Suitable Radical Precursors

As summarized in Table 7, a number of trisubstituted olefins can act as suitable radical precursors if the substituents are not too bulky. The synthesis of spirotricyclic compounds, e.g., 48, is readily achieved in yields comparable to that of 16 (entry 1). To the best of our knowledge no simple method for the synthesis of these complex products is available. The bicyclo[4.3.0] system... 

B-alkylcatecholboranes, prepared by rhodium(I)-catalyzed hydroboration of alkenes, are suitable radical precursors for conjugate addition to activated olefins. This procedure is particularly useful for the control of the regio- and... 

From halides. Halides are easily converted into selenides. Since halides are also suitable radical precursors, this transformation is usually done when side reactions of halides with nucleophiles can occur. An example of this type is reported in Eq. (1). The bromide 5 was converted into a phenyl selenide, which could stand DIBALH reduction and imine formation. Tin mediated cyclization of 6 afforded the cyclopentylamine 7 in 72% yield [5]. 

Various methods of generation of Cl, C2, C3, C4 and C5 radicals from suitable radical precursors. 

Homoallylic alcohols are also suitable for controlling the introduction of an alkyl chain, as shown by the synthesis of the diterpenoid atractyligenin61, The starting tricyclic alcohol is converted to the selenocarbonate, a suitable radical precursor. Treatment with tributyltin hydride initiates the stereoselective cyclization which affords the bridged lactone system, an intermediate in the diterpenoid synthesis. Due to the low cyclization rate, tributyltin hydride is added slowly to suppress the formation of noncyclized reduction products. 

Kim developed a new entry into A -heterocycles by radical cyclizations onto alkyl azides. Iodides, bromides and thionocarbonates (Scheme 28, Eq. 28.1) are suitable radical precursors. 5-Exo cyclizations afford 3,3-triazenyl radicals that lose N2 to furnish an aminyl radical [79]. Following this work, Kilburn has applied this strategy to the formation of spiro-heterocycles from methylenecyclopropanes [80]. Finally, this reaction was applied as a key step in a very elegant cascade synthesis of aspi-dospermidine developed by Murphy (Scheme 28, Eq. 28.2) [81]. 

M.p. 296 C. Accepts an electron from suitable donors forming a radical anion. Used for colorimetric determination of free radical precursors, replacement of Mn02 in aluminium solid electrolytic capacitors, construction of heat-sensitive resistors and ion-specific electrodes and for inducing radical polymerizations. The charge transfer complexes it forms with certain donors behave electrically like metals with anisotropic conductivity. Like tetracyanoethylene it belongs to a class of compounds called rr-acids. tetracyclines An important group of antibiotics isolated from Streptomyces spp., having structures based on a naphthacene skeleton. Tetracycline, the parent compound, has the structure ... 

The radical carboazidation of alkenes has been achieved in water using triethylborane as initiator [118]. This efficient process is complete in one hour at room temperature in an open to air reaction vessel (Scheme 54, Eq. 54a). These new tin-free carboazidation conditions are environmentally friendly and allow to run reactions with an excess of either the alkene or the radical precursor. They are also suitable for simple radical azidation of alkyl iodides as well as for more complex cascade reactions involving annulation processes (Eq. 54b). In both reactions (Eq. 54a and 54b), an excess of triethylborane (3 equivalents) is required to obtain a good yield. This may be an indication that the chain process, more precisely the reaction between the phenylsul-fonyl radical and Et3B, is not efficient. 

As expected, 2-halo-l,3-dithianes react with nucleophiles under Sn conditions. Suitable nucleophiles are enamines <2002TL9517, 2004T6931> and phenols <1997MOL7>. The reaction with EtOC(S)S K, followed by oxidation, provided a xanthate which generated a 1,3-dithiane 1-oxide radical upon treatment with Bu3SnH (Scheme 69) <2004T7781>. An efficient one-carbon radical precursor has also been obtained by addition of 2,2,6,6-tetramethyl-piperidine-l-oxyl (TEMPO) to 2-lithio-l,3-dithiane. The reactivity of this compound has been demonstrated <2005S1389>. 

