- Lewis Acid-Mediated S(N)2 type displacement by grignard reagents on chiral perhydropyrido[2,1-b]pyrrolo[1,2-d][1,3,4]oxadiazine. Chirality induction in asymmetric synthesis of 2-Substituted piperidines
-
Et2AlCl-mediated nucleophilic alkylation with Grignard reagents on chiral perhydropyrido[2,1-b]pyrrolo[l,2-d][1,3,4]oxadiazine has proved to proceed via an S(N)2 mechanism at low temperatures (below -80°C) with high to excellent inversive stereoselection, while, at an elevated temperature, hydrazonium ions are formed preferentially leading to retentive stereoselection. This methodology provides useful access to enantioselective preparation of 2-substituted piperidines and is used for asymmetric synthesis of (+)-coniine.
- Yamazaki, Naoki,Kibayashi, Chihiro
-
-
Read Online
- Polymer-supported (-)-8-phenylmenthyl auxiliary as an effective solidphase chiral inductor in the addition of nucleophiles to N-acyliminium Ions
-
Aim and Objective: According to our interest in developing new methods for the construction of intricate molecules, a reliable polymer-supported (-)-8-phenylmenthyl chiral auxiliary for the addition of different nucleophiles to chiral-supported N-acyliminium precursors were developed. Material- and Method-: Merrifield resin was employed to anchor (-)-8-phenylmenthol, which was prepared by nitration of (-)-8-phenylmenthyl chloroacetate followed by reduction of nitro group and subsequent Merrifield resin coupling. Treatment of a suspension of polymer-supported chloroformate and piperidinone in the presence of Et3N resulted in attachment of the substrate onto the solid-support. Treatment of the resulting resin with LiEt3BH/MeOH afforded methoxypiperidine in 87% yield. Then, the addition of allyltrimethylsilane, TMSCN, 2-(trimethylsiloxy)propene and triisopropylsilyloxyfuran and others to the N-acyliminium ion derived from chiral 2-methoxypiperidine carbamate was studied. Results: The stereochemical outcome of the addition of nucleophiles to the supported N-acyliminium ion derived from 2-methoxypiperidine carbamate was proposed through the Si-face, affording after resin cleavage 2-substituted piperidines in 70%-84% yields and selectivities ranging from 4:1-11.1. Moreover, the key intermediates of chiral piperidines have been employed for the synthesis of simple chiral alkaloids such as (R)-pipecolic acid, (R)-pelletierine, (S)-coniine and (R,R)-myrtine. Conclusion: The proposed supported-chiral auxiliary for asymmetric approach may be expected to result not only in efficient solid-phase syntheses of a wide range of alkaloids but also in the development of useful new solid-phase methodologies, particularly for the asymmetric additions to iminium precursors. This work describes the first example of solid-phase synthesis by using supported (-)-8-phenylmenthyl as an effective chiral inductor and would be useful for the synthesis of chiral building block libraries.
- Forero-Doria, Oscar,Santos, Leonardo S.,Nachtigall, Fabiane M.,Shankaraiah, Nagula
-
p. 696 - 702
(2018/02/27)
-
- Structure, activity and stereoselectivity of NADPH-dependent oxidoreductases catalysing the S-selective reduction of the imine substrate 2-methylpyrroline
-
Oxidoreductases from Streptomyces sp. GF3546 [3546-IRED], Bacillus cereus BAG3X2 (BcIRED) and Nocardiopsis halophila (NhIRED) each reduce prochiral 2-methylpyrroline (2MPN) to (S)-2-methylpyrrolidine with >95 % ee and also a number of other imine substrates with good selectivity. Structures of BcIRED and NhIRED have helped to identify conserved active site residues within this subgroup of imine reductases that have S selectivity towards 2MPN, including a tyrosine residue that has a possible role in catalysis and superimposes with an aspartate in related enzymes that display R selectivity towards the same substrate. Mutation of this tyrosine residue - Tyr169 - in 3546-IRED to Phe resulted in a mutant of negligible activity. The data together provide structural evidence for the location and significance of the Tyr residue in this group of imine reductases, and permit a comparison of the active sites of enzymes that reduce 2MPN with either R or S selectivity.
