The application of the sulphide contraction to the synthesis of some simple pyrrolidine alkaloids

Ghirlando, Rodolfo; Howard, Arthur S.; Katz, Ruth B.; Michael, Joseph P.

doi:10.1016/s0040-4020(01)91297-9

Cited by 23 publications

(7 citation statements)

References 20 publications

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“…The reaction condition was also applicable to methyl 2-phenylethylene ketone ( 4j ) to afford the corresponding products ( 5ja and 5jb ) in good yields. We demonstrated that this methodology provided a facile and concise synthesis of (±)- N -methylruspolinone ,, ( 5hb ) and (±)-dehydrodarlinine ,, ( 5jb ). A series of alkyl methyl ketones ( 4n – o ) and other acetyl derivatives ( 4p – r ) were also tested.…”

Section: Resultsmentioning

confidence: 99%

“…Compound 5ja was prepared from 1-benzylproline (2a) and 2,17,19 (5jb, dehydrodarlinine) Compound 5jb was prepared from 1-methylproline (2b) and …”

Section: (E)-1-(1-benzylpyrrolidin-2-yl)-4-phenylbut-3-en-2-one (5ja)mentioning

confidence: 99%

“…Methylpyrrolidin-2-yl)-1-(3,4-dimethoxyphenyl)ethanone3,17,18 (5hb,N-methylruspolinone)Compound 5hb was prepared from 1-methylproline (2b) and3',4'-dimethoxyacetophenone (4h) by General procedures B and C. The product was purified by flash column chromatography (Hex / EtOAc = 7.5 : 2.5) to give 5hb (oilCDCl 3 , 125 MHz) δ 196.8, 153.6, 149.1, 129.9, 123.1 (CH), 110.13 (CH), 110.07 (CH), 63.3 (CH), 56.5 (CH 2 ), 56.1 (CH 3 ), 56.0 (CH 3 ), 41.3 (CH 2 ), 40.1 (CH 3 ), 31.2 (CH 2 ), 22.0 (CH 2 ); MS (ESI) m/z 264 (100) (M + 1); HRMS (ESI, TOF) Calcd for C 15 H 22 NO 3 (M + H): 264.1600. Found: 264.1590.…”

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confidence: 99%

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Biomimetic Approach toward the Total Synthesis of rac-2-(Acylmethylene)pyrrolidine Alkaloids

et al. 2015

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2-(Acylmethylene)pyrrolidine derivatives were synthesized via intermolecular decarbonylative Mannich reaction from various methyl ketones and 1-alkyl-1-pyrroliniums, generated in situ from 1-alkylprolines. This approach mimics the biosynthetic pathway and provides a direct access to a series of 2-(acylmethylene)pyrrolidine alkaloids, including hygrine, N-methylruspolinone, dehydrodarlinine, and ruspolinone.

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Section: Resultsmentioning

confidence: 99%

“…Compound 5ja was prepared from 1-benzylproline (2a) and 2,17,19 (5jb, dehydrodarlinine) Compound 5jb was prepared from 1-methylproline (2b) and …”

Section: (E)-1-(1-benzylpyrrolidin-2-yl)-4-phenylbut-3-en-2-one (5ja)mentioning

confidence: 99%

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confidence: 99%

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Biomimetic Approach toward the Total Synthesis of rac-2-(Acylmethylene)pyrrolidine Alkaloids

et al. 2015

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“…We have in the past been able to reduce the double bond of related vinylogous amides selectively with lithium aluminium hydride under carefully controlled conditions without affecting the carbonyl group. 22 As one might have expected, however, this reagent also partially reduced the quinazolinone unit of 15, as did milder hydride reducing agents such as sodium cyanoborohydride or sodium triacetoxyborohydride. We eventually achieved the desired reduction by catalytic hydrogenation at three atmospheres over platinum dioxide in methanol containing aqueous hydrochloric acid solution (8.5 M).…”

Section: Figurementioning

confidence: 90%

A Versatile Synthesis of (±)-Deoxyfebrifugine, an Antimalarial Alkaloid Analogue, and Related Compounds

Michael¹,

Koning²,

Pienaar³

2006

Synlett

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The title compound was prepared by a simple route involving Eschenmoser sulfide contraction between 3-(3-bromo-2-oxopropyl)quinazolin-4(3H)-one (11) and piperidine-2-thione (13) followed by chemoselective catalytic hydrogenation. This short but flexible procedure also permitted access to N-alkyl analogues, and to analogues in which the piperidine ring was replaced by other saturated nitrogen-containing heterocycles.

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“…Other tertiary amines and phosphorous thiophiles 23 are reported in the literature as being effective, as well as reaction performed in the absence of a thiophile. 24 While trisubstituted b-enaminocarbonyl compounds are readily prepared starting from thiolactams and a-bromoesters under the usual protocol, the tetrasubstituted derivatives, such as 2, require carefully controlled conditions to avoid undesired side reactions.…”

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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The application of the sulphide contraction to the synthesis of some simple pyrrolidine alkaloids

Cited by 23 publications

References 20 publications

Biomimetic Approach toward the Total Synthesis of rac-2-(Acylmethylene)pyrrolidine Alkaloids

Biomimetic Approach toward the Total Synthesis of rac-2-(Acylmethylene)pyrrolidine Alkaloids

A Versatile Synthesis of (±)-Deoxyfebrifugine, an Antimalarial Alkaloid Analogue, and Related Compounds

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

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