- Hydroamination of Dihapto-Coordinated Benzene and Diene Complexes of Tungsten: Fundamental Studies and the Synthesis of γ-Lycorane
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Reactions are described for complexes of the form WTp(NO)(PMe3)(η2-arene) and various amines, where the arene is benzene or benzene with an electron-withdrawing substituent (CF3, SO2Ph, SO2Me). The arene complex is first protonated to form an η2-arenium species, which then selectively adds the amine. The resulting η2-5-amino-1,3-cyclohexadiene complexes can then be subjected to the same sequence with a second nucleophile to form 3-aminocyclohexene complexes, where up to three stereocenters originate from the arene carbons. Alternatively, 1,3-cyclohexadiene complexes containing an ester group at the 5 position (also prepared from an arene) can be treated with acid followed by an amine to form trisubstituted 3-aminocyclohexenes. When the amine is primary, ring closure can occur to form a cis-fused bicyclic γ-lactam. Highly functionalized cyclohexenes can be liberated from the tungsten through oxidative decomplexation. The potential utility of this methodology is demonstrated in the synthesis of the alkaloid γ-lycorane. An enantioenriched synthesis of a lactam precursor to γ-lycorane is also described. This compound is prepared from an enantioenriched version of the tungsten benzene complex. Regio- and stereochemical assignments for the reported compounds are supported by detailed 2D-NMR analysis and 13 molecular structure determinations (SC-XRD).
- Chordia, Mahendra D.,Dickie, Diane A.,Ericson, Megan N.,Harman, W. Dean,Nedzbala, Hannah S.,Simpson, Spenser R.,Westendorff, Karl S.,Wilson, Katy B.
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- Total synthesis of (±)-γ-lycorane via the electrocyclic ring closure of a divinylpyrroline
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A concise total synthesis of (±)-γ-lycorane is described. The key step in the synthesis is the 6π-electrocyclic ring closure of a divinylpyrroline to give a tetrahydroindole, which is subsequently hydrogenated to give the all-cis indolizidine core.
- Huntley, Raymond J.,Funk, Raymond L.
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- Formal total synthesis of (±)-γ-lycorane and (±)-1-deoxylycorine using the [4+2]-cycloaddition/rearrangement cascade of furanyl carbamates
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The total syntheses of γ-lycorane and (±)-1-deoxylycorine were accomplished using an intramolecular Diels-Alder cycloaddition of a furanyl carbamate as the key step. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The key intermediate used in both syntheses corresponds to hexahydroindolinone 20. Removal of the t-Boc group in 20 followed by reaction with 6-iodobenzo[1,3]dioxole-5-carbonyl chloride afforded enamide 22. Treatment of this compound with Pd(OAc)2 employing the Jeffrey modification of the Heck reaction provided the galanthan tetracycle 24 in good yield. Compound 24 was subsequently converted into (±)-γ-lycorane using a four-step procedure to establish the cis-B,C-ring junction. A radical-based cyclization of the related enamide 33 was used for the synthesis of 1-deoxylycorine. Heating a benzene solution of 33 with AIBN and n-Bu3SnH at reflux gave the tetracyclic compound 38 possessing the requisite trans fusion between rings B and C in good yield. After hydrolysis and oxidation of 38 to 40, an oxidative decarboxylation reaction was used to provide the C2-C3-C12 allylic alcohol unit characteristic of the lycorine alkaloids. The resulting enone was eventually transformed into (±)-1-deoxylycorine via known synthetic intermediates.
- Padwa,Brodney,Lynch
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- Short, Gram-Scale Syntheses of β- And γ-Lycorane Using Two Distinct Photochemical Approaches
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The synthesis of two diastereomeric members of the lycorane alkaloid family is reported. Although the routes are quite different in their approach, both involve the use of photochemistry as a key step, enabling the synthesis of gram quantities in the case of β-lycorane.
- Yu, Wai L.,Nunns, Thomas,Richardson, Jeffery,Booker-Milburn, Kevin I.
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- Palladium-Catalyzed Stereoselective Aza-Wacker-Heck Cyclization: One-Pot Stepwise Strategy toward Tetracyclic Fused Heterocycles
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Palladium-catalyzed intramolecular tandem cyclization reactions were conducted for the synthesis of densely cis/cis-fused aza-tetracyclic structures. The process involved a palladium(II)-catalyzed aerobic aza-Wacker reaction, followed by a palladium(0)-catalyzed Heck reaction. The effects of the solvent and benzene substitution pattern on the one-pot, two-step cascade reaction were studied systematically, and a probable mechanism was proposed. Strained pentahydrobenzo[f]cyclopenta[hi]indolizin-6-one and racemic γ-lycorane can also be synthesized rapidly using this palladium-catalyzed aza-Wacker-Heck cyclization reaction.
