Xanthates radical allylation

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. 

This problem is not so severe when acyl xanthates are used as precursors because these substrates absorb in the visible region, while the products do not (however, the products might still be recycled to the radical pool by radical addition-elimination). Visible light photolysis of benzoyl xanthane (42) and allyl acetate provides (43) in 60% yield. Standard (ionic) 3-elimination of the xanthane is a facile reaction that gives (44). When the tertiary acyl xanthane (45) is irradiated in the presence of W-benzylmaleimide... 

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. 

A number of sulfur-centered radical scavengers have been employed for Meerwein type carbothiolation reactions [109, 110]. The most prominent of those are certainly xanthates [111-113] and thiocyanates, among which the latter have received special attention recently. As shown in Scheme 21, thiocyanates are well-suited for the functionalization of activated and non-activated alkenes [114, 115]. Remarkably, the reaction of 56 with 2-methallyl chloride to give 57 is not significantly impeded by the possible (3-fragmentation of a chlorine radical, which would lead to allylation products [116]. With an activated and a non-activated alkene present in a substrate... 

Organosulfone-mediated allylation, vinylation and azidation represent very effective tin-free radical processes. However, the reported methods do not work well with primary alkyl iodides and xanthate as radical precursor, owing to in-... 

A free-radical approach has also been successfully applied to the synthesis of primary allylic tributylstannanes (Eq. 8) [10]. The sequence involves a thermal [3,3] rearrangement of an allylic methyl xanthate then addition of a BusSn radical to the double bond of the derived dithiocarbonate intermediate and subsequent loss of COS in a chain-propagating step. 

There is one other synthetically interesting O S transformation based on a hetero-Cope reaction, which is worth mentioning here. This rearrangement (equation 18) is so easy that on attempting to prepare allylic xanthates (20) one isolates instead the rearranged ( )-thiocarbonates (21), which can be used in synthesis, e.g. as protected thiol derivatives or as precursors for allylic radicals. ... 

Acyl radical sources, other than aldehydes, are also available. The group transfer addition of an acyl radical has been reported by Zard and co-workers, where S-acyl xanthates serve as acyl radical sources [44]. Crich and co-workers reported that an acyl radical, generated from an aromatic acyl telluride by photolysis, adds to an allylic sulfide which contains an ethoxycarbonyl group to form the corre-.sponding y-unsaturated ketones [45]. The addition pathway involves Sh2 type reaction with extrusion of a /ert-butylthiyl radical. 

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. 

The most important synthetic asset of the xanthate transfer methodology lies in its ability to induce carbon-carbon bond formation by intermolecular addition to unactivated olefins. Again, this is possible because the initial radical has a comparatively long lifetime in the medium. Unhindered, terminal olefins are the best substrates, but other types of olefins (especially strained or lacking allylic hydrogens) may be made to react in some cases. Three examples of additions are collected in Scheme 18. The first involves formation and capture of a trifluoroacetonyl radical, a species hitherto only studied by mass spectrometry but never employed in synthesis [34a]. This reaction represents a convenient route to various, otherwise inaccessible, trifluoromethyl ketones. In the second example a tetrazolylmethyl radical, also a previously unused intermediate, is intercepted by a latent allyl glycine [34b]. The amino acid moiety may be part of the xanthate partner as highlighted by the last example [34c]. 

Radical addition-fragmentation processes have been exploited in synthetic organic chemistry since the early 1970 s. Ally transfer reactions with allyl stannancs and the Barton-McCombic deoxygenation process with xanthates arc two examples of reactions known to involve a S[j2 mechanism. However, the first reports of addition-fragmentation transfer agents in polymerization appeared in the... 

Radicals generated thermally with photochemical AIBN initiation from sugars containing halogen, phenylthio, phenylseleno, thiono-carbonate, or xanthate substituents can react with allyl- or methallyl-tributylstannane, leading to extended chain compounds, branched chain compounds and allyl C-glycosldes (e g. 

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