Another interesting procedure is the free radical addition-fragmentation developed by Keck [117]. A radical is generated from a suitable carbohydrate precursor 86 and reacts with allyltributyltin to provide the allyl branched sugar 87 in good yield (Scheme 31) [118]. 

Scheme 10.18 illustrates the key features of the intramolecular reaction in general and also the specific radical intermediates in the mechanistic study [18]. After initial radical formation from a suitable halide precursor, in the vast majority of cases using Bu3SnH and... 

The general strategy for generating radical adducts to heterocyclic molecules relies on selective protonation of a suitable neutral precursor to prepare a cation of a well-defined structure. The gas-phase acid is chosen so as to attack only the most basic site in the molecule, or alternatively, non-selective protonation can be used to prepare a mixture of ions. For example, protonation of imidazole with NH4+ occurs selectively on the imine nitrogen atom (N-l), which has the highest proton affinity and is the only position that can be protonated by an exothermic reaction (Scheme 22) [239]. 

The reductive cyclization protocol was then applied to a suitably A-protected radical precursor to allow further access to the alkaloid calothrixin B. Satisfactorily, 2-indolylacyl radicals derived from A-(methoxymethyl) selenoester 57 underwent cyclization under TTMSS-AIBN conditions with an even higher efficiency than their A-methyl counterparts. The reaction nevertheless followed a different course as, after the radical addition and quinoline rearomatization, pentacyclic phenol 58, a fully aromatic tautomeric form of ketone P, was isolated in 90% yield. The same phenol 58 was isolated although in lower yields (50-70%) using either stannane-AIBN or AIBN-irradiation protocols. 

Renaud and coworkers have also recently found that related TBDMS-protected B-alkylboronate esters are suitable radical (see Radicals) precursors for conjugate addition to activated olefins such as methyl acrylate (equation 12). Catalyzed hydroborations gave the 1,3-addition products with regioselectivity opposite to those obtained in uncatalyzed reactions. 

From aziridines. N-Tosylaziridines, easily obtained by aziridination of the corresponding alkenes, can be opened by selenolate reagents and furnish, after straightforward N-alkylation, radical precursors suitable for the preparation of pyrrolidine derivatives [12]. The preparation of octahydro-lff-indole 24 is shown in Eq. (4). A competing process involving radical azi-doselenenylation of alkenes has also been developed and will be discussed later (Sect. 5.2). 

Acyl radicals are very useful synthetic intermediates. Their preparation is not simple since the corresponding halides are highly electrophilic and cannot be used as radical precursors. Organocobalt compounds were proposed as suitable source of acyl radicals [44]. However, the use of acyl selenides proved to be more general [45, 46]. These radical precursors can be efficiently prepared from the corresponding carboxylic acids and esters [47]. Acyl phenyl selenides should be preferred, when possible, relative to acyl methyl selenides due to the consumption of two equivalents of tin hydride with this last system (Scheme 1) [4]. Acyl selenides have found many applications in tandem radical additions to alkenes. Examples of intermole-cular [Eq. (18)] [48,49] and intramolecular reactions [Eq. (19)] [50a] are reported. The enoyl selenide 68 give the unsaturated acyl radicals 69. This intermediate... 

Alternating copolymer graft copolymers are also produced when comonomers that yield alternating copolymers with but not without a complexing agent are copolymerized in the presence of a complexing agent and a suitable polymer, either with or without a free-radical precursor (14). 

Phenylmenthyl esters are also suitable chiral groups for inducing stereoselectivity in radical addition reactions, as shown in the allylation of phenylmenthyloxycarbonyl-substituted xanthates. The photoinitiated reaction of the radical precursor with tributyl(2-propenyl)stannane at — 78 =C affords only one diastereomer4. The absolute configuration of (— )-8-phenylmenthyl 2-methyl-2-phenyl-4-pentenoate (5) is not known. 

This cleavage will therefore be discussed first. Several substrates have proven useful for the generation of the pivotal oxiranylcarbinyl radicals. Sharpless epoxides are valuable starting materials for radical precursors [18]. After formation of the oxygen-centered radical, reactions typical for radicals are observed. With a suitably positioned double bond, cyclization occurs as shown in Scheme 10 [19]. It is interesting that the cw-disubstituted carbon-centered radical can react further to yield a bicyclo[2.2.1] system. 

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