On the Regioselectivity of the Cyclization of Enyne−Ketenes:  A Computational Investigation and Comparison with the Myers-Saito and Schmittel Reaction

Abstract

The Moore (C(2)-C(7)) cyclization and the alternative C(2)-C(6) cyclization of enyne-ketenes belong to the family of biradical cyclization reactions such as the Bergman reaction of ene-diynes, both the cyclizations of enyne-allenes and enyne-cumulenes. The latter garnered substantial interest due to their antitumor efficacy. The mechanisms of both cyclization modes of enyne-ketenes are still unclear, but as the enyne-ketenes can formally be regarded as heteroanalogues of enyne-allenes, both cyclizations are expected to react via biradical routes. Nevertheless, as shown recently for cyclic allenes, the substitution of a methylene group by oxygen can lead to different energetic ordering of the electronic states of the key intermediates. To elucidate the mechanism, the present work investigates the course of both cyclization modes for various model compounds. To reveal general motifs for the large family of biradical cyclizations, a comparison with enyne-allenes is performed.

Exploring Diradical Chemistry: A Carbon‐Centered Radical May Act as either an Anion or Electrophile through an Orbital Isomer

“…[17,18] In line with the work of others, [19] our analysis gave a DE value for the diradical 13 A and it was 4.1 kcal mol À1 lower than that for the zwitterionic isomer 13 B (see Figure 1a nd the Supporting Information). To test that hypothesis,w e modelled the reaction using DFT calculations [at the UB3LYP/6-311G(d,p) level].…”

Cycloaddition and Electrocyclic Reactions of Vinylketenes, Allenylketenes, and Alkynylketenes

“…Such enyne electrocyclizations have been studied by computational methods and have been compared with related cyclizations. 47 The factors that favor formation of either 5-or 6-membered rings are also discussed below.…”

Intramolecular Diels–Alder reaction in enyne–allenes: a computational investigation and comparison with the Myers–Saito and Schmittel reactions

“…The Myers–Saito C 2 C 7 cyclization of enyne–allenes1–4 has been a hot topic in recent years since α ,3‐didehydrotoluene biradicals play an important role in DNA‐cleavage reactions5 and subsequent reactions of synthetic interest 6, 7. The regioselectivity was first discovered by Schmittel and co‐workers,8–10 who induced a complete switch‐over from the well‐known C 2 C 7 (Myers–Saito)11, 12 cyclization (Scheme ) to a novel C 2 C 6 cyclization by using the aryl, or butyl group to replace the hydrogen at the alkyne terminus (R 1 = Ph or R 1 = t ‐Bu, SiMe 3 ).…”