Gold‐Catalyzed Cyclization of Diynes: Controlling the Mode of 5‐endo versus 6‐endo Cyclization—An Experimental and Theoretical Study by Utilizing Diethynylthiophenes

Abstract

Herein, a dual-gold catalyzed cyclization of 3,4-diethynylthiophenes generating pentaleno[c]thiophenes through gold-vinylidenes and CÀH bond activation is disclosed. Various new heteroaromatic compounds-substrate classes unexplored to date-exhibiting three five-membered annulated ring systems could be synthesized in moderate to high yields. By comparison of the solid-state structures of the corresponding gold-acetylides, it could be demonstrated that the cyclization mode (5-endo versus 6-endo) is controlled by the electronic and not steric nature of the diyne backbone. Depending on different backbones, we calculated thermodynamic stabilities and full potential-energy surfaces giving insight into the crucial dual-activation cyclization step. In the case of the 3,4-thiophene backbone, in which the initial cyclization is rate and selectivity determining, two energetically distinct transition states could be localized explaining the observed 5-endo cyclization mode by classical transition-state theory. In the case of vinyl and 2,3-thiophene backbones, the theoretical analysis of the cyclization mode in the bifurcated cyclization area demonstrated that classical transition-state theory is no longer valid to explain the high experimentally observed selectivity. Herein, for the first time, the influence of the backbone and the aromatic stabilization effect of the 6-endo product in the crucial cyclization step could be visualized and quantified by calculating and comparing the full potential-energy surfaces.

New Pathways for the Dual Gold‐Catalyzed Cyclization of Diynes

“…Interestingly, regioisomeric compound 3 b also reacted rapidly, but in this case an inseparable equimolar mixture of products 4 a and 4 b′ was formed (determined from NMR spectra; Table , entry 2). This mixture of two products could originate from a bifurcation pathway in dual gold catalysis that has already been proposed from calculations . Furan derivative 3 c reacted slower than the corresponding thiophene derivative.…”

“…Depending on the connecting tether between the two alkyne moieties, either 5‐ or 6‐ endo cyclization reactions are possible. The activation of diynes based on a benzene backbone, as well as 3,4‐diethynylthiophenes, lead to 5‐ endo cyclization to form gold vinylidenes (Scheme , top), whereas 2,3‐diethynylthiophenes and vinyl‐tethered diynes undergo 6‐ endo cyclization (Scheme , bottom). The 6‐ endo cyclization reaction is also possible in the case of benzene‐tethered diynes when followed by the addition of an external nucleophile ,.…”

“…During studies on the cyclization of dialkynyl‐substituted thiophene derivatives, it was observed that, independent of the first cyclization, the terminating C−H insertion always provided five‐membered rings (Scheme , top) . Thus, we wanted to investigate the reaction with shorter alkyl substituents without γ‐C−H groups.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…1358) in a process where the digold-vinylidene complex (e.g. 1357) forms through attack of the alkynylgold at the gold π-complex, which forms the final product through a net C-H insertion process [1239]. This mechanistic pathway was supported through computational studies, which also sought to uncover the preferences for 5-exo over 6-endo cyclization.…”

Au‐ and Pt‐Catalyzed CH Activation/Functionalizations for the Synthesis of Heterocycles

“…In these cases, 5-endo-dig cyclization pathway was observed. This protocol can be used to construct thiophene/furan or thiophene/pyrrole 101 system skeleton from 3,4-diethynylthiophene derivatives 100 (Scheme 12.46) [49].…”