An Unusual Access to Medium Sized Cycloalkynes by a New Gold(I)‐Catalysed Cycloisomerisation of Diynes

Abstract

Dedicated with admiration to Professor Samir Z. ZardOver the last decade, gold catalysis has demonstrated a high synthetic potential for the formation of various functionalised structures by the addition of a wide range of nucleophiles to gold-activated alkynes or allenes.[1] While a series of carbon nucleophiles (alkene, allene, aryl) have been used for this purpose, it is surprising that only little attention has been given to the use of alkynes.[2] Such a lack of interest is probably due to the inherent reduced nucleophilicity of the alkyne functionality combined with constraints related to its linear geometry in the case of intramolecular transformations. Herein we report that a series of 1,9-and 1,10-diynes can indeed be efficiently cycloisomerised into medium sized cycloalkynes by an apparently unprecedented gold-catalysed alkyne-alkyne coupling (Scheme 1)In the course of our recent study of the [2 + 2] cycloaddition of 1,8-enynes, [3,4] we attempted to transform symmetrical substrate 1 a into the corresponding cyclobutene 3. The reaction was performed by using 4 mol % of gold complex 4 [5] in CD 2 Cl 2 at room temperature and was monitored by using 1 H NMR spectroscopy. The conversion of substrate 1 a was surprisingly slow, whereas a series of other 1,8-enynes reacted rapidly to give the corresponding [2 + 2] cycloaddition products.[3] Moreover, no trace of cyclobutene formation could be observed. Instead, another product was cleanly formed that could be accumulated to a maximum of 53 % yield after three days of reaction (79 % yield in CDCl 3 ). [6] This new compound could not be isolated in a pure form [7] but its structure could, however, be assigned as cycloalkyne 2 a by NMR spectroscopic analysis of the crude reaction mixture.[8] This unexpected gold-catalysed alkyne-alkyne coupling is remarkable given the mildness of the reaction conditions under which cycloalkyne 2 a is formed.[9] This highly unsaturated compound did not suffer further transformation and was stable in the presence of electrophilic gold complex 4. It should also be noted that the formation of cycloalkyne 2 a from diyne 1 a is rather unique in the field of gold catalysis, in view of the extremely limited number of known transformations that involve alkynes as nucleophiles [2] or lead to medium-sized ring products.[10]The reaction of analogous diyne substrate 1 b was more rapid and a complete conversion was observed after 40 h at room temperature (Table 1, entry 1). The corresponding cycloalkyne 2 b was isolated as a solid in 95 % yield, from which single crystals suitable for X-ray crystal structure determination could be obtained. [11] A rapid screening of catalysts and experimental conditions was next undertaken to optimise the formation of cycloalkyne 2 b (Table 1)

Eine einfache Gold‐katalysierte Synthese von Benzofulvenen – gem‐diaurierte Spezies als “Instant‐Dual‐Activation”‐Präkatalysatoren

“…Wie in den verwandten Reaktionspfaden, [2a] muss die Bildung eines Goldacetylids 4 als erster Schritt ablaufen. Eine Option ist die einfache Bildung eines Acetylids und die Freisetzung der korrespondierenden Säure, [14] die andere der Katalysatortransfer. Hat sich das .…”

Metalltriflimidate sind bessere Katalysatoren für die organische Synthese als Metalltriflate – der Effekt eines stark delokalisierten Gegenions

“…Es wurde angenommen, dass der Prozess über den nucleophilen Angriff eines Goldacetylids am goldaktivierten Alkin abläuft. [52] Ph 3 PAuNTf 2 katalysierte auch die Cycloisomerisierung von Eninen für die Synthese von racemischen [114] und nichtracemischen [115] axial-chiralen Biarylen. Die Nachahmung von enzymkatalysierten Polyen-Carbocyclisierungen ist für Chemiker und Biochemiker ein faszinierendes Forschungsgebiet.…”

Silver-free Gold(I) Catalysts for Organic Transformations

“…If the substituents of the tertiary phosphine or of the carbene have any σ -or π-donor properties, this may also stabilize the cation, but any too high donor capacity may of course deactivate the [(L)Au] + species. In the work by Echavarren et al, and later also by the group of Gagosz and others, suitably positioned aryl groups have proved to be almost ideal supporting substituents (U), because on the one hand these groups are partly shielding the acceptor function of the gold cation, while on the other hand the (arene)-Au π-interaction is of very low bond energy, lower than that with alkenes, allenes or alkynes, and hence these incoming unsaturated substrates are readily given access to the metal atom [38,39]. The influ-…”

“…(Scheme 17) [66], b) the cyclization of 1-(prop-2-yn-1-yl)-2-alkenylbenzenes to produce naphthalenes proceeding with fragmentation of the alkene (Scheme 18) [67], c) the ring closure of α,ω-alkane-diynes to give macrocylic olefins (Scheme 15) [39], …”