Nitriles, oxazoline synthesis

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

Bromoamidation of cyclic olefins allowed the synthesis of bicyclic oxazolines. For instance, treatment of cyclohexene with A-bromoacctamidc as the halogen source and different nitriles at 0 °C, in the presence of SnCU or BF3 Et20 and water, led to oxazolines 128 through intermediate traw.v-bromoamides 127. The scope of the bromoamidation appears quite broad with regard to olefinic and nitrile components <06JA9644>. 

The synthesis is similar to that of the PHOX catalysts (Scheme 29.6), starting with oxazoline formation from the pyrrole nitrile and an amino alcohol, followed by introduction of the phosphine group. 

Oxazolines [1] can be synthesized by several routes two common methods are described below (Fig. 1). Readily available j5-amino alcohols 1 can be coupled with an acid chloride to yield the amide 2 which is then cyclized to the oxazoline 3 in the presence of zinc(II) chloride. Alternatively a one step synthesis of 3 can be achieved by reacting 1 with nitriles. Both methods are reliable... 

Dihydrooxazoles continue to occupy an important place in organic synthesis and medicinal chemistry as they have found use as versatile synthetic intermediates, protecting groups/pro-drugs for carboxylic acids, and chiral auxiliaries in asymmetric synthesis. There are several protocols in the literature for the transformations of functional groups such as acids, esters, nitriles, hydroxyl amides, aldehydes, and alkenes to 2-oxazolines. Newer additions to these methods feature greater ease of synthesis and milder conditions. 

Reaction of lithiodithianes with acyl chlorides, esters or nitriles leads to the fOTination 1,2-dicarbonyl compounds in which one of the carbonyl groups is protected as the thioacetal. d76043j44 Optically active amino ketones of type (69) are inepared via acylation of dithiane with an oxazoline-protected (5)-serine methyl ester (Scheme 41). Optically active (5)-2-alkoxy-l-(l,3-dithian-2-yl)-l-propanones were prepaid by the reaction of the corresponding methyl (5)-lactate with 2-lithio-l,3-enantioselective synthesis of (-)-trachelanthic acid. Enantioselective synthesis of L-glyceraldehyde involves the acylation of a dithiane glycolic acid derivative followed by bikers yeast mediated reduction. ... 

Direct irradiation of amino substituted azirines leads to neutral nitrile ylides which can be trapped with electron-deficient double bonds. H. Heimgartner described the synthesis of triazolines and oxazolines via trapping of a nitrile ylide with diethylazodicarboxylate and methyl trifluoroacetate, respectively. An elegant application of 1,3-dipolar cycloaddition chemistry is the photolysis of a tetrazole leading to a reactive nitrile imine which is trapped in an intramolecular fashion. 

The first asymmetric intermolecular synthesis of 0-methylancistrocladine (2) involved the use of a Meyers biaryl coupling, successfully utilised in the earlier synthesis of dehydroancistrocladine (66), to construct the biaryl linkage atropisomer-selectively (ref. 60,61). It was envisaged that 2 could arise from the acetamide 102 which in turn could be derived from biaryl 103 (Scheme 14). A coupling between the Grignard reagent 104 and chiral oxazoline 105 could then provide 103 stereospecifically. This approach required the synthesis of chiral oxazoline 105 which is outlined in Scheme 15 and begins with the nitrile 71 available in three steps from 1,5-diacetoxynaphthalene (see Scheme 8). 

The results showed that the supports did not present significant catalytic activity (Table 1.7, entry 11-13). On the other hand, the catalytic activity of TPA supported on high-surface-area Si02, active carbon, and PMP has been increased with respect to the use of TPA alone (Table 1.7, entry 10). The optimized reaction conditions were used for the synthesis of several 2-oxazoline derivatives (19) starting from various aromatic (or heteroaromatic) nitriles and 2-aminoethanol (or 2-amino-2-methylpropanol). As reported in Table 1.8, in all entries, high to excellent yields were obtained. Notably, the authors reported that both mono- and bis-oxazolines can be obtained by this... 

Synthesis of 2-oxazolines and bis-oxazolines from nitriles and ethanol amine was reported under conventional reflux or ultrasound irradiation using SSA as the catalyst (Schemes 5.19 and 5.20). 2-lmidazolines and Ins-imidazolines can also be obtained under similar conditions. Eventually, the synthesis of such heterocyclic compounds was found to be better using ultrasound (Mohammadpoor-Baltork et al., 2008). 

Various oxazoline-based organocatalysts were prepared and applied to enantioselective Strecker reactions of different N-benzhydrylimines with TMSCN. In particular, derivative 156 allowed the synthesis a-amino nitriles in high yield and with excellent chiral induction (13CEJ14224). 

In 1998, Herrmann et al. reported the synthesis of the first chiral carbene containing an oxazoline unit. In this bidentate ligand, the oxazoline ring is linked in its 2-position to the imidazole ring via a methylene bridge [48]. The key step in the synthesis of the imidazolium precursor is the acid-catalyzed cyclization of the oxazoline by reaction of an iminoester, formed in situ from a nitrile function, and the amino alcohol (Scheme 15.12). 

In a stereoselective one-pot synthesis, (ii)-olefins of the styrene type are reacted with stoichiometric amounts of nitriles, NBS, H2O, and NuHCOb in the presence of Cu or Zn triflate as Ltwis-acidic catalysts to give 2,4,5-trisubstituted oxazolines 2, in which the 4,5-substituents attain trans-configuration [294] ... 

The ambident nature of cyanotrimethylsilane can lead to the formation of nitriles or isocyanides, depending on the nature of the catalyst. For example, cyanotrimethylsilane reactions with epoxides and oxetanes catalyzed by soft Lewis acids give rise to 2-(trimethylsiloxy) isocyanides arising by attack on the more substituted carbon (eqs 15 and 16).Milder reaction conditions and better yields of isocyanides can be realized when the reaction of cyanotrimethylsilane with oxiranes is carried out in the presence of Pd(CN)2, SnCL, or MesGa (eq 17). Isocyanides are useful precursors for the synthesis of /3-amino alcohols and oxazolines. 

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