- Chen, Li-Yuan,Chuang, Ta-Hsien,Lai, Chin-Hung,Tang, Rong-Shiow
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supporting information
p. 9337 - 9341
(2020/12/21)
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- A Four-Step Synthesis of (±)-γ-Lycorane via Pd0-Catalyzed Double C(sp2)-H/C(sp3)-H Arylation
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An expedient synthesis of lycorine alkaloids is reported using a palladium(0)-catalyzed double C-X/C-H arylation as the key step. The selectivity of this reaction was controlled through the judicious choice of the two halogen atoms, and its generality was
- Rocaboy, Ronan,Dailler, David,Baudoin, Olivier
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p. 772 - 775
(2018/02/09)
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- Synthesis of (±)-γ-Lycorane by Using an Intramolecular Friedel-Crafts Reaction
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A total synthesis of γ-lycorane has been achieved by employing N -tosylpyrrole as a key building block. The synthesis employs both an intermolecular and an intramolecular Friedel-Crafts reaction, as well as a completely diastereoselective hydrogenation of
- Doan, Bao Nguyen Do,Tan, Xin Yi,Ang, Chin May,Bates, Roderick W.
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p. 4711 - 4716
(2017/10/06)
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- Short Total Synthesis of (±)-γ-Lycorane by a Sequential Intramolecular Acylal Cyclisation (IAC) and Intramolecular Heck Addition Reaction
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An intramolecular acylal cyclisation (IAC) approach to the synthesis of a range of bicyclic heterocycles is reported. As an example of the utility of the IAC reaction, the methodology was applied in a protecting-group-free five-step total synthesis of (±)-γ-lycorane, incorporating a new intramolecular Heck addition reaction to generate the pentacyclic core structure of the natural product in good yield.
- Monaco, Alessandra,Szulc, Blanka R.,Rao, Zenobia X.,Barniol-Xicota, Marta,Sehailia, Moussa,Borges, Bruno M. A.,Hilton, Stephen T.
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supporting information
p. 4750 - 4755
(2017/04/14)
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- Total synthesis of lycorine-type alkaloids by cyclopropyl ring-opening rearrangement
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A practical method for the synthesis of lycorine-type alkaloids with cis-B/C ring structure has been developed. Based on the reactions of aminocyclization, palladium-mediated arylation and especially cyclopropyl ring-opening rearrangement, the synthesis o
- Liu, Dandan,Ai, Long,Li, Fan,Zhao, Annan,Chen, Jingbo,Zhang, Hongbin,Liu, Jianping
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p. 3191 - 3200
(2014/05/06)
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- Visible-light-promoted selenofunctionalization of alkenes
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A visible-light-promoted method for the selenofunctionalization (and tellurofunctionalization) of alkenes has been developed. This method obviates the prepreparation of moisture-sensitive chalcogen electrophiles. The experimental setup is simple, and supe
- Conner, Elizabeth S.,Crocker, Katherine E.,Fernando, Ranelka G.,Fronczek, Frank R.,Stanley, George G.,Ragains, Justin R.
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supporting information
p. 5558 - 5561
(2013/11/19)
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- A general and efficient strategy for 7-aryloctahydroindole and cis-3a-aryloctahydroindole alkaloids: Total syntheses of (±)-γ- lycorane and (±)-crinane
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A general and efficient approach to both 7-aryloctahydroindole and cis-3a-aryloctahydroindole alkaloids has been developed. The key step involves Michael additions of the corresponding kinetics and thermodynamics lithium enolates of ketone 9 to the versat
- Gao, Shuanhu,Tu, Yong Qiang,Song, Zhenlei,Wang, Aixia,Fan, Xiaohui,Jiang, Yijun
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p. 6523 - 6525
(2007/10/03)
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- Efficient synthesis of (±)-γ-lycorane employing stereoselective conjugate addition to nitroolefin
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(±)-γ-Lycorane 3 was synthesized in 52% overall yield via seven steps from 5 by employing the highly stereoselective nitro-Michael cyclization of 5 to 9 and diastereoselective conjugate addition of aryllithium to a nitroolefin 10 as two key steps.
