Aldehydes radical addition reactions

The Mn mediated radical additions offer an inherently flexible carbon carbon bond construction approach to amine synthesis. Because of the broad functional group compatibility in both the radical precursor and the aldehyde hydrazone acceptor, the roles of these precursors can be switched to result in the construction of either of two C C bonds at the chiral amine (Scheme 2.10) with excellent stereocontrol. The epimeric configuration can be selected by either (a) employing the enantiomeric auxiliary or (b) interchanging the roles of R and in the alkyl halide and aldehyde precursors [47]. By combining these two tactics, the optimal roles of R and with respect to yield and selectivity can be chosen. Such strategic flexibility contributes to the synthetic potential of these radical addition reactions. 

Commercial phosphine derivatives are produced either by the acid-cataly2ed addition of phosphine to an aldehyde or by free-radical addition to olefins, particulady a-olefins. The reactions usually take place in an autoclave under moderate pressures (<4 MPa (580 psi)) and at temperatures between 60 and 100°C. 

A modified version of the Brown-Negishi reaction using B-alkylcatechol-boranes was reported (Scheme 32). This novel method is based on a simple one-pot procedure involving the hydroboration of various substituted alkenes with catecholborane, followed by treatment with catalytic amount of oxygen/DMPU/water and a radical trap. Efficient radical additions to a,ft-unsaturated ketones and aldehydes have been reported. Primary alkyl radicals are efficiently generated by this procedure and the reaction has been applied to a 300 mmol scale synthesis of the y-side chain of (-)-perturasinic... 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

Scheme 55, Eq. 55a) [119]. A plausible mechanism is depicted in Scheme 55 and involves radical addition of the 2-tetrahydrofuryl radical to the aldehyde followed by a rapid reaction of the alkoxyl radical with Et3B. Triethylborane has a crucial role since by reacting with the alkoxyl radical it favors the formation of the condensation product relative to the -fragmentation process (back reaction). A similar reaction with tertiary amines, amides and urea is also possible (Eq. 55b) [120]. 

It is clear that the aldehydes produced in the oxidation of butenes arise from addition reactions as already assumed by several workers (4, 16, 17). Nothing in the present work indicates whether the aldehydeforming addition product is a peroxy alkyl (17), (Reaction 2) or an alkoxy alkyl (16) radical (Reaction 3) as has been postulated, or both. 

The addition of substituted allylic zinc reagents to aldehydes is usually unselective" . Furthermore, the direct zinc insertion to substituted allylic halides is complicated by radical homocoupling reactions. Both of these problems are solved by the fragmentation of homoallylic alcohols. Thus, the ketone 166 reacts with BuLi providing a lithium alcoholate which, after the addition of ZnCl2 and an aldehyde, provides the expected addition product... 

Radical X , which initiates the reaction, is regenerated in a chain propagation sequence that, at the same time, produces an organic peroxide. The latter can be cleaved to form two additional radicals, which can also react with the unsaturated fatty acids to set up the autocatalytic process. Isomerization, chain cleavages, and radical coupling reactions also occur, especially with polyunsaturated fatty acids. For example, reactive unsaturated aldehydes can be formed (Eq. 21-14). 

Likewise, 03 reacts with hydrocarbons to produce unknown numbers of H02 and R02 (or RC002) [see below]. From the computer analysis of simulated smog formation involving the hypothetical illumination of N0-N02-H20-butene-aldehydes-C0-CH4 mixtures in air, Calvert and McQuigg (184) estimate that H02 and R02 radicals, formed mainly by the addition of OH to butene, account for 10% of NO to N02 conversion. The H02 and R02 radicals formed from the photolysis of aldehydes and OH reactions with aldehydes are responsible for 25% of the conversion. Carbon monoxide is only 5% effective for the NO to N02 conversion. The effect of paraffins on the NO to N02 conversion rate is very small. 

Major destruction routes of OH radicals are the addition to olefins, the 11 atom abstraction from olefins and aldehydes, and the reaction with C( > Another radical, hydroperoxyl (H02), has been considered as a major oxidizing agent for NO and to a lesser extent for hydrocarbons. The HO, radicals are probably formed by the photolysis of formaldehyde [see Section VI1-4, p. 277]... 

Exercise 16-35 A radical-chain reaction similar to that described for the air oxidation of benzaldehyde occurs in the peroxide-initiated addition of aldehydes to alkenes (see Table 10-3). Write a mechanism for the peroxide-induced addition of ethanal to propene to give 2-pentanone. 

A number of other substances, for example CC14, CCl3Br, and several other alkyl poly halides, aldehydes, and thiols, add successfully to olefins.150 Addition of Cl2, frequently looked upon as ionic, often occurs as a radical chain reaction, particularly in nonpolar solvents and in the presence of light or peroxides.151... 

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