Hydroxy‐Directed Ruthenium‐Catalyzed Alkene/Alkyne Coupling: Increased Scope, Stereochemical Implications, and Mechanistic Rationale

Abstract

The recognition of the dual binding mode of propargyl and allyl alcohols to [Cp*Ru] fragments fostered the development of a highly regioselective intermolecular Alder-ene-type reaction of alkynes with 1,2-disubstituted alkenes. The increased substrate scope opens new perspectives in stereochemical terms. As the loaded catalyst is chiral-at-metal, stereochemical information is efficiently relayed from the propargylic site to the emerging C-C bond. This interpretation is based on the X-ray structure of the first Cp*Ru complex carrying an intact enyne ligand, and provides valuable insights into bonding and activation of the substrates. Computational data draw a clear picture of the principles governing regio- and stereocontrol.

Site‐Selective trans‐Hydrostannation of 1,3‐ and 1,n‐Diynes: Application to the Total Synthesis of Typhonosides E and F, and a Fluorinated Cerebroside Analogue

“…We infer from our previouss tudies that this spectralf eature indicates strong hydrogen bonding to the chloride ligand on the metal. [6,7,10] Likewise, the complexation-inducedd eshielding of the alkyne signals is more pronounced for the proximal than for the distal triple bond (Dd C1 = 73.9 ppm versus Dd C3 = 47.2 ppm), [20] in line with the notion that the propargylic site binds to the metal, whereas the distal alkyne is primarily affected via conjugation.…”

“…[6][7][8][9] Ample experimental and computational evidence suggests that an incipient hydrogen bond between the -XH group (X = O, NR) and the polarized [Ru-Cl] entity of the catalyst favors substrate binding. [6,7,10] Moreover,t his inter-ligand interaction imposes directionality on the loaded complex B and the ensuing transition state, which explains the generally excellent levels of regio-and stereoselectivity in favor of the a/transproduct C.O ft he different hydrometalation reactions investigated, trans-hydrostannation provedt ob em ost receptive to this effect. [6,7] In any case, compounds of type C provide many opportunities for downstream functionalization, as witnessed by ag rowing number of applicationst ot arget-and/ord iversity-oriented synthesis.…”

Hydrogenative Cyclopropanation and Hydrogenative Metathesis

“…[17] In contrast, the closely related substrate 9a failed to undergo hydrogenative cyclopropanation (Scheme 3). Thec onstitution of the resulting product 10 a suggests that metallacycle formation by oxidative enyne cyclization [18,19] is faster than gem-hydrogenation, even though the exact mechanism that results in concomitant loss of MeOH is unknown. Theanalogous primary ether 9b gave arather complex mixture.…”

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

“…Selected bond distances (Å) and angles (deg. ): C1-C2, 1.565(2); C1-C8, 1.539(2); C2-C3, 1.473(2); C2-C15, 1.337(2); C3-C8, 1.390(2); C15-C16, 1.456(2); C16-C17, 1.337(2); C17-C18, 1.516(2); C2-C1-C8, 84.14(11); C1-C2-C3, 89.27(11); C1-C2-C15, 133.32 (14); C3-C2-C15, 137.20 (15); C2-C3-C8, 93.11 (12); C1-C8-C3, 93.48 (12).…”

“…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.…”