- Man, Henry,Wells, Elizabeth,Hussain, Shahed,Leipold, Friedemann,Hart, Sam,Turkenburg, Johan P.,Turner, Nicholas J.,Grogan, Gideon
-
p. 1052 - 1059
(2015/05/05)
-
- Bisnucleophilic substitution as a synthetic tool for ready access to the piperidine alkaloids (+)-Connine, (+)-β-conhydrine, (+)-8-ethylnorlobelol, and (-)-halosaline
-
Herein we report the stereoselective total synthesis of (+)-connine, (+)-β-conhydrine, (+)-8-ethylnorlobelol, and (-)-halosaline via bisnucleophilic substitution with benzylamine as the key step.
- Raju, Galla,Anitha, Kadimi,Krishna, Palakodety Radha
-
p. 937 - 941
(2015/04/27)
-
- Characterization of three novel enzymes with imine reductase activity
-
Imine reductases (IRED) are promising catalysts for the synthesis of optically pure secondary cyclic amines. Three novel IREDs from Paenibacillus elgii B69, Streptomyces ipomoeae 91-03 and Pseudomonas putida KT2440 were identified by amino acid or structural similarity search, cloned and recombinantly expressed in E. coli and their substrate scope was investigated. Besides the acceptance of cyclic amines, also acyclic amines could be identified as substrates for all IREDs. For the IRED from P. putida, a crystal structure (PDB-code 3L6D) is available in the database, but the function of the protein was not investigated so far. This enzyme showed the highest apparent E-value of approximately Eapp = 52 for (R)-methylpyrrolidine of the IREDs investigated in this study. Thus, an excellent enantiomeric purity of >99% and 97% conversion was reached in a biocatalytic reaction using resting cells after 24 h. Interestingly, a histidine residue could be confirmed as a catalytic residue by mutagenesis, but the residue is placed one turn aside compared to the formally known position of the catalytic Asp187 of Streptomyces kanamyceticus IRED.
- Gand,Müller,Wardenga,H?hne
-
p. 126 - 132
(2015/02/19)
-
- A [3+3] cyclization strategy for asymmetric synthesis of alkyl substituted piperidine-2-ones using 1,2-cyclic sulfamidates: A formal synthesis of (S)-coniine from l-norvaline
-
Regioselective ring-opening reactions of a set of representative 1,2-cyclic sulfamidates with lithium triethylorthopropiolate proceeded efficiently to deliver the corresponding δ-amino-α,β-unsaturated esters after acidic hydrolysis. Hydrogenation of the unsaturated esters and subsequent thermal cyclization afforded the related alkyl substituted piperidine-2-ones. This approach represents a novel [3+3] cyclization strategy for the asymmetric synthesis of alkyl substituted piperidin-2-ones. Efficiency of the cyclization process is illustrated by a formal asymmetric synthesis of (S)-coniine from l-norvaline.
- Karanfil, Abdullah,Balta, Berrin,Eskici, Mustafa
-
p. 10218 - 10229,12
(2020/09/02)
-
- Cyclohydrocarbonylation-based strategy toward poly-substituted piperidines
-
Chemical equations presented. Convenient accesses to enantiomerically pure 2-, 2,3-, 2,6-, 2,3,6-substituted piperidines and 1,4-substituted indolizine are described. At first, indium-mediated aminoallylation and -crotylation of aldehydes with (R)-phenylglycinol or (1R,2S)-1-amino-2-indanol gave homoallylamines with high stereocontrol. Then, these products, submitted to a Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation, afforded perhydrooxazolo[3,2-a]piridines whose oxazolidines are opened with nucleophiles. Finally, the removal of the chiral auxiliaries delivered the enantiomerically pure piperidines.
