TROST Cyclopentanation

TRAHANOVSKY Oxidation 386 TRAUBE Purina synthesis 387 TREIBS Alylic oxidation 388 Trochmwwsla t2l TROST Cyclopentanation 389 Trost 392... 

Trost et al 1 have observed product distribution to be dependent in part on the steric and electronic properties of the substrate. For example, linear enyne 48 (Equation (30)) cyclized exclusively to the Alder-ene product 49, whereas branching at the allylic position led to the formation of 1,3-diene 50 (Equation (31)) under similar conditions. Allylic ethers also give 1,3-dienes this effect was determined not to be the result of chelation, as methyl ethers and tert-butyldimethylsilyl ethers both gave dialkylidene cyclopentanes despite the large difference in coordinating ability. 

Organometallic methods, with the possible exception of those involving the stoichiometric generation of enolates and other stabilized carbanionic species 140], have seldom been used in carbohydrate chemistry for the synthesis of cyclohexane and cyclopentane derivatives. The present discussion will not cover these areas. The earliest of the examples using a catalytic transition metal appears in the work of Trost and Runge [41], who reported the Pd-catalyzed transformation of the mannose-derived intermediate 22 to the functionalized cyclopentane 23 in 98% yield (Scheme 10). Under a different set of conditions, the same substrate gives a cycloheptenone 24. Other related reactions are the catalytic versions of the Ferrier protocol for the conversion of methylene sugars to cyclohexanones (see Chap. 26) [40,42,43]. 

Versatile [3 + 2]-cycloaddition pathways to five-membered carbocycles involve the trimethylenemethane (= 2-methylene-propanediyl) synthon (B.M. Trost, 1986). PaIladium(0)-induced 1,3-elimination at suitable reagents generates a reactive n - -methylene-1,3-propa-nediyl complex which reacts highly diastereoselectively with electron-deficient olefins. The resulting methylenecyclopentanes are easily modified, e.g., by ozonolysis, hydroboration etc., and thus a large variety of interesting cyclopentane derivatives is accessible. 

Enyne cycloisomerizations can also be exploited to annulate a cyclopentane onto an existing ring system. An example drawn from Trost and co-workers asymmetric total synthesis of picrotoxinin (119) is the conversion of bridged bicyclic intermediate 117 into tricycle 118 (Scheme 6-20) [46]. The optimal cyclization conditions in this case were unusual, requiring an internal proton delivery and a bidentate phosphine. A related example is the conversion of 120 to 121, which was the pivotal step in Trost s synthesis of (—)-dendrobine (122) [47]. An all-carbon tether is not required, as is exemplified by the conversion of 123 to 124 in the total synthesis of ( )-phyllanthocin (125) [48]. Note that in-situ reduction of the o-palladium species prior to /5-hydride elimination has occuined in this latter-example. The enyne disconnection in the synthesis of ( )-phyllanthocin was... 

Laitalainen, T. Selenium dioxide oxidation of cyclohexanone derivatives. Preparation of cyclopentane-1,2-dione derivatives and characterization of organic selenium compounds. Annates Academiae Scientiarom Fennicae, Series A2 Chemica 1982, 195, 51 pp. Bulman Page, P. C., McCarthy, T. J. Oxidation Adjacent to C=C Bonds, in Comp. Org. Synth, (eds. Trost, B. M.,Fleming, I.), 7, 83-117 (Pergamon, Oxford, 1991). 

D.iii. Trimethylenemethane Equivalents. Palladium catalysts can be used to convert trimethylsilyl acetate 390 to a trimethylene methane (TMM, 391) equivalent. Reaction with alkenes via [3+2]-cycloaddition (sec. 11.11) generates cyclopentanes (this process constitutes a quinane annulation reaction).229 in this reaction, the trimethylsilyl unit is a carbanion equivalent and acetate is a carbocation equivalent. In one example, Trost reacted 390 and 392 with palladium acetate and triisopropyl phosphite [P(Oi-Pr)3] to generate 393 in... 

When TMM equivalents are tethered to alkenes, intramolecular cyclization generates bicyclic methylene-cyclopentane derivatives. Cyclization of 394, for example, led to a 51% yield of 395 along with 18% of the uncyclized triene, 396. 35 jhe cyclization reaction proceeded with excellent diastereoselectivity, as shown. Trost has also examined the attachment of chiral auxiliaries to the alkene partner to give asymmetric induction in reactions with TMM equivalents.231... 

Cyclopentane anndation. Trost and Keeley have described a new method for cyclopentane annelation (equation I). Yields are high in all steps, and the... 

Condensation Reactions.—Trost has reviewed the preparation and synthetic uses of cyclopropyldiphenylsulphonium ylides. The regioselectivity and chemospecificity of the cyclopentane and cyclopentenone annelation reactions have been examined. Whereas diphenylsulphonium methylide does not cyclopropanate simple, unactivated olefins such as tetramethylethylene, transfer of a methylene group from the ylide can be effected stereospecifically in the presence of a copper catalyst and this reaction may provide a model for biological cyclopropanations by the ylide derived from S-adenosyl-methionine. Attempts to catalyse a similar transfer to unactivated olefins using PdCl2 were not successful. ... 

Trost and Whitman have established a new route to diphenylcyclopropenone, using the photochemical decomposition of the aa -bisdiazoketone (161). The product (162) was stable to the reaction conditions when irradiation (436 nm) was carried out in methanol, but in toluene decarbonylation afforded a quantitative yield of diphenyl-acetylene. Application of the reaction to oea -bisdiazocyclohexanone gave only cyclopentane derivatives (Scheme 13), indicative of the transient intermediacy of a cyclopropenone. 

Trost and Coppola [87] have put this methodology to good use in an intramolecular synthesis of exo-methylene cyclopentanes (3) (Scheme 26). 

Introduction. The development by Trost and co-workers of palladium-trimethylenemethane (TMM) cycloadditions en5)loy-ing the title reagent (1) and related reagents was a seminal advance in ring-construction methodology. The generality and versatility of these reactions is illustrated below by their use in [3 + 2] cycloadditions to form both cyclopentanes and heterocycles, [3 +4] and [3 + 6] cycloadditions, and applications in total synthesis. 

General Methods.—Trost and his co-workers have extended their earlier studies of the synthesis of cyclopentanes based on thermolysis of vinylcyclopropanes, and shown that it is expedient to use the recently developed 1-lithiocyclopropyl phenyl sulphide (32) for the preparation of the appropriate vinylcyclopropane precursor. Thus addition of (32) to ketone (33), followed by dehydration of the intermediate hydroxy-sulphide with SOCI2, led to (34), which on thermolysis in the vapour phase at 350 °C, then hydrolysis, gave the cyclopentenone (35). An identical approach to cyclopentane annelation has been used by Miller in a synthesis of (36) from cyclopent-2-enone. 

The route to cyclopentanes via thermolysis of vinylcyclopropanes is an attractive one, limited only by the availability of the vinylcyclopropane. Trost s use of (32) offers one solution to this problem, but in related investigations Piers et and also Marino and Browne, have demonstrated that the vinylcyclopropanes are smoothly produced by reaction between lithium cyclopropylcuprates (37) and jS-halogeno-ajS-unsaturated ketones, according to Scheme 13. Furthermore, Marino and Browne have found that conjugate addition of (37) to acetylenic ketones offers additional scope for the synthesis of monocyclic vinylcyclopropanes, e.g. (38) (39). 

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