Sequential Five-Component Construction of the Cyclopenta[e][1,3]oxazine Skeleton Using Stable 2-Azetine Derivatives.
TL;DR: In this paper, the 2-azetine system 1,2-dihydroazete, which has a strained cyclic enamine ring, is particularly elusive.
Abstract: 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. The 2-azetine system 1,2-dihydroazete, which has a strained cyclic enamine ring, is particularly elusive. 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. 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. 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, alkynyl selenides, or alkynyl sulphides, 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. 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. These compounds are particularly useful in organic synthesis, and our preliminary results have revealed significant differences in the reactivity of both heteroatomand 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 C4 bond, rather than the expected N C4 bond, and the formation of three C C bonds and one C O bond (Scheme 1).
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TL;DR: In this article , a review of the synthesis and applications of azetines is presented, with a focus on synthetic methods to access 1-and 2-azetines developed since 2018.
Abstract: Four-membered nitrogen-containing heterocycles are highly desirable functional groups with synthetic and biological applications. Unsaturated four-membered N-heterocycles, 1- and 2-azetines, are historically underexplored, but have recently been gaining interest due to the development of new synthetic methods to access these compounds, and to their potential as reactive intermediates. This review covers both the synthesis and applications of azetines, with a focus on synthetic methods to access azetines developed since 2018, and a comprehensive review of the reactivity and applications of azetines as starting materials or intermediates to access both other heterocycles and complex products.
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TL;DR: An efficient and straightforward phosphine-promoted tandem aza-Michael addition/intramolecular Wittig reaction was developed for the synthesis of polyfunctionalized 2-azetines as mentioned in this paper .
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TL;DR: The [2+2] cycloaddition reaction of alkynyl-substituted (pentacarbonyl)chromium or -tungsten carbene complexes with imines is reported as a suitable procedure for accessing stable 2-azetine derivatives and allows for a facile synthesis of novel cyclopenta[e][1,3]oxazines involving treatment with alkynes.
Abstract: 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. The 2-azetine system 1,2-dihydroazete, which has a strained cyclic enamine ring, is particularly elusive. 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. 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. 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, alkynyl selenides, or alkynyl sulphides, 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. 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. These compounds are particularly useful in organic synthesis, and our preliminary results have revealed significant differences in the reactivity of both heteroatomand 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 C4 bond, rather than the expected N C4 bond, and the formation of three C C bonds and one C O bond (Scheme 1).
32 citations