- Arena, Giada,Zill, Nicolas,Salvadori, Jessica,Girard, Nicolas,Mann, Andre,Taddei, Maurizio
-
scheme or table
p. 2294 - 2297
(2011/06/26)
-
- Regioselective and stereoselective copper(I)-Promoted allylation and conjugate addition of N -Boc-2-lithiopyrrolidine and N -Boc-2-lithiopiperidine
-
Copper salts have been screened for transmetalation and electrophilic quench of N-tert-butoxycarbonyl-2-lithiopyrrolidine (N-Boc-2-lithiopyrrolidine) and N-Boc-2-lithiopiperidine, formed by deprotonation of N-Boc-pyrrolidine and N-Boc-piperidine, respectively. Transmetalation with zinc chloride then (lithium chloride solubilized) copper cyanide followed by allylation typically gives mixtures of regioisomers (SN2 and SN2′ products), whereas transmetalation with copper iodideTMEDA then allylation occurs regioselectively (SN2 mechanism). Addition to an enone or α,β-unsaturated ester occurs by 1,4-addition. Asymmetric deprotonation of N-Boc-pyrrolidine or dynamic resolution in the presence of a chiral ligand of N-Boc-2-lithiopiperidine followed by the zinc/copper chemistry was successful and gave the allylated pyrrolidine and piperidine products with good enantioselectivity, although use of the copper iodide chemistry resulted in some loss of enantiopurity. The chemistry provides formal syntheses of (+)-allosedridine, (+)-lasubine II, and (+)-pseudohygroline and has been used for the synthesis of (+)-coniine, (-)-pelletierine, (+)-coniceine, (-)-norhygrine, and the ant extract alkaloids cis- and trans-2-butyl-5- propylpyrrolidine.
- Coldham, Iain,Leonori, Daniele
-
experimental part
p. 4069 - 4077
(2010/08/20)
-
- Asymmetrie synthesis of unsaturated monocyclic and bicyclic nitrogen heterocycles
-
Hydrolysis of scalemic trichloroacetamides Cl3CCONHCH(R) CHCH2 and allylatlon, or acylatlon with but-3-enoic acid, followed by ring-closing metathesis resulted In the formation of unsaturated pyrrolidine and piperidine building blocks. These were employed in the synthesis of (S)-coniine (R = Pr) and a formal synthesis of (+)-anlsomycln (R = p-MeOC 6H4). Extension of this methodology with R = CH 2CHCH2 employing two ring-closing metatheses resulted In the synthesis of unsaturated quinolizidinone and indolizidinone frameworks.
- Nomura, Hiroshi,Richards, Christopher J.
-
supporting information; experimental part
p. 2892 - 2895
(2009/12/06)
-
- Enantioselective organocatalytic intramolecular aza-Michael reaction: A concise synthesis of (+)-sedamine, (+)-allosedamine, and (+)-coniine
-
(Chemical Equation Presented) The intramolecular aza-Michael reaction of carbamates bearing remote α,β-unsaturated aldehydes under organocatalytic conditions took place with good yields and excellent ee's when Jorgensen catalyst IV was used in the process, giving rise to the enantioselective formation of several five- and six-membered heterocycles. The developed methodology was applied to the synthesis of three piperidine alkaloids.
- Fustero, Santos,Jimenez, Diego,Moscardo, Javier,Catalan, Silvia,Del Pozo, Carlos
-
p. 5283 - 5286
(2008/09/18)
-
- A general and enantiodivergent method for the asymmetric synthesis of piperidine alkaloids: concise synthesis of (R)-pipecoline, (S)-coniine and other 2-alkylpiperidines
-
A simple and very efficient protocol for the preparation of highly enantioenriched 2-alkylpiperidines has been set up, which allows the preparation of the final heterocycles with any wanted configuration at the stereogenic center starting from the same starting material. The key step of the synthesis relies on a diastereodivergent aza-Michael reaction protocol using the readily available and cheap reagent (+)-(S,S)-pseudoephedrine as chiral auxiliary.
