Max M. Hansmann

Mechanistic Switch in Dual Gold Catalysis of Diynes: C(sp3)–H Activation through Bifurcation—Vinylidene versus Carbene Pathways

The other side of the mountain: Changing the framework of diyne systems opens up new cyclization modes for dual gold catalysis. Instead of a 5-endo cyclization and gold vinylidenes a 6-endo cyclization gives rise to gold-stabilized carbenes as key intermediates for selective C-H insertions.

Synthesis of Highly Substituted 3‐Formylfurans by a Gold(I)‐Catalyzed Oxidation/1,2‐Alkynyl Migration/Cyclization Cascade

3-Formylfuran derivatives are core structures of a variety of bioactive natural products. However, procedures for their preparation are still rare and generally inefficient in terms of atom economy: These methods require multiple steps or harsh reaction conditions and show selectivity problems. An efficient gold(I)-catalyzed cascade reaction that leads to 3-formylfurans from easily accessible starting materials is now described. A wide variety of 3-formylfurans were obtained from the corresponding symmetric and unsymmetric 1,4-diyn-3-ols in the presence of an N-oxide in good to excellent yields. Isotope-labeling experiments as well as DFT calculations support a mechanism in which, after an initial oxygen transfer, a 1,2-alkynyl migration is favored over a hydride shift; a cyclization ensues to afford the desired functionalized furan core.

Gold–allenylidenes – an experimental and theoretical study

Herein we describe the isolation and characterisation of the first “gold–allenylidene” complexes [AuCCCR2]+ X− (R = N(CH2)n, OMe; n = 3, 4; X− = OTf−) and present a bonding model for these species based on an experimental and theoretical analysis. Heteroatom stabilisation (oxygen and nitrogen donors) overpowers the ligand effect on gold and has a large impact on the distribution of electron density in the allenylidene fragment. The description of a gold-stabilised propargylic cation rather than a gold–vinylidene complex is favoured, clearly indicated by experimental and theoretical work. Removing this heteroatom stabilisation by means of a theoretical analysis shows that the choice of ligand can fine-tune the electronics ranging from a gold-stabilised carbocation towards a Au–allenylidene. This observation is in excellent agreement with the recent gold “carbene vs. carbocation” discussion and expands the understanding of Au–carbocation interactions to include gold–cumulene systems.

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

Herein, a dual-gold catalyzed cyclization of 3,4-diethynylthiophenes generating pentaleno[c]thiophenes through gold-vinylidenes and C-H 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.

Gold meets rhodium: tandem one-pot synthesis of β-disubstituted ketones via Meyer-Schuster rearrangement and asymmetric 1,4-addition.

An asymmetric one-pot tandem Au/Rh-catalyzed synthesis of highly enantioenriched β-disubstituted ketones starting from racemic propargyl alcohols is disclosed. The compatibility of the two metal complexes (Au/Rh) and their orthogonal ligand systems (NHC/diene) in this bimetallic catalytic system is investigated.

Singlet (Phosphino)phosphinidenes are Electrophilic

A room-temperature stable (phosphino)-phosphinidene reacts with carbon monoxide, stable singlet carbenes, including the poor π-accepting imidazol-2-ylidene, and phosphines giving rise to the corresponding phosphaketene, phosphinidene-carbene and phosphinidene-phosphine adducts, respectively. Whereas the electronic ground-state calculations indicate a PP multiple bond character in which the terminal phosphorus is negatively charged, the observed reactivity clearly indicates that (phosphino)phosphinidenes are electrophilic as expected for an electron-deficient species. This is further demonstrated by competition experiments as well as by the results of Fukui function calculations.

Palladium‐Catalyzed Alkylation of 1,4‐Dienes by CH Activation

Activated: the title reaction proceeds with a broad range of nucleophiles and variously substituted 1,4-dienes under mild conditions, and provides direct access to the corresponding 1,3-diene-containing products with high regio- and stereocontrol (see scheme; 2,6-DMBQ=2,6-dimethylbenzoquinone, EWG=electron-withdrawing group). This is the first catalytic allylic C-H alkylation that proceeds in the absence of sulfoxide ligands.

