Cyclopentannulation by an Iterative Process of Sequential Claisen Rearrangement and Enyne Radical Closure:  Routes to Triquinane and Propellane Systems and Use in the Synthesis of (±)-Ceratopicanol

Abstract

Cycloalkenyl acetylenes 4, which are easily prepared from allylic alcohols by Claisen rearrangement and homologation (1 → 4), generally undergo radical cyclization (4 → 6) on treatment with stannyl radicals. The products (6) can themselves be converted into allylic alcohols, so that the annulation sequence can then be repeated. In certain cases enyne cyclization initiated by stannyl radicals does not work, but an alternative process (cf. Scheme 9) of epoxide opening with bis(cyclopentadienyl)titanium(III) chloride can then be used. Di- and triquinanes (Scheme 3) were made by the stannyl radical approach; the epoxide route was used to prepare a simple propellane (Scheme ) and in a synthesis of (±)-ceratopicanol (Schemes and 9).

Linear Triquinane Sesquiterpenoids: Their Isolation, Structures, Biological Activities, and Chemical Synthesis

“…In 1996, Baralotto and co-workers [ 99 ] proposed a total synthesis of racemic (±)-ceratopicanol ((±)- 109 ), employing seven steps, in which the key one was an intramolecular meta photocycloaddition of the phenylpentene derivative 200 , which constituted a typical holosynthon ( Scheme 49 ). In 1996, Clive and co-workers [ 100 ] also reported a method to synthesize (+)-ceratopicanol ( 109 ) ( Scheme 50 ). This method has been used to form many compounds of the triquinane class.…”

Bis(cyclopentadienyl)titanium(III) Chloride

“…Under these circumstances the unpaired electron can be trapped by a second equivalent of Cp 2 TiCl to give an enolate anion which is hydrolyzed in a separate step. 24 A similar approach provides ready access to propellane systems 24 and to the heterocyclic natural product, methylenolactocin. 16 The carbon-centered radicals generated by Cp 2 TiCl-induced homolysis of epoxides can undergo intramolecular addition to a suitably positioned unsaturation elsewhere in the molecule.…”

Biscyclopentadienyltitanium(III) chloride dimer

“…6,14, 15 The intramolecular reaction also proceeds smoothly through a 5-exo cyclization pathway. Thus, for example, ω-vinylic and ωacetylenic epoxides afford 1-hydroxymethyl-2-methylcyclopentane (eq 10) 6,16 and 1-hydroxymethyl-2-methylenecyclopentanes (eq 11), 17 (11) Pinacol Coupling of Aldehydes. The Cp 2 TiCl reagent promotes the reductive homo-coupling of aromatic and α,β-unsaturated aldehydes to provide symmetrical 1,2-diols with high dlselectivity (eq 12).…”