- Etxebarria, Juan,Vicario, Jose L.,Badía, Dolores,Carrillo, Luisa
-
p. 11421 - 11428
(2008/03/13)
-
- Anodic cyanation of (S)-(-)-1-1(1-phenylethyl)piperidine: An expeditious synthesis of (S)-(+)-coniine
-
A short and efficient asymmetric synthesis of enantiopure (S)-(+)-coniine is reported. Anodic cyanation of (-)-1-[(1S)-1-phenylethyl]piperidine, derived from [(1S)-1-phenylethyl]amine, results in regioselective formation of the corresponding α-amino-nitrile, which was alkylated with propyl iodide to give a bifunctional derivative. The latter underwent a stereoselective reductive decyanation (80% de), the product of which was hydrogenolyzed to afforded (S)-(+)-coniine (99% ee) with an overall 35% yield from (-)-1 -[(1S)-1-phenylethyl]piperidine. Georg Thieme Verlag Stuttgart.
- Girard, Nicolas,Pouchain, Laurent,Hurvois, Jean-Pierre,Moinet, Claude
-
p. 1679 - 1682
(2008/02/04)
-
- Practical highly enantioselective synthesis of propargylamines through a copper-catalyzed one-pot three-component condensation reaction
-
The one-pot three-component reaction of terminal alkynes, aldehydes and secondary amines in the presence of copper(1) bromide/quinap is reported. The reaction scope has been determined and a broad variety of all three components has been used, which afforded the corresponding propargylamines in good to excellent yields and moderate to very good enantioselectivities. The reaction showed a strong positive nonlinear effect. The transformation of a propargylamine intermediate into the alkaloid (S-(+)-coniine has also been described.
- Gommermann, Nina,Knochel, Paul
-
p. 4380 - 4392
(2008/02/07)
-
- Mn-mediated coupling of alkyl iodides and chiral N-acylhydrazones: Optimization, scope, and evidence for a radical mechanism
-
Stereoselective radical additions have excellent potential as mild, nonbasic carbon-carbon bond constructions for direct asymmetric amine synthesis. Efficient intermolecular radical addition to C=N bonds with acyclic stereocontrol has previously been limited mainly to secondary and tertiary radicals, a serious limitation from the perspective of synthetic applications. Here, we provide full details of the use of photolysis with manganese carbonyl to mediate stereoselective intermolecular radical addition to N-acylhydrazones. Photolysis (300 nm) of alkyl halides and hydrazones in the presence of Mn 2(CO)10 and InCl3 as a Lewis acid led to reductive radical addition; diastereomer ratios ranged from 93:7 to 98:2 at ca. 35 °C. The reaction tolerates additional functionality in either reactant, enabling subsequent transformations as shown in an efficient asymmetric synthesis of coniine. A series of hydrazones bearing different substituents on the oxazolidinone auxiliary were compared; consistently high diastereocontrol revealed that the identity of the substituent had little practical effect on the diastereoselectivity. Further mechanistic control experiments confirmed the intermediacy of radicals and showed that independently prepared alkyl- or acylmanganese pentacarbonyl compounds do not undergo efficient addition to the N-acylhydrazones under thermal or photolytic (300 nm) conditions. These Mn-mediated conditions avoid toxic tin reagents and enable stereoselective intermolecular radical additions to C=N bonds with the broadest range of alkyl halides yet reported, including previously ineffective primary alkyl halides.
