Addition of a Chiral Boron Enolate to Cyclic <i>N</i>-Acyliminium Ions. Stereocontrolled Synthesis of the Pyrrolizidine Ring System

Pilli, Ronaldo A.; Russowsky, Dennis

doi:10.1021/jo9513020

Cited by 46 publications

(18 citation statements)

References 22 publications

(19 reference statements)

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“…The Mannich reaction is one of the most available methods of the synthesis of new macrocyclic structures [4,5], involving calix [4] resorcinols [6][7][8][9]. To introduce less reactive substrates to the Mannich reaction, preformed or in situ generated iminium [10] or N-acyliminium ions [11,12], as well as carbon nucleophiles, are used.…”

Section: Variousmentioning

confidence: 99%

“…Various substrates are used as CH-acidic components in the Mannich reaction, namely ketones, ß-ketoethers, malonates, nitro compounds, and phenol derivatives [1,2]. To introduce less reactive substrates to the Mannich reaction, preformed or in situ generated iminium [10] or N-acyliminium ions [11,12], as well as carbon nucleophiles, are used. To introduce less reactive substrates to the Mannich reaction, preformed or in situ generated iminium [10] or N-acyliminium ions [11,12], as well as carbon nucleophiles, are used.…”

Section: Introductionmentioning

confidence: 99%

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Modification of Bicyclic Phosphonates Based on Resorcinols and Its Derivatives via the Mannich Reaction

et al. 2015

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Amino‐containing derivatives of various structures have been obtained via the Mannich reaction in a series of bicyclic phosphonates based on 2‐methylresorcinol, resorcinol, and pyrogallol with paraformaldehyde and secondary amines via the Mannich reaction. The structure and composition of the obtained compounds have been determined using 31Р and 1Н NMR spectroscopy, IR spectroscopy, mass spectrometry (MALDI‐TOF), and X‐ray analysis.

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Section: Variousmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modification of Bicyclic Phosphonates Based on Resorcinols and Its Derivatives via the Mannich Reaction

et al. 2015

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“…Close to this, an enantioselective synthesis of (2S,2%S)-erythro-methylphenidate was recently published by Prashad and co-workers. 16 Due to this fact and relating to our interest in the synthesis of b-aminocarbonyl compounds 17,18 we would like to communicate in this paper our approach to the synthesis of (+/−)-erythro-methylphenidate 1 applying a new concise stereoselective synthetic strategy.…”

Section: Thementioning

confidence: 99%

A concise and stereoselective synthesis of (+/−)-erythro-methylphenidate

Russowsky

Neto

2003

Tetrahedron Letters

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Abstract-A concise and stereoselective synthesis of racemic erythro-methylphenidate (1) is described. The coupling reaction between piperidine-2-thione (3) and 2-bromo-2-phenylmethylacetate (4) afforded the b-enaminocarbonyl compound 2 in 60% yield by a modified Eschenmoser sulfide contraction reaction. In most cases the bicyclic thiazolidinone 5 was produced. Diastereoselective reduction of 2 in the presence of borohydrydes furnished the (+/−)-erythro-methylphenidate in good yields with dr >95%. © 2003 Elsevier Science Ltd. All rights reserved. The(+/−)-threo-methylphenidate hydrochloride (Ritalin ® ), is an indirect catecholamine agonist, 1 and is the drug treatment of choice for the attention deficit/ hyperactivity disorder (AD/HD), 2 one of the most common behavioral disorders of childhood which affects 5-10% of the general population. 3 The activity of Ritalin ® promotes an enhancement of the cognitive performance in both adults and children diagnosed with AD/HD. 4 Although Ritalin ® is available in the market as the racemate, the (2R,2%R)-(+)-threo-methylphenidate has been reported to be up to 38 times 5 more active than (2S,2%S)-(−)-threo-methylphenidate and several racemic 6-9 and chiral 10-13 synthesis of threo-methylphenidate were reported previously.Although the erythro-methylphenidate exhibits very few therapeutic properties and toxic hypertensive effects, 14 the stereoselective synthesis of the erythro-isomer can be helpful due to the possibility of resolution and epimerization of the erythro-isomer. 2,15 This approach was used early in the original synthesis of (+/−)-threomethylphenidate. Close to this, an enantioselective synthesis of (2S,2%S)-erythro-methylphenidate was recently published by Due to this fact and relating to our interest in the synthesis of b-aminocarbonyl compounds 17,18 we would like to communicate in this paper our approach to the synthesis of (+/−)-erythro-methylphenidate 1 applying a new concise stereoselective synthetic strategy.We envisaged obtaining 1 based on a stereoselective reduction of a b-enaminocarbonyl compound 2 which is readily accessible by the Eschenmoser sulfide contraction reaction 19,20 (Scheme 1).The needed piperidine-2-thione (3) was prepared in 91% yield after reaction of piperidine-2-one with Lawesson reagent. 21 The bromoester 4 was obtained by sterification and subsequent a-bromination 22 of 2-phenylacetic acid in 71% overall yield after purufication by horizontal destilation at reduced pressure. Next, the condensation reaction of compounds 3 and 4 was carried out under the Eschenmoser sulfide contraction reaction Scheme 1. The retrosynthetic analysis of 1 based on the eschemoser sulfide contraction reaction.

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“…It is a powerful tool in routes for the synthesis of various β-amino ketones or esters, which are versatile synthetic building blocks for the preparation of many nitrogen-containing, biologically important compounds [13][14][15][16][17] . In the bimolecular version of the classical Mannich reaction the use of preformed or in situ generated iminium 18 or N-acyliminium ions [19][20] . On the other hand, the reaction of phenols and their derivatives with amines in the Mannich synthesis has been reported using different conditions and using different catalysts.…”

Section: Introductionmentioning

confidence: 99%

A novel one pot Mannich synthesis of methylpiperidin phenols, methylphenylmorfolin phenols and methyltiophenylmorpholin phenols solvent-free and using infrared light irradiation

Velázquez¹,

Torres²,

Díaz³

et al. 2006

Arkivoc

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Addition of a Chiral Boron Enolate to Cyclic N-Acyliminium Ions. Stereocontrolled Synthesis of the Pyrrolizidine Ring System

Cited by 46 publications

References 22 publications

Modification of Bicyclic Phosphonates Based on Resorcinols and Its Derivatives via the Mannich Reaction

Modification of Bicyclic Phosphonates Based on Resorcinols and Its Derivatives via the Mannich Reaction

A concise and stereoselective synthesis of (+/−)-erythro-methylphenidate

A novel one pot Mannich synthesis of methylpiperidin phenols, methylphenylmorfolin phenols and methyltiophenylmorpholin phenols solvent-free and using infrared light irradiation

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