1,3-Dipolar Cycloadditions to Bicyclic Olefins. V. The Stereo- and Regiochemistry of 1,3-Dipolar Cycloadditions to Several Unsymmetrical Bicyclic Olefins
Abstract:Each of the 1,3-dipolar cycloadditions of phenylglyoxylonitrile oxide (1), methylglyoxylonitrile oxide (2), benzonitrile oxide (3), and phenyl azide to 2-phenylsulfonyl-2-azabicyclo[3.2.1]octa-3,6-diene (6) occurs only to the C6–C7 double bond, affording two exo regioisomers. Each of the cycloadditions of 1, 2, and 3 to 2-phenylsulfonyl-2-azabicyclo[3.2.1]oct-3-ene (7) gives only one exo adduct. The cycloaddition of C,N-diphenylnitrone to 2-methylenenorbornane (8) gives a mixture of two exo adducts. These resu… Show more
“…Similar reactions of 2-azabicyclo[2.2.2]hept-5-en-3-ones reportedly required high pressure for the cycloaddition reaction to occur 17c. The exo- specificity of the reaction is in agreement with what has been reported in the literature in related reactions of bicyclo[2.2.1]hept-5-ene-2,3-dicarboximides,16h ABH ( 2 ) and derivatives, 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives, and 3 . , …”
supporting
confidence: 88%
“…Intermolecular [3 + 2] cycloaddition reactions of azides to strained bicyclic alkenes are well-documented in the literature 2,3-diazabicyclo[2.2.1]hept-5-enes 3 to afford 1,4-dihydropyridines, as well as many other strained systems. 16h, However, the addition of azides to bicyclic oxazines such as 1 has not been disclosed in the literature. …”
The addition of azides to acylnitroso hetero-Diels-Alder cycloadducts derived from cyclopentadiene affords exo-triazolines in excellent yield. The reaction is greatly affected by the level of alkene strain, while sterically demanding azides do not hinder the reaction. Conversion of the triazolines to aziridines is also described.
“…Similar reactions of 2-azabicyclo[2.2.2]hept-5-en-3-ones reportedly required high pressure for the cycloaddition reaction to occur 17c. The exo- specificity of the reaction is in agreement with what has been reported in the literature in related reactions of bicyclo[2.2.1]hept-5-ene-2,3-dicarboximides,16h ABH ( 2 ) and derivatives, 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives, and 3 . , …”
supporting
confidence: 88%
“…Intermolecular [3 + 2] cycloaddition reactions of azides to strained bicyclic alkenes are well-documented in the literature 2,3-diazabicyclo[2.2.1]hept-5-enes 3 to afford 1,4-dihydropyridines, as well as many other strained systems. 16h, However, the addition of azides to bicyclic oxazines such as 1 has not been disclosed in the literature. …”
The addition of azides to acylnitroso hetero-Diels-Alder cycloadducts derived from cyclopentadiene affords exo-triazolines in excellent yield. The reaction is greatly affected by the level of alkene strain, while sterically demanding azides do not hinder the reaction. Conversion of the triazolines to aziridines is also described.
Early researchers studying the condensation product of carbonyl compounds with
N
‐substituted hydroxylamines elected to coin the term “nitrone” as a combination of the words “nitrogen” and “ketone.” This was done to emphasize the parallel between this newly discovered functionality and the already rich chemistry of the carbonyl group.
For example, nitrones are capable of reacting with carbanions of various types, a consequence of the iminium species embedded in the nitrone that renders the functionality susceptible to nucleophilic attack. Thus
C
‐phenyl‐
N
‐methylnitrone undergoes a Reformatsky reaction with ethyl bromoacetate in complete analogy with benzaldehyde. The intermediate zinc alkoxide cyclizes to 2‐methyl‐3‐phenylisoxazolidin‐5‐one, a type of compound that can also be prepared by the related nucleophilic addition of dialkyl malonates to nitrones.
This chapter deals with a unique property of nitrones not shared by the corresponding carbonyl compounds, namely, a marked ability to undergo a [3 + 2] cycloaddition reaction in the presence of a dipolarophile. The reactions of nitrones with substituted olefins, both intermolecular and intramolecular are addressed. This process yields isoxazolidines directly, affording products related to those obtained in the Reformatsky reaction but arising by a different reaction mode.
The intent of the review presented in this chapter is to provide a thorough understanding of the nitrone–olefin [3 + 2] cycloaddition reaction and to illustrate its power by describing some significant applications to complex synthetic problems. Various aspects have been reviewed. This documentation of the nitrone–olefin cycloaddition reaction begins with the preparation and stability of the nitrone component and is followed by mechanistic considerations. A presentation of the dipolarophile syntheses is beyond the scope of this chapter; however, the tabular survey provides leading references to specific examples. The important concepts of regio‐ and stereo‐selectivities are introduced next. Since the general rules of regiochemistry that apply in the intermolecular version of the reaction are often reversed in the intramolecular version, the latter are dealt with separately. Finally, important applications to the total synthesis of natural products are presented. The versatile utility of the nitrone–olefin cycloaddition reaction in the synthesis of natural products has been the major driving force in the development of this long‐neglected chemistry. An in‐depth understanding of the key transformations of the isoxazolidines afforded by the reaction will place this chemistry firmly within the arsenal of organic reactions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
