Endocyclic alkenes

SCHEME 7.21 Examples of metathesis reaction from alkene endocyclic bonds (a) to form bridged compounds or (b) strained cyclobutenes. 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

Finally, in a study of Lewis-acid-catalysed intramolecular attack of acetals on vinylsilanes, to produce allylically unsaturated oxacyclics, it has been found (75) that the alkene stereochemistry can control the mode of cyclization in an exo- or endocyclic sense, as shown here ... 

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. ... 

Halogenation of 106 with triphenylphosphine, iodine, and imidazole provided the iodo derivative 109. On treatment with lithium aluminum hydride, 109 was converted into two endocyclic alkenes, 110 and di-O-isopro-pylidenecyclohexanetetrol, in the ratio of 2 1. Oxidation of 110 with dimethyl sulfoxide - oxalyl chloride afforded the enone 111.1,4-Addition of ethyl 2-lithio-l,3-dithiane-2-carboxylate provided compound 112. Reduction of 112 with lithium aluminum hydride, and shortening of the side-chain, gave compound 113, which was converted into 114 by deprotection. ... 

The IH of exocyclic alkenes allows the construction of bicyclic amines bearing one methyl group at the ring junction. Although long reaction times (2-7 days) are necessary (Eq. 4.22), amines are obtained in good yield. In contrast, endocyclic aminoalkenes are resistant to cyclization [134]. 

Reaction of the aldehyde-tethered furanone 244 with pipecolinic acid results in the formation of the oxazolopyr-idine derivative 245, which undergoes spontaneous decarboxylation to give the ylide 246. This in turn undergoes an intramolecular cycloaddition with the tethered exomethylene group to give 247, or with the endocyclic alkene to give the furoindolizine 248 <1997T10633> (Scheme 66). 

Similar cyclic ammonium systems with a variety of double bonds, triple bonds, and aromatic rings have been shown to undergo similar reactions. Endocyclic alkenes can also be utilized to give tetracyclic azoniaspiroalkanes, such as 115 (Equation 24) <1996KGS328>. 

A related approach consists in the generation of endocyclic iminium ions from fV-acylaminals 209. As in the previous case, their treatment with boron trifluoride induces a diastereoselective cyclization, and thiazolo[3,4- ]pyridines 210 are isolated in good yields (Scheme 59) <2001EJ01267>. Alkenes can also participate and react well with the intermediate... 

An alternative substrate design, in which the alkene radical cation is substituted only at the internal position, forces the nucleophilic cyclization into the endocyclic mode, leading overall to bicyclic systems with a bridgehead nitrogen (Scheme 31) [139,140]. 

Scheme 31 Nucleophilic cyclization of an alkene radical cation in the endocyclic mode...

Activation of one the double bonds of the allene by coordination to an electrophilic metal center such as Hg(II), Ag(I), Pd(II), Rh(I), Cu(I) or Au(III). Then an intramolecular nucleophile can attack and the product is formed by protodemetallation of the intermediate (Scheme 15.1). Depending on electronic and steric factors, either the proximal or the distal Jt-bond of the allene 1 is activated in that way (2 and/or 3). For each of these two possibilities now an exo or endo attack of the nucleophile is conceivable, leading to intermediates 4—7. An equilibrium between both 5 and 6 and 9 is possible. Finally, from 4 the vinyl-substituted 8 is formed. From 5, 6 or 9 the exocyclic alkene 10 and/or the endocyclic alkene 11 can be observed. Compound 7 would deliver the endocyclic alkene 12. 

There are other possibilities for selective reduction in the hydrogenation of symmetrically substituted dienes. Raney-nickel afforded 1-alkenes, whereas supported Pd catalysts gave a mixture of 1- and 2-alkenes148. A selective reduction of a terminal double bond was carried out in the presence of an endocyclic double bond, which was trisubstituted149-152. 

Unfortunately, efforts were thwarted by the formation of the endocyclic alkene 134. In these cases, use of sodium naphthalide afforded the desired adducts, 135 and 137, though the yields in both of the cases portrayed in Scheme 8, were poor. 

Ideally, the Stanger demonstration should be an expression of the stretch-bend interaction in the Bj normal mode in benzene. Thus, it is instructive to examine the nature of the stretch-bend interaction in typical monocyclic and bicyclic alkenes. The IR spectra of monocyclic and bicyclic alkenes shift hypsochromically for exomethylenes and bathochromically for endocyclic alkenes with decreasing ring size. " This effect has been shown to be dominated by mode-coupling for the monocyclic series, but consistent with a pure angular effect or the bicyclic series.Further investigation in this vein is likely to resolve the paradox initiated by Stanger s work. 

The extensive delocalization and aromatic character of pyridones, pyrones, etc. are shown by their chemical shift and coupling constant values (Table 8). By contrast, pyrans and thiins show chemical shifts characteristic of alkenic systems (Table 9). For these and for rings containing only a single endocyclic bond (Table 10), H NMR spectroscopy offers a most useful tool for structure determination. 

This result has been explained72 390 by the particular instability of the alkene complex resulting from exocyclic addition (14) relative to endocyclic addition (15) in the cyclohexyl system. This rationale is supported by the results obtained by the use of the considerably more sterically bulky tri-o-tolylphos-phine instead of triphenylphosphine. A 13 83 exocyclic endocyclic ratio is obtained with the bulky phosphine. This result is nicely explained by the ability of the bulky phosphine to magnify the instability of the endocyclic alkene-palladium complex (14) relative to the exocyclic alkene complex (15) and favor endocyclic addition. 

Cycloalkyl(silyl)carbenes with an a-C—H bond have not yet been investigated systematically. When cyclohexyl(trimethylsilyl)carbene was generated by thermal a-elimination from cyclohexyl-bis(trimethylsilyl)methanol at 500 °C, only the (1,2) hydride shift took place, whereas cyclopentyl(trimethylsilyl)carbene, generated analogously, gave both the endocyclic alkene and the 1,3-C,H insertion product85,86 (equation 47). 

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. 

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