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

Abstract

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.

Intramolecular Didehydro-Diels–Alder Reaction and Its Impact on the Structure–Function Properties of Environmentally Sensitive Fluorophores.

“…Modeling was performed at SMD(DCE)-UM06-2X/6-31+G(d,p) level of theory with free energy estimates at 180°C, and the tosyl group of 17 was replaced with a methanesulfonyl group to simplify the calculations. 9 Hydrogen atom abstraction by triplet oxygen from the tetraene intermediate was predicted to be more favorable than the direct expulsion of H 2 by 9.8 kcal/mol, which correlates with the data in Table 1, where lower reaction temperatures afforded predominantly dihydronaphthalene 16-D and higher temperatures produced naphthalene 16-N as the major product. Prior to these experimental and computational studies, either a mechanistic rationale for the formation of the naphthalene product via the IMDDA reaction of styrene-ynes was not described, or its formation was attributed to the purported ease of dihydronaphthalene auto-oxidation.…”

Cascade Reactions of α‐Phenylcinnamic Acid to Polycyclic Compounds Promoted by High Valent Transition Metal Halides

“…Subsequent HCl capture (from hydrolysis, see below) by the resulting alkene function leads to 3 . Supported by previous experimental and theoretical studies,, H 2 O 2 produced in the O 2 ‐driven dehydrogenation step is likely to be responsible for the lactonization process affording 2 . In order to give insight into this hypothesis, the hydrolytic treatment of the reaction mixture cis ‐PhCH=CPhC(=O)OH/WCl 6 was repeated in anaerobic conditions, i. e. using deaerated water under a nitrogen atmosphere (Scheme f).…”

Copper-catalyzed [1,2]-rearrangements of allylic iodides and aryl α-diazoacetates

“…9 The resulting internal alkynes 11 were subjected to directed reduction with LiAlH 4 to selectively yield ( E )-cinnamyl alcohols 12 . 10 A subsequent Appel reaction converted these allylic alcohols to the desired ( E )-allylic iodides 1a–i . 11 …”