Cyclization allylation mechanisms

As a preliminary mechanistic proposal, we hypothesize that the palladimn(ll)-phosphoramidite catalyst acts as a chiral n-acid to activate the amine iV-oxide substrate (Scheme 1S.291. similar to the mechanism proposed for the Overman rearrangement of allylic trichloroacetimidates. While it is not clear whether the reactive species is oxide-bound complex 119a or olefin-bound complex 119b, we propose heterocycle 120 as an intermediate in this cyclization-induced mechanism Grob-type fragmentation eventually reveals O-allylhydroxylamine 117 and the palladium(n)-phosphoramidite catalyst, which can reenter the catalytic cycle. 

Although only the 6-endo cyclization pathways in the postulated cyclization-induced mechanism were explored, recent work by Tantillo et al. [11] suggests that both the 6-endo and 5-exo pathways are feasible for allylic acetimidates, and in some cases the 5-exo cyclization is favored (Figure 5.8). Consistent with Watson s results, the 6-endo cyclization (10 Figure 5.8) is favored over the 5-exo cyclization for this particular system by about 5 kcal mol . ... 

The mechanism of the rearrangement catalyzed by Pd(fl), typically by PdCl2(RCN)2, is explained by the oxypalladation of an alkene to form 810 as an intermediate, or cyclization-induced rearrangement. As a limitation, no rearrangement takes place when the allylie ester 812 is substituted at the C-2 position of the allyl group, while a smooth rearrangement of 811 takes place[500]. 

Trost and Ghadiri19 have found a Lewis-acid-mediated intramolecular cyclization of allyl sulfones. When the allyl sulfone 40 is treated with A1C13, polycondensed aromatic system 41 can be obtained in good yield (equation 24). The mechanism probably involves... 

Tetraene 4 (Scheme 1.3), when treated with 40 mol % of triflic acid in methylene chloride at -23 °C for 1 h, gives the adducts 5 and 6 in a 1 1 ratio as the main reaction products. The formation of these adducts has been justified [21] by a stepwise mechanism that requires an initial reversible protonation of 4 to produce the allyl cation 7, which then cyclizes to 8 and 9 in a non-reversible process. Deprotonation of 8 and 9 gives 5 and 6, respectively. 

While little biosynthetic information is available, it has been suggested [38] that 25 and 26 may be formed from AA (24) and EPA (14) via a cyclization mechanism (Scheme 3) similar to that which forms trans-cyclopropyl-containing diol 28 upon treatment of linoleic acid with performic acid [40]. An alternative biogenetic mechanism (Scheme 4), based upon that proposed for the structurally related red algal metabolites constanolactone A and B [41], would involve the formation and opening of an allylic epoxide intermediate created as a result of a 15-/ -LPO acting on either AA or EPA. Related compounds have been isolated from the coral Plexaura homomalla and the mollusc Aplysia kurodai (see below). 

Allyl methylcarbonate reacts with norbornene following a ruthenium-catalyzed carbonylative cyclization under carbon monoxide pressure to give cyclopentenone derivatives 12 (Scheme 4).32 Catalyst loading, amine and CO pressure have been optimized to give the cyclopentenone compound in 80% yield and a total control of the stereoselectivity (exo 100%). Aromatic or bidentate amines inhibit the reaction certainly by a too strong interaction with ruthenium. A plausible mechanism is proposed. Stereoselective CM-carboruthenation of norbornene with allyl-ruthenium complex 13 followed by carbon monoxide insertion generates an acylruthenium intermediate 15. Intramolecular carboruthenation and /3-hydride elimination of 16 afford the -olefin 17. Isomerization of the double bond under experimental conditions allows formation of the cyclopentenone derivative 12. 

A mechanism was proposed in which entry into the catalytic cycle is achieved via Et2AlCl-mediated cobalt hydride generation. Diene hydrometallation affords the cobalt-complexed -jr-allyl A-5, which inserts the tethered alkene to furnish intermediate B-4. Elimination of LnCoOBn provides the cyclization product. Reduction of LnCoOBn by Et2AlCl regenerates cobalt hydride to complete the catalytic cycle (Scheme 17). 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

A proposed mechanism of the bis(allene) cyclization involves the formation of the allyl(stannyl)palladium species 6, which undergoes carbocyclization to give vinyl(stannyl)palladium intermediate 7 (Scheme 36). Reductive elimination and cr-bond metathesis may lead to the formation of the m-pentane derivative and the bicyclic product, respectively. The cyclization of allenic aldehydes catalyzed by a palladium complex was also reported.163... 

FIGURE 6 Speculative mechanism of Crl hydrocarbon biosynthesis from fatty acid hydroperoxides in algae. Homolytic cleavage of the hydroperoxide is assumed to give an allyl radical, which cyclizes to the thermolabile (1S,2R)-cyclopropane. The sequence is terminated by transfer of a hydrogen radical from C(16) to the -X-0 function. The cyclopropane rearranges to (6S)-ectocarpene as shown in Figure 4. 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

The relative amounts of these produced at various temperatures are shown in Table VII. The formation of these products may be explained using carbanionic mechanisms. The cyclic material may form by addition of an allylic carbanion to a molecule of the styrene, followed by a cyclization to yield a benzylic carbanion [Reaction (33a, b, c)]. 

Aryl diazonium ions are converted to iodides in high yield by reaction with iodide salts. This reaction is initiated by reduction of the diazonium ion by iodide. The aryl radical then abstracts iodine from either I2 or I3. A chain mechanism then proceeds which consumes I- and ArN2+.105 Evidence for the involvement of radicals includes the isolation of cyclized products from o-allyl derivatives. 

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