Benzyloxy cyclopentanone

A different approach was adopted in the synthesis by Justoni and Pessina (111). The Japp-Klingemann reaction of p-benzyloxyphenyl-hydrazine with cyclopentanone carboxylic ester gave the p-benzyloxy-phenylhydrazone of a-ketoadipic acid (XIV) Fischer cyclization of the corresponding dimethyl ester then yielded 5-benzyloxyindole-2-car-boxylic-3-jS-propionic acid (XV). Decarboxylation of XV followed by Curtius degradation and debenzylation eventually afforded 5-hydroxy-tryptamine. 

By treating o-chloromethylaniline hydrochloride with cu-benzyloxy-butyro- and -valeronitriles in refluxing o-dichlorobenzene in the presence of stannic chloride, Mufloz and Madroilero obtained the tricyclic compounds 124 and 202, respectively. The pyrido[2,l- )]quinazolines 289 were prepared by refluxing o-chloromethylaniline hydrochloride in dichlorobenzene with 2-chloropyridine and its tetrahydro derivative. The latter was obtained in situhy Beckmann rearrangement of cyclopentanone oxime with phosphorus pentachloride. 

We then subjected the collection of cyclopentanone and cyclohexanone substrates to the optimised reaction conditions and the enantioselectivities obtained are summarised in Scheme 6.5. The highest level of enantioselectivity was observed for the bulky 2-benzyloxy-napththyl substimted cyclopentanone substrate (7i, 92 % ee). This high ee was unfortunately not transferred to the cyclohexanone substrate (24i) which had a more moderate ee of 60 %. In most cases the cyclopentanone substrates resulted in a higher level of enantioinduction compared to their cyclohexanone counterpart. The best ee achieved in the cyclohexanone series was 74 %... 

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