Carbocyclization cascades

Rhodium-catalyzed, silane-initiated cascade cyclization of 1,6,11-triynes 83 was proposed to occur via a silane-initiated cascade carbocyclization to form the silylated bicyclic triene (Z,Z)-In. / -Migratory insertion of the silylated G=G bond into the Rh-G bond of (Z,Z)-In followed by / -hydride elimination from frans-lln could then form 84a. Alternatively, cisitrans isomerization of (Z,Z)-In followed by / -migratory insertion of the silylated G=G bond into the Rh-G bond of resulting isomer ( ,Z)-In could form cis-Wn. Subsequent / -silyl elimination from m-IIn would form unsilylated tricycle 84b (Scheme 21). 

Recent advances in the cyclizations catalyzed by transition metals and their complexes are reviewed. The catalytic cyclizations discussed here include various carbocyclizations, for example, cycloisomerization, cycloaddition, reductive cyclization, and so on cascade carbocyclizations, for example, cyclotrimerization, silylcarbocyclization, and Heck reaction carbonylative carbocyclizations cyclohy-drocarbonylations intramolecular hydrosilylations intramolecular silylformyla-tions and aldol cyclizations. These reactions serve as efficient and useful methods for the syntheses of a variety of heterocycles and carbocycles that are important... 

It is worth noting that product 443 was not obtained without silicon assistance, which means that the reaction is in fact initiated by an Si-[Rh] species (Scheme 112). Fused tricyclic benzenes such as 443 are formed exclusively using an exactly stoichiometric amount of silane. On the other hand, 2 equiv. of silane preferably lead to the formation of silylated benzenes such as 447 through a hydrosilyIation-carbocyclization-/ -hydride elimination cascade process. 

Keyword Carbocycles a Cascade Reactions a Cycloadditions a Combinatorial Chemistry a Domino Reactions a Enantioselective Transformations a Ene Reactions a Eieterocydes a Natural products a Preservation of Resources and Environment a Sigmatropic Rearrangements a Tandem Reactions a Transition Metal-Catalyzed Transformations... 

Cascade silylcarbocyclization reactions tiave been developed based on the fact that it is possible to realize successive intramolecular carbocyclizations, as long as the competing reductive elimination is slower than the carbometallation. For example, the reaction of dodec-6-ene-l,ll-diyne 67 with PhMe2SiH catalyzed by Rh(acac)(CO)2 at 50°C under 1 atm CO gives bis(exo-methylenecyclopentyl) 68 in 55% yield [44]. The reaction is stereo-specific that is, (6 )- and (6Z)-dodec-6-ene-l,ll-diynes, ( )-67 and (Z)-67, afford R, R )-68 and (S, R -68 respectively. A possible mechanism for this reaction is outlined in Scheme 7.20. It should be noted that none of the tricyclic product is formed even though a third carbocyclization in the intermediate III.2c is conceptually possible. 

This chapter covers the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions from 1993 to early 2005. In addition, technical development in carbonylation processes with the use of microwave irradiation as well as new reaction media such as supercritical carbon dioxide and ionic liquids are also discussed. These carbonylation reactions provide efficient and powerful methods for the syntheses of a variety of carbonyl compounds, amino acids, heterocycles, and carbocycles. 

Reaction of 3,3-disubstituted-l,4-pentadiene 92 with a primary amine under cyclohydrocarbonylation conditions yielded cyclopenta[. ]pyrrole 96 as the predominant product accompanied by a small amount of cyclopentanone 95 (Scheme 15). This unique reaction is proposed to proceed through a cascade hydrocarbonylation-carbonylation process. The first hydrocarbonylation of 92 and the subsequent carbocyclization formed cyclopentanoylmethyl-Rh complex 93. If 93 immediately reacts with molecular hydrogen, 2-methylcyclopentanone 95 is formed. However, if CO insertion takes place faster than the hydrogenolysis, cyclopentanoylacetyl-Rh complex 94 is generated, which undergoes the Paal-Knorr condensation with a primary amine to yield cyclopenta[. ]pyrrole 96. ... 

In the pioneering work by Wilcox and Gaudino, a straightforward route to the carbocyclic analogue of D-fructofuranose, 64, and its 6-phosphate derivative was delineated [14a,b]. As shown in Scheme 9, the first move consisted of Wittig olefination of benzyl-protected arabinose 60 with carboxy-tert-butylmethylene triphenyl phosphorane to deliver unsaturated ester 61, which was then cleverly elaborated into dibromide 62 via a reaction cascade encompassing Swem oxidation of the secondary OH, ester hydrolysis, diastereoselective addition of dibromomethyl lithium, and carboxylic acid methylation. 

Diynes are also used to perform intermolecular enyne metathesis. With the objective of producing functionalized hetero- and carbocycles, a cascade diyne-alkene cross metathesis leading to five-membered cyclic products has recently been proposed [27] (Scheme 13). 

This intriguing regioselectivity induced by the fused carbocycle triggered a cascade of papers addressing the question of the electrophilic reactivity of annelated benzenes [2-7], which have continued to flow until nowadays [8-14]. 

Kilburn has extensively studied radical cascades centered on the use of methylenecyclopropane derivatives. An addition-fragmentation process ap-parented to pathway c opened new routes for the synthesis of carbocycles. In a recent work, a Sml2-promoted cascade of propargyl ether 73 has been used to give bicyclic ether 78 with good diastereoselectivity (Scheme 24), thus providing a short route to the monoterpenoid paeonilactone B. The observed stereoselectivity in the 74 75 cyclization step was shown to be critically dependent on the presence of HMPA [84]. 

The addition of thiyl and sulfonyl radicals, either in stoichiometric or in catalytic amounts, is used as the first step of tandem processes which have been widely applied to prepare carbocyclic compounds. The catalytic procedure will be further described in Section 5.5.4.3 during the discussion of cascade processes involving fragmentation reactions. The mechanism of the stoichiometric procedure, which can involve thiols, disulfides, or any sulfonyl radical precursor, is represented in Scheme 7. It consists of (i) the initial addition step, (ii) the cyclization with formation of the final radical species, and (iii) the quenching of the final radical to give the product. 

If the oxidation is performed in the presence of an external dienophile, the respective products of [4+2] cycloaddition are formed [351-356]. Typical examples are illustrated by a one-pot synthesis of several silyl bicyclic alkenes 283 by intermolecular Diels-Alder reactions of 4-trimethylsilyl substituted masked o-benzoquinones 282 generated by oxidation of the corresponding 2-methoxyphenols 281 [351] and by the hypervalent iodine-mediated oxidative dearomatization/Diels-Alder cascade reaction of phenols 284 with allyl alcohol affording polycyclic acetals 285 (Scheme 3.118) [352]. This hypervalent iodine-promoted tandem phenolic oxidation/Diels-Alder reaction has been utilized in the stereoselective synthesis of the bacchopetiolone carbocyclic core [353]. 

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