- Friestad, Gregory K.,Marie, Jean-Charles,Suh, YoungSung,Qin, Jun
-
p. 7016 - 7027
(2007/10/03)
-
- Practical highly enantioselective synthesis of terminal propargylamines. An expeditious synthesis of (S)-(+)-coniine
-
The one-pot three-component addition reaction of trimethylsilylacetylene, aldehydes and dibenzylamine provides in the presence of CuBr/Quinap as catalyst, various enantiomerically enriched propargylamines in good yields (up to 99%) and excellent enantiomeric excess (up to 98% ee) which can be used as a key intermediate in the synthesis of the alkaloid (S)-(+)-coniine.
- Gommermann, Nina,Knochel, Paul
-
p. 2324 - 2325
(2007/10/03)
-
- Asymmetric synthesis and applications of β-amino Weinreb amides: Asymmetric synthesis of (S)-coniine
-
Conjugate addition of lithium (S)-N-benzyl-N-a-methylbenzylamide to a range of α,β-unsaturated Weinreb amides proceeds with high levels of diastereoselectivity (>95% de). The β-amino Weinreb amide products may be transformed into β-amino ketones via reactions with Grignard reagents, while treatment with DIBAL-H furnishes β-amino aldehydes. Trapping of the aldehyde via Wadsworth-Emmons reaction and subsequent manipulation offers an efficient route to homochiral δ-amino acid derivatives and 2-substituted piperidines. The application of this methodology for the synthesis of (S)-coniine is demonstrated.
- Burke, Anthony J.,Davies, Stephen G.,Garner, A. Christopher,McCarthy, Tom D.,Roberts, Paul M.,Smith, Andrew D.,Rodriguez-Solla, Humberto,Vickers, Richard J.
-
p. 1387 - 1394
(2007/10/03)
-
- Efficient asymmetric hydrogenation of pyridines
-
Up to four stereocenters can be created efficiently in a single step by the asymmetric hydrogenation of oxazolidinone-substituted pyridines (see scheme). Furthermore, selective chirality transfer and nondestructive cleavage of the chiral auxiliary occur under the same reaction conditions, making an additional cleavage step unnecessary.
- Glorius, Frank,Spielkamp, Nick,Holle, Sigrid,Goddard, Richard,Lehmann, Christian W.
-
p. 2850 - 2852
(2007/10/03)
-
- Intramolecular Hydroamination/Cyclization of Conjugated Aminodienes Catalyzed by Organolanthanide Complexes. Scope, Diastereo- and Enantioselectivity, and Reaction Mechanism
-
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.
- Hong, Sukwon,Kawaoka, Amber M.,Marks, Tobin J.
-
p. 15878 - 15892
(2007/10/03)
-
- Asymmetric synthesis of cyclic β-amino acids and cyclic amines via sequential diastereoselective conjugate addition and ring closing metathesis
-
Diastereoselective conjugate addition of lithium (S)-N-allyl-N-α-methylbenzylamide to a range of α,β-unsaturated esters followed by ring closing metathesis is used to afford efficiently a range of substituted cyclic β-amino esters in high d.e. Alternatively, conjugate addition to α,β-unsaturated Weinreb amides, functional group conversion and ring closing metathesis affords cyclic amines in high d.e. The further application of this methodology to the synthesis of a range of carbocyclic β-amino esters via conjugate addition, enolate alkylation and ring closing metathesis is also described. Application of this methodology affords, after deprotection, (S)-homoproline, (S)-homopipecolic acid, (S)-coniine and (1S,2S)-trans-pentacin.
- Chippindale, Ann M.,Davies, Stephen G.,Iwamoto, Keiji,Parkin, Richard M.,Smethurst, Christian A. P.,Smith, Andrew D.,Rodriguez-Solla, Humberto
-
p. 3253 - 3265
(2007/10/03)
-
- Ring closing metathesis for the asymmetric synthesis of (S)-homopipecolic acid, (S)-homoproline and (S)-coniine
-
Diastereoselective conjugate addition of lithium (S)-N-allyl-N-α-methylbenzylamide to α,β-unsaturated esters or Weinreb amides, followed by ring closing metathesis is used to afford the cyclic β-amino acids (S)-homopipecolic acid and (S)-homoproline and the amine (S)-coniine in high ee.
