Tandem reactions olefins

Figure 3.42 shows some examples of such tandem-metathesis-olefination reactions. 

Cycloisomerization represents another approach for the construction of cyclic compounds from acyclic substrates, with iridium complexes functioning as efficient catalysts. The reaction of enynes has been widely studied for example, Chatani et al. reported the transformation of 1,6-enynes into 1-vinylcyclopentenes using [lrCl(CO)3]n (Scheme 11.26) [39]. In contrast, when 1,6-enynes were submitted in the presence of [lrCl(cod)]2 and AcOH, cyclopentanes with two exo-olefin moieties were obtained (Scheme 11.27) [39]. Interestingly, however, when the Ir-DPPF complex was used, the geometry of olefinic moiety in the product was opposite (Scheme 11.28) [17]. The Ir-catalyzed cycloisomerization was efficiently utilized in a tandem reaction along with a Cu(l)-catalyzed three-component coupling, Diels-Alder reaction, and dehydrogenation for the synthesis of polycyclic pyrroles [40]. 

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

Blechert carried out a tandem reaction of enynes in the presence of olefins instead of ethylene (Scheme 21). Treatment of cyclopentenol derivative 58a with Ic in the presence of an alkene affords 59a. The five-membered ring in estrone 58b is cleaved by Ic to give 59 and an alkene part is introduced on the six-membered C ring. However, cycloalkenyl amine derivative 60 is treated in a similar manner in the presence of an allyl alcohol derivative to give pyrrolidine derivative 61, and in this case, an alkene part is introduced on the diene moiety. Presumably, ruthenium carbene complex XVI reacts with an alkyne part to produce the pyrrolidine ring with a regioselectivity opposite to the other cases. 

A tandem reaction was also tried by Floreancig et al., who reported an example of intramolecular addition of alcohol to olefin [57]. In this case, reaction started with the... 

A review of intramolecular 4 + 3-cycloadditions of allyl cations has been presented.277 The 4 + 3-cycloaddition reaction of C(2)-substituted furans with 1,3-dimethyloxyallyl cations show high endo diastereoselectivity and a cis dia-stereospecificity.278 The tandem Peterson olefination/[4 + 3]-cycloaddition of tertiary alcohols (149) in the presence of filran and Lewis acids (TiCLt) furnishes cycloheptanes (150) in modest yields (Scheme 57).279 (Trimethylsilyl)methyl allylic sulfones (151) were used to investigate the scope and limitations of intramolecular 4 + 3-cycloadditions of allylic sulfones (Scheme 58).280 Lewis acid-catalysed 4 + 3-... 

The group of activated olefins, which has so far probably received most attention in radical cyclizations, are enamides. Syntheses of various natural products, especially alkaloids, have been successfully completed using this strategy. Cyclizations onto enamides of the 6-endo type led to erysotrine [76] and lycorine alkaloids [77-79]. The skeleton of hydroapoerysopines [80] was successfully constructed by a 1-endo cyclization. Two new examples of radical tandem reactions, which commence with a 1-endo type cyclization, have appeared in recent literature. Construction of the cephalotaxine core structure 29 was achieved from enamide 30 in only one step (Scheme 11) [81]. 

The formation of ring systems by the anionic cyclization of olefinic alkyl, aryl and vinyl-lithiums is an interesting synthetic transformation that provides a regiospecific and highly stereoselective route to five-membered carbocycles and heterocycles99. Most importantly, it is possible to functionalize the initially formed cyclization product by a tandem reaction with electrophiles, a reaction that is not generally possible in the case of radical cyclizations. 

Under the conditions necessary for the addition of the XH-acidic group onto the C=C bond of 11, a rapid intramolecular Wittig olefination normally ensues, making for an expedient overall tandem reaction. Ylide 11 is readily prepared in molar quantities in three steps from methyl bromoacetate and triphenylphosphane.26 It is fairly air-stable and can be stored at room temperature for months, and it is also commercially available from Merck-Schuchardt. 

