Oxazolines, bicyclic-—

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 photocycloaddition of aliphatic and aromatic aldehydes with 2,4,5-trimethyloxazole (131) gave bicyclic oxetanes 132 in almost quantitative yields hydrolitic cleavage led selectively to erytro a-amino-P-hydroxy methyl ketones 133 <00CC589>. The oxazolium salt 134 was converted to the azomethine ylide 136 via electrocyclic ring opening of the oxazoline 135. Intramolecular cycloaddition afforded 137 in 66% overall yield which was transformed into the aziridinomitosene derivative 138 . 

When a chiral auxiliary is present in the oxazoline ring and the boron part is replaced with an achiral bicyclic system (46 bearing 9-BBN), erythro-j/-hydroxy esters (syn-53) can be obtained as the major product upon reaction of the eno-late with several aldehydes.37... 

Reaction between D-Cys and an oxazoline aldehyde, prepared from l-Phe gave the bicyclic compound 83 [92H(34)903], A derivative of the same system was obtained from penicillamine with a functionalized AA (88CC1128). 

A series of publications by Vedejs et al. (17-19) outlined the use of oxazolines in the generation of azomethine ylides. Reduction of the oxazolium salts 71 (R = Ph or Me) with PhaSiH/CsF led to formation of the unstable 4-oxazolines (72) and their valence bond azomethine ylide tautomers (17), which could be trapped in situ with DM AD to afford the bicyclic adducts 73, where R and R = Ph or Me, in 75% yield via [2 + 2] cycloaddition (Scheme 3.18). 

Trimethyloxazole 257 undergoes photochemically induced [2 + 2] cycloaddition with aromatic and aliphatic aldehydes to provide bicyclic oxazolines 258 with excellent regiochemical and stereochemical control. Diastereoselec-tivities from 75-99% can be achieved, which is the first reported example of a Paterno-Biichi reaction involving an oxazole. The oxetane cycloadducts can be hydrolyzed to a-amino-(3-hydroxy ketones. Other oxazoles have not been evaluated to determine if they undergo the photochemical cycloaddition (Scheme 8.71). 

Bazureau and co-workers reported an unusual hydrolysis of the tetrasubstituted oxazoline 323. In this case, 323 was unstable and hydrolyzed quickly to the tetra-hydroisoquinoline amino ester 324 under mildly basic conditions (Scheme 8.97). Although the authors did not discuss the reaction mechanism, it is possible that the facile hydrolysis is facilitated by the formation of the bicyclic intermediate 325 produced via intramolecular trapping of 326. 

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. 

In a series of papers, Jarry and co-workers demonstrated the utility of a 2-aminooxazoline 647 (Fig. 8.26) to prepare bicyclic heterocycles. This oxazoline undergoes annulation reactions with bifunctional electrophiles to give triazinones or pyrimidinones. Selected examples are summarized in Table 8.42. ... 

Diels-Alder reaction of oxazolines and thiazolines (134) with tetrazines yield bicyclic compounds... 

In intramolecular cyclopropanation, Doyle s catalysts (159) show outstanding capabilities for enantiocontrol in the cyclization of allyl and homoallyl diazoesters to bicyclic y-and <5-lactones, respectively (equations 137 and 138)198 205. The data also reveal that intramolecular cyclopropanation of Z-alkenes is generally more enantioselective than that of E-alkenes in bicyclic y-lactone formation198. Both Rh(II)-MEPY enantiomers are available and, through their use, enantiomeric products are accessible. In a few selected cases, the Pfaltz catalyst 156 also results in high-level enandoselectivity in intramolecular cyclopropanation (equation 139)194. On the other hand, the Aratani catalyst is less effective than the Doyle catalyst (159) or Pfaltz catalyst (156) in asymmetric intramolecular cyclo-propanations201. In addition, the bis-oxazoline-derived copper catalyst 157b shows lower enantioselectivity in the intramolecular cyclopropanation of allyl diazomalonate (equation 140)206. 

The DFT study of the 3 + 2-cycloaddition between ketene and TV-silyl-, IV-germyl-, and TV-stannyl-imines shows that the TV-germylimine reaction is a two-step process the TV-stannylimine reaction is a competition between two- and three-step processes whereas the TV-silyl process follows a three-step process44 A new and convenient synthesis of functionalized furans and benzofurans based on 3 + 2-cycloaddition/oxidation has been reported. The cyclization of cyclic 1,3-bis-silyl enol ethers (48) with l-chloro-2,2-dimethoxyethane (49), via a dianion, produced 5,6-bicyclic 2-alkylidenetetrahydrofurans (50), which are readily oxidized with DDQ to 2,3-unsubstituted benzofurans (51) (Scheme 13)45 The Evans bis(oxazoline)-Cu(II) complex catalyses the asymmetric 1,3-dipolar cycloaddition of a -hydroxyenones with nitrones to produce isoxazolidines.46 The... 

Photolysis in wet acetonitrile led to bicyclic oxazolines such as 85 (Equation 4). 

DielsAlder reaction of oxazolines and thiazolines 141 with tetrazines yields bicyclic compounds 142 (Scheme 85) <1984AP(317)237>. 

In a study of the synthesis of marine 2-aminoimidazole alkaloids, the aminal C-N bond of bicyclic 898 was cleaved regioselectively to form the allylic amine 899. Deuterium exchange results in H-1, H-2, and H-5, but not H-7 exchange, although the C(6)-C(7) double bond underwent isomerization 901. This is atributed to the assistance of the carbamoyl group that formed the oxazoline 900. Hydrolysis of the carbamate group of 899 under basic conditions affords either pyrrole 902 or pyridine 903 (Scheme 218) <2004OL3933>. 

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