2-Phenyl-4,5-dihydrooxazole

Condensation of 2-bromoethylamine hydrobromide with benzoyl chloride in benzene in the presence of 5 equivalents of EtsN gave 2-phenyl-4,5-dihydrooxazole (1) in 67% yield [1]. Treatment of 1 with 3 equivalents of NBS in boiling CCL in the presence of AIBN led to 5-bromo-2-phenyloxazole (2). Presumably, sequential bromination and dehydrobromination of 1 led to 2-phenyloxazole, which underwent further bromination to afford 2. 

A recent approach to the synthesis of 5-bromooxazoles reacted 2-phenyl-4,5-dihydrooxazole with NBS in the presence of a.a-azobisisobu-tyronitrile (AIBN). The 2-aryloxazole product (83) resulted from a bromi-nation-dehydrobromination process. Further bromination then gave 84. With two equivalents of NBS the yields of 83 and 84 were 45 and 10%, respectively, whereas three equivalents raised the yield of dibromo product to 56% (89S873) (Scheme 29). When treated with bromine in neutral conditions, 2,5-diphenyloxazole formed an N-bromo adduct [59LA(626)83]. 

These in situ generated unstable vinyllead triacetates react with soft carbon nucleophiles to give moderate to good yields of C-vinylated products. This method is potentially very useful in organic synthesis. As an example, styryllead triacetates reacted with 4-ethoxycarbonyl-2-phenyl-4,5-dihydrooxazol-5-one (64, R=Ph) to afford, after hydrolysis, the a-styryl-V-benzoylaminoesters in relatively modest yields.82 Better yields were obtained with the 2-mcthyM,5-dihydrooxazol-5-one analog (64, R = Me) (Equation (60)).83... 

In all the reactions discussed so far in this section, the heterocyclic nucleus reacts via an endocyclic carbon-carbon double bond. However, recently Koch et a/.183,184 reported the (2 + 2)-cycloaddition via a carbon-nitrogen double bond. 3-Ethoxyisoindol-l-one yielded (2 + 2)-cycloadducts (162) with both electron-rich and electron-neutral olefins, but not with electron-deficient olefins.183 2-Phenyl-4,5-dihydrooxazol-4-... 

The or /io-positions of the benzene ring in 4,4-dimethyl-2-phenyl-4,5-dihydrooxazole 13, prepared from benzoyl chloride and the amino alcohol 12, are activated to such an extent that lithiation is possible. On reaction with an electrophile, e.g. a haloalkane, and followed by hydrolysis, 2-substituted or 2,6-disubstituted benzoic acids 14 or 15 are obtained [78] ... 

This regioselectivity is practically not influenced by the nature of subsituent R. 3,5-Disubstituted isoxazolines are the sole or main products in [3 + 2] cycloaddition reactions of nitrile oxides with various monosubstituted ethylenes such as allylbenzene (99), methyl acrylate (105), acrylonitrile (105, 168), vinyl acetate (168) and diethyl vinylphosphonate (169). This is also the case for phenyl vinyl selenide (170), though subsequent oxidation—elimination leads to 3-substituted isoxazoles in a one-pot, two-step transformation. 1,1-Disubstituted ethylenes such as 2-methylene-1 -phenyl-1,3-butanedione, 2-methylene-1,3-diphenyl- 1,3-propa-nedione, 2-methylene-3-oxo-3-phenylpropanoates (171), 2-methylene-1,3-dichlo-ropropane, 2-methylenepropane-l,3-diol (172) and l,l-bis(diethoxyphosphoryl) ethylene (173) give the corresponding 3-R-5,5-disubstituted 4,5-dihydrooxazoles. 

An iridium(I) complex with the l,2-bis(tcrt-butylmethylphosphino)ethane (4) and tetrakis(3,5-bis(trifluoromethyl)phenyl)borate as the counter anion catalyzes the hydrogenation of several acyclic aromatic Ai-arylimines under atmospheric hydrogen pressure at room temperature, giving the desired chiral amines with high-to-excellent enantioselectivities (up to 99%, Fig. 6) [19]. The authors also tested (S )-BINAP (Fig. 1) and (/ )-Ph-PHOX (PHOX = 2-[2-(diphenylphosphino) phenyl]-4,5-dihydrooxazole) hgands with lower enantioselectivities [19]. Both steric and electronic properties of the ligand and the combination with the BArF anion are in the base of the efficacy of this catalytic system. On the other hand, attempted hydrogenations of Ai-(2,2,2-trifluoro-l-phenylethylidene)aniline and M-(l,2,2-trimethyl-propylidene)aniline under the same conditions resulted in... 

Chiral 4,5-dihydrooxazoles 1 are readily prepared2 by condensing (+)-(1S,2.S)-2-amino-1 -phenyl-1,3-propanediol with imino ethers at 0 °C. The isomeric side product 2 is removed upon crystallization. 