As vinyl ethers were known to be poor substrates in Ru-catalyzed olefin metath-eses, it has been difficult to obtain cydic enol ethers by RCM of the vinyl ethers. Recently, a novel method to obtain cyclic enol ethers has been reported, which afforded cydic enol ethers directly from easily prepared dienes containing an allyl ether moiety [46]. Treatment of 70 with diene 99 in CH2CI2 in the presence of small amount of H2 resulted in a formation of dihydropyran 101 (Eq. 12.40). Treatment of 70 with H2 has been thought to produce an active catalyst for the olefin isomerization, and only metathesis products are formed until a small amount of H2 is introduced in the reaction. These results implied that this reaction most likely proceeded by way of a formation of the cyclic olefin 100, which was subsequently converted to dihydropyran 101 by the newly formed isomerization catalyst. In addition to the tandem reaction shown in Eq. 12.40, another method for obtaining cydic enol ethers from allyl ethers has also been demonstrated [46b]. This method induded addition of the hydride donor, such as NaBH4, to the reaction solution after the metathesis reaction had been completed. Although attempts to observe an active species for olefin isomerization in the presence H2 failed, these results suggested participation of hydride species in the olefin isomerization. 

With Mn(OAc)3, generated by oxidation of Mn(OAc)2 as mediator, a tandem reaction consisting of an intermolecular radical addition followed by an intramolecular electrophilic aromatic substitution can be accomplished [Eq. (21b)] [225b]. Further Mn(III)-mediated additions of 1,3-dicarbonyl compound to olefins are shown in Table 11 (numbers 8b,c, and 9a). Mediated by in situ generated Mn(III), methyl dibromoacetate, trichloro-bromomethane, perfluoroctyl iodide, dimethyl bromomalonate, and active methylene compounds have been added via radicals to olefins [225d]. 

The synthesis of seven-membered rings from furans and a,a -dibromoketones via oxyallyl intermediates is well known. It was reported that this reaction occurs quite easily when water is used as solvent <97TL8031>. In a study on the influence of steric and electronic effects on a function attached at C-2 of furans in the yield and diastereoselectivity of [4 + 3] cycloaddition reactions with oxyallyl cations it was found that in almost all cases a c/x-diastereospecificity and a high endo diastereoselectivity is obtained <97T11669>. A tandem Peterson olefination-[4 + 3] cycloaddition reaction with furans has been reported <97JOC1578 97TL386l>. For an intramolecular [4 -t- 3] cycloaddition see <97JOC6051>. The first asymmetric [4 + 3]... 

More complex small molecules can also be made by metathesis cascades and tandem reaction sequences involving olehn metathesis components [41], The examples illustrated in Fig. 4.13 include inter- and intramolecular enyne metathesis between an olefin and an alkyne [42], ring-opening cross metathesis to form new substituted acyclic olefins [43], ring-opening ring-closing sequences... 

Highly functionalized olefins are easily accessible via silyformylation of alkynes. When coupled to other reaction systems, silylformylation reactions become even more powerful. Eilbracht et al. demonstrated that stabilized phosphorous ylides 74 could be trapped by P-silylated a-P-unsaturated aldehydes formed via silylformylation of alkynes in a one-pot synthesis. The tandem reaction proceeds with high yields for both alipathic and aromatic terminal alkynes. Protected propargyl alcohols also showed good reactivity however, propargyl amines react with low selectivity. The reaction shown below is the best-afforded result for this process. ... 

The first organometallic Pd(III) complexes (44-46) were reported in 2006 (Fig. 25) [98]. Complexes 44 47 have been used as precatalysts for both the diborylation of terminal olefins and diborylation/cross-coupling tandem reactions (Fig. 26) [99]. The role of the Pd(III) complexes in these reactions has not been established the diborane reagents employed have been shown to immediately reduce the dinuclear Pd(III) complexes to Pd(II) species, and thus the Pd(III) complexes may be a precatalyst for lower-valent active catalysts. 

Starting with -hexane (Cg) metathesis, dehydrogenation should give the corresponding 1-hexene, followed by its homo-metathesis to yield ethylene and decene, which upon hydrogenation, should ideally produce ethane and decane (Cj q products) as the major products (Scheme 2.18, path a). However, this tandem reaction process was not selective since -decane represented <50% of the total primary products of heavy alkanes when the reaction was catalyzed with Ir-2(H2). The authors attributed this unexpected distribution of alkanes to the isomerization of the (x-olefin prior its metathesis, as depicted in pathway b (Scheme 2.18). 

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