Tricyclic oxazolines

Unlike ynamines, ethyl vinyl ether requires the more electron-deficient 4-nitro-2-phenyl-5-oxazolecarboxylic acid methyl ester 271b for reaction to occur. The initial [4 + 2] cycloadduct 279 undergoes further reaction with ethyl vinyl ether to give the tricyclic oxazoline 280 in 76% yield (Scheme 8.79). 

In all cases, the initial addition to generate 520 was diastereospecific, that is, the isocyanate always adds to 519 from the face opposite to the 4-ethyl substituent of the oxazoline. In the cases wherein 521 was isolated (Entries 17-20 from Table 8.33), the stereochemistry of the two additional chiral centers from the secondary [2 + 2] cycloaddition was controlled by the chiral center formed during the initial reaction, that is, the isocyanate reacts with 520 from the opposite face of the neighboring Ri group. For Ri = H, R2 = Me, 519 reacted with an arylisocyanate (R3 = Ar) to give tricyclic adducts 521a and 521b as a 1.7 1 mixture of diaster-eomers (Entries 18-20). For Rj = Ph, R2 = Me, 519 reacted with phenylisocyanate... 

On account of their very important biological activity, /9-lactams are important synthetic targets [4-9]. Fused polycyclic -lactam subunits appear in many natural products such as penicillins [4-6] and trinems/tribac-tams [10-13]. Fu et al. reported that such frameworks can be prepared with high levels of enantioselectivity via the intramolecular Kinugasa reaction [ 14, 15] of alkyne-nitrone in the presence of a planar chiral Cu/phosphaferrocene-oxazoline catalyst [16]. For instance, compound 1 was transformed into tricyclic /9-lactam 3 in good stereoselectivity and yielded (88% ee and 74% yield) using 5 mol % of CuBr and 5.5 mol % of complex 2 (Scheme 1). 

Palmer AM, Nettekoven U. Preparation of tricyclic imidazo-pyridines by asymmetric ketone hydrogenation in the presence of ruthenium phosphino-oxazoline catalyst. Tetrahedron Asymm. 2007 18(20) 2381-2385. 

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