SYNTHESIS OF (45)-[(i -l,5-CYCLOOCTADIENE)- 4-ferf-BUTYL-2-(3-DIPHENYLPHOSPHINO-THIOPHENE-2-YL)-4, 5-DIHYDROOXAZOLE IRIDIUM(I)]-TETRAKIS[3, 5-BIS(TRIFLUOROMETHYL)PHENYL]BORATE... 

G. Fronza, C. Fuganti, A. Mele, and G. Pedrocchi-Fantoni, On the use of (4S,5S)-2-phenyl-4,5-dimethyl-4-formyl-4,5-dihydrooxazole in the synthesis of N-protected 2,3,4,6-tetradeoxy-4-C-methyl-4-amino-L-hexose derivatives, J. Carbohydr. Chem. 70 197 (1991). 

Dihydrooxazoles are quite rare they are produced by the thermal rearrangement of C-acylaziridines (equation 161). Both cis- and trans-2-benzoyl-l-cyclohexyl-3-phenyl-aziridine react with diphenylcyclopropenone to yield compound (302 equation 162). ITie... 

This method has been exploited for the functionalization of [60]fullerene by using several aroyl azides166 and [2.4,6-tri-(tm-butyl)phenyl]oxycarbonyl azide16, which afforded the corresponding A -acylaziridines and subsequently the dihydrooxazoles, whereas azafulleroids were produced with [2-(trimethylsilyl)ethoxy]methyl azide and several benzylic azides presumably through the thermal decomposition of the intermediate dihydrotriazoles77. 

When the reactions of benzenetellurinyl acetate or trifluoroacetate to olefins were carried out with nitriles as solvents and boron trifluoride diethyl etherate as catalyst, 2-acylamino-1-alkyl phenyl telluroxides were obtained. Telluroxide elimination produces 4,5-dihydrooxazoles. ... 

Benzenetellurinyl trifluoroacetate converts olefins in the presence of acetonitrile, propionit-rile, or benzonitrile, in a reaction catalyzed by boron trifluoride-diethyl etherate to 2-acylamino-1-ethyl phenyl tellurium oxides. The mixture was then heated at 75° for 3 h to elfect elimination of the phenyltelluro group and cyclization to the dihydrooxazole. ... 

These compounds were not purified. The crude materials were reduced to cycloalkyl phenyl telluriums with hydrazine hydrate or treated with triethylamine in tetrahydrofuran to give dihydrooxazoles. ... 

S, S)-2-Amino-1-phenyl-1,3-propanediol (8) is commercially available and is a byproduct of the technical synthesis of the antibiotic chloramphenicol. It is comparatively inexpensive, so there is no need for laboratory synthesis. It is readily converted to dihydrooxazoles which are themselves useful auxiliaries. The synthesis of (72)-phenylalaninol from this aminodiol via a dihydrooxa-zole has been cited (Section 2.3.1.). Hydrolysis of the intermediate dihydrooxazole leads to an amino alcohol 9 methylated at oxygen which is used as a more convenient starting material for the preparation of dihydroxazoles used in enolatc reactions (Sections D. 1.3.1.4., B.2.). 

Many chiral dihydrooxazoles and oxazolidines are derived from amino alcohols, such as valinol (Section 2.3.1.). Thus, (5>)-4-isopropyIoxazolidine (15) was obtained from (S)-valinol by reaction with formaldehyde 7 and used for the formation of chiral amides in [2,3] sigmatropic rearrangements (Section D.1.6.3.2.). A bicyclic derivative of valinol 16 was obtained by reaction with 4-oxopentanoic acid8 and used as a chiral dienophile (Section D.1.6.1.1.2.1.2.). A detailed procedure for an analogous derivative from (S,S)-2-amino-l-phenyl-1.3-propanediol has been published9. 

The 2-methyl-4,5-dihydrooxazoles (358 Z = O) or 2-methyl-4,5-dihydrothiazole (358 Z = S) undergo 1,3-dipolar cycloaddition reactions with benzonitrile A -oxide to give the corresponding 7a-methyl-3-phenyl-5,6-dihydro-7a//-oxazolo[3,2- ][l,2,4]oxadiazoles (16) or -thiazolo[3,2-c ]-[l,2,4]oxadiazoles (17) (Equation (121)) <92T7703>. 

A chiral 2-alkyl-4,5-dihydrooxazole 7 is obtained by the use of (+)-( 5, 2 S)-1-phenyl-2-aminopropane-1,3-diol, available from the chiral pool (see p 115). From this, the methyl ether 8 is prepared using sodium hydride and iodomethane. As a result of internal asymmetric induction, the alkylation of its lithium derivative occurs diastereoselectively. In the case of = Me, = Et, hydrolysis yields the (+)-( S)-enantiomer of 2-methylbutanoic acid 9, with ee = 67 %, as the main product ... 

---