Activation of Alkynes with B(C6F5)3 – Boron Allylation Reagents Derived from Propargyl Esters

Novel allyl boron compounds are readily synthesized via rearrangement reactions between Lewis acidic B(C6F5)3 and propargyl esters. These reactions proceed through an initial cyclization followed by ring-opening and concurrent C6F5-group migration. In the absence of disubstitution adjacent to the ester oxygen atom, an allyl boron migration rearrangement leads to formal 1,3-carboboration products. These allyl boron compounds act as allylation reagents with aldehydes introducing both a C3-allyl fragment and a C6F5-unit as a single anti-diastereomer. In these reactions, B(C6F5)3 activates the alkynes, prompting the rearrangement processes and enabling installations of C6F5 and R-groups.

A Theoretical DFT‐Based and Experimental Study of the Transmetalation Step in Au/Pd‐Mediated Cross‐Coupling Reactions

In this work a combined theoretical and experimental investigation of the cross-coupling reaction involving two metallic reaction centers, namely gold and palladium, is described. One metal center (Au) hereby is rather inert towards change in its oxidation state, whereas Pd undergoes oxidative insertion and reductive elimination steps. Detailed mechanistic and energetic studies of each individual step, with the focus on the key transmetalation step are presented and compared for different substrates and ligands on the catalytic Pd center. Different aryl halides (Cl, Br, I) and aryl triflates were investigated. Hereby the nature of the counteranion X turned out to be crucial. In the case of X=Cl and L=PMe3 the oxidative addition is rate-determining, whereas in the case of X=I the transmetalation step becomes rate-determining in the Au/Pd-cross-coupling mechanism. A variety of Au-Pd transmetalation reaction scenarios are discussed in detail, favoring a transition state with short intermetallic Au-Pd contacts. Furthermore, without a halide counteranion the transmetalation from gold(I) to palladium(II) is highly endothermic, which confirms our experimental findings that the coupling does not occur with aryl triflates and similar weakly coordinating counteranions--a conclusion that is essential in designing new Au-Pd catalytic cycles. In combination with experimental work, this corrects a previous report in the literature claiming a successful coupling potentially catalytic in both metals with weakly coordinating counteranions.

Tandem Palladium(0) and Palladium(II)-Catalyzed Allylic Alkylation Through Complementary Redox Cycles†

Among the strategies that seek to address the challenges inherent to performing chemical synthesis in our increasingly resource-conscious world, catalysis has provided the most significant contribution to conducting synthetic transformations in an atom-economical way, defining a paradigm in which starting materials are used efficiently and waste is minimized. In the interest of further enhancing the efficiency and sustainability of the production of fine chemicals, there has been a recent focus on performing sequential catalytic operations in a single reaction vessel. The application of such tandem processes has the potential to deliver important practical advantages, both with respect to the increase in material throughput and the concomitant decrease in the cost, labor, and time associated with the workup and isolation of intermediates. Just as importantly, such an approach also provides an opportunity to develop new methods that orchestrate the performance of several concurrent catalytic events, allowing for the discovery of new types of reactivity and selectivity for the direct construction of molecular complexity. Of the many types of tandem catalysis, those that employ one precatalyst to perform two mechanistically distinct bondforming events in the presence of a reagent that triggers this change in mechanism are called “assisted tandem catalysis”. Strategically, these methods offer advantages over other tandem processes because they obviate the need to either begin with or subsequently add a second catalyst, making efficient use of the typically valuable precatalyst, and they eliminate the possibility for deleterious interactions between two different catalytic species. Despite these attractive qualities, reports of assisted tandem catalysis are uncommon and the number of known chemical triggers is small. A significant fraction of such processes involve a Ru–carbene-catalyzed alkene metathesis event followed by a Ru-catalyzed non-metathetic transformation. For example, Grubbs and co-workers have reported that their second generation metathesis catalyst can perform a Ru-catalyzed ring-closing metathesis of hepta-1,6-dien -4-one to afford cyclopent-3-enone; addition of H2 under high pressure generates a different Ru species that hydrogenates the newly formed alkene (Scheme 1a). Similarly, Rawal and co-workers have demonstrated that a Pd catalyst which