Free radical addition intermolecular

Homolytic annulation of Schiff bases 56, via an intermolecular free-radical addition of its arylimidoyl radicals 57 to the azo group of diethyl azodicarboxylate (89CC757) in the presence of diisopropylperoxy dicarbonate (DPDC), gave 1,2-diethoxycarbonyl pyrido[l,2,4]triazines 60 via 58 and 59. No trace of the other isomer could be detected. 

Intermolecular free-radical addition reactions almost always proceed by chain mechanisms. Here light photoexcites acetone, and O then abstracts H- from the a-position of another molecule of acetone to complete the initiation. 

Intermolecular free-radical addition of iodoalkyl sulfones to vinylsilanes yields regios-electively the adduct 146 which can be further transformed to cyclopropene derivatives (equation 122)214. 

A tin-free radical cyclization of the xanthate 272 using dilauroyl peroxide (DLP), as the radical initiator, in chlorobenzene was used to give the 5//-pyrido[2,3-A azepin-8-one 273 (Scheme 35) <20040L3671>. The xanthate 272 was also made by an intermolecular free radical addition to allyl acetate, using the xanthate 271, as the radical precursor. Somewhat surprisingly in this latter case, intramolecular free radical attack on the pyridine ring did not take place. 

Sibi and Chen [42] reported a related tandem intermolecular nucleophilic free-radical addition-trapping reaction of enoate 168 establishing chirality at both a and /(-centers with control over both absolute and relative stereochemistry (Scheme 9.30) using a Lewis acid catalyst and the bisoxazoline ligand 169. They observed... 

Scheme 9.30. Enantioselective tandem intermolecular free-radical addition-trapping reaction of enoates.

Intermolecular free-radical additions of stannyl radicals to multiple bonds have emerged as important methods for the preparation of tetraorganostannanes which can be reacted further to afford new C—C bonds through transition metal mediated coupling processes (e.g. Stille coupling). There are numerous examples of this chemistry715-737, and this treatise will focus on a few selected examples. 

Addition of Lewis acid results in high diastereoselectivity in deselenidation performed by use of BujSnH/EtsB (Scheme 12.146) [260]. Addition of Lewis acid also improved diastereoselectivity in free radical-mediated intermolecular conjugate addition to a chiral a,/ -unsaturated N-enoyl oxazohdinone (Scheme 12.147) [261]. 

All attempts to obtain cyclized products from the 4-pentenyl radical using the same conditions under which the 5-hexenyl radical cyclizes readily failed. This was early recognized and confirmed later. Only in special cases, as by the use of vibrationally excited radicals in the gas phase or carbene triplets has cyclization been observed. In these instances, only (Cy5) and no (Cy4) products were obtained. In solution, cyclized products have been observed only from 4-pentenyl radicals possessing special features, e.g., the radical (A ) which results from intermolecular free radical addition to cis cis-1,5-cyclooctadiene (Scheme 15). 

In all these cases no methylcyclobutyl radicals have been observed. But even if they had been formed methylcyclobutyl radicals would open very easily. A familiar case is that of the (Cy 4) radical resulting from intermolecular free radical addition to a- or )8-pinene (Scheme 16). 

We now discuss an important case of the Cy5/Cy6 cyclization. Here the process begins with the intermolecular free radical addition of a free radical (Y ) to a diallylic substrate with the formation of an unsaturated radical (A") (Scheme 25). 

Sihi MP, JiJG, SauskerJB, Jasperse CP. Free radical-mediated intermolecular coryug te additions. Effect of the Lewis acid, chiral auxiliary, and additives on diastereoselectivity. JAm Chem Soc. 1999 121 7517-7526. 

The obtained value of a indicates the proximity of the rate constant values of the addition of TBSM to the macroradicals MA and of MA to TBSM This can be explained by a similar influence of intermolecular coordination on chain propagation. The values of pt and p2 indicate that in free-radical copolymerization of TBSM with MA both free and complex-bound monomers are involved in chain propagation with a higher contribution of the latter. 

The first attempts at ROP have been mainly based on anionic and cationic processes [4,5]. In most cases, polyesters of low molecular weight were recovered and no control on the polymerization course was reported due to the occurrence of side intra- and intermolecular transesterification reactions responsible for a mixture of linear and cyclic molecules. In addition, aliphatic polyesters have been prepared by free radical, active hydrogen, zwitterionic, and coordination polymerization as summarized in Table 2. The mechanistic considerations of the above-mentioned processes are outside the scope of this work and have been extensively discussed in a recent review by some of us [2 ]. In addition, the enzyme-catalyzed ROP of (di)lactones in organic media has recently been reported however, even though this new polymerization procedure appears very promising, no real control of the polyesters chains, or rather oligomers, has been observed so far [6]. 

