Experimental and Computational Study of the Conrotatory Ring Opening of Various 3-Chloro-2-azetines

Mangelinckx, Sven; Speybroeck, Véronique Van; Vansteenkiste, Peter; Waroquier, Michel; Kimpe, Norbert De

doi:10.1021/jo800522b

Cited by 42 publications

(26 citation statements)

References 61 publications

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“…Product yields were the highest in dichloromethane, and diphenylsulfur ylides gave higher product yields than their dimethyl or methylphenyl analogues (see Supplementary Table 1). Reactions were performed at room temperature to avoid electrocyclic ring opening of the azetine 27–29 . [3 + 1]-Cycloaddition occurred with the triisopropylsilyl(TIPS)-protected enoldiazoacetate, but not with the tert- butyldimethylsilyl(TBS)-protected enoldiazoacetate.…”

Section: Resultsmentioning

confidence: 99%

“…Treatment of azetine 3c with aromatic amines, which are weaker nucleophiles, showed negligible conversion in DCM at room temperature, but heating 3c with aniline (3 equiv.) at 65 °C in 1,2-dichloroethane (DCE) for 24 h resulted in ring-opening nucleophilic coupling; however, 13a was formed in only 65% yield together with the product from the known thermal electrocyclic ring opening of 3c 27–29 . Use of electron-rich 4-(dimethylamino)aniline with 3c in nitromethane at room temperature increased the yield of the ring-opened product to 93% ( 13b ).…”

Section: Resultsmentioning

confidence: 99%

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Chiral donor–acceptor azetines as powerful reactants for synthesis of amino acid derivatives

et al. 2019

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Coupling reactions of amines and alcohols are of central importance for applications in chemistry and biology. These transformations typically involve the use of a reagent, activated as an electrophile, onto which nucleophile coupling results in the formation of a carbon-nitrogen or a carbon–oxygen bond. Several promising reagents and procedures have been developed to achieve these bond forming processes in high yields with excellent stereocontrol, but few offer direct coupling without the intervention of a catalyst. Herein, we report the synthesis of chiral donor–acceptor azetines by highly enantioselective [3 + 1]-cycloaddition of enoldiazoacetates with aza-ylides and their selective coupling with nitrogen and oxygen nucleophiles via 3-azetidinones to form amino acid derivatives, including those of peptides and natural products. The overall process is general for a broad spectrum of nucleophiles, has a high degree of electronic and steric selectivity, and retains the enantiopurity of the original azetine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Chiral donor–acceptor azetines as powerful reactants for synthesis of amino acid derivatives

et al. 2019

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“…Whilst the chemistry of three‐membered nitrogen heterocycles has been widely reported, studies on their four‐membered counterparts have focused primarily on 2‐azetidinones and, to a much lesser extent, azetidine rings 1. The 2‐azetine system 1,2‐dihydroazete, which has a strained cyclic enamine ring, is particularly elusive 2. Most 2‐azetine compounds undergo spontaneous electrocyclic ring opening to afford their 1‐azadiene analogues; as such, there are few examples of stable 2‐azetines in the literature and those reported require electron‐withdrawing substituents, for example, carbonyl, carboxyl, sulfonyl, or nitro groups, attached to the nitrogen atom 3.…”

Section: Methodsmentioning

confidence: 99%

Sequential Five‐Component Construction of the Cyclopenta[e][1,3]oxazine Skeleton using Stable 2‐Azetine Derivatives

