Substituent effects on the cyclization of hex-5-enyl radical

Beckwith, A. L. J.; Blair, Ian A.; Phillipou, G.

doi:10.1016/s0040-4039(01)92225-7

Cited by 83 publications

(50 citation statements)

References 5 publications

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“…Selective formation of ketone from the biradical can be attributed most simply to a steric effect, with more rapid closure on the unsubstituted a-methylene carbon than on the disubstituted carbonyl carbon. This suggestion finds support in the recent demonstration that the rate of intramolecular radical addition to a double bond is strongly influenced by the degree of substitution a t the site of reaction 18. Only in a substrate such as 3, with restricted rotation about the C(a)-C(p) bond, does formation of a methylenecyclobutan-01 become the predominant mode of photochemical rearrangement.…”

mentioning

confidence: 55%

Photochemical formation of 12-methylene-cis-bicyclo[8.2.0]dodecan-1-ol from 2-methylenecyclododecanone. Restricted rotation in a biradical intermediate

Hemperly¹,

Wolff²,

Agosta³

1975

J. Org. Chem.

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Irradiation of 2-methylenecyclododecanone (3) leads to 12-methylene-cis-bicyclo[8.2.0]dodecan-l-01 (11) in 87% yield, unaccompanied by the cyclobutyl or cyclopropyl ketones usually formed photochemically from CYmethylene ketones. Pyrolysis of 11 leads to enone 15 and bicyclic ketone 14, which is the cyclobutyl ketone anomalously absent from irradiation of 3. The structures of 11,14, and 15 are supported by spectroscopic and chemical data. Restricted rotation about the C(a)-C(P) bond in biradical intermediate 13 is advanced as an explanation for the exceptional behavior of 3. These results suggest the importance of conformational mobility of a short-lived biradical in determining the products formed on photolysis of a-methylene ketones.Photochemical isomerization of a variety of a-methylene ketones leads to cyclobutyl ketones, accompanied in some cases by related cyclopropyl ketones and methylenecyclobutano1s.l Equation 1 gives a typical example in which all three types of products are found. There is good evidencethat the cyclopropyl and cyclobutyl ketones arise by way of biradical intermediates in which 0 hydrogen (1, for cyclopropyl ketones) or y hydrogen (2, for cyclobutyl ketones) has been abstracted by the carbonyl oxygen.2 It is quite likely that the methylenecyclobutanols also arise by way of biradical intermediates (as 2),' although there is no direct evidence for this, and the possibility remains open that these alcohols represent a concerted [ , , 2 + ,2] cycloaddition3 of the y carbon-hydrogen bond with the carbonyl group. The major photoproduct is cyclobutyl ketone in most cases, and frequently no methylenecyclobutanol is found a t all. An exception to this generalization is the photolysis of 2-methylenecyclododecanone (3), which furnishes solely a single isomer of the related methylenecyclobutanol 4 in high yield (eq 2).l Ketone 3 is the only medium-or large-ring compound investigated, and its exceptional photochemical behavior presumably is related to this structural feature. Our purpose in the present study was to investigate this isomerization of 3 in more detail; in this connection we have determined the stereochemistry of 4 and carried out sensitization and quenching experiments on its formation from 3. In addition we have studied the thermolysis of 4 and succeeded thereby in preparing the cyclobutyl ketone which is anomalously absent in photolysis of 3. The results are discussed in detail below; they permit us to offer a reasonable explanation for the behavior of 3 in terms of restricted rotation in a biradical intermediate, thus providing an instructive example of conformational control over the fate of a short-lived intermediate.The convenient availability of both isomers of bicyclo-[8.2.0]dodecan-l-o1, 5 and 6, from photolysis of cyclododecanone4 suggested that a simple proof of the stereochemistry of 4 would involve its correlation with one of these known alcohols. This approach was successful in demonstrating a cis ring fusion in 4, and the structural formulas showing the degradation ...

