Ruthenium-Catalyzed Cycloisomerization−Oxidation of Homopropargyl Alcohols. A New Access to γ-Butyrolactones

Abstract

Vinylidenemetal species, which readily form from terminal alkynes under mild conditions, have rarely been utilized as reactive intermediates in a catalytic cycle. The conversion of homopropargyl alcohols via such intermediates to metal-complexed oxacarbenes led to the development of an “oxidant” compatible with a ruthenium complex capable of performing the cycloisomerization, that would convert them to lactones. None of the oxidants known to stoichiometrically convert isolated metallooxacarbenes to esters are effective. The unconventional “oxidants”, N-hydroxyimides, proved to be capable of effecting the desired transformation, with N-hydroxysuccinimide being the “oxidant” of choice. The procedure of choice employs cyclopentadienyl (1,4-cyclooctadiene) ruthenium chloride and trifuryl phosphine as the precatalyst in the presence of tetra-n-butylammonium bromide or hexafluorophosphate with N-hydroxysuccinimide as the oxidant in DMF−water at 95°. In this way, a wide diversity of homopropargyl alcohols were converted to γ-butyrolactones with excellent chemoselectivity. Lactones synthesized include an intermediate toward a platelet aggregation inhibitor, a fruit flavor principle, an inhibitor of binding of phorbol esters to PKC-α, a tobacco constituent, a wood constituent (quercus lactone), an aldosterone antagonist (spironolactone) precursor, and an acetogenin known for pesticidal and antitumor activities (muricatacin).

Metal Vinylidenes as Catalytic Species in Organic Reactions

“…The power of this reaction was demonstrated in a concise synthesis of the fully functionalized side chain of the steroid ganoderic acid (48,Scheme 16). [31] The terminal alkyne substrate 44 was prepared by Corey-Fuchs homologation of the commercially available 3-oxopregn-4-ene-20β-carboxaldehyde (43).…”

“…[48] Studies on the related reactions of bis-homopropargyl alcohols showed that employing the electron-donating ligand tris(4-methoxphenyl)phosphine gave δ-valerolactone products (Scheme 30). Interestingly, the electronics of the ligand could be tuned to give a different product.…”

Ruthenium‐Catalyzed Reactions—A Treasure Trove of Atom‐Economic Transformations

“…(8)]. [44] This methodology was applied in a short asymmetric synthesis of (À)-muricatacin, a natural product with antitumor properties (Scheme 3). [45,46] The chemoselectivity of this oxidative cyclization of 35 for the formation of a fivepreferentially to a six-membered ring is noteworthy.…”

“…The initial stages of the catalytic cycle are common for both pathways. Thus, vinylidene 43 is formed, and nucleophilic attack of the hydroxy group at the vinylidene carbon atom leads to the pivotal intermediate 44 …”

Ruthenium‐katalysierte Reaktionen – eine Schatzkiste für atomökonomische Umwandlungen

“…(8)]. [44] Diese Methode fand auch Verwendung bei einer kurzen, asymmetrischen Synthese von (À)-Muricatacin, einem natür-lichen Tumortherapeutikum (Schema 3). [45,46] [48] Im vorliegenden Fall ist die Wahl einer koordinierenden Base, speziell N-Hydroxysuccinimid, entscheidend für den Umsatz, da mit anderen Basen überhaupt keine Hydropyrane erhalten wurden.…”