Ring Expansion of 2‐(1‐Hydroxyalkyl)azetidines to 4‐(2‐Chloroethyl)oxazolidinones

Couty, François; Drouillat, Bruno; Lemée, Frédéric

doi:10.1002/ejoc.201001375

Cited by 22 publications

(8 citation statements)

References 24 publications

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“…According to a recent report by Couty and coworkers, the addition of organolithiums or Grignard reagents to azetidine carboxylic esters ( R, S )- 2b , occurred with low chemoselectivity, providing the corresponding tertiary alcohol as the main product (Couty et al, 2011). This prompted us to consider the approach reported in Scheme 2 as an alternative route to 2-acylazetidines.…”

Section: Resultsmentioning

confidence: 99%

“…Methods for the preparation of 2-acylazetidines could be traced back to 1969 with the first synthesis reported by Cromwell, by cyclization of 2,4-dibromoketones with primary amines (Scheme 1, A) or the addition of organolithiums to azetidines carboxylic acids (Rodebaugh and Cromwell, 1969, 1971; Kulkarni and Cromwell, 1977; Arnould et al, 1980; Scheme 1, B). Selected examples, for the stereoselective synthesis of 2-acylazetidines, include the nucleophilic addition of aryllithiums (Couty and Prim, 2002) and Grignard reagents (Couty et al, 2011) to optically active 2-cyanoazetidines (Scheme 1, E) or the addition of Grignard reagents to enantiopure Weinreb amides prepared from methyl 1-phenylethylazetidine-2-carboxylates (Ma et al, 2007; Scheme 1, C). Recently, the synthesis of 2-acylazetidines, by a one-pot tetramethylguanidine/I 2 -mediated formal [2+2] cycloaddition reaction of α-amidomalonate with enones, has been reported by Miao and Sun (Miao et al, 2013; Scheme 1, F).…”

Section: Introductionmentioning

confidence: 99%

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Stereo- and Enantioselective Addition of Organolithiums to 2-Oxazolinylazetidines as a Synthetic Route to 2-Acylazetidines

et al. 2019

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A new synthetic route to N-alkyl-2-acylazetidines was developed through a highly stereoselective addition of organolithiums to N-alkyl-2-oxazolinylazetidines followed by acidic hydrolysis of the resulting oxazolidine intermediates. This study revealed an unusual reactivity of the C=N bond of the oxazoline group when reacted with organolithiums in a non-polar solvent such as toluene. The observed reactivity has been explained considering the role of the nitrogen lone pair of the azetidine ring as well as of the oxazolinyl group in promoting a complexation of the organolithium, thus ending up with the addition to the C=N double bond. The high level of stereoselectivity in this addition is supported by DFT calculations and NMR investigations, and a model is proposed for the formation of the oxazolidine intermediates, that have been isolated and fully characterized. Upon acidic conditions, the oxazolidine moieties were readily converted into 2-acylazetidines. This synthetic approach has been applied for the preparation of highly enantioenriched 2-acylazetidines starting from chiral not racemic N-alkyl-2-oxazolinylazetidines.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stereo- and Enantioselective Addition of Organolithiums to 2-Oxazolinylazetidines as a Synthetic Route to 2-Acylazetidines

et al. 2019

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“…The first one showed the ring expansion of functionalized azetidinols 236, fitted with a hydroxyalkyl moiety at C-2, into 2-chloroethyl oxazolidinones 238 upon reaction with BTC, a well-known substitute for phosgene [119]. This reaction was also recently studied in the case of aziridines (see above section).…”

Section: Expansions Into Oxazolidinonesmentioning

confidence: 96%

Ring Expansions of Nonactivated Aziridines and Azetidines

Couty

David

2015

Topics in Heterocyclic Chemistry

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Ring expansions promoted by ring strain in aziridines and azetidines are reviewed in this chapter, putting emphasis on recent applications from the last decade. This vast subject cannot be surveyed here exhaustively, and the reader will be guided to relevant precedent reviews or key reports. Rather, special attention will be put on selected examples and their mechanistic details, aiming to demonstrate that high selectivity can be reached in these reactions. In this issue, this fastgrowing topic has been divided into two distinct chapters, this one dealing with "nonactivated" aziridines and azetidines. Therefore, the reader will only find here examples involving NH-or N-alkylaziridines and N-azetidines as substrates for ring expansions, while N-acyl, N-carbamoyl, or N-tosyl compounds, defined as "activated" substrates, will be presented in the next chapter. This distinction can appear quite arbitrary at first sight but is amply justified by the great difference in reactivity of these distinct substrates. The first part focuses on the ring expansions of nonactivated aziridines into up to seven-membered rings and is further divided into expansions involving the incorporation of one (or more) heteroatoms, followed by ring expansions involving only incorporation of carbon atoms. The same model is then followed for azetidines.

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“…[27] For example, we recently disclosed a new possibility leading to functionalized oxazolidinones. [34] The strategy here consists of treating (α-hydroxymethyl)azetidines such as 77 with triphosgene: produced intermediate Nacylammonium ion 78 is then opened regioselectively by the chloride anion, which leads to (2-chloroethyl)oxazolidinones 79 (Scheme 13). Scheme 13.…”

Section: Ring Expansion Of Azetidinesmentioning

confidence: 99%

2‐Cyanoazetidines and Azetidinium Ions: Scaffolds for Molecular Diversity

et al. 2013

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Ring strain in azetidines and azetidinium ions can be efficiently used to promote ring‐expansion and ring‐opening reactions, and this renders these four‐membered heterocycles ideal scaffolds for diversity oriented synthesis. This microreview focuses on 2‐cyanoazetidines, which are easily prepared from β‐amino alcohols through a ring‐closing reaction involving C–C bond formation. The azetidines can be readily expanded to five‐ to eight‐membered nitrogen heterocycles after suitable functionalization and/or activation. Alternatively, N‐alkylated derivatives, namely, azetidinium ions, are easily prepared and displayed rich reactivity as new electrophilic building blocks and as sources of nitrogen ylides.

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Ring Expansion of 2‐(1‐Hydroxyalkyl)azetidines to 4‐(2‐Chloroethyl)oxazolidinones

Cited by 22 publications

References 24 publications

Stereo- and Enantioselective Addition of Organolithiums to 2-Oxazolinylazetidines as a Synthetic Route to 2-Acylazetidines

Stereo- and Enantioselective Addition of Organolithiums to 2-Oxazolinylazetidines as a Synthetic Route to 2-Acylazetidines

Ring Expansions of Nonactivated Aziridines and Azetidines

2‐Cyanoazetidines and Azetidinium Ions: Scaffolds for Molecular Diversity

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