- Davies, Stephen G.,Iwamoto, Keiji,Smethurst, Christian A. P.,Smith, Andrew D.,Rodriguez-Solla, Humberto
-
p. 1146 - 1148
(2007/10/03)
-
- Highly stereoselective intramolecular hydroamination/cyclization of conjugated aminodienes catalyzed by organolanthanides
-
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
- Hong, Sukwon,Marks, Tobin J.
-
p. 7886 - 7887
(2007/10/03)
-
- Kinetic resolution of amines with enantiopure 3-N,N-diacylaminoquinazolin-4(3H)-ones
-
The title compounds (DAQs) are chiral when the two N-acyl groups are different because of the absence of rotation around the N-N bond (a chiral axis). Enantiopure DAQs have been obtained by incorporation of a chiral centre in enantiopure form either into the substituent at the Q2-position or into one of the N-acyl groups, or into both, followed by separation of diastereoisomers. This separation is unnecessary in one case because conversion of the N-monoacylaminoquinazolinone (MAQ) into the DAQ is completely diastereoselective. Neither is separation of diastereoisomers necessary with 3-[N,N-di-(S)-2-acetoxypropanoylamino]-2-diphenylmethylquinazolin-4(3H)-one 37a: this DAQ 37a has its N-N bond rendered a chiral axis by the bias in its imide moiety wholly in favour of one exo/endo conformation. The high chemoselectivity exhibited by N,N-diacetyl- or N,N-dibenzoylaminoquinazolinones in reaction with the less hindered of two secondary amines (pyrrolidine in the presence of 1 eq. of piperidine) has a stereoselective counterpart: reaction of the above enantiopure DAQs enantioselectively with racemic amines leading to kinetic resolution. Using 1 eq. of DAQ and 2 eq. of amine, both the derivatised and unreacted amine enantiomers are recovered with high enantiomeric excess (ee) (better than 90% ee in some cases). Some of the higher ees are found in the recovered amides where non-chemoselective attack on both N-acyl groups of the DAQ has occurred: from the opposite configurations of the amine component in the two amides and from the low enantiopurity of the recovered unreacted amine, reaction of each of the N-acyl groups with complementary enantiomers of the amine is occurring (parallel kinetic resolution). Although higher ees are, in general, obtained using secondary amines, high ees are obtained in some cases using 1-phenylethylamine and, in particular, amino acid esters (valine and alanine). The sense of enantioselectivity in the reactions of these DAQs with amines is controlled by the configuration of the N-N axis: replacing the Q group in an N-(S)-2-acetoxypropanoyl-N-acetyl-bearing DAQ by phthalimide, thus eliminating the N-N chiral axis, drastically reduces the level of kinetic resolution.
- Al-Sehemi, Abdullah G.,Atkinson, Robert S.,Fawcett, John
-
p. 257 - 274
(2007/10/03)
-
- Asymmetric piperidine synthesis via 1,3-cyclic sulfates
-
Cyclic sulfates undergo a double alkylation with stabilized C,N-dianions derived from 3a/b to provide the piperidine ring system. The 4-substituted variant 7 affords a formal but stereochemically efficient synthesis of (S)-coniine.
- Eskici,Gallagher
-
p. 1360 - 1362
(2007/10/03)
-
- 3-Di-[(S)-2-acetoxypropanoyl] aminoquinazolin-4(3H)-ones: Stereostructure and application in kinetic resolution of amines
-
Whereas 3-diacylaminoquinazolin-4(3H)-ones (DAQs) have been previously shown to undergo rapid exo/endo-endo/exo conformational interconversion of their imide carbonyl groups, the title DAQs are believed to exist in one single exo/endo form and consequently their N-N bonds are chiral axis: one of these DAQs, substituted with a diphenylmethyl group on the Q-2 position, reacts preferentially with one enantiomer of racemic 2-methyl-piperidine at the 2-acetoxypropanoyl imide carbonyl group (ee 94%). (C) 2000 Elsevier Science Ltd.
