Competitive Gold‐Activation Modes in Terminal Alkynes: An Experimental and Mechanistic Study

Abstract

The competition between π- and dual σ,π-gold-activation modes is revealed in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable effect of various ligands in gold complexes on the choice of these activation modes is described. The cationic [Au(IPr)](+) (IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes the π activation of terminal alkynes, whereas [Au(PtBu3 )](+) favors intermediate σ,π species. In this experimental and mechanistic study, which includes kinetic and cross-over experiments, several σ-gold, σ,π-gold, and other gold polynuclear reaction intermediates have been isolated and identified by NMR spectroscopy, X-ray diffraction, or MALDI spectrometry. The ligand control in the simultaneous or alternative π- and σ,π-activation modes is also supported by deuterium-labeling experiments.

Well‐Defined Dinuclear Gold Complexes for Preorganization‐Induced Selective Dual Gold Catalysis

“…Having established that dinuclear complex 3 engages in well‐defined σ,π‐activation of C−C triple bond systems, the heterocyclization (intramolecular hydroamination) of urea‐functionalized alkyne 6 was selected as a proof‐of‐concept reaction to probe the catalytic competence of this well‐defined Au 2 species. Markovnikov addition to generate a six‐membered ring ( 8 ) involves π‐activation by a single gold species, whereas dinuclear σ,π‐activation results in anti‐Markovnikov addition to give a five‐membered ring ( 7 ; Scheme ) . Using 2.5 mol % of 3 in DMF at 60 °C for five hours leads to full conversion and high regioselectivity for the five‐membered indole 7 (85 %), in accordance with a selective σ,π‐acetylide mechanism.…”

“…The findings clearly validate our hypothesis, as the high regioselectivity for 7 obtained with catalyst 3 is independent of the catalyst concentration (Figure ). In contrast, dilution experiments with mononuclear AuCl(P t Bu 3 )—reported as the best catalyst to form 7 by σ,π‐activation—result in a sharp drop in selectivity . These results demonstrate the benefits of well‐defined preorganization of two gold centers to enforce selective σ,π‐activation and to mediate regioselective dual gold catalysis with functionalized alkynes, even at low catalyst loadings.…”

Synthesis of tetra- and octa-aurated heteroaryl complexes towards probing aromatic indoliums

“…Many mononuclear organogold(I) compounds have been synthesized by the reactions of allene/alkene/alkyne substrates and nucleophiles with stoichiometric gold(I) compounds 18 19 20 33 . For example, σ - and π -activation of the ethynyl group of o -alkynylanilines by a gold(I) species led to the formation of 2- and 3-aurated indole complexes, respectively 34 35 . In view of the acknowledged isolobality of the proton and the LAu + fragment (L=phosphine or carbene ligands) 36 , we therefore assume that an aurated imido species in an o -alkynylaniline derivative may act like an amine group to undergo a similar annulation reaction to react with the π - and/or σ -activated ethynyl group.…”

Ring strain strategy for the control of regioselectivity. Gold-catalyzed anti-Markovnikov cycloisomerization initiated tandem reactions of alkynes

“…Especially, the terminal alkynes can undergo various highly regioselective transformations catalyzed by gold, thus providing an efficient way for CAC, CAH and CAX bond formation. However, a Markovnikov regioselectivity was normally observed in this kind of nucleophilic addition, except those involving the formation of indoles driven by aromatization (Scheme 1) [13][14][15]. A likely reason is that the regioselectivity in such a gold-catalyzed nucleophilic addition is dominated by the electronic nature of alkyne.…”