Sequential Aminodiene Diels−Alder Approach to the Ergoline Skeleton

Through a novel sequence of aminodiene Diels−Alder reactions, several substituted amidofurans
were readily converted to tricyclic ketones in good yield. The formation of the tricyclic ketone system
is the result of a ring opening and dehydration of a transient oxabicyclic adduct formed by an
intramolecular Diels−Alder cycloaddition of an amidofuran with a cyclohexenone moiety tethered
such that it participates in the cycloaddition as the 2π component. A convenient way to construct
the cyclohexenone is to make use of some aminodiene chemistry developed by Rawal. An angular
carbomethoxy group is required in order to activate the olefin toward cycloaddition with Rawal's
diene. The presence of this activating group not only prevents the isomerization of the advanced
ergoline intermediate to a naphthalene but can also be leveraged for an oxidation to provide Uhle's
ketone (13). The easily formed Kornfeld ketone analogue 25 was readily transformed into the
corresponding triflate 41 by the action of triflic anhydride and a base. Oxidative addition of vinyl
triflate 41 to Pd(0) and the ability of the resulting vinyl palladium species to undergo cross-coupling
with terminal alkynes prompted us to devise an expeditious route to lysergic acid. Unfortunately,
our inability to carry out a regioselective Heck reaction using vinyl triflate 41 and the methylene
amino acrylate ester 48 thwarted the completion of the synthesis of lysergic acid.