32223-12-4Relevant academic research and scientific papers
Demystifying Cp2Ti(H)Cl and Its Enigmatic Role in the Reactions of Epoxides with Cp2TiCl
Gordon, Jonathan,Hildebrandt, Sven,Dewese, Kendra R.,Klare, Sven,Gans?uer, Andreas,Rajanbabu,Nugent, William A.
, p. 4801 - 4809 (2019/01/08)
The role of Cp2Ti(H)Cl in the reactions of Cp2TiCl with trisubstituted epoxides has been investigated in a combined experimental and computational study. Although Cp2Ti(H)Cl has generally been regarded as a robust species, its decomposition to Cp2TiCl and molecular hydrogen was found to be exothermic (ΔG = -11 kcal/mol when the effects of THF solvation are considered). In laboratory studies, Cp2Ti(H)Cl was generated using the reaction of 1,2-epoxy-1-methylcyclohexane with Cp2TiCl as a model. Rapid evolution of hydrogen gas was demonstrated, indicating that Cp2Ti(H)Cl is indeed a thermally unstable molecule, which undergoes intermolecular reductive elimination of hydrogen under the reaction conditions. The stoichiometry of the reaction (Cp2TiCl:epoxide = 1:1) and the quantity of hydrogen produced (1 mol per 2 mol of epoxide) is consistent with this assertion. The diminished yield of allylic alcohol from these reactions under the conditions of protic versus aprotic catalysis can be understood in terms of the predominant titanium(III) present in solution. Under the conditions of protic catalysis, Cp2TiCl complexes with collidine hydrochloride and the titanium(III) center is less available for "cross-disproportionation" with carbon-centered radicals; this leads to byproducts from radical capture by hydrogen atom transfer, resulting in a saturated alcohol.
Ti-catalyzed transannular cyclization of epoxygermacrolides. Synthesis of antifungal (+)-tuberiferine and (+)-dehydrobrachylaenolide
Justicia, José,de Cienfuegos, Luis álvarez,Estévez, Rosa E.,Paradas, Miguel,Lasanta, Ana M.,Oller, Juan L.,Rosales, Antonio,Cuerva, Juan M.,Oltra, J. Enrique
scheme or table, p. 11938 - 11943 (2009/04/06)
We present a divergent strategy for the stereoselective synthesis of both eudesmanolides (+)-tuberiferine and (+)-brachylaenolide starting from the accessible germacrolide (+)-costunolide. The key steps of these syntheses are the Ti-catalyzed transannular cyclization of a 1,4-epoxygermacrolide in the presence or absence of water, respectively. The catalytic cycle operating in the presence of water probably involves the reduction of a tertiary radical by H-atom transfer from aquacomplex Cp2TiIII(OH2)Cl. The catalytic cycle under anhydrous conditions presumably occurs through mixed disproportionation between a tertiary radical and Cp2TiIIICl. Synthetic (+)-tuberiferine and (+)-brachylaenolide displayed an antifungal potency against Phycomyces blakesleeanus comparable or even higher than amphotericin B, the gold standard for antifungal therapy.
Unified synthesis of eudesmanolides, combining biomimetic strategies with homogeneous catalysis and free-radical chemistry
Barrero, Alejandro F.,Rosales, Antonio,Cuerva, Juan M.,Oltra, J. Enrique
, p. 1935 - 1938 (2007/10/03)
(Matrix presented) A general procedure for the synthesis of both 12,6- and 12,8-eudesmanolides has been developed. The key step is the titanocene-catalyzed radical cyclization of accessible epoxygermacrolides. The novel reagent 2,4,6-trimethyl-1-trimethylsilylpyridinium chloride, both compatible with oxiranes and capable of regenerating Cp2TiCl 2 from Cp2Ti(Cl)H and Cp2Ti(Cl)OAc, played an important role in the catalytic cycle leading to exocyclic alkenes.
Effects of solvents and water in Ti(III)-mediated radical cyclizations of epoxygermacrolides. Straightforward synthesis and absolute stereochemistry of (+)-3α-hydroxyreynosin and related eudesmanolides
Barrero, Alejandro F.,Enrique Oltra,Cuerva, Juan M.,Rosales, Antonio
, p. 2566 - 2571 (2007/10/03)
The Cp2TiCl-mediated rearrangement of 1,10-epoxy-11β,13-dihydrocostunolide (4) was carried out using different solvents and additives to develop an expeditious procedure for the synthesis of natural eudesmanolides via free-radical chemistry. In the nonhalogenated solvents THF, benzene, and toluene the transannular cyclization, initiated by the homolytic opening of the oxirane ring, selectively led to the desired exocyclic alkene 5. When water was added to THF, however, the main product was reduced eudesmanolide 8. Experiments with D2O confirmed that the H-4 of 8 comes from water. To rationalize these results, a mechanistic hypothesis based on a water-solvated Cp2TiCl complex is proposed. Finally, the usefulness of Cp2TiCl for the synthesis of natural eudesmanolides has been proved using this reagent in the key step for the chemical preparation of (+)-3α-hydroxyreynosin (1) and (+)-reynosin (17). These syntheses confirmed the chemical structure of 1 and established the absolute stereochemistry of the natural products 1 and 17. The results obtained suggest that the combination of the biomimetic strategy employed, with Ti(III)-mediated free-radical chemistry, may come to represent a general method for the enantiospecific synthesis of more than 170 natural eudesmanolides containing an exocyclic double bond between C-4 and C-15.
Guaianolides as immunomodulators. Synthesis and biological activities of dehydrocostus lactone, mokko lactone, eremanthin, and their derivatives
Yuuya, Saori,Hagiwara, Hisahiro,Suzuki, Toshio,Ando, Masayoshi,Yamada, Atsushi,Suda, Kouji,Kataoka, Takao,Nagai, Kazuo
, p. 22 - 30 (2007/10/03)
The naturally occurring guaianolides, namely mokko lactone (1), dehydrocostus lactone (2), eremanthin (3), and related guaianolides, 16, 17, 21, 22, 28-31, 33, 36, 37, and 39, have been synthesized starting from l-α- santonin in an effort to examine their structure-activity relationship as inhibitors of the killing function of cytotoxic T lymphocytes (CTL) and the induction of intercellular adhesion molecule-1 (ICAM-1). It was observed during the present study that the guaianolides possessing an α-methylene γ- lactone moiety, i.e., 2, 3, 30, 33, 37, and 39, exhibited significant inhibitory activity toward the killing function of CTL and the induction of ICAM-1.
TOTAL SYNTHESES OF MOKKO LACTONE, DEHYDROCOSTUS LACTONE, AND EREMANTHIN
Ando, Masayoshi,Ono, Akio,Takase, Kahei
, p. 493 - 496 (2007/10/02)
A series of guaianolides such as mokko lactone, dehydrocostus lactone, and eremanthin which posses a common structural unit in A ring have been synthesized from 1-oxoeudesm-2-eno-13,6α-lactone in 7 steps.The key step involves solvolytic rearrangement of 1β-mesyloxyeudesm-4(14)-eno-13,6α-lactone.
THE TOTAL SYNTHESIS OF 1-OXYGENATED EUDESMANOLIDES
Hijfte, Luc Van,Vandewalle, Maurits
, p. 4371 - 4382 (2007/10/02)
A route towards 1-oxygenated eudesmanolides, via a (2+2) photocycloaddition reaction for constructing the decalin framework is described.The following natural substances have been synthesized. (+/-)-dihydroreynosin (1), (+/-)-1-oxo-dihydromagnolialide (2)
