Stereoselective Synthesis of <i>cis</i>-3,4-Disubstituted Piperidines through Ring Transformation of 2-(2-Mesyloxyethyl)azetidines

Mollet, Karen; Çatak, Şaron; Waroquier, Michel; Speybroeck, Véronique Van; D’hooghe, Matthias; Kimpe, Norbert De

doi:10.1021/jo201556t

Cited by 33 publications

(11 citation statements)

References 80 publications

(50 reference statements)

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“…This reaction is favored when the heterocumulene is electron poor and the alkyl group on the nitrogen of the azetidine is not too bulky. Regio-and stereoselectivity of this reaction are excellent since complete diastereoselectivity By analogy with the ring expansion leading to pyrrolidines described in detail in the previous section, the homologous reaction producing piperidines was studied only recently [148][149][150]. Primary mesylates 340 or bromides 343 (prepared by reduction of the corresponding beta-lactams) can be used as well, and it was calculated that the ring expansion goes through an intermediate bicyclic azetidinium ion such as 341, whose stability is comparable to the starting compound.…”

Section: Expansions Into 2-iminopiperidines Piperidin-2-ones and Pimentioning

confidence: 99%

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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Section: Expansions Into 2-iminopiperidines Piperidin-2-ones and Pimentioning

confidence: 99%

Ring Expansions of Nonactivated Aziridines and Azetidines

Couty

David

2015

Topics in Heterocyclic Chemistry

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“…[36] Primary bromides 86 or mesylates 83 (prepared by reduction of the corresponding lactam) can be used in this process, and it was calculated that the ring expansion goes through an intermediate Quite similarly, seven-membered ring azepanes can be produced from ring opening of azabicyclo[3.2.0]heptane derivatives, which can be readily obtained in enantiomerically pure form from proline [Scheme 4, Eq. Recently, D'hoogue and De Kimpe reported the ring expansion of azetidines to piperidines, which is homologous to the ring expansion depicted in Scheme 10.…”

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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“…The subsequent reaction of 168 with sodium acetate in acetonitrile, followed by basic hydrolysis, gave cis -3-alkoxy/phenoxy-4-hydroxypiperidines 170 in moderate overall yields through two-carbon ring expansion (Scheme 44). 142 This ring expansion process involves the ammonium ion of 1-azabicyclo[2.2.0]hexane 169 as the key intermediate, which can explain the 3,4- cis stereochemistry of 170 as the result of exo -attack of acetate ion to cleave the 1–4 bond. 142 Closely related reactions using 3-alkoxyl-4-(2-bromo-1,1-dimethylethyl)-β-lactams afforded 3,3-dimethyl-4-X-5-alkoxypiperidines (X = Br, OAc, OH, CN, N 3 ) in high-to-excellent yields.…”

Section: Synthesis Of 3- To 8-membered Nitrogen-heterocycles From mentioning

confidence: 99%

“…142 This ring expansion process involves the ammonium ion of 1-azabicyclo[2.2.0]hexane 169 as the key intermediate, which can explain the 3,4- cis stereochemistry of 170 as the result of exo -attack of acetate ion to cleave the 1–4 bond. 142 Closely related reactions using 3-alkoxyl-4-(2-bromo-1,1-dimethylethyl)-β-lactams afforded 3,3-dimethyl-4-X-5-alkoxypiperidines (X = Br, OAc, OH, CN, N 3 ) in high-to-excellent yields. 143,144 The reaction of 168 (R 1 = i -Pr) with LiBr in acetonitrile gave cis -3-alkoxy-4-bromopiperidine 171 , which was converted into piperidin-3-one 172 via the enol-ether in fairly good yield for 2 steps (Scheme 44).…”

Section: Synthesis Of 3- To 8-membered Nitrogen-heterocycles From mentioning

confidence: 99%