词条 | Bis(cyclopentadienyl)titanium(III) chloride |
释义 |
| ImageFile = DCCPTI02.png | ImageSize = | ImageAlt = | IUPACName = | OtherNames = titanocene monochloride Nugent–RajanBabu reagent |Section1={{Chembox Identifiers | CASNo = 1271-18-7 | PubChem = 101376209 | StdInChI=1S/2C5H5.ClH.Ti/c2*1-2-4-5-3-1;;/h2*1-5H;1H;/p-1 | StdInChIKey = GCXNJJRCRJQDSV-UHFFFAOYSA-M | SMILES = C1=C[CH]C=C1.C1=C[CH]C=C1.[Cl-].[Ti] |Section2={{Chembox Properties | C=20|H=20|Cl=2|Ti=2 | MolarMass = | Appearance = green solid | Density = | MeltingPt = | BoilingPt = | Solubility = }} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }} Bis(cyclopentadienyl)titanium(III) chloride, also known as the Nugent–RajanBabu reagent, is the organotitanium compound which exists as a dimer with the formula [(C5H5)2TiCl]2. It is an air sensitive green solid. The complex finds specialized use in synthetic organic chemistry as a single electron reductant. In the presence of a suitable solvent that can act as a two-electron donor ("solv"), such as an ether like tetrahydrofuran, the dimer separates and forms a chemical equilibrium between the forms [(C5H5)2TiCl] and [(C5H5)2Ti(solv)Cl]. It is these forms that are responsible for much of the chemical properties of this reagent, which is also the reason that the substance is sometimes written as [(C5H5)2TiCl] or [Cp2TiCl], where Cp− represents the cyclopentadienyl anion. An example of an application of this reagent is in the preparation of vinorelbine, a chemotherapeutic agent which can be prepared in three steps from the nautrally-occurring alkaloid leurosine. Synthesis and structureIt was first reported in 1955 by Geoffrey Wilkinson[1] It is commonly prepared by reducing titanocene dichloride with zinc,[2] manganese, or magnesium.[3] For use in organic synthesis, the reagent is often prepared and used directly in situ.[4] The molecule adopts a dimeric structure with bridging chlorides,[5] though in an appropriate solvent such as THF,[4] exists in a chemical equilibrium with monomeric structures:[5] The compound is also known as the Nugent–RajanBabu reagent, after scientists William A. Nugent and T. V. (Babu) RajanBabu, and has found applications in free radical and organometallic chemistry.[6] Use in organic synthesisBis(cyclopentadienyl)titanium(III) chloride effects the anti-Markovnikov opening of epoxides to a free radical intermediate and is tolerant of alcohols and some basic nitrogen functional groups, however it is sensitive to oxidizing functional groups such as nitro groups.[7] As can be seen in the above illustration, subsequent reaction proceeds along a pathway determined by added reagents and reaction conditions:[10]
The reagent has been used in the synthesis of over 20 natural products.[6][7][13] Ceratopicanol is a naturally-occurring sesquiterpene and its carbon skeleton is incorporated with the structures of both anislactone A and merrilactone A.[10][13] A regioselective epoxide opening and 5-exo dig radical cyclization to forge the core of ceratopicanol.[13][17] Addition of a hydrochloride salt to the reaction facilitates release of the oxygen-bound titanium(IV) intermediate, allowing the reagent to be recycled.[18] The Madagascan periwinkle Catharanthus roseus L. is the source for a number of important natural products, including catharanthine and vindoline[19] and the vinca alkaloids it produces from them: leurosine and the chemotherapy agents vinblastine and vincristine, all of which can be obtained from the plant.[20][21][22][23] The newer semi-synthetic chemotherapeutic agent vinorelbine is used in the treatment of non-small-cell lung cancer[22][24] and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine[22][25] or from leurosine,[41] in both cases by synthesis of anhydrovinblastine, which "can be considered as the key intermediate for the synthesis of vinorelbine."