Experiments towards the Synthesis of the Ergot Alkaloids and Related Structures.Part 7.1 Novel Syntheses of some 4-Acyl-2,3,4,4a,5,6-hexahydrobenzo[f]quinolin-2-ones

Abstract

Reaction of the N-formyl enol-lactone 4 and the corresponding N-acetyl 10 and N-methoxycarbonyl 11 derivatives with bis(trimethylsilyl)potassiomalonate in THF at 60 8 8C followed by treatment with aqueous sodium hydrogen carbonate and cyclisation as above, yielded the 4-formyl-, 4-acetyl-and 4-methoxycarbonyl-tricyclic ketones 7, 13 and 14 in yields of 31, 35 and 36%, respectively.

Experiments Towards the Synthesis of the Ergot Alkaloids and Related Structures. Part 8.17 The Total Synthesis of 4-Methyl-2,3,4,4a,5,6-hexahydro-benzo[f]quinoline-2-carbonitrile Hydrochloride Hemihydrate, an Immediate Precursor of the Despyrrole Analogues of Lysergic Acid and Its Amides

“…The ultimately successful approach involved the development of a novel five stage one-pot Streckertype reaction 26 -28 starting from 3-phenylpropionaldehyde (17), which was first converted to its sodium bisulphite adduct (18) in situ. Aqueous sodium glycinate was then added followed later by potassium cyanide to yield, presumably, the sodium and/or potassium salt of cyano-amino-acid (19).…”

“…Progress 15 towards a novel general synthesis of lysergic acids capable of scale-up came to an abrupt halt when cyclisation of the des-pyrrole analogue N-methoxycarbonyl-tricyclic-diketone 1a to the crucial tetracyclic monoketone 2a under basic conditions failed despite the successful cyclisation of the related N-methylindoline-diketone 1b to the corresponding tetracyclic ketone 2b under the same conditions. 16 More recently, the cyclisation problem was solved in the model 1-tetralone series starting from the N-acyl-keto-acids 3, 4 and 5 followed by cyclisation via the bis-sodium salts of the corresponding diketo-acids 6 to give the tricyclicketones 7, 8 and 9 in 31-36% yield 17 (Scheme 1).…”