alkenes afforded the desired aziridines without allylic C-H amidation products. In the hterature, only one example of the enantioselective aziridination of styrene using chiral bis (oxazoline)-based copper catalyst was demonstrated. At the... 

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