Alkyne–Aldehyde Reductive CC Coupling through Ruthenium‐Catalyzed Transfer Hydrogenation: Direct Regio‐ and Stereoselective Carbonyl Vinylation to Form Trisubstituted Allylic Alcohols in the Absence of Premetallated Reagents

Abstract

Nonsymmetric 1,2-disubstituted alkynes engage in reductive coupling to a variety of aldehydes under the conditions of ruthenium-catalyzed transfer hydrogenation by employing formic acid as the terminal reductant and delivering the products of carbonyl vinylation with good to excellent levels of regioselectivity and with complete control of olefin stereochemistry. As revealed in an assessment of the ruthenium counterion, iodide plays an essential role in directing the regioselectivity of C–C bond formation. Isotopic labeling studies corroborate reversible catalytic propargyl C–H oxidative addition in advance of the C–C coupling, and demonstrate that the C–C coupling products do not experience reversible dehydrogenation by way of enone intermediates. This transfer hydrogenation protocol enables carbonyl vinylation in the absence of stoichiometric metallic reagents.

Alkynes as Allylmetal Equivalents in Redox-Triggered C–C Couplings to Primary Alcohols: (Z)-Homoallylic Alcohols via Ruthenium-Catalyzed Propargyl C–H Oxidative Addition

“…6a The previously observed products of vinylation, allylic alcohol Ia and enone dehydro - Ia , were generated in 65% and 17% yield, respectively. Along with these materials, careful analysis of the 1 H NMR spectra of Ia did indeed reveal trace quantities of ( Z )-homoallylic alcohol IIa .…”

“…4 Such branched products of allylation are formed in related iridium 5a and ruthenium 5b catalyzed C-C couplings of primary alcohols and allenes, suggesting alkyne-to-allene isomerization is evident in this process. These observations, in combination with our ongoing studies of the ruthenium catalyzed C-C coupling of alkynes and primary alcohols or aldehydes to form allylic alcohols or enones, 6 prompted us to explore the use of alkynes as allyl donors 7 under the conditions of ruthenium catalysis. Here, we report that the cationic ruthenium complexes generated through the acid-base reaction of H 2 Ru(CO)(PPh 3 ) 3 and 2,4,6-(2-Pr) 3 PhSO 3 H catalyzes 8 the redox-triggered C-C coupling of alkynes and primary alcohols to furnish ( Z )-homoallylic alcohols with good to complete control of olefin geometry (Scheme 1, eq.…”

Brønsted Acid Enabled Nickel‐Catalyzed Hydroalkenylation of Aldehydes with Styrene and its Derivatives

“…[1] Thet raditional method uses preformed alkenylmetal reagents to couple with various carbonyl compounds (Scheme 1a). [4] Another important alternative method employs transitionmetal-catalyzed reductive coupling of alkynes with carbonyls in the presence of metallic reductants, [5] hydrogen gas,o r hydrogen donors, [6,7] thereby avoiding the use of pre-formed alkenylmetal reagents (Scheme 1b). [4] Another important alternative method employs transitionmetal-catalyzed reductive coupling of alkynes with carbonyls in the presence of metallic reductants, [5] hydrogen gas,o r hydrogen donors, [6,7] thereby avoiding the use of pre-formed alkenylmetal reagents (Scheme 1b).…”

“…First, the hydroalkenylation method could easily be carried out on agram scale with excellent yields.For instance,the reaction of amino acid derived aldehyde 2i with styrene afforded 1.59 g of allylic alcohol 3i (90 %y ield), which could be further transformed into various biologically active molecules. over two steps.Likewise,direct coupling between styrene and pivalaldehyde produced a5 0% yield of the drug molecule stiripentol (7). [b] 5equivalents of styrene were used.…”

Enantioselective Ruthenium-Catalyzed Carbonyl Allylation via Alkyne–Alcohol C–C Bond-Forming Transfer Hydrogenation: Allene Hydrometalation vs Oxidative Coupling

“…The possibility of promoting such transformations using a ruthenium catalyst appeared tenuous, as established alkyne-alcohol C-C couplings are known to form allylic alcohols. 13,14 Despite this precedent, we recently found that ruthenium catalysts generated upon the acid-base reaction of H 2 Ru(CO)(PPh 3 ) 3 and 2,4,6-(2-Pr) 3 PhSO 3 H convert 2-alkynes and primary alcohols to ( Z )-homoallylic alcohols through pathways involving alkyne-to-allene isomerization with subsequent allene-carbonyl oxidative coupling (Scheme 1, eq. 3).…”