A Synthetic and Mechanistic Investigation of the Chromium Tricarbonyl-Mediated Masamune–Bergman Cyclization. Direct Observation of a Ground-State Triplet p-Benzyne Biradical

Abstract

A new room-temperature chromium tricarbonyl-mediated cycloaromatization of enediynes is reported. The reaction occurs with both cyclic and acyclic enediynes in the presence of [Cr(CO)3(η6-naphthalene)] and both a coordinating solvent and a hydrogen atom source, providing chromium–arene complexes in reasonable yield and good diastereocontrol. The mechanism of the reaction has been probed through DFT computational and spectroscopic methods. These studies suggest that direct C1–C6 bond formation from an η6-enediyne complex is the lowest-energy path, forming a metal-bound p-benzyne biradical. NMR spectroscopy suggests that enediyne alkene coordination occurs in preference to alkyne coordination, forming a THF-stabilized olefin intermediate; subsequent alkyne coordination leads to cyclization. While biradical quenching occurs rapidly and primarily via the singlet biradical, the triplet state biradical is detectable by EPR spectroscopy, suggesting intersystem crossing to a triplet ground state

Selective Cross-Coupling of Organic Halides with Allylic Acetates

“…An aryl radical could abstract a hydrogen atom from the solvent to form Ar-H. If this was the case, then a reaction conducted in a fully deuterated solvent mixture could be expected to form Ar-D instead of Ar-H. 19 Because deuterated NEP and DMA are not commercially available, we conducted the experiment in a THF- d 8 /DMF- d 7 mixture. 20 We did not observe an increase in the amount of C 6 H 5 D produced when compared to a reaction in protic solvents (GC/MS).…”

Oxaenediynes through the Nicholas‐Type Macrocyclization Approach

“…The Nicholas reaction is a precise synthetic tool for the synthesis of strained cycles including cycloalkynes . Up to now it has been successfully applied to the synthesis of the macrocyclic core of natural enediynes and their analogues, and it is surprising that it has never been used for the synthesis of hetero analogues of macrocyclic enediynes. Herein we report the synthesis of 10‐membered oxaenediynes fused to a benzothiophene by a Nicholas‐type macrocyclization reaction as well as the exploration of reactivity of enediynes in the Bergman cyclization and their DNA cleavage ability.…”

Photoactivated Transition-Metal Triggers for Ambient Temperature Enediyne and Dienyne Cyclization: Ruthenium-η6-Naphthalene Complexes

“…We previously demonstrated that [Cp*Ru­(NCMe) 3 ]­PF 6 cycloaromatizes enediynes in the presence of a hydrogen atom donor, in the dark, to give [Cp*Ru­(η 6 -arene)]­PF 6 complexes. , The ruthenium approach is unique in that it triggers the room-temperature cycloaromatization of acyclic enediynes, such as 3 - Pr - Z , which do not undergo either thermal or photochemical cycloaromatization in the absence of ruthenium. The reaction was found to be catalytic in ruthenium under photochemical conditions (Scheme ).…”