Generation of Radical Intermediates

Similar oxidative cyclization reactions involving the direct oxidation of acyclic 1,3-dicarbonyl compounds have not been reported. However, the generation of radical intermediates by the direct oxidation of cyclic 1,3-dicarbonyl compounds at an anode surface has been reported. Yoshida and coworkers have shown that the anodic oxidation of cyclic 1,3-dicarbonyl compounds in the presence of olefin trapping groups gives rise to a net cycloaddition reaction (Scheme 10) [23]. These cycloaddition reactions proceeded by initial oxidation of the 1,3-dicarbonyl compound at the anode followed by a radical addition to the second olefin. Following a second oxidation reaction, the material then... 

The fundamental mechanistic difference between the SN2 and electron transfer processes is whether after the single electron shift takes place, an intermediate is formed or not. Any factor capable of delaying N—R coupling (77) after the single electron shift may lead to the actual generation of radical intermediates. Let us explore what these factors may be. 

Four-membered rings may be generated in a less systematic manner by a variety of photochemical transformations, many of which are multistep reactions. In the field of radical chemistry, the photochemical generation of radical intermediates is frequently applied such that, when the stereoelectronic requirements are fulfilled, the cyclization steps lead to four-membered rings. The oxime derivative 99 undergoes photochemical sensitized cleavage at the fragile N—O bond (Scheme 5.19, reaction... 

V. GENERATION OF RADICAL INTERMEDIATES A. The Difficulty with Cleaving the S-5 -Deoxyadenosyl Bond... 

Polymerization is normally dependent on an initiator, which begins the chain reactions in the polymerization mixture. Typical initiators are molecules that have rather low thermal stability and generate radicals on decomposition. Other initiator systems depend on photolytic decomposition or on the generation of radical intermediates as the result of redox reactions. The rate constants for the individual propagation steps that follow initiation are usually very large, but polymerizations are normally carried out in such a way that the concentration of the reacting chains is very low (<10 M). As a result, the overall rate of polymerization is moderate. 

Radical Coupling and Cyclization Reactions. Phenyl thionocarbonate esters derived from alcohols serve as efficient precursors for the generation of radical intermediates which can be used for the formation of new carbon-carbon bonds. For example, a 4-thionocarbonate ester derived from L-lyxose undergoes a stereoselective allylation upon photolysis in toluene in the presence of 2.0 equiv of allyltributylstannane (eq 6). Photochemical initiation is preferable to chemical initiation using azobisisobu-tyronitrile which results in the formation of side products at the... 

The process allows the possibility of affording the snbstitntion of an unreactive Nu," throngh entrainment conditions (Scheme 10.5) [16]. Entrainment is nseful when the NU " is unreactive at initiation but quite reactive at propagation. Under these conditions, the addition of a second Nn ", more reactive at initiation, increases the generation of radical intermediates and allows Nu,", less reactive at initiation, to establish its own propagation [17]. 

This section primarily surveys reduction reactions with synthetic potential, which utilize vanadium compounds in low oxidation states to serve as versatile one-electron reductants for the generation of radical intermediates, but their synthetic utility in this respect has been limited. The efficiency of the one-electron transfer systan depends on the redox potential of both the vanadium compounds and ladicophiles. 

More recently, we demonstrated the first alkynylation of benzylic C-H bonds not adjacent to a heteroatom with 1 mol% of a CuOTf-toluene complex in the presence of 1.5 equiv. of DDQ. Various allq nes were successfully coupled with diphenylmethane derivatives (Scheme 1.8). Aromatic allq nes were smoothly converted and the use of electron-rich derivatives resulted in a slightly improved jdeld, rationalized by the nucleophilicity of the substrates. However, aliphatic allq nes [i.e., n-heiq ne) did not give the corresponding CDC product under standard conditions. The mechanism was proposed to proceed via the generation of radical intermediates, which were converted into a benzylic cation in the presence of DDQ through two successive SET steps. The resulting hydroquinone subsequently then abstracted the acidic proton from the allq ne to form the copper acetylide, which added to the benzylic cation to afford the desired product. 

Photodecarboxylation of organic carboxylic acids in solution can be achieved via photoinduced electron transfer using electron acceptors such as aza aromatic compounds, dyes, or polycyanoaromatics as photosensitizers.This methodology induces photodecarboxylation through generation of radical intermediates which can be useful in organic synthesis. ... 

