501-02-0Relevant academic research and scientific papers
Intramolecular Hydroamination/Cyclization of Conjugated Aminodienes Catalyzed by Organolanthanide Complexes. Scope, Diastereo- and Enantioselectivity, and Reaction Mechanism
Hong, Sukwon,Kawaoka, Amber M.,Marks, Tobin J.
, p. 15878 - 15892 (2007/10/03)
Organolanthanide complexes of the general type Cp′ 2LnCH(TMS)2 (Cp′ = η5-Me 5C5; Ln = La, Sm, Y; TMS = SiMe3) and CGCSmN(TMS)2 (CGC = Me2Si(η5-Me 4C5)(tBuN)) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization of primary and secondary amines tethered to conjugated dienes. The rates of aminodiene cyclizations are significantly more rapid than those of the corresponding aminoalkenes. This dienyl group rate enhancement as well as substituent group (R) effects on turnover frequencies is consistent with proposed transition state electronic demands. Kinetic and mechanistic data parallel monosubstituted aminoalkene hydroamination/cyclization, with turnover-limiting C=C insertion into the Ln-N bond to presumably form an Ln-η3 allyl intermediate, followed by rapid protonolysis of the resulting Ln-C linkage. The rate law is first-order in [catalyst] and zero-order in [aminodiene]. However, depending on the particular substrate and catalyst combination, deviations from zero-order kinetic behavior reflect competitive product inhibition or self-inhibition by substrate. Lanthanide ionic radius effects and ancillary ligation effects on turnover frequencies suggest a sterically more demanding Ln-N insertion step than in aminoalkene cyclohydroamination, while a substantially more negative ΔS? implies a more highly organized transition state. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de). Formation of 2-(prop-1-enyl)piperidine using the chiral C1-symmetric precatalyst (S)-Me2Si(OHF)(CpR* )SmN(TMS)2 (OHF = η5-octahydrofluorenyl; Cp = η5-C5H3; R* = (-)-menthyl) proceeds with up to 71% ee. The highly stereoselective feature of aminodiene cyclization is demonstrated by concise syntheses of naturally occurring alkaloids, (±)-pinidine and (+)-coniine from simple diene precursors.
Highly stereoselective intramolecular hydroamination/cyclization of conjugated aminodienes catalyzed by organolanthanides
Hong, Sukwon,Marks, Tobin J.
, p. 7886 - 7887 (2007/10/03)
Efficient intramolecular hydroamination/cyclization of primary and secondary conjugated aminodienes can be effected by using organolanthanide precatalysts of the type Cp-2LnCH(TMS)2 (Cp- = η5-Me5C5; Ln = La, Sm, Y; TMS = SiMe3) and CGCSmN(TMS)2 (CGC = Me2Si(η5-Me4C5)(tBuN)). The transformation proceeds cleanly (≥ 90% conversion) at 25-60 °C with good rates and high regioselectivities, and with electronic effects leading to significant rate enhancements. Some features of the reaction parallel monosubstituted aminoalkene hydroamination/cyclization, including rate law (zero order in [aminodiene]), and rate enhancements observed with larger lanthanide ionic radii and/or more open catalyst ligation structures. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de) with using the corresponding α-methyl aminodiene precursors. Formation of 2-(prop-1-enyl)piperidine with the chiral C1-symmetric precatalyst (S)-Me2Si(OHF)(CpR*)SmN(TMS)2 (OHF = η5-octahydrofluorenyl; Cp = η5-C5H3; R* = (-)-menthyl) proceeds with up to 69% ee. Copyright
The use of the aza-Diels-Alder reaction in the synthesis of pinidine and other piperidine alkaloids
Bailey, Patrick D,Smith, Peter D,Morgan, Keith M,Rosair, Georgina M
, p. 1071 - 1074 (2007/10/03)
The imine Ph2CHN=CHCO2Et, generated from benzhydrylamine and ethyl glyoxylate, provides a Diels-Alder adduct with 1,3-pentadiene from which a range of cis-2,6-disubstituted piperidines can be accessed; the benzhydryl group confers high diastereocontrol for derivatising the six-membered ring, allowing access to 2,5,6-trisubstituted piperidines, and to 2,6-disubstituted piperidines such as pinidine.
Hypervalent λ(n)-iodane-mediated fragmentation of tertiary cyclopropanol systems II: Application to asymmetric syntheses of piperidine and indolizidine alkaloids
Kirihara, Masayuki,Nishio, Takashi,Yokoyama, Satoshi,Kakuda, Hiroko,Momose, Takefumi
, p. 2911 - 2926 (2007/10/03)
The asymmetric synthesis of (-)-pinidine and its enantiomer was accomplished by starting from norgranatanone via the asymmetric enolization, stereoselective cyclopropanation, and oxidative ring cleavage of the resulting cyclopropanol system with a hypervalent λ(n)-iodane as key steps. Formal asymmetric synthesis of (+)-indolizidine 223AB was also performed via the asymmetric enolization and oxidative ring cleavage of the resulting cyclopropanol system as key steps.
Efficient synthesis of an enantiomeric pair of pinidine: An illustration of organochemical carving on the rigid bridged system as the stereochemical tactics
Momose, Takefumi,Nishio, Takashi,Kirihara, Masayuki
, p. 4987 - 4990 (2007/10/03)
Asymmetric synthesis of (-)-pinidine and its enantiomer was accomplished by starting from norgranatanone via the asymmetric enolization, stereoselective cyclopropanation, and oxidative ring cleavage of the resulting cyclopropanol system with a hypervalent iodoid as key steps.
Synthesis of (-)-Pinidine via Asymmetric, Electrophilic Enolate Hydroxyamination/Nitrone Reduction
Oppolzer, Wolfgang,Merifield, Eric
, p. 957 - 962 (2007/10/02)
Enantiomerically pure (-)-pinidine (1) has been synthesized in 18.5 percent overall yield by a nine-step sequence starting from keto-ester 2.The key step 5 -> 6 involves an asymmetric, electrophilic enolate hydroxyamination.Diastereoselective hydrogenatio
A chirospecific synthesis of (-)-pinidine
Takahata,Bandoh,Hanayama,Momose
, p. 607 - 608 (2007/10/02)
A chirospecific synthesis of the cis-2,6-dialkylpieperidine alkaloids 1 and 2 has been achieved in eight steps (23%) and six steps (32%) from the known iodide 3, respectively.
Asymmetric Synthesis with α,β-Bis Ketones. Enantioselective Total Synthesis of Natural (+)-Indolizidine 195B (Bicyclic Gephyrotoxin 195B) and (-)-Pinidine and Their Enantiomers from a Common Chiral Synthon
Yamazaki, Naoki,Kibayashi, Chihiro
, p. 1396 - 1408 (2007/10/02)
The first enantioselective total synthesis of naturally occurring (+)-indolizidine 195B (bicyclic gephyrotoxin 195B) and (-)-pinidine and their enantiomers has been achieved starting from 4-O-benzyl-2,3-O-bis(methoxymethyl)-L-threitol as a single and comm
AN EFFICIENT SYNTHESIS OF (+/-)-PINIDINE
Arseniyadis, Simeon,Sartoretti, Jacques
, p. 729 - 732 (2007/10/02)
A total synthesis of (+/-)-pinidine I was accomplished starting from the readily available propargylic tosylate 1 and 5-bromo-2-pentanone 2.