[22] The leurosine pathway uses the Nugent–RajanBabu reagent in a highly chemoselective de-oxygenation of leurosine.[13][26] Anhydrovinblastine is then reacted sequentially with N-bromosuccinimide and trifluoroacetic acid followed by silver tetrafluoroborate to yield vinorelbine.[25] Additional reactivityCyclic and benzylic ketones are reduced to their respective alcohols.[27]Bis(cyclopentadienyl)titanium(III) chloride also effects both Pinacol[28][29] and McMurry[30] couplings of aldehydes and ketones. Barbier-type reactivity is observed between aldehydes or ketones and allyl electrophiles under catalytic conditions.[31] The proposed mechanism involves titanium(III)-mediated generation of an allyl radical species which intercepts a titanium(III)-coordinated carbonyl. Another application involves the single electron reduction of enones to generate allylic radicals which can undergo intermolecular trapping with acrylonitirles to afford Michael type adducts.[32] Benzylic and allylic alcohols can be de-oxygenated under mild conditions using super-stoichiometric Cp2TiCl, however the reported scope for aliphatic alcohols is currently limited.[30] MechanismThe dimeric titanium(III) complex reversibly dissociates to the monomer Cp2TiCl. This 15 electron species is Lewis acidic and thus binds epoxides and carbonyl compounds.[33] The complex transfers a single electron to the coordinated substrate generating an alkyl centered radical and an oxygen bound titanium(IV) species. This process is driven by the strength of the titanium-oxygen bond, as well as strain release in the case of epoxides.[34] {{-}}References1. ^{{cite journal|last1 = Birmingham|first1 = J. M.|last2 = Fischer|first2 = A. K.|last3 = Wilkinson|first3 = G.|authorlink3 = Geoffrey Wilkinson|year = 1955|title = The reduction of bis-cyclopentadienyl compounds|journal = Naturwissenschaften|volume = 42|issue = 4|page = 96|doi = 10.1007/BF00617242}} {{Titanium compounds}}2. ^{{cite journal|journal = Inorganic Syntheses|title = Cyclopentadienyl Complexes of Titanium(III) and Vanadium(III)|first1 = L. E.|last1 = Manzer|first2 = E. A.|last2 = Mintz|first3 = T. J.|last3 = Marks|doi = 10.1002/9780470132524.ch18|volume = 21|year = 1982|pages = 84–86}} 3. ^{{cite journal|journal = Tetrahedron Letters|volume = 28|issue = 46|year = 1987|pages = 5717–5718|title = A highly stereoselective pinacolization of aromatic and α, β-unsaturated aldehydes mediated by titanium(III)-magnesium(II) complex|first1 = Yuichi|last1 = Handa|first2 = Junji|last2 = Inanaga|doi = 10.1016/S0040-4039(00)96822-9}} 4. ^1 {{cite journal|last1 = Nugent|first1 = William A.|last2 = RajanBabu|first2 = T. V.|title = Transition-metal-centered radicals in organic synthesis. Titanium(III)-induced cyclization of epoxy olefins|journal = Journal of the American Chemical Society|volume = 110|issue = 25|pages = 8561–8562|doi = 10.1021/ja00233a051|year = 1988}} 5. ^1 {{cite journal|title = Structural and magnetic properties of di-μ-chloro-bis[bis(η5-cyclopentadienyl)titanium(III)] and di-μ-bromo-bis[bis(η5-methylcyclopentadienyl)titanium(III)]|pages = 1645–1655|journal = Inorganic Chemistry|year = 1977|volume = 16|issue = 7|last1 = Jungst|first1 = Rudolph|last2 = Sekutowski|first2 = Dennis|last3 = Davis|first3 = Jimmy|last4 = Luly|first4 = Matthew|last5 = Stucky|first5 = Galen|doi = 10.1021/ic50173a015}} 6. ^1 {{cite journal|title = The Nugent Reagent: A Formidable Tool in Contemporary Radical and Organometallic Chemistry|first1 = Antonio|last1 = Rosales|first2 = Ignacio|last2 = Rodríguez-Garcia|first3 = Juan|last3 = Muñoz-Bascón|first4 = Esther|last4 = Roldan-Molina|first5 = Natalia M.|last5 = Padial|first6 = Laura P.