The Preparation of 2-Alkylbutadienes<sup>1</sup>

Marvel, C. S.; Myers, Robert L.; Saunders, J. H.

doi:10.1021/ja01185a006

Cited by 47 publications

(15 citation statements)

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“…Removal of the protecting acetal group in 23 by acid resulted in aldehyde 24. Finally, introduction of the methylene group to form the a,bunsaturated aldehyde 25 was achieved in almost quantitative yield by applying the Eschenmoser salt (Me 2 N CH 2 Cl À ) generated in situ from dimethylamine hydrochloride and formaldehyde [37] [38]. The 1 H-and 13 C-NMR, FT-IR, and mass spectra were consistent with the structure of the model compound 25 (see also Fig.…”

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confidence: 59%

Mimicking the Reaction of Phenylalanine Ammonia Lyase by a Synthetic Model

Rettig¹,

Sigrist²,

Rétey³

2000

HCA

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Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday Phenylalanine and histidine ammonia lyases (PAL and HAL) catalyze the reversible conversion of aamino acids to the corresponding acrylic acids by elimination of ammonia. The prosthetic group 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) at the active site of both enzymes supposedly undergoes an electrophilic attack at the aromatic nucleus in the first step of the mechanism of action. Since no chemical analogy existed for such an electrophile-assisted elimination, we synthesized model compounds, some portion of which mimicked the essentials of the substrate phenylalanine and another portion the electrophilic Michael acceptor in a sterically appropriate distance. The first model, (AE)-rel-(1R,2S,3S)-3-[1-methylidene-2-oxo-2-(pyrrolidin-1-yl)ethyl]-2-phenylcyclohexanamine (7) did not react under Friedel-Crafts conditions in the expected way (Scheme 2). The second model compound (AE)-2-rel-(1R,2S,3S)-3-(dimethylamino)-2-(3-methoxyphenyl)cyclohexyl]prop-2-enal (12) with a more nucleophilic methoxyphenyl and a more electrophilic a,b-unsaturated carbonyl moiety, underwent an intramolecular Friedel-Crafts-type substitution, but no elimination of the dimethylamino group (Scheme 4). The third model compound, (AE)-g-[(dimethylamino)methyl]-3-methoxy-2,4,6-trimethyl-a-methylidenebenzenebutanal (25) eliminated dimethylamine upon treatment with Lewis acids and subsequent hydrolysis of the intermediate (Scheme 6). When the 3-methoxy-2,4,6-trimethylphenyl moiety of 25 was replaced by the 2,4,6-trimethyl-3-nitrophenyl group, no elimination product could be observed (Scheme 7).

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confidence: 59%

Mimicking the Reaction of Phenylalanine Ammonia Lyase by a Synthetic Model

Rettig¹,

Sigrist²,

Rétey³

2000

HCA

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“…[38][39][40][41] In our system, trans isomer 20 was obtained as a sole product. Comparison of the optical rotation with that reported 42) showed that the product was (Ϫ)-epieburnamonine (20).…”

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confidence: 74%

“…4). Compound 8 was obtained from known allyl alcohol 5 20) through Johnson-Claisen rearrangement, reduction of the resultant ester to alcohol, oxidation with IBX, 21) reductive amination, and chlorocarbonylation with triphosgene. Chloroformamide 8 was found to be stable for aqueous extraction, silica gel column chromatography and storage in refrigerator for several weeks, as expected.…”

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confidence: 99%

“…Oxidation and methylation followed by removal of the Boc group under microwave irradiation afforded methyl ester 19, from which syntheses of eburnamonine, eburnamine and vincamine have been reported. [35][36][37] Methyl ester 19 was converted to epieburnamonine (20) through Bischler-Napieralski reaction and reduction with NaBH 4 . It is known that reduction of the related compounds with NaBH 4 gives a mixture in which the trans isomer is in excess of the cis isomer.…”

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Toward General Access to the <i>Aspidosperma</i>-Type Terpenoid Indole Alkaloids: Synthesis of the Key 3,3-Disubstituted Piperidones through Enantioselective Intramolecular Heck-Type Reaction of Chloroformamides

2008

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An enantioselective intramolecular Heck-type reaction of chloroformamides has been developed for the synthesis of 3,3-disubstituted piperidones. The desired piperidone was formed in the presence of a palladium catalyst, an optically active phosphoramidite ligand, K 3 PO 4 and Ag 3 PO 4 . The obtained piperidone was converted to epieburnamonine.Key words enantioselective reaction; total synthesis; terpenoid indole alkaloid Chem. Pharm. Bull. 56(11) 1567-1574 (2008) © 2008 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: takemoto@pharm.kyoto-u.ac.jp under normal conditions (entries 1-3). However, lactam 9 was isolated in 60% yield when Ag 3 PO 4 was added to the reaction (entry 4). The combination of Pd 2 (dba) 3 and BINAP was also able to promote the cyclization in the presence of Ag 3 PO 4 (entry 5). Nolan's NHC catalyst was not effective (entry 6).With these results in hand, syntheses of each cis-trans isomer of alkenyl chloroformamide 2 were performed. Alkene (E)-4 was synthesized through hydroalumination as a key step (Fig. 5). 4-Pentyn-1-ol (10) was transformed into alcohol 11 through oxidation, acetalization, and hydroxymethylation using benzotriazolylmethanol (BtCH 2 OH). 22) Alcohol 11 was then subjected to the hydroalumination-iodination sequence 23,24) to give (Z)-iodo alkene 12, whose configuration was confirmed by NOE experiment. Ethylation by Suzuki coupling, followed by benzylation gave the desired alkene (E)-4.Change of the starting material afforded the alternative stereoisomer (Fig. 6). (Z)-Iodoalkene 14 was synthesized from 2-pentyn-1-ol (13) through hydroalumination and iodination. Since benzylation of the hydroxy group under either basic or acidic conditions competed with decomposition of the starting material, protection by THP group was carried out. The resultant THP ether 15 underwent Negishi coupling with 3,3-(dimethoxy)propylzinc chloride 16. 25) Selective hydrolysis of the THP ether and benzylation afforded the desired alkene (Z)-4.Alkenyl acetals (E)-4 and (Z)-4 were coupled with tryptamine 3 26) through hydrolysis and reductive amination to give amines (E)-17 and (Z)-17, respectively (Fig. 7). These compounds were converted to the corresponding chloroformamides (E)-2 and (Z)-2 by treating with triphosgene and Et 3 N.Before the enantioselective Heck-type reaction, a racemic reaction was attempted to find out a suitable palladium source ( Table 2). The cyclized product 1 was isolated after hydrolysis of the resultant enol ether. At the early stage, poor reproducibility was a serious problem. After several attempts, it was found that the activity of the catalyst is highly associated with the conditions used to mix palladium sources and ligands prior to the addition of chloroformamide 2. When [Pd(h 3 -C 3 H 5 )Cl] 2 was premixed with (p-tol) 3 P at 30°C for 30 min, the disappearance of 2 was slow and the yield was 30% after 24 h (entry 1). In contrast, the starting material disappeared in 3 h and yield reached 49% when premixing was performed at 40°C...

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“…К сожалению, труднодоступность и неус-тойчивость 2-алкил-1,3-бутадиенов [12] не позволили успешно использовать аналогичную конденсацию для синтеза 4-алкил-3-циклогексен-карбоновых кислот (Vб-г).…”

Section: результаты и их обсуждениеunclassified