Intermolecular 2+2 photocycloadditions represent a powerful method for the synthesis of highly strained, four-membered rings. Although this approach is commonly employed for the synthesis of oxetanes ...and cyclobutanes, the synthesis of azetidines via intermolecular aza Paternò-Büchi reactions remains highly underdeveloped. Here we report a visible-light-mediated intermolecular aza Paternò-Büchi reaction that utilizes the unique triplet state reactivity of oximes, specifically 2-isoxazoline-3-carboxylates. The reactivity of this class of oximes can be harnessed via the triplet energy transfer from a commercially available iridium photocatalyst and allows for 2+2 cycloaddition with a wide range of alkenes. This approach is characterized by its operational simplicity, mild conditions and broad scope, and allows for the synthesis of highly functionalized azetidines from readily available precursors. Importantly, the accessible azetidine products can be readily converted into free, unprotected azetidines, which represents a new approach to access these highly desirable synthetic targets.
Azetidines are four-membered nitrogen-containing heterocycles that hold great promise in current medicinal chemistry due to their desirable pharmacokinetic effects. However, a lack of efficient ...synthetic methods to access functionalized azetidines has hampered their incorporation into pharmaceutical lead structures. As a 2+2 cycloaddition reaction between imines and alkenes, the aza Paternò-Büchi reaction arguably represents the most direct approach to functionalized azetidines. Hampered by competing reaction paths accessible upon photochemical excitation of the substrates, the current synthetic utility of these transformations is greatly restricted. We herein report the development of a visible light-enabled aza Paternò-Büchi reaction that surmounts existing limitations and represents a mild solution for the direct formation of functionalized azetidines from imine and alkene containing precursors.
The olefin-olefin metathesis reaction has emerged as one of the most important carbon-carbon bond-forming reactions, as illustrated by its wide use in the synthesis of complex molecules, natural ...products and pharmaceuticals. The corresponding metathesis reaction between carbonyls and olefins or alkynes similarly allows for the formation of carbon-carbon bonds. Although these variants are far less developed and utilized in organic synthesis, they possess attractive qualities that have prompted chemists to incorporate and explore these modes of reactivity in complex molecule synthesis. This review highlights selected examples of carbonyl-olefin and carbonyl-alkyne metathesis reactions in organic synthesis, in particular in the total synthesis of natural products and complex molecules, and provides an overview of current advantages and limitations.
This tutorial review provides an introduction to metathesis reactions between carbonyls and olefins or alkynes and their application in natural product synthesis.
Polycyclic aromatic hydrocarbons are important structural motifs in organic chemistry, pharmaceutical chemistry, and materials science. The development of a new synthetic strategy toward these ...compounds is described based on the design principle of iron(III)-catalyzed carbonyl–olefin metathesis reactions. This approach is characterized by its operational simplicity, high functional group compatibility, and regioselectivity while relying on FeCl3 as an environmentally benign, earth-abundant metal catalyst. Experimental evidence for oxetanes as reactive intermediates in the catalytic carbonyl–olefin ring-closing metathesis has been obtained.
Abstract
This short review summarizes recent advances relating to the application of ring-closing olefin-olefin and carbonyl-olefin metathesis reactions towards the synthesis of unsaturated five- and ...six-membered nitrogen heterocycles. These developments include catalyst modifications and reaction designs that will enable access to more complex nitrogen heterocycles.
1 Introduction
2 Expansion of Ring-Closing Metathesis Methods
3 Evaluation of Catalyst Design
4 Indenylidene Catalysts
5 Unsymmetrical
N
-Heterocyclic Carbene Ligands
6 Carbonyl-Olefin Metathesis
7 Conclusions
A New Twist on Cooperative Catalysis Schindler, Corinna S.; Jacobsen, Eric N.
Science (American Association for the Advancement of Science),
05/2013, Letnik:
340, Številka:
6136
Journal Article
Recenzirano
Two independent catalysts working synergistically allow the controlled synthesis of all four stereoisomers in a reaction that forms carbon-carbon bonds.
Also see Research Article by
Krautwald
et al.
...The stereochemical configuration of an organic compound is often linked directly to its physical and biological properties. Larger molecules can contain multiple stereochemical elements, and chiral catalysts are often used to control each of these defined spatial arrangements in the efficient synthesis of a complex target (
1
). Many powerful enantioselective catalysts, which control the handedness or absolute configuration of a product, have been developed (
2
), but full control of the relative configuration in compounds can be a greater challenge if multiple stereocenters are generated; high diastereoselectivity, where one relative configuration is established, may be achieved, but access to the complementary diastereomeric product usually requires major redesign of the catalyst, substrate, and/or reaction conditions, and in some cases is not possible at all (see the figure, panel A) (
3
). On page 1065 of this issue, Krautwald
et al.
(
4
) demonstrate an elegant solution to this challenge based on the cooperative action of multiple chiral catalysts in a single reaction.
The 2 + 2 photocycloaddition reaction between an imine and an alkene component, the aza Paternò-Büchi reaction, is one of the most efficient ways to synthesize functionalized azetidines. However, the ...application of the aza Paternò-Büchi reaction has been met with limited success due to the inherent challenges associated with this approach. This review covers the current scope and limitations of reported examples of aza Paternò-Büchi reactions in organic synthesis. An outlook is provided, which highlights recent improvements and the discovery of new reaction protocols that have overcome some long-standing challenges within this field of research.
This review discusses the current scope and limitations of the 2 + 2 photocycloaddition reaction between an imine and an alkene component, the aza Paternò-Büchi reaction, and highlights recent improvements within this area of research.
Azetines, four-membered unsaturated nitrogen-containing heterocycles, hold great potential for drug design and development but remain underexplored due to challenges associated with their synthesis. ...We report an efficient, visible light-mediated approach toward 1- and 2-azetines relying on alkynes and the unique triplet state reactivity of oximes, specifically 2-isoxazolines. While 2-azetine products are accessible upon intermolecular 2 + 2-cycloaddition via triplet energy transfer from a commercially available iridium photocatalyst, the selective formation of 1-azetines proceeds upon a second, consecutive, energy transfer process. Mechanistic studies are consistent with a stepwise reaction mechanism via N–O bond homolysis following the second energy transfer event to result in the formation of 1-azetine products. Characteristic for this method is its operational simplicity, mild conditions, and modular approach that allow for the synthesis of functionalized azetines and tetrahydrofurans (via in situ hydrolysis) from readily available precursors.
The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis ...reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
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