Olefins exocyclic alkenes

Examples of reported hydrozirconations of alkenes and alkynes are summarized in Tables 2-6. Simple alkenes appear always to react as long as they are no more than trisubstituted. The only reported failure is that of a long chain internal alkene, triacont-15-ene, but such alkenes have subsequently been successfully hydrozirconated, albeit at slightly elevated temperature. The order of reactivity, based primarily on qualitative observations, is terminal alkene > internal alkene (cis = trans) > exocyclic alkene > cyclic alkene = trisubstituted alkene. Trisubstituted cyclic olefins and tetrasubstituted olefins do not react. Representative examples are shown in Table 2. 

Jin and Weinreb [137, 138] reported enantioselective total syntheses of the 5,11-methanomorphanthridine Amaryllidaceae alkaloids (—)-pancracine and (-)-coccinine. They nsed a specific Mizoroki-Heck-cyclization to convert bromo olefin 197 into seven-membered exocyclic alkene 198 in good yield (Scheme 6.57). 

A synthesis of the related sesquiterpenoid pentalene, 26, also began with the Weiss-Cook reaction product 12 (R = R" = H). Wittig olefination was carried out on the mono-ketal of 12 followed by hydrolysis of the ketal. The resultant ketone was reduced to the corresponding alcohol and the exocyclic alkene underwent cyclopropanation to produce 23. Oxidation of the alcohol generated a ketone that could be converted to the enone using the... 

Hydroxyl is a weak directing group for coordination to the transition metals, and the alcohol is also known to be easily oxidized or decomposed by Pd(II) complex thus it is envisioned difficult to implement the direction of C-H activation [37]. In 2010, Yu s group reported a Pd(II)-catalyzed cascade C-H olefination/oxidative cyclization reaction with the direction of a hydroxy group (Scheme 3.17) [38]. In the assistant of an amino acid, a diversity of primary, secondary, and tertiary alcohol could be converted to the corresponding pyran derivatives with exocyclic alkene moieties. 

This method provides a convenient synthesis of alkenes with the double bond in a relatively unstable position. Thus reduction of the p-toluenesulfonylhydrazones of a,(3-unsaturated aryl ketones and conjugated dienones gives rise to nonconjugated olefins. Unsaturated ketones with endocyclic double bonds produce olefins with double bonds in the exocyclic position. The reduction of p-toluenesulfonylhydrazones of conjugated alkynones furnishes a simple synthesis of 1,3-disubstituted allenes. ... 

In the case of r)2-coordination of the exocyclic C=C bond, it becomes substantially elongated compared with the double bond of free alkenes, as a result of back donation from the metal to the 7t orbitals of the double bond. For instance, in complex 17b the coordinated bond length is 1.437 A (see Fig. 3.2).18 This is also reflected in the loss of planarity around the quaternary exocyclic carbon, the methylenic carbon being bent out of the ring plane by 10.78°.18 Similar structural features were also observed with other P2Pd conjugated olefin complexes.39... 

Reaction of p-nitrobenzenesulfonyl azide with alkylidenecycloalkanes 22-25187 does not yield isolable triazolines as expected, but the reaction products derived from alkenes 22 and 23 suggest a single triazoline intermediate, whereas in the case of tetrasubstituted derivative 24 both possible reaction modes are present,187 owing to weak double bond dissymmetry. Product analysis from 25 indicates some conflict between electronic and steric control in the addition, but provides evidence that electronic factors are much more important than steric effects in controlling regioselectivity.187 Reaction of the exocyclic olefins 22 and 23 appears to be controlled more by the interaction of the LUMO of the azide and the HOMO of the alkene.187 p-Nitrobenzenesulfonyl azide is reported to react with members of the novel... 

Analogously, the thermal formation of fused strained tricycles 77 can be rationalized by a mechanism which includes an exocyclic diradical intermediate 80 through an initial carbon-carbon bond formation, involving the proximal allene carbon and the internal alkene carbon atom (path C, Scheme 28). The alternative pathway leading to tricyclic 2-azetidinones 77 is proposed in path D (Scheme 28). This proposal involves an endocyclic diradical intermediate 81 arising from the initial attack of the terminal olefinic carbon onto the central allene carbon. The final ring-closure step of the diradical intermediates account for the cyclobutane formation. 

As the proceeding chapters demonstrate, Ni(0)- and Pd(0)-catalyzed [3-1-21-cycloadditions of methylenecyclopropanes with alkenes open a new, simple, and useful route to a number of substituted methylenecyclopentanes. This catalytic generation of a trimethylenemethane synthon and its addition to olefinic double bonds not only lead to five-membered rings but also introduce an exocyclic methylene group, which is a useful functionality for further structural elaboration. 

Doyle has put forward arguments against the intermediacy of such complexes in catalytic cyclopropanation . Firstly, metal coordination activates the alkene to nucleophilic attack. Hence, an electrophilic metal carbene would add only reluctantly or not at all. Secondly, the stable PdCl2 complexes of dienes 8 and 428 do not react with ethyl diazoacetate, even if Rh fOAc) or PdCljfPhCbOj is added. The diazoester is decomposed only when it is added to a mixture of the Pd complex and excess diene. These results exclude the metal-carbene-olefin intermediate, but they leave open the possibility of metal carbene interaction with an uncomplexed olefin molecule. The preferred formation of exo-cyclopropanes in the PdCyPhCN) -catalyzed reactions between 8 and N2CHCOOEt or N2CPh2, with exo. endo ratios virtually identical to those observed upon cyclopropanation of monoolefin 429, also rule out coordination of a palladium carbene to the exocyclic double bond of 8 prior to cyclopropanation of the endocyclic double bond. 

Anchoring the allyl sulfoxide at an exocyclic carbon, with the alkene situated within a stereochemically defined ring, provides the opportunity for diastereoselective installation of a hydroxyl group on the ring, along with an exocyclic olefin that serves as a handle for further elaboration. Ohfune and Shinada applied this Mislow-Evans-based strategy effectively in... 

The B-alkyl-9-BBN undergoes an interesting reverse reaction to afford the parent alkene when treated with benzaldehyde. Consequently, the reaction is uniquely employed for the synthesis of exocyclic olefins (Chart 24.3). The hy-droboration of cyclic olefins with an internal double bond, followed by homologation with carbon monoxide in the presence of lithium trimethoxyaluminum hydride afford B-(cycloalkylmethyl)-9-BBN. This intermediate on treatment with benzaldehyde leads to an exocyclic methylene compound (Chart 24.3) [16]. Since the synthesis proceeds from the cycloalkene, thus it provides a valuable alternative to the customary methylenation of carbonyl compounds by Wittig and related procedures. The method also provides a clean synthesis of deuterium-labeled compounds (Eq. 24.10) [16], without positional scrambling or loss of label. Consequently, methylmethylene-d -cyclopentane in 52% isolated yield is obtained. 

Exocyclic bis-silylated olefins have been constructed through the Pd(OAc)2-catalyzed reaction of alkynes with a tethered disi-lanyl group. The reactions are carried out in the presence of a tert-alkyl isocyanide, although the precise role of this ligand is unclear. Diimide reduction of the disilylated alkene so-formed followed by Fleming-Tamao-type oxidation of the two C-Si bonds in the saturated product then affords 1,2,4-triols in a stereoselective manner (eq 83).l ... 

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