In 1981 it was shown that rhodium(II) carboxylates smoothly catalyze the addition of ethyl diazoacetate to a variety of alkanes11. While some differentiation between possible sites of insertion was observed, selectivity is not as high for this carbenoid process as it is for the free radical process above. Rhodium-catalyzed intermolecular C-H insertion is thought to proceed via electrophilic addition of an intermediate rhodium carbene into the alkane C—IT bond. 

The free-radical carbonylation of iodoalkanes in SCCO2 initiated by AIBN (0.2-0.3 equiv.) with (TMS)3SiH (1.5 equiv.) was studied for both intermolecular reactions and intramolecular reactions (Scheme 42). For example, the carbonylative addition of 1-iodooctane 304 to acrylonitrile was carried out at 80°C and 50 atm of CO in SCCO2 under a total pressure of 310 atm to give 4-oxododecanenitrile 305 in 90% yield. Also, the intramolecular carbonylation of 6-iodohexyl acrylate 306 under similar conditions afforded 11-membered macro-lide 307 in 68% yield. 

Intennoleciilar Reactions. The intermolecular version of free radical reactions of sugar-derived radicals consists mainly of addition onto suitably activated olefins, such as acrylonitrile, generally used in excess. This approach has been explored by Giese [102]. The stereochemical course of the reaction is dictated by steric effects of the vicinal substituents, as seen from the reaction of radical 71 where equatorial attack is favored over the axial with acrylonitrile (Scheme 28). Only equatorial attack is observed using... 

Technically, the addition of carbon-centered radicals to C-N double bonds is as yet of little if any importance. In the free-radical chemistry of DNA it plays, however, a considerable role in the formation of the C(5 )-C(8) linkage between the sugar moiety and the purines (Chap. 10.5). Because of its importance, even an immune assay has been developed for the sensitive detection of this kind of damage in DNA (Chap. 13.2). The addition of the C(5 ) radical to the C(8) position of a purine is obviously facilitated for steric reasons (formation of a six-membered ring), but the same kind of reaction also occurs as an intermolecular reaction. Since alkyl radicals are nucleophilic, the rate of this reaction is noticeably increased upon protonation of the purine (Aravindakumar et al. 1994 for rate constants see Chap. 10.5). 

Tin-free photolytic conditions for addition of formyl radical equivalents to 3a have been reported by Alonso [53]. Photolysis of 1,3-dioxolane solutions of 3a in the presence of 1 equiv of benzophenone led to formation of the l,3-dioxalan-2-yl radical from solvent, followed by intermolecular radical addition in 87% yield (entry 6). A one-pot variant without isolation of 3a increased the yield and selectivity (entry 7). These conditions gave good yields across a range of chiral /V-acylhydrazones (not shown), but synthetically useful levels were restricted to aliphatic aldehyde precursors. 

Polyynes have served as starting materials for the synthesis of a wide variety of heterocyclic ring systems. The reactions used involve addition to triple bonds, and any of the common mechanistic pathways may be followed, i.e. nucleophilic, electrophilic or free radical attack as well as concerted cycloadditions. Although the evidence does not permit unequivocal classification of many of the reactions into one of these categories, the ones considered here are those which most likely involve nucleophilic attack at some stage. In a formal sense the reactions amount to successive additions of a divalent nucleophile to two triple bonds the first involves intermolecular and the second intramolecular attack, as illustrated in equation (19) for the addition of HoS to a diyne. 

Both intermolecular and intramolecular additions of carbon radicals to alkenes and alkynes continue to be a widely investigated method for carbon-carbon bond formation and has been the subject of a number of review articles. In particular, the inter- and intra-molecular additions of vinyl, heteroatomic and metal-centred radicals to alkynes have been reported and also the factors which influence the addition reactions of carbon radicals to unsaturated carbon-carbon bonds. The stereochemical outcome of such additions continues to attract interest. The generation and use of alkoxy radicals in both asymmetric cyclizations and skeletal rearrangements has been reviewed and the use of fi ee radical reactions in the stereoselective synthesis of a-amino acid derivatives has appeared in two reports." The stereochemical features and synthetic potential of the [1,2]-Wittig rearrangement has also been reviewed. In addition, a review of some recent applications of free radical chain reactions in organic and polymer synthesis has appeared. The effect of solvent upon the reactions of neutral fi ee radicals has also recently been reviewed. ... 

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