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

Abstract

[Cp*RuCl] (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 RMH (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 RM- 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.

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

“…This is particularly true for products derived from propargyl alcohold erivatives, which react in ah ydroxy-directed manner with notably high levels of regio-and stereoselectivity. [12,13] The resulting prodScheme3.Hydroxy-directed hydrosilylation of propargyl alcohols followed by C-alkylation via Brook rearrangement. ucts of type B provide ample opportunity for downstream functionalization: [42] The copper-mediated C-alkylation reactions described above further complement the portfolioi n that they open ar eliable, functional group toleranta nd hence potentially broadly applicable entry into stereochemically welldefined trisubstituted alkenes;m ost notably,t he (E)-2-methylbut-2-en-1-ol motif is well within reach,w hich is prevalent in innumerousb ioactive natural products.…”

“…[34,35] We conjectured that the mandatory use of triphenylsilanes likely reflects the need to lower the energy of the C-Si antibondingo rbital as ap reludef or successfula ttack of the adjacent alkoxide onto the silicon atom that triggers the critical Brook rearrangement; [36,37] this step is arguably challenging as it passes throughaf our-membered intermediate O.U nder the premise that orbitale nergy lowering is the key to success, however,s ilanes of type B carrying electronegative heteroatoms at silicon should also qualify as substrates. [38] Alkoxysilanes B (X = OR), which are easy to make via the ruthenium catalyzed trans-hydrosilylation referred to above, [12,13] fall into this category and were therefore deemed ap otentially very attractive and versatile class of startingm aterials.…”

Ruthenium-Catalyzed Dimerization of 1,1-Diphenylpropargyl Alcohol to a Hydroxybenzocyclobutene and Related Reactions

“…1 H (399.8 MHz) and 13 C{ 1 H} (100.53 MHz) NMR spectra were obtained on a JEOL JNM-ECX-400 spectrometer (JEOL Ltd., Tokyo, Japan). 1 H NMR shifts are relative to the residual CHCl3 (δ 7.26), while 13 C shifts are referenced to CDCl3 (δ 77.0). Elemental analyses were performed on a Perkin-Elmer 2400II CHN analyzer (PerkinElmer, Waltham, MA, USA).…”

“…For example, the Hidai's thiolato-bridged dinuclear Cp*Ru (Cp* = η 5 -C 5 Me 5 ) complexes catalyze nucleophilic propargylic substitution of terminal propargylic alcohols owing to facile and reversible formation of an allenylidene intermediate [10][11][12]. Recently, Fürstner and co-workers described that regioselective hydrometalation [13,14] and ene-yne coupling [15] of propargylic alcohols are catalyzed by Cp*RuCl complexes. The latter reactions are guided by the intramolecular hydrogen bonds between the hydroxy group in the alcohol and the chlorido ligand.…”

Iridium‐Catalyzed Hydroxyl‐Enabled Cycloaddition of Azides and Alkynes

“…Furthermore, the structure of triazole 3 c was unambiguously confirmed by X-ray analysis, which was in consistent with standard analysis. [15] Meanwhile, the phenolic hydroxy group was also varied, the reactivity of meta-substituted phenol substituent was very low and there is not any new product formation. The alkynes with functional groups like benzoxyl, phthalimide and TMS, were tolerable (3 g-3 i).…”