Alkenes intramolecular radical attack

Intramolecular radical cyclizations of acylsilanes containing the methyldiphenylsilyl moiety were investigated by the Tsai group (eq 29). As indicated in eq 29 products of radical addition to the carbonyl group involve silyl migration, whereas attack at the alkene center gives simple adducts. 

The reason these so-called cyclopolymerization reactions occur is not known with certainty. Perhaps the best explanation that seems to fit most of the experimental results is that the two alkenic groups are associated in the ground state. Intramolecular cyclopolymerization is thus favored over intermolecular polymerization even before attack by a radical, and the overall cyclization process, from attack by the radical to formation of the propagating cyclic radical, is concerted. 

Cyclobutanes can be formed by intramolecular addition of carbanions or radicals to C-C double bonds only if the latter are substituted with electron-withdrawing groups (see, e.g., Schemes 9.20 and 9.21) [81] or otherwise activated toward attack by nucleophiles. Activation by an alkynyl group or a cumulated double bond can be sufficient to promote cydobutane formation (Scheme 9.20). Unactivated alkenes, however, do not usually undergo cydization to cyclobutanes via intramolecular addition of carbanions or radicals. 

Intramolecular cyclization of N-alkenyl-2-bromoindoles has been described. The formation of five as well as six-membered ring in the radical cyclization proceeds in good yield [95TL4857]. A novel intramolecular free radical aromatic ipso substitution reaction has been reported [95CC1353]. Treatment of 138 with tributyltin hydride generates an alkyl radical which attacks the alkene at the carbon bearing the sulfur substituent. This is followed by elimination of the sulfur substituent to provide the cyclized products 139 in moderate yields. The efficiency of the reaction is dependent on the size of the ring formed and on the sulfur substituent. 

Enantioselective synthesis of 2-substituted piperidines with 60% ee has been reported via radical precursors being trapped in an intramolecular reaction (Scheme 17) <2003OL3767>. These cyclizations were rationalized in terms of chair-like transition states, with the maximum number of pseudoequatorial substituents, in which the nucleophilic amine attacks the alkene radical cation on the face opposite to the phosphate anion. 

The first cyclisations to be put to synthetic use were those of aryl lithiums onto carbonyl compounds, imines and epoxides. These are known as Parham cyclisations , and the method for transforming an aryl bromide to an aryllithium the Parham protocol , after W. E. Parham, who developed the reaction. We will survey the use of Parham cyclisations in synthesis, before assessing intramolecular attack of other electrophiles. The most important of these are the alkenes, and the usefulness of anionic cyclisations onto unactivated double bonds compares very favourably with radical cyclisations, particularly with regard to stereochemical control. 

Also developed by Hill is a (diotochemical system (equations 41 to 48) based on a polyoxoacid, H3PWi2O40 (P)> The excited state of the acid probably oxidizes the alkane in the first step. The radical can then either attack the solvent to give an iminium radical, wiiich leads to ketone on hydrolysis, or it can be oxidized to the caifaonium ion, in wdiich case attack on the solvent leads instead to the -alkyl-acetamide. If the substrate has two adjacent tertiary C—bonds, then alkenes tend to be formed, llie Barton reaction, normally kmwn as an intramolecular C—activation, can give some intermolecular reaction in some examples. Thus, vdien n-octyl nitrite is rf)otolyzed in heptane, some nitrosoheptane is observed. ... 

In contrast to the alkene theory the predominant mode of oxidation of the alkyl radicals is by oxygen addition and the alkylperoxy radical so formed then undergoes homogeneous intramolecular rearrangement (reaction (14)). Decomposition of the rearranged radical (reaction (16)) usually leads to a hydroxyl radical and stable products which include O-heterocycles, carbonyl compounds and alcohols with rearranged carbon skeletons relative to the fuel and alkenes. The chain-cycle is then completed by unselective attack on the fuel by the hydroxyl radical (reaction (12)). 

The formation of alkenes from TB or MDC derivatives of (3-hydroxy sulfides and sulfones is also a useful procedure. When the 1,4-bis-MDC derivative (88) was reacted with BusSnH, the tetrahydrothio-phene (89) was produced, presumably by the process shown in Scheme 8. The first intramolecular step is related to the attack on C=S by a carbon radical in the reactions of 1,2-bis-TB derivatives with BusSnH (equation 16). ... 

It occurred to us some time ago that since electronically excited states of functional groups such as ketone carbonyls and alkenes undergo reactions very similar to those of alkoxy and alkyl radicals, it might be possible to observe reactions of these excited states with three-coordinate phosphorus. Of particular interest would be attack at phosphorus in an intramolecular context as shown conceptually in the equations of Scheme II. In fact we observed the first example of a photorearrangement that may well proceed by such a mechanism over twenty years ago (10). 

Products of addition to styrene double bonds can arise as a result of light induced electron transfer reactions. Lewis has studied the intramolecular reaction of l-phenyl-w-amino alkenes (422) 289,290 products arise from electron transfer from the amine nitrogen to the excited state of the styryl group followed by intramolecular proton transfer in the radical ion pair produced. The resultant biradical then couples to yield the isolated products (423) and (424). Sensitisation of the intermolecular analogue of this reaction by 1,4-dicyanobenzene has been reported and is proposed to occur by electron transfer from the styrene to the excited state of the sensitiser followed by attack of an amine on the styrene radical cation. This ultimately leads to the product of anti-Markovnikov addition of the amine across the double bond of the styrene. This is similar to the sequence long since established by... 

Some interesting photo-NOCAS-type reaction (photochemical nucleophile-olefin combination, aromatic substitution) have been reported by three groups. Arnold has developed the photo-NOCAS reaction as three components photoaddition.Xu et al., reported the intramolecular photocyclization of A-(co-hydroxyalkyl)-tetrachlorophthalimide (138, 141) with alkenes to give medium- and large-ring heterocycles (140,143). These photoreactions proceeded via 1, n-biradicals generated from the nucleophilic attack of alcohols to alkenes between the radical anions of phthalimides and the radical cations of alkenes. 

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride. The net result is the addition of hydrogen and the nucleophile to the alkene. The regioselectivity is excellent and is in the same sense as is observed for proton-initiated additions. Scheme 4.1 includes examples of these reactions. Electrophilic attack by mercuric ion can affect cyclization by intramolecular capture of a nucleophilic functional group, as illustrated by entries 9-11. Inclusion of triethylboron in the reduction has been found to improve yields (entry 9). The reductive replacement of mercury using sodium borohydride is a free-radical process. ... 

The lowest-lying excited state of ketones most often corresponds to a o 7t c=o transition. The maximum of this band is around 280 nm with simple aldehydes or ketones and is shifted to the red for conjugated or aryl derivatives. As hinted above, the unpaired electron on the hq orbital gives to these states electrophilic properties similar to those of alkoxy radicals, and indeed the observed chemistry is similar in the two cases. Typical reactions are a-fragmentation, inter- or intramolecular (from the easily accessible y position) hydrogen abstraction and attack of alkenes (finally resulting in a formal 2h-2 cycloaddition to give an oxetane, the Paterno-Btichi reaction). 

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