Polycyclic lactams, formation

Many polycyclic aromatic amines and aldehydes are commercially available, but their supply is very limited. Preparation of these starting materials is necessary for studying the (3-lactam formation reaction [93]. Nitro compounds are the precursors for the amines. An important task was to prepare polycyclic aromatic nitro compounds, particularly those of chrysene, phenanthrene, pyrene, and dibenzofluorene in good yield. Nitration of these hydrocarbons with concentrated nitric acid in sulfuric acid is a widely used reaction for this purpose. Our research culminated in facile synthesis of polyaromatic nitro derivative 9 starting from polyaromatic hydrocarbons (PAHs) 8 through the use of bismuth nitrate impregnated with clay (Scheme 1) ([94, 95] for some examples of bismuth nitrate-catalyzed reactions... 

In further examples of sequential cycloaddition - palladium catalysed cyclisations, Grigg and co-workers have demonstrated the formation of polycyclic (3-lactams, e.g. (20) from the imine (19) (Scheme 3) <9stl9053>. 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

Alkaloids with polycyclic skdetal frameworks are, when it comes to their synthesis, excellent candidates for RCM. Illustrative are the indolizidines rhynchophylline (43) and its C(7)-epimer ixo-rhynchophylhne (44), both isolated from the plant Uncaria rhynchophytta (Rubiaceae) [26]. Deiters total synthesis of 43 and 44 started with the efficient construction of diallylamine 39 via amide formation between indole-3-acetic acid (38) and diallylamine (Scheme 2.10). One-pot RCM-carbomagnesation of 39 was smoothly achieved with only 1 mol% of [Ruj-I catalyst and 4 equiv. of EtMgCl to afford the 2-ethyl-3-butene-amine derivative in 71% yield. It appeared that the electron-withdrawing carbonyl moiety was critical to the success of the RCM-carbomagnesation steps. Amide reduction and subsequent treatment with acryloyl chloride dehvered the second metathesis precursor 40. Cyclization with [Ruj-I (5 mol%) then furnished the a,j8-unsaturated lactam 41 in a high yield of 91%. Continuation of the total synthesis of alkaloids 43 and 44 included a Bischler-Napieralski cychzation (42) and subsequent rearrangement into the oxindole framework. 

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