Karin Radkowski

A Functional-Group-Tolerant Catalytic trans Hydrogenation of Alkynes

Against the rules: during the hundred years following Sabatiers groundbreaking work on catalytic hydrogenation, syn delivery of the H atoms to the π system of a substrate remained the governing stereochemical rule. An exception has now be found with the use of cationic [Cp*Ru] templates, which accounts for the first practical, functional-group-tolerant, broadly applicable and highly E-selective semihydrogenation method for alkynes.

A chemo- and stereoselective reduction of cycloalkynes to (E)-cycloalkenes.

A stereoselective entry into (E)-cycloalkenes is described, comprising the ring closing alkyne metathesis (RCAM) of suitable diynes, a ruthenium-catalyzed trans-selective hydrosilylation of the cycloalkynes thus formed, followed by a desilylation of the resulting vinylsilanes mediated by AgF.

Interligand Interactions Dictate the Regioselectivity of trans-Hydrometalations and Related Reactions Catalyzed by [Cp*RuCl]. Hydrogen Bonding to a Chloride Ligand as a Steering Principle in Catalysis

Reactions of internal alkynes with R3M-H (M = Si, Ge, Sn) follow an unconventional trans-addition mode in the presence of [Cp*Ru(MeCN)3]PF6 (1) as the catalyst; however, the regioselectivity is often poor with unsymmetrical substrates. This problem can be solved upon switching to a catalyst comprising a [Ru-Cl] bond, provided that the acetylene derivative carries a protic functional group. The R3M unit is then delivered with high selectivity to the alkyne-C atom proximal to this steering substituent. This directing effect originates from the ability of the polarized [Ru-Cl] bond to engage in hydrogen bonding with the protic substituent, which helps upload, activate, and lock the alkyne within the coordination sphere. An additional interligand contact of the chloride with the -MR3 center positions the incoming reagent in a matching orientation that translates into high regioselectivity. The proposed secondary interactions within the loaded catalyst are in line with a host of preparative and spectral data and with the structures of the novel ruthenium π-complexes 10 and 11 in the solid state. Moreover, the first X-ray structure of a [Ru(σ-stannane)] complex (12a) is presented, which indeed features peripheral Ru-Cl···MR3 contacts; this adduct also corroborates that alkyne trans-addition chemistry likely involves σ-complexes as reactive intermediates. Finally, it is discussed that interligand cooperativity might constitute a more general principle that extends to mechanistically distinct transformations. The presented data therefore make an interesting case for organometallic chemistry that provides inherently better results when applied to substrates containing unprotected rather than protected -OH, -NHR, or -COOH groups.

Chiral heterobimetallic complexes of carbodiphosphoranes and phosphinidene–carbene adducts

Heterobimetallic complexes derived from carbodiphosphoranes or phosphinidene-carbene adducts are reported, in which the central atom accepts two lone-pairs from two different donor ligands and - at the same time - donates two lone-pairs to two different metal centers. Therefore these complexes are carbogenic yet captodative chiral entities.

Chiral Bidentate (Phosphinophenyl)benzoxazine Ligands in Asymmetric Catalysis

The new chiral bidentate (phosphinoaryl)benzoxazine ligands 2 were applied in asymmetric catalysis. Rhodium and copper complexes catalyzed the hydrosilylation of acetophenone and [4+2] cycloadditions with moderate enantioselectivity. Iridium complexes were used to hyrogenate di-, tri-, and tetrasubstituted alkenes, giving products with moderate to high enantiomer excesses. Enantioselective allylic substitution and Heck reactions catalyzed by [(phosphinoaryl)benzoxazine]palladium complexes occurred with high enantioselectivities. The results were similar to those obtained with the corresponding dihydro(phosphinoaryl)oxazole ligands. Comparison of the structures of (diphenylallyl)(benzoxazine)palladium and (diphenylallyl)(dihydrooxazole)palladium complexes showed that the coordination geometries and the chiral environments of the metal centers are very similar, which explains why the enantioselectivities induced by the two ligand classes are in the same range.

Ruthenium-Catalyzed Alkyne trans-Hydrometalation: Mechanistic Insights and Preparative Implications

[Cp*RuCl]4 (1) has previously been shown to be the precatalyst of choice for stereochemically unorthodox trans-hydrometalations of internal alkynes. Experimental and computational data now prove that the alkyne primarily acts as a four-electron donor ligand to the catalytically active metal fragment [Cp*RuCl] but switches to adopt a two-electron donor character once the reagent R3MH (M = Si, Ge, Sn) enters the ligand sphere. In the stereodetermining step the resulting loaded complex evolves via an inner-sphere mechanism into a ruthenacyclopropene which swiftly transforms into the product. In accord with the low computed barriers, spectral and preparative data show that the reaction is not only possible but sometimes even favored at low temperatures. Importantly, such trans-hydrometalations are distinguished by excellent levels of regioselectivity when unsymmetrical alkynes are used that carry an -OH or -NHR group in vicinity of the triple bond. A nascent hydrogen bridge between the protic substituent and the polarized [Ru-Cl] unit imposes directionality onto the ligand sphere of the relevant intermediates, which ultimately accounts for the selective delivery of the R3M- group to the acetylene C-atom proximal to the steering substituent. The interligand hydrogen bonding also allows site-selectivity to be harnessed in reactions of polyunsaturated compounds, since propargylic substrates bind more tightly than ordinary alkynes; even the electronically coupled triple bonds of conjugated 1,3-diynes can be faithfully discriminated as long as one of them is propargylic. Finally, properly positioned protic sites lead to a substantially increased substrate scope in that they render even 1,3-enynes, arylalkynes, and electron-rich alkynylated heterocycles amenable to trans-hydrometalation which are otherwise catalyst poisons.

Enantioselective total synthesis of the phytotoxic lactone herbarumin I

A concise total synthesis of the potent herbicide herbarumin I (1) is presented based on an (E)-selective RCM reaction forging the 10-membered ring of this macrolide.

Two Enabling Strategies for the Stereoselective Conversion of Internal Alkynes into Trisubstituted Alkenes

An expedient method for the C-methylation of alkenylstannanes with formation of trisubstituted alkenes is described, which relies on the use of MeI in combination with copper thiophene-2-carboxylate (CuTC) as promotor and tetra-n-butylammonium diphenylphosphinate as an effective tin scavenger; in some cases, it proved beneficial to further supplement the mixture with catalytic amounts of Pd(PPh3 )4 . Under these conditions, the reaction is robust, high yielding, and compatible with many functional groups that might not subsist under more traditional conditions used to C-alkylate organotin derivatives. A qualitative analysis of the reaction profile suggested that the in situ formation of a reactive organocopper intermediate and its interception by MeI is only barely faster than O-methylation of the phosphinate additive by the same alkylating agent. To guarantee high yields and prevent net protodestannation from occurring, the reaction protocol had to be optimized such that these competing processes are properly decoupled. The new method is particularly well suited for the stereoselective preparation of the (E)-2-methylbut-2-en-1-ol motif that is present in numerous natural products. Alternatively, this particular target structure can be accessed starting from α-hydroxy alkenylsiloxane precursors, which get C-methylated upon exposure to CuI/LiOtBu and MeI by what is thought to be a Brook rearrangement/ alkylation sequence. The required substrates are best prepared by ruthenium-catalyzed trans-hydrosilylation or trans-hydrostannation of propargyl alcohols.