- Yasuhara, Tomohisa,Osafune, Emi,Nishimura, Katsumi,Yamashita, Mitsuaki,Yamada, Ken-Ichi,Muraoka, Osamu,Tomioka, Kiyoshi
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p. 3043 - 3045
(2007/10/03)
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- Electrocyclic ring-opening/π-allyl cation cyclization reaction sequences involving gem-dihalocyclopropanes as substrates: Application to syntheses of (±)-, (+)-, and (-)-γ-lycorane
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The readily prepared gem-dibromocyclopropanes (±)-13 and (±)-19 each engage in a silver(I)-promoted electrocyclic ring-opening/π-allyl cation cyclization sequence to deliver the hexahydroindole (±)-20, which participates in a Suzuki cross-coupling reaction with arylboronic acid 3 to give the tetracyclic compound (±)-21. Catalytic hydrogenation of this last compound proceeds in a completely stereoselective manner to give the saturated analogue (±)-24, which undergoes Bischler-Napieralski cyclization on reaction with phosphorus oxychloride. The resulting lactam (±)-25 is then reduced with lithium aluminum hydride to give (±)-γ-lycorane [(±)-1]. By using (-)-menthyl-derived carbamates 27 and 28, this chemistry has been extended to the synthesis of the (+)- and (-)-modifications of the title compound.
- Banwell, Martin G.,Harvey, Joanne E.,Hockless, David C. R.,Wu, Angela W.
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p. 4241 - 4250
(2007/10/03)
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- An expedient synthesis of (±)-γ-lycorane
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A short synthesis of (±)-γ-lycorane is described featuring a radical cascade whereby rings B and D are formed in one step.
- Hoang-Cong, Xuan,Quiclet-Sire, Beatrice,Zard, Samir Z.
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p. 2125 - 2126
(2007/10/03)
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- Radical cyclizations. A convergent total synthesis of (±)-γ-Lycorane
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(±)-γ-Lycorane has been synthesized in 10 steps from piperonylic alcohol. Two radical reactions were used successively to build the D and B rings.
- Cossy, Janine,Tresnard, Ludovic,Gomez Pardo, Domingo
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p. 1125 - 1128
(2007/10/03)
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- Radical cyclizations - Synthesis of γ-lycorane
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(+)-γ-Lycorane has been synthesized in ten steps from piperonylic alcohol. Two radical reactions were used successively to build the D and B rings. A formal synthesis of (+)-γ-lycorane was achieved via an optically active unsaturated aldehyde intermediate
- Cossy, Janine,Tresnard, Ludovic,Pardo, Domingo Gomez
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p. 1925 - 1933
(2007/10/03)
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- A short synthesis of γ-lycorane using Ni/AcOH mediated radical cyclisation
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A short synthesis of (±)-γ-lycorane 6 is described using two different radical cyclisations. The key step is the formation of tetrahydroindolone 9 by a nickel-promoted 5-endo radical cyclisation. This is followed by a tributylstannane-mediated 6-endo ring closure to the tetracyclic lactam 10 which is readily reduced tb (±)-γ-lycorane 6.
- Cassayre, Jér?me,Zard, Samir Z.
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p. 501 - 503
(2007/10/03)
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- A Stereoselective Total Synthesis of (+/-)-γ-Lycorane
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The allylic acetate 2 has been converted, over a number of steps, into the gem-dibromocyclopropane 8 which reacts with solver acetate to give the hexahydroindole 9.This last compound is then readily elaborated to (+/-)-γ-lycorane 1.
- Banwell, G. Martin,Wu, Angela W.
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p. 2671 - 2672
(2007/10/02)
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- Syntheses of (+/-)-α- and (+/-)-γ-Lycorane via a Stereocontrolled Organopalladium Route
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Total syntheses of (+/-)-α- and (+/-)-γ-lycorane are described.The key steps in the syntheses are the stereocontrolled palladium-catalyzed intramolecular 1,4-chloroamidation of 12 to 13 and the subsequent anti-stereoselective copper-catalyzed SN/sub
- Baeckvall, Jan-E.,Andersson, Pher G.,Stone, Guy B.,Gogoll, Adolf
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p. 2988 - 2993
(2007/10/02)
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- Total Synthesis of γ-Lycorane
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The homophthalimide derivative was easily converted to the cis-octahydrophenanthridine derivative in good yield and this to γ-lycorane 1.
- Sugiyama, Naokazu,Narimiya, Mamoru,Iida, Hideo,Kikuchi, Toyohiko
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p. 1455 - 1457
(2007/10/02)
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- A SYNTHESIS OF (+/-)-Δ2-α-LYCOREN-7-ONE, THE KEY INTERMEDIATE FOR THE TOTAL SYNTHESIS OF (+/-)-LYCORINE
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(+/-)-α-Lycoran-3,5-dione (14a) was prepared from octahydrophenanthridin-3-one (8b) obtained by two methods starting from 5-aryl-4-nitrocyclohaxane (2) and 1-hydroxy-2-aryl-5-oxo-cyclohexanecarboxylic acid (10), both of which were prepared by the Diels-Al
- Umezawa, Bunsuke,Hoshino, Osamu,Sawaki, Shohei,Sashida, Haruki,Mori, Kazuhiko,et al.
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p. 1783 - 1790
(2007/10/02)
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