et al. 2010

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Dedicated to Professor Julius Rebek, Jr. on the occasion of his 65th birthday Small-ring heterocycles are of prominent importance because of their potential as bioactive compounds and synthetic building blocks. Whilst the chemistry of three-membered nitrogen heterocycles has been widely reported, studies on their four-membered counterparts have focused primarily on 2-azetidinones and, to a much lesser extent, azetidine rings. [1] The 2-azetine system 1,2-dihydroazete, which has a strained cyclic enamine ring, is particularly elusive. [2] Most 2-azetine compounds undergo spontaneous electrocyclic ring opening to afford their 1-azadiene analogues; as such, there are few examples of stable 2-azetines in the literature and those reported require electron-withdrawing substituents, for example, carbonyl, carboxyl, sulfonyl, or nitro groups, attached to the nitrogen atom. [3,4] As a consequence, the chemistry of 2azetines remains largely unexplored, and has been predominantly focused on their potential as a precursor to azadienes. Moreover, there are no general synthetic routes to 2azetines. [5] Although, the [2+2] cycloaddition of alkynes and imines appears to be a convenient route to this type of heterocyclic framework, only a few specific examples have been reported; in these cases, electron-rich alkynes, as ynamines, [6] alkynyl selenides, [7] or alkynyl sulphides, [8] are able to form the expected 2-azetine skeleton, which is not isolated but rapidly opens to the azadiene system. The [2+2] cycloaddition of electron-poor alkynes and imines has only previously been suggested as an intermediate in the cyclization reaction between an alkynyl(ethoxy)carbene of tungsten and imine fluorenones to afford pyrroline derivatives. [9] As part of our interest in Fischer-type metal carbenes, we have recently considered more-electrophilic metal carbenes, the so-called non-heteroatom-stabilized carbenes. [10] These compounds are particularly useful in organic synthesis, and our preliminary results have revealed significant differences in the reactivity of both heteroatom- [11] and non-heteroatomstabilized systems.Herein, we report the [2+2] cycloaddition reaction of alkynyl-substituted (pentacarbonyl)chromium or -tungsten carbene complexes with imines as a suitable procedure for accessing stable 2-azetine derivatives. Moreover, the conjugation of the resulting azetine unit with the metal carbene allows for a facile synthesis of novel cyclopenta[e]-[1,3]oxazines involving treatment with alkynes. This threecomponent process (azetine, alkyne, and CO ligand) features cleavage of the azetine C3 À C4 bond, rather than the expected N À C4 bond, and the formation of three C À C bonds and one CÀO bond (Scheme 1).Stable, easy-to-handle methoxycarbenes 1 are used as in situ precursors of alkynylcarbenes 3 using the methoxyacetylide 2 exchange reaction ( Table 1). The resultant solution of 3 in tetrahydrofuran was treated at À80 8C with 1.3-5.0 equivalents of imine 4 (see the Supporting Information) and the mixture was allowed to warm to 0 8C....

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“…Also, in contrast to the corresponding cycloaddition reaction of thioketenes, there is no competing formation of 1:2 or 2:1 cycloadducts. 4,41 However, in the simple form of the process, a competing reaction to give α,β-unsaturated thioamides 25 does occur ( 42 Further studies on the reaction of silyl sulfides 5 with azomethines 21 revealed that the electrocyclic process is totally suppressed if the reaction is carried out in the presence of a Lewis acid, especially zinc iodide, at low temperature (Table 3). 19c,25 β-Thiolactams 23 can occur as diastereomers with respect to the positions of the R 1 and R 3 groups.…”

Section: [2+2]-cycloaddition Reactions With Azomethinesmentioning

confidence: 99%

Alkynyl Silyl Sulfides as Versatile Thioketene Equivalents

Spanka

Schaumann

2014

Synlett

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This account covers the chemistry of alkynyl silyl sulfides and their use as substitutes for aldothioketenes. In contrast to the latter heterocumulenes, which can only be prepared and used in situ, many alkynyl silyl sulfides are stable at room temperature. Exceptions are bissilylated derivatives that are capable of rearranging to form the corresponding thioketenes. This reaction is promoted thermally or by the addition of silyl-accepting Lewis bases, but is suppressed by bulky S-silyl substituents. The reactivity of the highly electrophilic alkynyl silyl sulfides is comparable to that of the corresponding ketenes and thioketenes. Nucleophiles usually add to the alkyne α-carbon atoms to give, after desilylation, thiocarbonyl compounds. Particularly useful are the reactions with amines, imines, or ynamines, which give thioamides, β-thiolactams, and cyclobutenethiones, respectively. These transformations proceed under mild conditions and provide access to derivatives that could not previously be prepared by classical means. The scope of the [2+2]-cycloaddition reaction with imines to give β-thiolactams can be expanded by using Lewis acid catalysts, particularly zinc iodide. The mechanism of this reaction has been elucidated by careful characterization of byproducts. Further modifications of the β-thiolactams prepared by this methodology are also described. Reactions of alkynyl silyl sulfides with cyclic imines lead to bicyclic systems that can be considered as thio analogues of the core structures of β-lactam antibiotics. However, there is a competition from the ringexpansion reaction to form seven-membered thiolactams and dithiolactones.

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Experimental and Computational Study of the Conrotatory Ring Opening of Various 3-Chloro-2-azetines

Cited by 42 publications

References 61 publications

Chiral donor–acceptor azetines as powerful reactants for synthesis of amino acid derivatives

Chiral donor–acceptor azetines as powerful reactants for synthesis of amino acid derivatives

Sequential Five‐Component Construction of the Cyclopenta[e][1,3]oxazine Skeleton using Stable 2‐Azetine Derivatives

Alkynyl Silyl Sulfides as Versatile Thioketene Equivalents

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