- Al-Sehemi, Abdullah G.,Atkinson, Robert S.,Fawcett, John,Russell, David R.
-
p. 2243 - 2246
(2007/10/03)
-
- A new asymmetric synthesis of (S)-(+)-pipecoline and (S)-(+)- and (R)-(-)-coniine by reductive photocyclization of dienamides
-
(S)-(+)-Pipecoline and both enantiomers of coniine were synthesized, in good yields, by a reductive photocyclization of chiral dienamides. Enantioselectivities of up to 75% were obtained. (C) 2000 Published by Elsevier Science Ltd.
- Bois,Gardette,Gramain
-
p. 8769 - 8772
(2007/10/03)
-
- Convenient in situ synthesis of nonracemic N-protected β-amino aldehydes from β-amino acids. Applications in Wittig reactions and heterocycle synthesis
-
N-Z-γ-amino alcohols derived from nonracemic β-amino acids are smoothly oxidised by manganese dioxide in acetonitrile to afford aldehydes which can be trapped in situ in Wittig reactions with carbonyl-substituted phosphoranes. The application of this methodology to the synthesis of the alkaloids (S)-(+)-N-BOC-coniine, (S)-(-)-coniceine and a pipecoline precursor is described.
- Davies, Simon B.,McKervey, M. Anthony
-
p. 1229 - 1232
(2007/10/03)
-
- Efficient Routes to Chiral 2-Substituted and 2,6-Disubstituted Piperidines
-
The syntheses of chiral 2-substituted and 2,6-disubstituted piperidines, and piperidin-2-ylphosphonates, via benzotriazole methodology are described.
- Katritzky, Alan R.,Qiu, Guofang,Yang, Baozhen,Steel, Peter J.
-
p. 6699 - 6703
(2007/10/03)
-
- Short Enantioselective Total Syntheses of the Piperidine Alkaloids (S)-Coniine and (2R,6R)-trans-Solenopsin A via Catalytic Asymmetric Imine Hydrosilylation
-
The enantioselective syntheses of (S)-coniine and (2R,6R)-trans-solenopsin A are reported. The key step in both syntheses is the catalytic asymmetric hydrosilylation of a cyclic imine.
- Reding, Matthew T.,Buchwald, Stephen L.
-
p. 6344 - 6347
(2007/10/03)
-
- New highly enantioselective synthesis of 6-alkylpiperidin-2-ones and 2-substituted piperidines
-
A versatile and highly enantioselective approach to 2-substituted piperidines is described using phenylglycinol as chiral auxiliary.
- Freville,Celerier,Thuy,Lhommet
-
p. 2651 - 2654
(2007/10/03)
-
- Asymmetric aza-Diels-Alder reaction: Enantio- and diastereoselective reaction of imine mediated by Chiral Lewis acid
-
An efficient asymmetric aza-Diels-Alder reaction using chiral boron mediator is developed. The key to its success is the use of the chiral boron complex prepared in situ from (R)- or (S)- binaphthol and B(OPh)3. The enantiomeric reaction of prochiral imine affords products of up to 90% ee. The double asymmetric induction of chiral imine using α-benzylamine as a chiral auxiliary is achieved with almost complete diastereoselectivity for both aliphatic and aromatic aldimines. This method is applied to the efficient synthesis anabasine and coniine of piperidine alkaloides.