Intramolecular addition reactions are quite common when radicals are generated in molecules with unsaturation in a sterically favorable position. Cyclization reactions based on intramolecular addition of radical intermediates have become synthetically useful, and several specific cases will be considered in Section 10.3.4 of Part B. 

While generation of a Mn(V)oxo salen intermediate 8 as the active chiral oxidant is widely accepted, how the subsequent C-C bond forming events occur is the subject of some debate. The observation of frans-epoxide products from cw-olefins, as well as the observation that conjugated olefins work best support a stepwise intermediate in which a conjugated radical or cation intermediate is generated. The radical intermediate 9 is most favored based on better Hammett correlations obtained with o vs. o . " In addition, it was recently demonstrated that ring opening of vinyl cyclopropane substrates produced products that can only be derived from radical intermediates and not cationic intermediates. ... 

There are also procedures that form carbon-carbon bonds. Most of these reactions begin with an electron transfer that generates a radical intermediate, which then undergoes a coupling or addition reaction. These reactions are discussed in Section 5.6. 

Scheme 10.17 illustrates allylation by reaction of radical intermediates with allyl stannanes. The first entry uses a carbohydrate-derived xanthate as the radical source. The addition in this case is highly stereoselective because the shape of the bicyclic ring system provides a steric bias. In Entry 2, a primary phenylthiocar-bonate ester is used as the radical source. In Entry 3, the allyl group is introduced at a rather congested carbon. The reaction is completely stereoselective, presumably because of steric features of the tricyclic system. In Entry 4, a primary selenide serves as the radical source. Entry 5 involves a tandem alkylation-allylation with triethylboron generating the ethyl radical that initiates the reaction. This reaction was done in the presence of a Lewis acid, but lanthanide salts also give good results. 

The partial combustion of toluene, with the generation of the intermediate 2-methyl-phenyl radical (MP, in Scheme 2.15) leading to the prototype quinone methide, has recently been investigated by high-level post-HF and DFT theoretical studies.22... 

The multistep radical elimination may involve the generation of discrete intermediates, which for instance could be formed by a cyclization process7) such as 15- 16- 17e). Alternatively, there may be no intermediate involved in the elimination sequence, but the actual transition states 19, 22 are substantially lower in energy due to the anchimeric assistance of suitable functional groups9,10) (4). 

Radicals are versatile synthetic intermediates. One of the efficient procedures for radical generation is based on one-electron oxidation or reduction with transition metal compounds. An important feature is that the redox activity of transition metal compounds can be controlled by appropriate ligands, in order to attain chemoselectivity in the generation of radicals. The application to small ring compounds provides useful methods for organic syntheses. Reductive transformation are first reviewed here. 

Species with electron deficiency (e.g. carbocations), unpaired electrons (e.g. radicals, radical ions), electron excess (e.g. carbanions), or those with unusual oxidation states (e.g. metal complexes with low- or high-valent central atoms) are produced at the electrode. Electrochemical generation of such intermediates may be advantageous because of the mild reaction conditions employed (room temperature. 

A method for the mild generation of radicals (or other highly reactive intermediates) from unconventional (and green) precursors ... 

INT2, Scheme 10.7) undergoes further reaction (Li/Cu transmetalation) and generates a new organocuprate compound. (Note however that this difference could become more subtle since the product of conjugate addition (PD) might behave more like an a-cuprio(I) ketone complexed with a lithium cation [52] than a lithium enolate complexed with copper(I)). In neither reaction was any evidence of radical intermediates (i.e., SET) found by theoretical calculations [79]. 

One test for the involvement of radical intermediates is to determine if cyclization occurs in the 6-hexenyl system, in which radical cyclization is rapid (see Section 12.2.2 in Part A). Small amounts of cyclized products are formed upon preparation of the Grignard reagent from 5-hexenyl bromide.8 This indicates that cyclization of the intermediate radical competes to a small extent with combination of the radical with the metal. A point of considerable discussion is whether the radicals generated are free or associated with the metal surface.9... 

The most exciting applications of esr are in the study of radical intermediates in organic reactions. Considerable use has been made of the technique in biochemical reactions and it has been shown that radicals are generated and decay in oxidations brought about by enzymes. Radicals also have been detected by esr measurements in algae that fix carbon dioxide in photosynthesis. The character of the radicals formed has been found to depend upon the wavelength of the light supplied for photosynthesis. 

---