4- Amino-2-aryl-2-oxazolines

Oxazolines 168 and bisoxazolines can be synthesised starting from a prop-2-ynylamide in a reaction catalysed by Pd/C or Pdh in the presence of O2 and CO <02JOC4450>. 4-Amino-2-aryl-2-oxazolines 170 can be synthesised electrochemically starting from jV-(l-amino-2,2-... 

Aryl- and heteroaryl aldehydes give 2-amino-2-oxazolines, which are otherwise relatively inaccessible.470,471... 

Meyers and colleagues described the palladium-catalyzed carbonylative synthesis of oxazolines as early as 1992 [268]. Aryl or enol triflates made from the corresponding ketones and phenols, and also aryl halides, were used as starting materials and coupled with amino alcohols to give chiral a,)S-unsaturated or aryl oxazolines in good yields. Later on, Perry s group performed systematic studies on this one-pot, two-step process for the preparation of oxazolines (Scheme 2.37) [269, 270]. 

Linear polyethylenimine (LPEI), which contains only secondary amino functions, has been prepared in different ways. The one most used is the hydrolysis of poly(N-acyl ethyienimine), which is obtained by cationic polymerization of the corresponding N-alkyl or aryl oxazoline (see Chapter 4.24), (Scheme 5). This type of polymerization exhibits living characteristics so that polymers with controlled molecular weight and narrow distribution can be obtained. Consequently, the LPEI obtained from such a polymer will also have a... 

Meyers, A.I., Robichaud, A.], and McKermon, M.J. (1992) The synthesis of chiral a,P-unsaturated and aryl oxazolines from ketones and arols via their triflates and Pd-catalyzed CO and amino alcohol coupling. Tetrahedron Letters, 33, 1181—... 

Pargyline (= TV-Benzyl-jV1 methyl-2-propynylamine)] (aryl alkynyl tertiary amine) [Rilmenidine (= 2-[iV-(Dicyclopropylmethyl) amino] -oxazoline) (arylaminooxazoline) [Tetrahydro-P-carboline] ((3-carboline)... 

Oxazoles can react at the C-4 position with aromatic aldehyde electrophiles under Friedel-Crafts conditions when the C-5 position is substituted with an alkoxy group. This feature has been exploited in a chiral Lewis acid-catalyzed formal [3-1-2] cycloaddition of aromatic aldehydes and 2-aryl-5-methoxyoxazoles 45 to generate enantiomerically enriched 2-oxazoline-4-carboxylates 46 (Scheme 4) <2001AGE1884>. These products can serve as masked /3-hydroxy a-amino acids, which are useful synthetic intermediates and have been found in peptide-based natural... 

Dihydrooxazoles 275 can be made by the condensation of aryl nitriles with amino alcohols catalyzed by Bi(iii) salts <2005SL2747> or acidic clay <1998TL459> in good yields (Bi salts - 70-92% kaolinitic clay -56-96%) (Equation 16). The use of Bi salts is only applicable to the formation of 2-aryloxazolines while the latter method works well for both aromatic as well as aliphatic substrates. The conversion of carboxylic esters to 2-oxazolines 276 in good (44-82%) yields with lanthanide chloride as catalyst <1997TL7019> has also been described (Equation 17). 

Aryl-5,5-bis(oxazolin-2-yl)-l,3-dioxanes 169 have been easily prepared in three steps from diethyl bis(hydroxymethyl)malonate, amino alcohols, and aromatic aldehydes. They have been used for the copper-catalyzed asymmetric cyclopropanation of styrene with ethyl diazoacetate in up to 99% ee for the trawx-cyclopropane (maximum transicis ratio = 77/23) <05TA1415>. The same reaction performed on 2,5-dimethyl-2,4-hexadiene with tert-butyl diazoacetate in the presence of copper catalysts bearing ligand 170, prepared from arylglycines, exhibited remarkable enhancement of the rrawx-selectivity (transicis ratio = 87/13), with 96% ee for the trans product <05JOC3292>. 

Infrared absorption spectral data for several oxazole derivatives,86 90 including alkyl-98 186 and aryl-263 264 substituted oxazoles, 2-amino- and substituted-amino derivatives109 112 136, 5-amino179 198-201 and 5-alkoxy-oxazoles,66 carboxylic acids,112 147 esters,126 179 184 carboxamides,199 200 4-acetyloxazoles,147 halogenoalkyl oxazoles,91 oxazolines,262 and benzoxazoles262 have been reported. 

Hashimoto et al. [38] reported the synthesis of the P,N oxazoline-containing ligand 59 derived from ds-2-amino-3,3-dimethyl-l-indanol and its application to the intermolecu-lar Mizoroki-Heck reaction. Their best reaction conditions for arylation of various cy-cloalkenes (Scheme 11.23) showed conversions of up to 91% and enantiomeric excesses of up to 98% for the reaction of cyclohexenyl triflate (35) with 2,3-dihydrofuran (1). Reactions using 4,7-dihydro-l,3-dioxepin (46) as the substrate proved less successful, with low conversions of 37% achieved, albeit with high enantiomeric excesses of up to 90%. In all cases, low amounts of isomerization were observed. These results are consistent with, if not better than, many analogous phosphinooxazoline ligands. 

The chemistry of trimethylsilyl cyanide continues to feature in the literature, and the first of several examples described this year is the opening of epoxides to produce P-hydroxy-isocyanides, a reaction which provides entry to a general synthesis of oxazolines and P-amino-alcohols. By using the modified conditions outlined in Scheme 20 it is possible to prepare phenylacetic acids from aryl ketones in moderate to good yield by the MeaSiCN route. ... 

Chiral Q , -unsaturated oxazolines can be obtained by a carbonylation-amidation of enol triflates or aryl halides with chiral amino alcohols (eq 36). The palladium catalyst can be either Pd(PPh3)4, bis(dibenzylideneacetone)palladium(0) and PPh3, or Pd(OAc)2 and dppp in the presence of triethylamine. 

Pd-catalyzed carbonylation of aryl halides and triflates is a well-established process. Stephen L. Buchwald of MIT has now (/. Am. Chem. Soc. 2008,130, 2754) extended this transformation to much less expensive tosylates and mesylates such as 7. P-Amino acids have often been prepared from a-amino acids by Amdt-Eistert homologation. Geoffrey W. Coates of Cornell University has devised Angew. Chem. Int. Ed. 2008, 47, 3979) a more practical alternative, the direct Co-catalyzed carbonylation of an oxazoline 9 to the 2-oxazine-6-one 10. 

---