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confidence: 55%

Photochemical formation of 12-methylene-cis-bicyclo[8.2.0]dodecan-1-ol from 2-methylenecyclododecanone. Restricted rotation in a biradical intermediate

Hemperly¹,

Wolff²,

Agosta³

1975

J. Org. Chem.

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“…Substituents at C-1 (R 1,2 ) and C-6 (R 4,5 ) were consistently found to cause small rate enhancements (1.4-2.4) in 1,5-cyclizations except where there was geminal disubstitution as part of a ring, which caused a very small rate retardation (0.94). [25][26][27][28] In all cases, the amount of competing 1,6-cyclization either remained unchanged or was markedly decreased. In contrast, substituents at C-5 (R 3 ) led to strong rate retardations (e.g.…”

Section: Substituent Effectsmentioning

confidence: 88%

“…Athel extrapolated further and suggested that hence, in polymerizations and other intermolecular additions, 'the observed preference for radical attack at the less substituted terminus of an unsymmetrical olefin is due primarily to steric factors, and not, as is often supposed, to the stabilizing effect of alkyl substituents on the newly formed radical'. [27] An example where the uncertainties arising from formation of different ring sizes from addition to either end of the olefinic bond were obviated came from David Johnson's work on cyclizations of 2-(cyclopent-3-enyl)ethyl radicals 14a (R ¼ H) and 14b (R ¼ CH 3 ) (Scheme 6). The competing modes of cyclization gave the same ring size and were stereoelectronically equivalent.…”

Section: Substituent Effectsmentioning

confidence: 99%

Athelstan L. J. Beckwith and the Flowering of Hex-5-enyl Radical Cyclization Chemistry. The Adelaide Years

Serelis¹

2011

Aust. J. Chem.

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Athel Beckwith chose to embark on a career in free radical chemistry at a time when it was largely ignored by all but a small coterie within the broader Organic Chemistry community. Of his many contributions in this area, the mechanistic clarification and exploitation of the cyclization of hex-5-enyl radical-containing systems is undoubtedly the most significant, leading to what is now, in a multitude of variants, a universally-used, powerful, sophisticated, selective, general synthetic methodology. This account revisits and highlights the early studies carried out by the Beckwith group at The University of Adelaide from the late-1960s to 1980, a period when the main breakthroughs in kinetic and mechanistic understanding were made, and the implications for wider synthetic utility in more complex hex-5enyl systems became apparent.

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“…Kinetic studies on hex-5-en-1-yl radical cyclisations have indicated that E and Z isomers cyclise at similar rates. [44,51] In a previous report we showed that the linear/cyclised selectivity is best explained by use of the equations proposed by Saveant's group to interpret the selectivity observed in the yields of rearranged products in the vicinity of a cathode. [46,47,52] In these equations, the diffusion coefficients associated with the reactive species play a definite role.…”

Section: Entrymentioning

confidence: 99%

Structural Effects in Radical Clocks and Mechanisms of Grignard Reagent Formation: Special Effect of a Phenyl Substituent in a Radical Clock when the Crossroads of Selectivity is at a Metal/Solution Interface

et al. 2009

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A large class of radical clocks is based on the intramolecular trapping of a reactive radical by a suitably located unsaturated system. Depending on the substituents present on this unsaturated system, the rate of cyclisation may vary drastically. This property has been repeatedly used to diagnose the participation of very short-lived radicals in the mechanisms of a wide variety of reactions. For reactions occurring in homogeneous solution, a phenyl substituent capable of stabilizing the radical formed during the act of trapping has been one of the most widely used tools of this type. During study of the mechanisms of formation of Grignard reagents -reactions that occur at the interface of the metal and the solution -the phenyl substituent displayed a specific new behaviour pattern. Besides its stabilizing role, it was also able to play the role of mediator in redox catalysis of electron transfer. In this case, the first events on the pathway to the Grignard reagents involve a cascade of three (one intermolecular followed by two intramolecular) electron transfers. Introduction of a p-methoxy substituent on the phenyl ring, making the phenyl group a poorer electron acceptor, suppresses this

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Substituent effects on the cyclization of hex-5-enyl radical

Cited by 83 publications

References 5 publications

Photochemical formation of 12-methylene-cis-bicyclo[8.2.0]dodecan-1-ol from 2-methylenecyclododecanone. Restricted rotation in a biradical intermediate

Photochemical formation of 12-methylene-cis-bicyclo[8.2.0]dodecan-1-ol from 2-methylenecyclododecanone. Restricted rotation in a biradical intermediate

Athelstan L. J. Beckwith and the Flowering of Hex-5-enyl Radical Cyclization Chemistry. The Adelaide Years

Structural Effects in Radical Clocks and Mechanisms of Grignard Reagent Formation: Special Effect of a Phenyl Substituent in a Radical Clock when the Crossroads of Selectivity is at a Metal/Solution Interface

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