Three-component reaction of small-ring cyclic amines with arynes and acetonitrile

Stephens, David E.; Yu, Zhengkun; Cormier, M.; Chavez, Gabriel; Arman, Hadi D.; Larionov, Oleg V.

doi:10.1039/c3cc42854k

Cited by 63 publications

(29 citation statements)

References 67 publications

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“…However, applying an additional 0.5 eq of the Mitsunobu reagents (Method B) resulted in further improvement of the yield of aziridines 9 and 10 (Table 1). In an attempted exchange of the hydroxyl in 1 and 2 into the corresponding bromo-compounds using the Appel reaction [26] (2 eq of CBr 4 and PPh 3 , then K 2 CO 3 ), we again obtained aziridines 8 (a known compound [27]) and 9. The products were the same as those obtained in the Mitsunobu reaction, so they were also formed by the direct internal substitution of the oxyphosphonium group by the secondary amine.…”

Section: Synthesis Of Aziridinesmentioning

confidence: 99%

“…Since only one diastereomer of the product was observed in all the cases, it is assumed that the ring closure process also occurred through S N 2 type reaction, and inversion of the configuration should have been achieved. compound [27]) and 9. The products were the same as those obtained in the Mitsunobu reaction, so they were also formed by the direct internal substitution of the oxyphosphonium group by the secondary amine.…”

Section: Synthesis Of Aziridinesmentioning

confidence: 99%

Section: Reduction Of Azido Amines To Vic-diaminesmentioning

confidence: 99%

“…The azides 3, 4, 13, 14, and 19 were reduced to the primary amines 20-24 via the Staudinger [27,41] reaction using triphenylphosphine in aqueous dichloromethane in moderate to high yield (Table 4). The structures of the azides (1R,1′S)-3, (1S,1′S)-3, (1R,2R,1′S)-13, (1S,2S,1′S)-14, (1S,2R,1′S)-19, and (1R,2S,1′S)-19 were established based on NMR experiments.…”

Section: Reduction Of Azido Amines To Vic-diaminesmentioning

confidence: 99%

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Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

2020

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In this report, we describe the synthetic elaboration of the easily available enantiomerically pure β-amino alcohols. Attempted direct substitution of the hydroxyl group by azido-functionality in the Mitsunobu reaction with hydrazoic acid was inefficient or led to a diastereomeric mixture. These outcomes resulted from the participation of aziridines. Intentionally performed internal Mitsunobu reaction of β-amino alcohols gave eight chiral aziridines in 45–82% yield. The structural and configuration identity of products was confirmed by NMR data compared to the DFT calculated GIAO values. For 1,2,3-trisubstituted aziridines slow configurational inversion at the endocyclic nitrogen atom was observed by NMR at room temperature. Moreover, when aziridine was titrated with Zn(OAc)2 under NMR control, only one of two N-epimers directly participated in complexation. The aziridines underwent ring opening with HN3 to form the corresponding azido amines as single regio- and diastereomers in 90–97% yield. Different results were obtained for 1,2-disubstituted and 1,2,3-trisubstituted aziridines. For the later aziridines ring closure and ring opening occurred at different carbon stereocenters, thus yielding products with two inverted configurations, compared to the starting amino alcohol. The 1,2-disubstituted aziridines produced azido amines of the same configuration as the starting β-amino alcohols. To obtain a complete series of diastereomeric vic-diamines, we converted the amino alcohols into cyclic sulfamidates, which reacted with sodium azide in SN2 reaction (25–58% overall yield). The azides obtained either way underwent the Staudinger reduction, giving a series of six new chiral vic-diamines of defined stereochemistries.

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Section: Synthesis Of Aziridinesmentioning

confidence: 99%

Section: Synthesis Of Aziridinesmentioning

confidence: 99%

Section: Reduction Of Azido Amines To Vic-diaminesmentioning

confidence: 99%

Section: Reduction Of Azido Amines To Vic-diaminesmentioning

confidence: 99%

See 2 more Smart Citations

Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

2020

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“…In particular, the recent aryne-based chemistry has made great advances in synthetic chemistry [3][4][5][6][7][8][9][10][11][12][13][14]. Our laboratory is interested in developing domino reactions using arynes.…”

Section: Introductionmentioning

confidence: 99%

2,3,4,9-Tetrahydro-9-(3-hydroxy-1,4-dioxo-1H-dihydro-naphthalen-2-yl)-8-methoxy-3,3-dimethyl-1H-xanthen-1-one

Yoshioka

Kohtani

Miyabe

2015

Molbank

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Abstract:The title compound 2,3,4,9-tetrahydro-9-(3-hydroxy-1,4-dioxo-1H-dihydronaphthalen-2-yl)-8-methoxy-3,3-dimethyl-1H-xanthen-1-one (5) was obtained by the nucleophilic addition of 2-hydroxy-1,4-naphthoquinone (4) to 2H-chromene derivative 3, which was prepared by the domino three-component coupling reaction of aryne precursor 1 with DMF and the active methylene compound dimedone (2). The one-pot synthesis of the title compound 5 from aryne precursor 1 was also achieved.Keywords: multi-component reaction; domino reaction; arynes; heterocycles; synthesis Arynes are highly reactive and kinetically unstable intermediates for constructing multisubstituted arenes with structural diversity and complexity [1,2]. In particular, the recent aryne-based chemistry has made great advances in synthetic chemistry [3][4][5][6][7][8][9][10][11][12][13][14]. Our laboratory is interested in developing domino reactions using arynes. We have recently developed the efficient insertion of arynes, generated in situ from ortho-(trimethylsilyl)aryl triflates and the fluoride ion, into the C=O π-bond of DMF [15][16][17][18][19][20].Synthetic strategies involving domino processes offer the advantage of multiple carbon-carbon and/or carbon-heteroatom bond formations in a single operation [21,22]. In this paper, we report two synthetic methods for preparing the title compound 5 via a domino multicomponent coupling reaction starting from the generation of an aryne. Moreover, this molecule 5 has a pharmaceutically important structure, because a similar type of compound was studied as a neuropeptide Y Y5 receptor antagonist by Merck-Banyu researchers [23]. OPEN ACCESS

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Aryne‐Based Multicomponent Reactions

Yoshida

2014

Multicomponent Reactions in Organic Synthesis

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Three-component reaction of small-ring cyclic amines with arynes and acetonitrile

Cited by 63 publications

References 67 publications

Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

2,3,4,9-Tetrahydro-9-(3-hydroxy-1,4-dioxo-1H-dihydro-naphthalen-2-yl)-8-methoxy-3,3-dimethyl-1H-xanthen-1-one

Aryne‐Based Multicomponent Reactions

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