|last6 = Morales|first7 = Marta|last7 = García-Ocaña|first8 = J. Enrique|last8 = Oltra|doi = 10.1002/ejoc.201500292|year = 2015|volume = 2015|issue = 21|pages = 4567–4591|journal = European Journal of Organic Chemistry}} This review article was corrected to refer to the "Nugent–RajanBabu Reagent" rather than the "Nugent Reagent" by: {{cite journal|title = The Nugent–RajanBabu Reagent: A Formidable Tool in Contemporary Radical and Organometallic Chemistry|first1 = Antonio|last1 = Rosales|first2 = Ignacio|last2 = Rodríguez-Garcia|first3 = Juan|last3 = Muñoz-Bascón|first4 = Esther|last4 = Roldan-Molina|first5 = Natalia M.|last5 = Padial|first6 = Laura P.|last6 = Morales|first7 = Marta|last7 = García-Ocaña|first8 = J. Enrique|last8 = Oltra|doi = 10.1002/ejoc.201500761|year = 2015|volume = 2015|issue = 21|page = 4592|journal = European Journal of Organic Chemistry}} 7. ^1 2 3 {{cite book|title = Encyclopedia of Reagents for Organic Synthesis|last = Nugent|first = William A.|date = January 1, 2001|publisher = John Wiley & Sons|isbn = 9780470842898|doi = 10.1002/047084289x.rn00294}} 8. ^{{cite journal|last = RajanBabu|first = T. V.|last2 = Nugent|first2 = William A.|last3 = Beattie|first3 = Margaret S.|title = Free radical-mediated reduction and deoxygenation of epoxides|doi = 10.1021/ja00173a045|journal = Journal of the American Chemical Society|volume = 112|issue = 17|pages = 6408–6409|year = 1990}} 9. ^{{cite journal|last = RajanBabu|first = T. V.|last2 = Nugent|first2 = William A.|title = Selective generation of free radicals from epoxides using a transition-metal radical. A powerful new tool for organic synthesis|journal = Journal of the American Chemical Society|year = 1994|volume = 116|issue = 3|pages = 986–997|doi = 10.1021/ja00082a021}} 10. ^{{cite journal|last1 = Barrero|first1 = Alejandro F.|last2 = Oltra|first2 = J. Enrique|last3 = Cuerva|first3 = Juan M.|last4 = Rosales|first4 = Antonio|year = 2002|title = Effects of solvents and water in Ti(III)-mediated radical cyclizations of epoxygermacrolides. Straightforward synthesis and absolute stereochemistry of (+)-3α-hydroxyreynosin and related eudesmanolides|journal = Journal of Organic Chemistry|volume = 67|issue = 8|pages = 2566–2571|doi = 10.1021/jo016277e}} 11. ^{{cite journal|last1 = Rickborn|first1 = Bruce|last2 = Quartucci|first2 = Joe|title = Stereochemistry and mechanism of lithium aluminum hydride and mixed hydride reduction of 4-t-butylcyclohexene oxide|journal = Journal of Organic Chemistry|year = 1964|volume = 29|issue = 11|pages = 3185–3188|doi = 10.1021/jo01034a015}} 12. ^{{cite journal|title = Reduction of epoxides. II. The lithium aluminum hydride and mixed hydride reduction of 3-methylcyclohexene oxide|first1 = Bruce|last1 = Rickborn|first2 = Wallace E.|last2 = Lamke|year = 1967|volume = 32|issue = 3|pages = 537–539|journal = Journal of Organic Chemistry|doi = 10.1021/jo01278a005}} 13. ^1 2 3 4 5 {{cite journal|last1 = Morcillo|first1 = Sara P.|last2 = Miguel|first2 = Delia|last3 = Campaña|first3 = Araceli G.|last4 = Cienfuegos|first4 = Luis Álvarez de|last5 = Justicia|first5 = José|last6 = Cuerva|first6 = Juan M.|year = 2014|title = Recent applications of Cp2TiCl in natural product synthesis|journal = Organic Chemistry Frontiers|volume = 1|issue = 1|pages = 15–33|doi = 10.1039/c3qo00024a|url = http://pubs.rsc.org/en/content/articlepdf/2014/qo/c3qo00024a}} 14. ^{{Cite journal|last1 = RajanBabu|first1 = T. V.|last2 = Nugent|first2 = William A.|title = Intermolecular addition of epoxides to activated olefins: a new reaction|year = 1989|journal = Journal of the American Chemical Society|volume = 111|issue = 12|pages = 4525–4527|doi = 10.1021/ja00194a073}} 15. ^{{cite journal|last1 = Gansäuer|first1 = Andreas|last2 = Pierobon|first2 = Marianna|last3 = Bluhm|first3 = Harald|year = 2002|title = Stereoselective synthesis of tri- and tetrasubstituted olefins by tandem cyclization addition reactions featuring vinyl radicals|journal = Angewandte Chemie International Edition|volume = 41|issue = 17|pages = 3206–3208|doi = 10.1002/1521-3773(20020902)41:173.0.CO;2-2}} 16. ^{{cite journal|year = 2015|last1 = Zhao|first1 = Yang|last2 = Weix|first2 = Daniel J.