Marcel Wieteck

Simple Gold‐Catalyzed Synthesis of Benzofulvenes—gem‐Diaurated Species as “Instant Dual‐Activation” Precatalysts

In the field of homogeneous transition-metal chemistry, gold plays a major role in the discovery of new reactions. Most of the transformations are based on the electrophilic activation of a multiple bond. The decrease of electron density upon p coordination of a carbophilic gold center allows nucleophilic attack. Now, in independent and parallel work the group of Zhang and our team have discovered a different reactivity which was so far unprecedented in the field of gold chemistry. Initial activation of an alkyne by s coordination to gold increases the nucleophilicity of the b-carbon atom of this alkyne. This first alkyne combines with a second alkyne, which is activated by p coordination, and highly reactive gold vinylidene intermediates are formed by this dual s/p activation. The Zhang group s publication on the synthesis of benzofulvenes now prompts us to publish our additional findings on that specific reaction. Since alkyl-substituted alkynes are readily available, a new fascinating reaction pathway was opened for the gold vinylidene intermediates. The first two elementary steps of this reaction are identical to the previous reactions, which seem to be general for this new sector of gold catalysis. Herein we report on the use of tertiary alkyl groups, the isolation of gem-diaurated species which prove to be ideal precatalysts for this type of transformation, the dynamics of the equilibrium involving these diaurated species, and the catalyst transfer in the context of a detailed mechanistic discussion. We investigated several diyne systems 1 with a terminal alkynyl group and a tert-alkyl-substituted alkynyl group as potential substrates for the gold(I)-catalyzed intermolecular arene addition. A new reaction was observed, the clean formation of a benzofulvene derivative, a class of compounds that usually is not easily available. No incorporation of the solvent benzene was observed. To optimize the reaction, we performed reactions of substrate 1 a (Table 1) with different gold catalysts and different counterions (see the Supporting Information); the well-established catalyst [(IPr)AuCl], in combination with AgNTf2 gave the best results. To evaluate the substrate scope, a small library of substrates was transformed to the corresponding products under the optimized conditions (Table 1). One advantage of substrates 1 is their easy two-step synthesis (Sonogashira reaction, Seyferth–Gilbert homologation) from commercially available 2-bromobenzaldehydes. With our test substrate 1a,

Gold Vinylidene Complexes: Intermolecular C(sp3)H Insertions and Cyclopropanations Pathways

Highly reactive gold vinylidene species are used for intermolecular C(sp(3))-H insertions into unactivated alkanes (see scheme). In addition, they can be regarded as synthons for alkylidene carbenes. Initiated by cyclopropanation of the vinylidene species/alkylidene carbenoide, cyclobutene derivatives are formed in a diastereoselective fashion by a ring-enlargement cascade in only one step.

Gold Catalysis: Tandem Reactions of Diyne–Diols and External Nucleophiles as an Easy Access to Tricyclic Cage‐Like Structures

Different diyne-diols composed of two terminal homopropargylic alcohol groups were prepared by bi-directional synthesis. Subjection of the syn diastereomers to NAC-gold catalysts (NAC=nitrogen acyclic carbene) in the presence of external nucleophiles such as water or anilines provided substituted and highly rigid heterocyclic cages. The corresponding anti disastereomers polymerised. An intermediate of the reactions of the syn diastereomers could be isolated and even be characterised by crystal structure analysis. Overall, eight new bonds are formed in the reaction, which proceeds by a multistep sequence of highly selective hydroalkoxylations and hydrohydroxylation or hydroaminations. For furyl substituents and for internal alkynes competing reaction pathways could be identified. By the cross-coupling of a product with an iodoaryl substituent, the use of these cage compounds as geometrically defined linking groups by using orthogonal transition-metal-catalysed methodology, namely, gold and palladium catalysis, could be demonstrated.

Dual gold catalysis: a novel synthesis of bicyclic and tricyclic pyrroles from N-propargyl ynamides.

Various N-propargyl ynamides were converted to bicylic and tricyclic pyrroles by the use of a cationic dual-activation gold catalyst. This reaction starts with the nucleophilic addition of a gold acetylide onto an ynamide triple bond at the β-position of the nitrogen atom. Thus, gold vinylidene is formed, and then a second cyclization takes place. The formation of the gold vinylidene is indicated by the evidence that not only aryl ynamides but also alkyl ynamides undergo C-H activation in these reactions.

Dual Gold Catalysis: Synthesis of Polycyclic Compounds via CH Insertion of Gold Vinylidenes

New and interesting polycyclic compounds have been synthesized from non-conjugated diyne systems by dual gold catalysis. A quaternary carbon center in the backbone and the accompanying Thorpe-Ingold effect enabled the unprecedented insertion of sp(3) and sp(2) CH bonds that for the first time were incorporated within the backbone of the diyne system and allowed the construction of complex polycyclic carbon scaffolds inaccessible by previous approaches in which the CH bonds for the insertion were situated at the other end of the alkyne.

Gold Catalysis: Catalyst Oxidation State Dependent Dichotomy in the Cyclization of Furan–Yne Systems with Aromatic Tethers

Four different synthetic strategies led to a variety of furan-yne systems that contained an aryl system in the tether. Due to the short routes to these systems (four steps or less), a small library of substrates could easily be prepared. These were treated with AuCl(3) or with the Gagoszs catalyst Ph(3)PAuNTf(2) complex. The AuCl(3)-catalyzed reactions delivered highly substituted fluorene derivatives, a class of compounds of great importance as precursors for luminophores with extraordinary abilities. Conversely, a different mechanistic pathway was observed with the cationic gold(I) catalyst. In the latter case, a mechanistically interesting reaction cascade initiated a formal alkyne insertion into the furyl-sp(3)-C bond, which gave indene derivatives as the final products. This new reaction pathway depends on the aromatic moiety in the tether, which stabilizes a crucial cationic intermediate as a benzylic cation.

Different Selectivities in the Insertions into C(sp2)−H Bonds: Benzofulvenes by Dual Gold Catalysis Competition Experiments

An unprecedented, often almost quantitative access to tricyclic aromatic compounds by dual gold catalysis was developed. This synthetic route expands the scope of benzofulvene derivatives through a C(sp2 )-H bond insertion in easily available starting materials. The insertion takes place with an exclusive chemoselectivity with respect to the competing aromatic C-H positions. A bidirectional synthesis with two competing ortho-aryl C-H bonds in the selectivity-determining step also shows perfect selectivity; this result is explained by a computational investigation of the two conceivable intermediates. The intramolecular competition of two non-equivalent aryl C-H bonds with a benzylic methyl group also showed perfect selectivity.