- Hattori, Kouji,Yamamoto, Hisashi
-
p. 1749 - 1760
(2007/10/02)
-
- A New Asymmetric Synthesis of Both Enantiomers of Coniine by 1,2-Addition of RLi/YbCl3 to Aldehyde SAMP Hydrazones
-
Both enantiomers of the hemlock alkaloid coniine 8 are prepared by asymmetric synthesis in 98percent ee using only one enantiomer of the auxiliary.The key step of the synthesis consists in the 1,2-addition of organoytterbium reagents to aldehyde SAMP hydrazones with virtually complete asymmetric induction, followed by N-N bond cleavage and cyclization. Key Words: Coniine, enantioselective synthesis of/SAMP hydrazones, 1,2-addition of/Organoytterbium reagents/Synthon control of enantioselectivity.
- Enders, Dieter,Tiebes, Joerg
-
p. 173 - 178
(2007/10/02)
-
- Diastereofacial Selectivity in Intermolecular Nitrone Cycloadditions to Chiral Allyl Ethers. Application to Chiral Synthesis of Coniine
-
The intermolecular cycloadditions of a cyclic nitrone to chiral allyl ethers take place with erythro selectivity, where the degree of selectivity achieved is dependent upon the size of the alkyl substituent attached to the allylic chiral center, and these reactions are applied to the synthesis of optically active alkaloid coniine.
- Ito, Masayuki,Maeda, Masae,Kibayashi, Chihiro
-
p. 3765 - 3768
(2007/10/02)
-
- A Stereoselective Route to Enantiomeric 2-Alkyl-1,2,3,6-tetrahydropyridines
-
A synthesis of (R)- or (S)-2-alkyl-1,2,3,6-tetrahydropyridines (1), starting from (R)- or (S)-phenylglycinol and Zincke's salt (2), and proceeding via the new oxazolidine derivative (5) as a key intermediate, is described.
- Mehmandoust, Maryam,Marazano, Christian,Das, Bhupesh C.
-
p. 1185 - 1187
(2007/10/02)
-
- Asymmetric Synthesis via Allenes: Synthesis of (R)-(-)-Coniine
-
The silver(I)-catalysed cyclisation of an amine to a chiral allenic unit is described; the efficiency of this process has been evaluated by a synthesis of (R)-(-)-coniine.
- Lathbury, David,Gallagher, Timothy
-
p. 114 - 115
(2007/10/02)
-
- An Asymmetric Synthesis of 2-Substituted Piperidines through Ozonolysis of Cyclopentenes and Reductive Aminocyclization
-
By the action of ozone, sodium cyanoborohydride and the optically active benzylic amines 2, the 1-substituted cyclopentenes 1, 5 and 9 were converted to a diastereometric mixture of 1,2-disubstituted piperidines (3, 6 and 10), respectively.Hydrogenation of these compounds and the following work-up yielded optically active 2-alkylpiperidines (4, up to 68percente.e.), pipecolic acid (7, 84percent e.e.) and 2-(hydroxymethyl)piperidine (11, up to 85percente.e.).Chromatographic separation of the major isomers of 3b and 6 enabled optically pure coniine (4b) and pipecolic acid (7) to be prepared, respectively.
- Kawaguchi, Mamoru,Hayashi, Osamu,Sakai, Noriyuki,Hamada, Masayuki,Yamamoto, Yukio,Oda, Jun'ichi
-
p. 3107 - 3112
(2007/10/02)
-
- Optical Rotatory Dispersion and Absolute Configuration. Part 35. Chiroptical Properties and Conformation of Indolizidine
-
1H N.m.r. spectroscopy at 360 MHz confirms that indolizidine is trans-fused with the piperidine ring in a chair conformation.The pyrrolidine ring adopts an envelope conformation with the nitrogen atom displaced out of the plane of the four carbon atoms of the ring.An improved synthesis of (+)- and (-)-indolizidine from (-)- and (+)-coniine is described.The o.r.d. and c.d. spectra of indolizidine are compared with those of coniine.
- Ringdahl, Bjorn,Pinder, A. Reginald,Pereira, Wilfred E.,Oppenheimer, Norman J.,Craig, John Cymerman
-
-
