A series of benzyl propargyl ethers react with a gold(I) catalyst to furnish variously substituted allenes via a 1,5-hydride shift/fragmentation sequence. This transformation is rapid and practical. It can be performed under very mild conditions (room temperature or 60 degrees C) using terminal as well as substituted alkyne substrates bearing a primary, secondary, or tertiary benzyl ether group. The allenes thus formed can be reacted in situ with an internal or external nucleophile, corresponding to an overall reductive substitution process, to produce more functionalized compounds.

A study concerning a two-step sequence leading to the formation of diversely 1,5-disubstituted oxazolones is described. The mild conditions employed allow the efficient and rapid synthesis of a variety of such compounds via an initial Cu(II)-catalyzed coupling of a bromoalkyne with a secondary tert-butyloxycarbamate followed by a Au(I)-catalyzed cycloisomerization of the N-alkynyl tert-butyloxycarbamates thus obtained.

Abstract:The gold(I)-catalysed isomerisation of 1,8-enynes allows the efficient synthesis of functionalised bicycloA C H T U N G T R E N N U N G [5.2.0]nonenes. Notably, these cyclobutenes derivatives can be isolated as reactive intermediates that could undergo subsequent gold(I)-catalysed transformations such as isomerisation, fragmentation or ene reaction to furnish more structurally complex products. This study also provides useful information related to the mechanism leading to metathesis-type derivatives, examples of which were shown to be produced, in the present case, by a gold(I)-catalysed ring fragmentation of the cyclobutene moiety.

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)

In the presence of a Cu(I) catalyst and a pyridine oxide, alkynyl oxiranes and oxetanes can be converted into functionalized five- or six-membered α,β-unsaturated lactones or dihydrofuranaldehydes. This new oxidative cyclization is proposed to proceed via an unusual allenyloxypyridinium intermediate.

A series of alkynyl ethers react with an electrophilic gold(I) catalyst to produce a range of structurally complex spiro or fused dihydrofurans and dihydropyrans via a 1,5-hydride shift/cyclization sequence. This hydroalkylation process, which is performed under practical experimental conditions, can be applied to terminal as well as ester-substituted alkynes. It allows the efficient conversion of secondary or tertiary sp(3) C-H bonds into new C-C bonds by the nucleophilic addition of a vinylgold species onto an oxonium intermediate. The stereoselectivity of the cycloisomerization process toward the formation of a new five- or six-membered cycle appears to be dependent on steric factors and the alkyne substitution pattern.

A gold mine of results: A series of ynamides have been dimerized in the presence of a gold(I) complex. This unprecedented transformation involves the formation of a key keteniminium intermediate that reacts to form a variety of cyclic and acyclic products. The substitution pattern of the ynamide determines which product is formed (see scheme; EWG=electron‐withdrawing group, Ts=p‐toluenesulfonyl).

Deviant behavior: In a deviation from “normal” reactivity, isocyanides underwent co‐trimerization with carboxylic acids in the presence of ZnBr2 to smoothly provide oxazoles (see scheme). The reaction is thought to occur by initial nucleophilic addition of the carboxylic acid to a ligated isonitrile molecule, followed by a sequence involving double migratory insertion, metal‐salt elimination, acyl migration, cyclization, and dealkylation.