4- -2-phenyloxazolines

Phenyloxazolines of the type 18 are susceptible to directed metalation (H-metal exchange [297]) in ortho-position to the oxazoline ring due to intramolecular complexation of the Uthioarene moiety 19 ... 

Cationic complexes of rran.s-chelating tridentate ligand, (/ ,/ )-4,6-dibenzo-furandiyl-2,2 -bis(4-phenyloxazoline), with transition metal(II) perchlorates as effective catalysts for asymmetric cycloaddition of nitrones 98YGK368. 

An investigation of the reactions of cis- and tra 5-2-methyl-4-phenyloxazoline-5-methylcarboxylate 31 with an azide anion shows that the transition state of the... 

Kanemasa et al. discovered an asymmetric Diels-Alder reaction of acryloyl-oxazolidi-none and cyclopentadiene catalyzed by a chiral aqua complex of 4,6-dibenzofurani-dyl-2,2 -bis(4-phenyloxazoline) 16 (vide infra) [22]. Unlike the Diels-Alder reaction of acryloyloxazolidinone, for which NiBr2/AgC104 and Znl2/AgC104 are the most suitable sources of the central metal, the best for the Diels-Alder reaction of a-bromo-... 

Bis(oxazoline)-type complexes, which have been found useful for asymmetric aldol reactions, Diels-Alder, and hetero Diels-Alder reactions can also be used for inducing 1,3-dipolar reactions. Chiral nickel complex 180, which can be prepared by reacting equimolar amounts of Ni(C10)4 6H20 and the corresponding (J ,J )-4,6-dibenzofurandiyl-2,2 -bis(4-phenyloxazoline) (DBFOX/Ph) in dichloromethane, can be used for highly endo-selective and enantioselective asymmetric nitrone cycloaddition. The presence of 4 A molecular sieves is essential to attain high selectivities.88 In the absence of molecular sieves, both the diastereoselectivity and enantioselectivity will be lower. Representative results are shown in Scheme 5-55. 

An electrochemical method for the synthesis of a series of 4-(alkylamino)-2-phenyloxazolines 139a-f from A -(2,2-dichlorovinyl)amides 135 has been reported. The starting A -(2,2-dichlorovinyl)amide 135, readily available from chloral and amides, undergoes facile reaction with amines to give 136. Cathodic reduction of 136 generates chlorocarbanionic intermediates 137 and 138 that... 

Yokozawa reported that the 2-substituent strongly affects the reactivity of a 2-substituted-oxazoline 360 with dimethyl 2,2-dicyano-3-ethoxy-l,l-dicarboxylate as shown in Scheme 8.115. Thus, oxazoline itself, 360 (R = H), gave the annulated bicyclic product 361 that resulted from collapse of the zwitterionic intermediate 362, whereas simple 2-alkyloxazolines, 360 (R = Me, Et), gave an alternating (1 1) copolymer. 2-Phenyloxazoline, 360 (R = Ph), was unreactive under the reaction conditions. The zwitterionic intermediate 362 (R = Me) was trapped by acetic acid to give the open-chain adduct 363 that resulted from nucleophilic ring opening at the 5-position of the oxazolinium zwitterion. 

Although lithiation remains the most frequently used metalation reaction, there have been a number of new reports of direct palladation of aryloxazolines. For example, Smoliakova and co-workers prepared the dimeric palladium complex 457 by direct reaction of Pd(OAc)2 with 2-phenyloxazoline in the presence of NaOAc/ HOAc (Scheme 8.150). ° The dimeric complex 457 was converted to the monomeric triphenylphosphine complex 458 for which the X-ray crystal structure was determined. A similar reaction sequence was observed for naphthalenes. Muller... 

Diels-Alder reactions of benzo[fc]furan-43-diones and benzo[b]furan-4,7-diones have been reported <99H(50)1137>. The activation of a C-0 bond in a Mn(C0>3 complexed benzo[i>]furan was examined <99AG2343>. The enzyme-catalyzed dealkylation of (+)-marmesin to the phototoxic psoralene (and acetone) has been investigated <99AG413>. A hi yielding synthesis of bidentate bisoxazoline DBFOX/Ph [(R,R)-4,6-dibenzofutandiyl-2 2 -bis(4-phenyloxazoline)] was developed. DBFOX/Ph was subsequently tested in enantio-selective conjugate radical additions onto 3-(3-phenyl-2-propenoyl)-2-oxazolidinone <99TA2417>. 

As described in many reviews, Trost and his co-workers have carried out a pioneering work on the molybdenum-and tungsten-catalyzed allylic alkylation of allylic esters regioselectivity of the reaction is often complementary to the palladium-catalyzed allylic alkylation. The first asymmetric version was disclosed by Pfaltz and Lloyd-Jones in 1995 (Equation (63)). They used a catalytic amount of a novel tungsten complex, prepared from [W(CO)3(MeCN)3] or [W(cycloheptatriene) (COIs] and optically active (diphenylphosphino)phenyloxazolines 57, for the allylic alkylation of 3-aryl-2-propenyl phosphate with dimethyl sodiomalonate to isolate the corresponding branched alkylated compounds as a major isomer with an excellent enantioselectivity (96% ee). Unexpectedly, 3-aryl-2-propenyl carbonates are shown to be unreactive. It is worth noting that an isostructural molybdenum complex does not promote the catalytic alkylation under the same reaction conditions. In contrast, Lloyd-Jones and Lehmann reported the stereocontrolled... 

For the 2-phenyloxazolines, the reaction is performed, for example, by treating tri-0-acetyl-2-benzamido-2-deoxy-a-D-glucopyranosyl bromide (134) with hydrobromic acid158- 184 to give 135. Alternatively, the unacetylated 2-acylamido-2-deoxy-D-glucose is treated with hydrochloric acid in acetone, and the 5,6-isopropylidene acetal (136) is obtained.165 Compound 136 has proved a valuable intermediate in the synthesis of several amino sugars.186- 172... 

