Highly stereoselective 6-exo ring-closure of 5-substituted hept-6-enyl radicals

Ogura, Katsuyuki; Kayano, Akio; Fujino, T.; Sumitani, Naoko; Fujita, Makoto

doi:10.1016/s0040-4039(00)61419-3

Cited by 19 publications

(2 citation statements)

References 16 publications

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“…The data in Table support this hypothesis. Although experimental evidence is scanty, it appears that the cyclization of substituted hept-6-enyl radicals and related species is subject to the usual thermodynamic and steric guidelines. 8a,8b Thus, a 2-substituted heptenyl radical would be expected to afford a cis-disubstituted product via a chairlike transition structure in which both substituents are pseudoequatorial. The radical 16 (Scheme ) derived from 4h conforms to this hypothesis and affords mainly the cis-disubstituted radical 18 via the transition structure 17 .…”

Section: Discussionmentioning

confidence: 99%

Formation of Some Oxygen-Containing Heterocycles by Radical Cyclization: The Stereochemical Influence of Anomeric Effects

Beckwith

Page

1998

J. Org. Chem.

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The influence of the anomeric effect on radical cyclization has been examined by determining the stereochemical outcome of the ring closure of 10 suitably substituted radicals. The stereochemistry of the products formed from the acyclic precursors 4a-f indicates that for suitably constituted radicals anomeric interactions stabilize pseudoaxially substituted transition structures 14 thus affording products with stereochemistry the reverse of that normally observed.In recent times, the use of free radical reactions for chemical synthesis has grown steadily in popularity as the processes which govern and control their outcomes have become better understood. 1 Intramolecular addition reactions of suitably constituted alkenyl radicals and related species are particularly interesting since they readily afford a variety of ring systems commonly found in many natural products. 1 The advantages offered by such reactions generally include high regioselectivity, modest to good stereoselectivity, 1-5 and high chemoselectivity. [1][2][3][4][5] The highly regioselective exo-cyclization of the hex-5-enyl radical has been intensively studied. The accurate determination of its kinetics 6 has underpinned its widespread use as a mechanistic probe and as a radical clock. 7 Most monosubstituted hex-5-enyl radicals also undergo regioselective exo-cyclization while conforming to the general stereochemical guideline that 1-or 3-substituted radicals afford predominantly cis-disubstituted products, while 2-or 4-substituted radicals give mainly transdisubstituted products. 5 It is now generally accepted that the cyclization behavior of simple hex-5-enyl systems reflects the stereoelectronic demands of the transition structure. [2][3][4][5] The hypothesis that the strain energy engendered in attaining the optimum orbital overlap for 1,6-ring closure outweighs the steric and thermodynamic factors which would otherwise favor six-membered ring formation 2-5 has received support from theoretical analyses 8 and the modeling of transition structures by a combination of molecular orbital and molecular mechanics calculations. 8 These calculations confirm the original hypothesis that the transition structure for 1,5-exo-cyclization of hex-5-enyl radicals and related species resembles cyclohexane in its chair form. 2-5 Hence the stereoselectivity exhibited in the ring closure of monosubstituted hexenyl radicals and related species is seen to arise from the propensity of cyclizations to proceed through the more stable pseudoequatorially substituted cyclohexane-like conformation of the transition structure rather than through its less stable pseudoaxially substituted conformer. 8 Since calculations of the relative selectivities of the cyclized products tend to be overestimated when only axially substituted chairlike structures are considered, it appears that boatlike transition structures might also be involved in some reactions. 4,8 Cyclizations of hex-5-enyl type radicals containing heteroatoms have also been studied. 1,9,10 In general such spec...

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Section: Discussionmentioning

confidence: 99%

Formation of Some Oxygen-Containing Heterocycles by Radical Cyclization: The Stereochemical Influence of Anomeric Effects

Beckwith

Page

1998

J. Org. Chem.

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“…Intramolecular addition of electron-rich radicals to vinyl sulfones has been successfully demonstrated with systems of varying degrees of complexity. The presence of the vinyl sulfone results in efficient 6- exotrig ring closure , in addition to the more common 5- exotrig closures (Scheme ) . In the former case, trans -configured products prevailed, while in the latter, cis products were preferred.…”

Section: Phenylsulfone a Chemical Chameleon And Nearly Ideal Function...mentioning

confidence: 99%

Evolving Organic Synthesis Fostered by the Pluripotent Phenylsulfone Moiety

et al. 2009

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Radical Cyclization Reactions

et al. 1996

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Radical cyclization reactions are among the most powerful and versatile methods for the construction of mono‐ and polycyclic systems. The advantages these reactions offer to the synthetic organic chemist include high functional group tolerance and mild reaction conditions combined with high levels of regio‐ and stereochemistry. Furthermore, the recent progress in radical chemistry has led to the development of a broad range of very useful practical methods to conduct radical cyclization reactions. In general, radical cyclization reactions comprise three basic steps: selective radical generation, radical cyclization, and conversion of the cyclized radical to the product. For the generation of the initial radical a broad variety of suitable precursors can be employed, such as halides, thio‐ and selenoethers, alcohols, aldehydes and hydrocarbons. The cyclization step usually involves the intramolecular addition of a radical to a multiple bond. Most often carbon–carbon multiple bonds are employed; however, there are also examples known for the addition to carbon–oxygen and carbon–nitrogen bonds. Depending on the method employed, the cyclized radical is converted to the desired product by trapping with a radical scavenger, by a fragmentation reaction, or by an electron transfer reaction. The section Mechanism, Regio‐ and Stereochemistry provides an introduction to the key features of radical cyclization with a special emphasis on the factors controlling the regio‐ and stereochemistry. The section Scope and Limitations covers the different methods used to conduct radical cyclization. The basic principles of radical chemistry and general practical considerations when conducting radical cyclizations are not discussed in detail. Several excellent review articles and books dealing with these topics are available.

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Highly stereoselective 6-exo ring-closure of 5-substituted hept-6-enyl radicals

Cited by 19 publications

References 16 publications

Formation of Some Oxygen-Containing Heterocycles by Radical Cyclization: The Stereochemical Influence of Anomeric Effects

Formation of Some Oxygen-Containing Heterocycles by Radical Cyclization: The Stereochemical Influence of Anomeric Effects

Evolving Organic Synthesis Fostered by the Pluripotent Phenylsulfone Moiety

Radical Cyclization Reactions

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