|title = Enantioselective cross-coupling of meso-epoxides with aryl halides|journal = Journal of the American Chemical Society|volume = 137|issue = 9|pages = 3237–3240|doi = 10.1021/jacs.5b01909|pmc = 4415026|pmid = 25716775}} 17. ^{{cite journal|title = 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|first1 = D. L. J.|last1 = Clive|first2 = Steven R.|last2 = Magnuson|first3 = Hartford W.|last3 = Manning|first4 = Darrin L.|last4 = Mayhew|journal = Journal of Organic Chemistry|volume = 61|issue = 6|pages = 2095–2108|doi = 10.1021/jo951930h|year = 1996}} 18. ^{{cite journal|last1 = Gansäuer|first1 = Andreas|last2 = Pierobon|first2 = Marianna|last3 = Bluhm|first3 = Harald|year = 1998|title = Catalytic, highly regio- and chemoselective generation of radicals from epoxides: Titanocene dichloride as an electron transfer catalyst in transition metal catalyzed radical reactions|journal = Angewandte Chemie International Edition|volume = 37|issue = 1-2|pages = 101–103|doi = 10.1002/(SICI)1521-3773(19980202)37:1/23.0.CO;2-W}} 19. ^{{cite book|chapter = Catharanthus roseus L. (Periwinkle): Production of Vindoline and Catharanthine in Multiple Shoot Cultures|first1 = K.|last1 = Hirata|first2 = K.|last2 = Miyamoto|first3 = Y.|last3 = Miura|title = Biotechnology in Agriculture and Forestry 26|series = Medicinal and Aromatic Plants|volume = VI|editor-first = Y. P. S.|editor-last = Bajaj|publisher = Springer-Verlag|year = 1994|pages = 46–55|url = https://books.google.com.au/books?id=e64hCDBddowC&pg=PA47|isbn = 9783540563914}} 20. ^1 2 3 {{cite book|title = Metal Catalyzed Reductive C—C Bond Formation: A Departure from Preformed Organometallic Reagents|volume = 279|series = Topics in Current Chemistry|pages = 25–52|year = 2007|chapter = Reductive C—C bond formation after epoxide opening via electron transfer|first1 = Andreas|last1 = Gansäuer|first2 = José|last2 = Justicia|first3 = Chun-An|last3 = Fan|first4 = Dennis|last4 = Worgull|first5 = Frederik|last5 = Piestert|doi = 10.1007/128_2007_130|url = https://books.google.com.au/books?id=A5xcVmT9iIQC&pg=PA25|editor-first = Michael J.|editor-last = Krische|editorlink1=Michael J. Krische|publisher = Springer Science & Business Media|isbn = 9783540728795}} 21. ^{{cite book|chapter = Africa's gift to the world|pages = 46–51|url = https://books.google.com.au/books?id=aXGmCwAAQBAJ&pg=PA46|title = Botanical Miracles: Chemistry of Plants That Changed the World|first1 = Raymond|last1 = Cooper|first2 = Jeffrey John|last2 = Deakin|publisher = CRC Press|year = 2016|isbn = 9781498704304}} 22. ^1 2 3 {{cite journal|journal = Molecules|year = 2012|volume = 17|pages = 5893–5914|doi = 10.3390/molecules17055893|title = Modifications on the basic skeletons of vinblastine and vincristine|first1 = Péter|last1 = Keglevich|first2 = Laszlo|last2 = Hazai|first3 = György|last3 = Kalaus|first4 = Csaba|last4 = Szántay|pmid = 22609781|url = http://www.mdpi.com/1420-3049/17/5/5893/pdf}} 23. ^{{cite book|last = Raviña|first = Enrique|title = The evolution of drug discovery: From traditional medicines to modern drugs|year = 2011|publisher = John Wiley & Sons|isbn = 9783527326693|pages = 157–159|chapter = Vinca alkaloids|url = https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA157}} 24. ^{{cite journal|journal = Oncology|year = 2011|volume = 5|pages = 131–144|doi = 10.4137/CMO.S5074|pmc = 3117629|title = Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer|first1 = Bryan A.|last1 = Faller|first2 = Trailokya N.