Tandem reactions alkene derivatives

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. 

Tandem GM-RGM (see Scheme 20) can be employed for the synthesis of complex ring systems from simple starting materials. A very noteworthy example of this reaction serves as the cornerstone for the total synthethis of the natural product cyclindrocyclophane. The GM-RGM reaction of diene 182 was completely selective for formation of the head-to-tail isomer 183. The selectivity was attributed to thermodynamic control the head-to-head dimer 184 is considerably less stable. In an effort to synthesize pyrenophorin derivatives, the formation of cyclic dimers (e.g., 186) and trimers (e.g., 187) from treatment of acrylate ester-alkene derivatives (e.g., 185) with various ruthenium metathesis catalysts was examined.The product distribution was very time and concentration dependent higher concentrations favor the trimer over the dimer. 

Zhu and coworkers have recently reported a tandem cycloisomerisation/ carbene transfer reaction for the synthesis of highly functionalised furan derivatives. Starting from enyone and alkene derivatives they were able to synthesise several furan species using as little as 1 ppm of [Au(IPr)Cl] and 10 mol% of Selectfluor . This methodology was applicable to a wide range... 

Hydroformylation can be incorporated efficiently into tandem reactions [17]. Various tryptamine-based pharmaceuticals were prepared by hydroformylation carried out in the presence of hydrazine derivatives. The aldehydes were generated in situ from the alkenes and trapped by the hydrazines to form the hydrazones that on cyclization gave the indole products. Application of water-soluble ligands such as TPPTS made it possible to execute hydroformylation and cyclization in one step in aqueous sulfuric acid [18]. 

The palladium-catalyzed preparation of vinyl ethers through a tandem reaction consisting of an initial C—H olefination of a tertiary alcohol by an activated alkene followed by an intramolecular oxidative cychzation has been achieved using a palladium catalyst and an unusual supporting ligand (Scheme 2.107) [154]. This ligand was a leucine derivative... 

Diarylfuroxans were found to give diarylacetylenes upon irradiation at 254 nm (Equation 9, Table 2). Cyclobutaphenanthrenes were also obtained when reaction was carried out in the presence of alkenes (Equation 10). The acetylenic derivative is supposed to arise by loss of (NO)2 from a diazete-iV,iV-dioxide. Unimolecular and collision-activated dissociation studies by tandem mass spectrometry also support the loss of (NO)2 from diarylfuroxans molecular ions <1997T17407>. 

A tandem one-pot elimination-intramolecular Diels-Alder reaction occurs when the mesylate of 4-homoallylic azetidinone having a orc-alkene or alkyne substituent is heated in a sealed tube in the presence of an equimolecular quantity of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The method has been used to produce derivatives of oxace-pham. In a similar way, the 3,4-disubstituted azetidinone mesylate 473 afforded an 88% yield of 474. The method can be further elaborated through the introduction of a novel [3,3]-sigmatropic rearrangement of a-allenic mesylates thus, 475 yielded 476 on thermolysis C1999TL1015, 2000JOC3310, 2005EJ098>. 

More recently, van der Donk and coworkers reported radical cyclizations catalyzed by vitamin B12 using titanium(III) citrate as a stoichiometric reducing agent (Fig. 69, entry 17) [330]. Here /V-allylic 2-(isopropenyl) pyrroles 290 or allyl 2-phenylallyl ethers serve as the starting material in tandem hydrocobaltation/ radical 5-exo cyclization sequences giving dihydropyrrolizine derivatives 291 or 292. The mechanistic course is not completely clear. However, it is assumed that the reactions start with an initial hydrocobaltation of the isopropenyl unit in the presence of the allylic alkene (see Sect. 5.7). The benzylic cobalt intermediate is subject to homolysis of the very weak cobalt-carbon bond and initiates the radical 5-exo cyclization. Interestingly, the fate of the cyclized radical is dependent on the... 

The chiral anisole derivative 37 has been used in the synthesis of several asymmetric functionalized cyclohexenes (Table 9) [22]. In a reaction sequence similar to that employed with racemic anisole complexes, 37 adds an electrophile and a nucleophile across C4 and C3, respectively, to form the cyclohexadiene complex 38. The vinyl ether group of 38 can then be reduced by the tandem addition of a proton and hydride to C2 and Cl, respectively, affording the alkene complex 39. Direct oxidation of 39 liberates cydohexenes 40 and 41, in which the initial asymmetric auxiliary is still intact. Alternatively, the auxiliary may be cleaved under acidic conditions to afford /y3 -allyl complexes, which can be regioselectively attacked by another nucleophile at Cl. Oxidative decomplexation liberates the cyclohexenes 42-44. HPLC analysis revealed high ee values for the organic products isolated both with and without the initial asymmetric group. 

A catalytic tandem cyclopropanation-ring-closing metathesis of dienyne 80 led to derivative 81 in good yield (Scheme 30 <2004JA9524>). For internal alkynes, carbene-mediated ring-closing enyne metathesis was observed. Less favorable alkyne binding leads to preferential reactions of the metal carbene with the 1-alkene moiety. 

The reaction proceeds via a tandem Michael addition-HBr elimination in which the carbanion (48) is the key intermediate to produce cyclopropanation. The success of the method depends from the correct addition of (46) to the basic solution of the alkenes (47). In fact, it is important to add bromonitromethane in several fractions in order to avoid its decomposition (that can happen under basic conditions). The cyclopropanation proceeds in good to excellent yields (75-96%) with a variety of substrates, but with moderate diastereoselectivity. The procedure works well even with cyclic alkenes, such as 7V-alkylmaleimides, with the exclusive formation of exocyclopropane derivatives. 

As 1,/2-alkenes, 1,6-derivatives are used very frequently leading to five-membered heterocycles, while the use of 1,7-derivatives, which produce six-mem-bered heterocycles, is very rare. The reactions of 1,6-dienes, -enynes, and -diynes are classified into three groups (a) cycloisomerization, (b) tandem addition— cyclization, and (c) cycloaddition, such as the Pau-son—Khand reaction, cyclotrimerization, and the Diels—Alder reaction (Scheme 15).97 In these reactions five-membered heterocycles are constructed upon the carbon—carbon bond-forming processes. 

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