Exploring the reactivity of electrophilic trisphosphine platinum(II) complexes in the cycloisomerization of dienes

The cycloisomerization of 1,5-dienes bearing nucleophilic traps with electrophilic trisphosphine Pt(II) complexes generates a cationic Pt-alkyl species which is stable to protonolysis by bulky diaryl ammonium acids. An investigation of tridentate pincer ligand effects in a model system where the alkyl group was -Me revealed that small electron donating substituents at phosphorus enhanced the rate of protonolysis by almost two orders of magnitude. Mechanistic experiments suggested that protonation at Pt generated a 5-coordinate intermediate which eliminated methane by reductive coupling and rapid associative ligand substitution. The large difference in protonolysis rates between pincer and non-pincer systems was attributed to torsional strain inherent to square planar pincer systems. Polyene cyclizations with dicationic Pt complexes typically resulted in a large forward rate constant for cyclization with diastereoselectivity of the polycyclic products governed by the Stork-Eschenmoser postulate. Ligand effects, more specifically electronics, were observed to affect the mode of cyclization (concerted or stepwise). The first direct observation of the equilibrating species in a polycyclization reaction (Pt( 2-alkene) and Pt-alkyl) was made using the electron donating bis(2- diethylphosphinoethyl)ethylphosphine (EtPPPEt) ligand and a 1,5-dienyl sulfonamide. Cyclization was determined to be stepwise in nature, generating the more thermodynamically favored cis ring junction in the 6,5-bicyclic Pt-alkyl product. The variables which affect the cyclization equilibrium were investigated and included: solvent polarity, metal electrophilicity, acid/base strength, and ring strain. These factors were used as a guideline to control stereoselectivity in polyene cascade cyclizations. Medium range stereocontrol was observed using a 1,5-dienol substrate but such control was not present in the cyclization of trienol substrates. The effects of ligand design on Pt(II) catalyzed cyclopropanation reactions was also investigated. Deconstructing the PPP ligand framework into a combination of mono- and bidentate phosphine ligands allowed for a modular approach to catalyst optimization. The optimal achiral catalyst for the cyclopropanation of 1,6- and 1,7-dienes was found to be (dppm)(PMe3)Pt2+. This catalyst was extremely electrophilic and carbophilic; increasing rates by a factor of 20 and allowing for more functional group tolerance. An asymmetric ligand with a similar bite angle to dppm was also synthesized and tested for enantioselective catalysis

Reversibility Effects on the Stereoselectivity of Pt(II)-Mediated Cascade Poly-ene Cyclizations

Cyclization of 1,5-dienes bearing nucleophilic traps with electrophilic trisphosphine pincer ligated Pt(II) complexes results in the formation of a polycyclic Pt-alkyl via an Pt(η2-alkene) intermediate. With electron rich triphosphine ligands an equilibrium between the Pt(η2-alkene) and Pt-alkyl was observed. The position of the equilibrium was sensitive to ligand basicity, conjugate acid strength, solvent polarity, and ring size. In cases where the ligand was electron poor and did not promote retro-cyclization, then kinetic products adhering to the Stork-Eschenmoser postulate were observed (E-alkenes give trans-ring junctions). When retrocyclization was rapid, then alternative thermodynamic products resulting from multi-step rearrangements were observed (cis [6,5]-bicycles). Under both kinetic and thermodynamic conditions remote methyl substituents led to highly diastereoselective reactions. In the case of trienol substrates, long-range asymmetric induction from a C-ring substituent was considerably attenuated and only modest diastereoselectivity was observed (~2:1). The data suggests that for a tricyclization, the long-range stereocontrol results from diastereo-selecting interactions that develop during the organization of the nascent rings. In contrast, the bicyclization diastereoselectivities result from reversible cascade cyclization

Asymmetric Oxidative Cation/Olefin Cyclization of Polyenes: Evidence for Reversible Cascade Cyclization

Ag und Pt arbeiten zusammen: Die Aktivierung von [(xylyl-phanephos)PtCl2] durch Silber erzeugt einen elektrophilen Katalysator, der enantio-, diastereo- und regioselektiv die stereospezifische oxidative Cyclisierung von Polyenolen vermittelt (siehe Schema; Tr=Trityl). Mechanistische Experimente lassen darauf schließen, dass der konfigurationsbestimmende Schritt nicht die einleitende Cyclisierung ist, sondern ein Folgeschritt der Reaktion

Synthesis of 3‐Oxaterpenoids and Its Application in the Total Synthesis of (±)‐Moluccanic Acid Methyl Ester

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94262/1/ange_201205981_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/94262/2/10771_ftp.pd

Synthesis of a Novel Type of 2,3'-BIMs via Platinum-Catalysed Reaction of Indolylallenes with Indoles

Optimisation, scope and mechanism of the platinum-catalysed addition of indoles to indolylallenes is reported here to give 2,3'-BIMs with a novel core structure very relevant for pharmaceutical industry. The reaction is modulated by the electronic properties of the substituents on both indoles, with the 2,3'-BIMs favoured when electron donating groups are present. Although simple at first, a complex mechanism has been uncovered that explains the different behaviour of these systems with platinum when compared with other metals (e.g. gold). Detailed labelling studies have shown Pt-catalysed 6-endo-trig cyclisation of the indollylallene as the first step of the reaction and the involvement of two cyclic vinyl-platinum intermediates in equilibrium through a platinum carbene, as the key intermediates of the catalytic cycle towards the second nucleophilic attack and formation of the BIMs

Construction and in vivo assembly of a catalytically proficient and hyperthermostable de novo enzyme

Although catalytic mechanisms in natural enzymes are well understood, achieving the diverse palette of reaction chemistries in re-engineered native proteins has proved challenging. Wholesale modification of natural enzymes is potentially compromised by their intrinsic complexity, which often obscures the underlying principles governing biocatalytic efficiency. The maquette approach can circumvent this complexity by combining a robust de novo designed chassis with a design process that avoids atomistic mimicry of natural proteins. Here, we apply this method to the construction of a highly efficient, promiscuous, and thermostable artificial enzyme that catalyzes a diverse array of substrate oxidations coupled to the reduction of H2O2. The maquette exhibits kinetics that match and even surpass those of certain natural peroxidases, retains its activity at elevated temperature and in the presence of organic solvents, and provides a simple platform for interrogating catalytic intermediates common to natural heme-containing enzymes