|last2 = Pandi}} 25. ^1 {{cite journal|last1 = Ngo|first1 = Quoc Anh|last2 = Roussi|first2 = Fanny|last3 = Cormier|first3 = Anthony|last4 = Thoret|first4 = Sylviane|last5 = Knossow|first5 = Marcel|last6 = Guénard|first6 = Daniel|last7 = Guéritte|first7 = Françoise|title = Synthesis and biological evaluation of Vinca alkaloids and phomopsin hybrids|journal = Journal of Medicinal Chemistry|year = 2009|volume = 52|issue = 1|pages = 134–142|pmid = 19072542|doi = 10.1021/jm801064y}} 26. ^1 {{cite journal|title = Concise synthesis of anhydrovinblastine from leurosine|first1 = Christophe|last1 = Hardouin|first2 = Eric|last2 = Doris|first3 = Bernard|last3 = Rousseau|first4 = Charles|last4 = Mioskowski|journal = Organic Letters|year = 2002|volume = 4|issue = 7|pages = 1151–1153|doi = 10.1021/ol025560c}} 27. ^{{cite journal|last1 = Barrero|first1 = Alejandro F.|last2 = Rosales|first2 = Antonio|last3 = Cuerva|first3 = Juan M.|last4 = Gansäuer|first4 = Andreas|last5 = Oltra|first5 = J. Enrique|year = 2003|title = Titanocene-catalysed, selective reduction of ketones in aqueous media. A safe, mild, inexpensive procedure for the synthesis of secondary alcohols via radical chemistry|journal = Tetrahedron Letters|volume = 44|issue = 5|pages = 1079–1082|doi = 10.1016/S0040-4039(02)02703-X}} 28. ^{{cite journal|last1 = Gansäuer|first1 = Andreas|year = 1997|title = Pinacol coupling of aromatic aldehydes catalysed by a titanocene complex: A transition metal catalysed radical reaction|journal = Chemical Communications|volume = 1997|issue = 5|doi = 10.1039/A608438I|pages = 457–458}} 29. ^{{cite journal|last1 = Paradas|first1 = Miguel|last2 = Campaña|first2 = Araceli G.|last3 = Estévez|first3 = Rosa E.|last4 = Cienfuegos|first4 = Luis Álvarez de|last5 = Jiménez|first5 = Tania|last6 = Robles|first6 = Rafael|last7 = Cuerva|first7 = Juan M.|last8 = Oltra|first8 = J. Enrique|title = Unexpected TiIII/Mn-promoted pinacol coupling of ketones|journal = Journal of Organic Chemistry|volume = 74|issue = 9|pages = 3616–3619|doi = 10.1021/jo9005238}} 30. ^1 {{cite journal|last1 = Diéguez|first1 = Horacio R.|last2 = López|first2 = Armando|last3 = Domingo|first3 = Victoriano|last4 = Arteaga|first4 = Jesús F.|last5 = Dobado|first5 = José A.|last6 = Herrador|first6 = M. Mar|last7 = Moral|first7 = José F. Quílez del|last8 = Barrero|first8 = Alejandro F.|title = Weakening C—O bonds: Ti(III), a new reagent for alcohol deoxygenation and carbonyl coupling olefination|journal = Journal of the American Chemical Society|volume = 132|issue = 1|pages = 254–259|doi = 10.1021/ja906083c}} 31. ^{{cite journal|last1 = Rosales|first1 = Antonio|last2 = Oller-López|first2 = Juan L.|last3 = Justicia|first3 = José|last4 = Gansäuer|first4 = Andreas|last5 = Oltra|first5 = J. Enrique|last6 = Cuerva|first6 = Juan M.|year = 2004|title = Unprecedented Barbier-type reactions catalysed by titanocene(III)|journal = Chemical Communications|volume = 2004|issue = 22|doi = 10.1039/B411173G|pages = 2628–2629}} 32. ^{{cite journal|last = Streuff|first = Jan|year = 2011|title = A titanium(III)-catalyzed redox Umpolung reaction for the reductive cross-coupling of enones with acrylonitriles|journal = Chemistry – A European Journal|volume = 17|issue = 20|pages = 5507–5510|doi = 10.1002/chem.201100501}} 33. ^{{cite journal|last1 = Cangönül|first1 = Asli|last2 = Behlendorf|first2 = Maike|last3 = Gansäuer|first3 = Andreas|last4 = Gastel|first4 = Maurice van|title = Radical-based epoxide opening by titanocenes|journal = Inorganic Chemistry|year = 2013|volume = 52|issue = 20|pages = 11859–11866|doi = 10.1021/ic401403a}} 34. ^{{cite journal|last1 = Gansäuer|first1 = Andreas|last2 = Barchuk|first2 = Andriy|last3 = Keller|first3 = Florian|last4 = Schmitt|first4 = Martin|last5 = Grimme|first5 = Stefan|last6 = Gerenkamp|first6 = Mareike|last7 = Mück-Lichtenfeld|first7 = Christian|last8 = Daasbjerg|first8 = Kim|last9 = Svith|first9 = Heidi|title = Mechanism of titanocene-mediated epoxide opening through homolytic substitution|journal = Journal of the American Chemical Society|year = 2007|volume = 129|issue = 5|pages = 1359–1371|doi = 10.1021/ja067054e}} 5 : Titanocenes|Cyclopentadienyl complexes|Chlorides|One-electron reducing agents|Chloro complexes |
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