Mechanistic Insight into the Dehydro-Diels–Alder Reaction of Styrene–Ynes

The
Diels–Alder reaction represents one of the most thoroughly
studied and well-understood synthetic transformations for the assembly
of six-membered rings. Although intramolecular dehydro-Diels–Alder
(IMDDA) reactions have previously been employed for the preparation
of naphthalene and dihydronaphthalene substrates, low yields and product
mixtures have reduced the impact and scope of this reaction. Through
the mechanistic studies described within, we have confirmed that the
thermal IMDDA reaction of styrene–ynes produces a naphthalene
product via loss of hydrogen gas from the initially formed cycloadduct,
a tetraenyl intermediate. Alternatively, the dihydronaphthalene product
is afforded from the same tetraenyl intermediate via a radical isomerization
process. Moreover, we have identified conditions that can be used
to achieve efficient, high-yielding, and selective IMDDA reactions
of styrene–ynes to form either naphthalene or dihydronaphthalene
products. The operational simplicity and retrosynthetic orthogonality
of this method for the preparation of naphthalenes and dihydronaphthalenes
makes this transformation appealing for the synthesis of medicinal
and material targets. The mechanistic studies within may impact the
development of other thermal transformations.