Chemistry of Indoles Carrying a Basic Function. Part IX. Unexpected Cyclizations of Diketones Derived from Uhle’s Ketone

Abstract

Starting from a tricyclic diketone (14) obtained by Bowman's method, a tetracyclic oxonaphthalene derivative (17) has been prepared through intramolecular aldol condensation followed by indole → naphthalene isomerization. An unexpected formation of a lactol ether (16) was observed as a result of acidic treatment of 14. Two modified reaction sequences starting from Nmethyl derivatives have also been presented. The keto ketal (26) gave a macrocyclic lactol (27) with unexpected structure as a result of deketalization with trimethylsilyl iodide. The formation of a tetracyclic lactam (37) was observed while applying the modified Reformatsky reaction to ketone (33). About two decades after the first successful synthesis of racemic lysergic acid (1; Figure 1) by the Woodward-Kornfeld group, 2 Bowman and co-workers tried to adopt the key elements of the results of this legendary American cooperation. Their experiments 3 supplied two instructive facts. While the 4bromo derivative of the so-called Kornfeld's ketone (2) reacts smoothly with methylaminoacetone ethylene ketal (3) yielding a tertiary amine (4, 71 %), 2 the corresponding indole derivative (e.g. 1-acetyl-4-bromo-Uhle ketone; 5) did not afford any basic material using the same reaction conditions. 3d 14 O N Ts N CO 2 Me Me Scheme 1-reagents and conditions: a) KOH/TsCl, TBAHS, CH 2 Cl 2 , 0 o C rt, 1.5 h, 91 %; b) Br 2-1,4-dioxane, CCl 4 +CHCl 3 +Et 2 O,

Asymmetric Synthesis of Lysergic Acid via an Intramolecular (3+2) Dipolar Cycloaddition/Ring-Expansion Sequence

“…Oxidation of the allylic alcohol to produce the enone proved to be delicate, presumably due to overoxidation leading to a 3-oxidopyridinium species. 19 However, IBX/DMSO cleanly produced the desired enone 16, a compound that Szańtay and co-workers had converted to lysergic acid (1) in four steps utilizing the van Leusen reaction. 4 Our NMR data for 16 matched those reported by Szańtay (see the Supporting Information), thus constituting a formal synthesis of 1.…”

“…Reductive removal of the indole protecting group (Mg/MeOH) gave compound 15 . Oxidation of the allylic alcohol to produce the enone proved to be delicate, presumably due to overoxidation leading to a 3-oxidopyridinium species . However, IBX/DMSO cleanly produced the desired enone 16 , a compound that Szántay and co-workers had converted to lysergic acid ( 1 ) in four steps utilizing the van Leusen reaction .…”