The cross-coupling of aromatic and heteroaromatic rings has been carried out extensively[555]. Tin compounds of heterocycles such as oxazo-lines[556,557], thiophene[558,559], furans[558], pyridines[558], and seleno-phenes [560] can be coupled with aryl halides. The syntheses of the phenyloxazoline 69I[552], dithiophenopyridine 692[561] and 3-(2-pyridyl)qui-noline 693[562] are typical examples. 

There has been little systematic study of the chemistry of 1,4-oxazepines. Vigorous acid hydrolysis cleaves the amide linkage in (369 R1=Ph, R2 = H) and recyclization gives 2-o-hydroxyphenyl-5-phenyloxazoline and l,2,3,4-tetrahydro-l,8-dihydroxy-3-phenyl-isoquinoline. The l,4-benzoxazepin-5-one (353) can be alkylated at N but on treatment with triethyloxonium fluoroborate it is converted to 5-ethoxy-3-phenyl-l,4-benzoxazepine — one of the very few examples of a fully unsaturated 1,4-oxazepine ring. This product is isomerized to l-ethoxy-4-hydroxy-3-phenylisoquinoline when boiled in methanol. The 4,l-benzoxazepine-2,5-diones (348) are converted to quinazolines by reaction with ammonia. The dihydro-l,4-oxazepin-5-one (343) can be acetylated at nitrogen and bromi-nated at the 6-position. 

With Chiral Mono(oxazoline)/metal Complexes 2-(Tosylamino)phenyloxazoline can also be utilized as a chiral ligand for the enantioselective Diels-Alder addition of acryloyl oxazolidi-nones. The requisite chiral magnesium complex is derived from methylmagnesium iodide and this chiral ligand [38] (Eq. 8A.20). 

Bis(cyclopentadienyl)dichlorozirconium(lI). Chlorotris(isopropoxy)titanium. Di-n-butylboryl trifluoromethanesulfonate. (4S, 5S)-2-Ethyl-4-(methoxymethyl)-5-phenyloxazoline Methyl O-me thy lactate. 2-Methyl-2-trimethylsilyloxypentane-3 one. Morpholine-Camphoric acid. Tin. Tin(II) trifluoromethanesulfonate. 

Sakamoto et al. provided an example of absolute asymmetric synthesis involving hydrogen abstraction by thiocarbonyl sulfur (Scheme 6). [24] Achiral A -diphenylacetyl-iV-isopropylthiobenzamide 33 and Y-diphenylacetyl-A-isopropyl(p-chloro)thio-benzamide 33 crystallize in chiral space group P2 2 2. Photolysis of the chiral crystals in the solid state gave optically active azetidin-2-ones whereas achiral thioketones were obtained as main products. When 33a was irradiated in the solid state at -45°C followed by acetylation (at -78°C), 2-acetylthio-3,3-dimethyl-l-diphenylacetyl-2-phenylaziridine (34a 39% yield, 84% ee), 4-acetylthio-5,5-dimethyl-2-diphenylmetyl-4-phenyloxazoline (35a 10% yield, 50% ee), 3,3-diphenyl-1-isopropy 1-4-... 

Analogous reactions of pyridylolefins (Eq. 104) [163] and 2-phenyloxazolines [ 164] lead to a mixture of products. 

Pyrazinecarbohydrazide (204) and 4-ethoxymethylene-2-phenyloxazolin-5-one (206) gave N,N -bis(2-pyrazinecarbonyl)hydrazine (207) and 4-benzami-dopyrazolin-3-one (208) (dioxane, reflux, 30 min 90% the mechanism of hydrogen removal is discussed).1605... 

A new carbon-carbon bond is formed during the reaction of lactim ethers with compounds containing active methylene groups, such as malonic ester and its derivatives, acetylacetone, barbituric acid, rhodanine, nitromethane, and oxindole.8 9 33 100-102 Examples are the condensation of the lactim ether of tetrahydro-/S-carbolinone with acetoacetic ester103 [Eq. (5)] and the condensation of the bislactim ether of 2,2 -dipyrrolidine-5,5 -dione (48) with butyl cyanoacetate20 [Eq. (6)]. Another instance is the reaction of 2 (R = Me) with 2-phenyloxazolin-5-one, to give 3,4-pentamethyleneimidazoles (49) via the intermediate 4-(homopiperid-2-ylene)oxazolin-5-one (50)104 (Scheme 16). 

Scheme 13.14 4-Substituted-2-phenyloxazolin-5-one as substrates for lipases or esterases, with opposite selectivity allowing DKR with in situ racemization.

A method based on the DKR of 4-substituted-2-phenyloxazolin-5-one has been apphed to the large-scale synthesis of N-benzoyl-t-t-leucine-butyl ester 19, an important non-natural amino acid intermediate of several biomimetic peptides. The procedure is based on the alcoholysis of 4-t-butyl-2-phenyloxazoUn-5-one 18 with -butanol catalyzed by the lipase from Mucor miehei (Scheme 13.15) [42]. The unreactive enantiomer is racemized in situ by a base-catalyzed reaction. The... 

Related Reagents. (5,5)-2,2 -(Dimethylmethylene)bis-(4-/-butyl-2-oxazoline) Bis(dimethylglyoximato)(methyl)(pyridine)-cobalt(III) Copper(II) Trifluoromethanesulfonate (15,95)-1,9-Bis [(/-butyl)dimethylsilyloxy]methyl -5-cyanosemicorrin (5)-2-[2-(Diphenylphosphino)phenyl]-4-phenyloxazoline Ethyl Diazoacetate. 

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