Esters, conjugated, radical addition

Radical cyclization is not limited to reaction with a C=C unit (see 15-29 and 15-30), and reactions with both C=N and C=0 moieties are known. Reaction of MeON=CH(CH2)3CHO with Bu3SnH and AIBN, for example, led to trans-2-(methoxyamino)cyclopentanol in good yield.Conjugated ketones add to aldehyde via the p-carbon under radical conditions (2 equivalents of Bu3SnH and 0.1 equivalent of CuCl) to give a p-hydroxy ketone.Addition of radical to the C=N unit of R C=N SPh ° or R—C=N—led to cyclic imines. Radical addition to simple imines leads to aminocycloalkenes. Radical also add to the carbonyl unit of phenylthio esters to give cyclic ketones. 

In some examples, the stereochemistry of radical reactions was controlled by chiral carbohydrate auxiliaries. As a radical counterpart to the ionic conjugate additions discussed above, Garner et al. [169] prepared carbohydrate linked radicals that were reacted with a,P-unsaturated esters. The radical precursor, the carboxylic acid 256, generated by the addition of ( Sj-methyl lactate to tri-O-benzyl-D-glucal and subsequent ester hydrolysis, was decarboxylated by Barton s procedure (Scheme 10.84) [170]. Trapping of the chiral radical 258 with methyl acrylate furnished the saturated ester 259 in 61% yield and with high diastereoselectivity (11 1). The auxiliary caused a preferential addition to the si-facQ of radical 258, probably due to entropic effects. The ester 259 was transformed in acceptable yield to the y-butyrolactone 261 by reductive removal of the thiopyridyl group followed by acid hydrolysis. 

Conjugate additions. Indoles react with electron-deficient alkenes at the P-carbon. Michael addition in water using p-ketoesters as donors gives quantitative yields. The addition of amines to unsaturated esters is favored by both the catalyst and pressure. Interestingly, YbfOTOj also promotes radical addition to A -enoyloxazolidinones. ... 

Hydrostannation of conjugated esters and nitriles leads to /J-stannylatcd derivatives by a free radical mechanism (equation 26)58. The additions are highly stereoselective, but the relative stereochemistry of the adducts was not determined. Since both (E)- and (Z)-alkenoates gave rise to the same stereoisomeric adduct, it can be concluded that a stepwise process is involved. 

Not only electrophilic 1,4-addition, as shown above, but also radical 1,4-addition to conjugated enynes such as selenosulfonation is known to yield acceptor-substituted allenes [118]. Finally, monotitanation of conjugated diynes followed by treatment with benzaldehyde and aqueous workup leads to an ester of penta-2,3,4-tri-enoic acid, which is formally also a product of 1,4-addition [147]. 

Vitamin B12 reacts with alkyl halides to form a cobalt (III) alkyl intermediate. Irradiation with visible light leads to the expulsion of a carbon-centered radical and a cobalt (II) species. The latter is easily reduced at —0.8 V to reconvert it to a cobalt (I) intermediate that reenters the catalytic cycle by reacting with a second molecule of the halide. The radical is capable of undergoing a number of interesting transformations, including conjugate addition to a Michael acceptor. The example illustrated in Scheme 9 provided a straightforward route to ester... 

Photohydroalkylations are in most cases carbon-centered radical conjugate additions onto electron-deficient olefins [7]. Scheme 3.3 summarizes in detail the pathways for the photogeneration of radicals from R-H(Y) 1. In path a, a photocatalyst P (when excited) cleaves homolytically a suitable C—H bond, and the resultant radical adds to the olefin 2 to form the adduct radical 3. a,(3-Unsaturated nitriles, ketones, and esters... 

The photoaddition of alkanes onto electron-poor alkynes (e.g., propiolate or acetilendicarboxylate esters) can be accomplished by a radical conjugate addition reaction [7]. Radicals have been generated either via hydrogen abstraction from cycloalkanes or via electron transfer from 2-alkyl-2-phenyl-l,3-dioxolanes. In the first case, the irradiation was pursued on an alkane solution of an aromatic ketone (used as the photomediator) and the alkyne. Under these conditions, methyl propiolate was alkylated upon irradiation in the presence of 4-trifluoromethylacetophenone to form acrylate 48 in 97% yield (E/Z= 1.3 1 Scheme 3.31) [78]. 

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