1,3,5-hexatriene derivatives

Knoke and de Meijere [60] recently developed a highly flexible domino Heck-Diels-Alder reaction of a symmetrically substituted cumulene 125, which also involves cross-couplings of an allene at the central position. Both aryl and hetaryl halides react efficiently with l,3-dicyclopropyl-l,2-propadiene (125) and furnish 1,3,5-hexatriene derivatives 126 as intermediates, which are usually trapped by acceptor-substituted olefins in a subsequent cycloaddition, providing adducts 127a/b in moderate to good overall yields (Scheme 14.30). 

The scope of the synthetic procedure to substituted 1,3-butadienes 16 was later broadened by the same group, with the report of 18 examples of the 1 1 1 coupling of iodoarenes, diarylacetylenes, and monosubstituted alkenes. The mixture Pd(OAc)j, LiQ, and NaHCOj led to the desired products in moderate yields, although minor amounts of the Mizoroki-Heck-type product (ArCH=CHR) were also formed [30]. For the synthesis of 1,3,5-hexatriene derivatives 17, a modification of the former procedure consisting of using silver acetate as a base leads to the 1 2 1 coupling of iodoarenes. 

H. Horiguchi, K. Hirano, T. Satoh, M. Miura, Adv. Synth. Catal. 2009, 351, 1431-1436. Palladium-catalyzed three-component 1 2 1 coupling of aryl iodides, alkynes, and aUcenes to produce 1,3,5-hexatriene derivatives. 

Shibata et al. demonstrated an intermolecular three-component coupling of aryl or vinylhalides, diarylacetylenes, andmonosubstitutedalkenes, leading to the corresponding 1,3-butadiene or 1,3,5-hexatriene derivatives in the presence of palladium species [40] (Scheme 6.23). 

The higher homologue of 3-sulfolene, 2,7-dihydrothiepin-l,1-dioxide could be similarly metallated at low temperatures. Reaction with reactive electrophiles followed by extrusion of sulfur dioxide led [549] to the corresponding hexatriene derivatives, as in the stereoselective synthesis of (Z,E)-l,3,5-decatriene (considered as an undecatriene in the publication) shown here. 

By using nanosecond laser flash photolysis of 51, Leigh and coworkers have studied alcohol addition reactions of the l,3,5-(l-sila)hexatriene derivative 52 (Scheme 16)80,81 and of 1,1-diphenylsilene82-84. 

Diphenylsilene (19a), produced by photolysis of 1,1-diphenyl- or 1,1,2-triphenylsilacyclobutane (17a and 18, respectively equation 11), has been particularly well studied, and absolute rate constants have been reported for a wide variety of silene trapping reactions in various solvents at room temperature (see Table 3)40-46. Not all of these have been accompanied by product studies, unfortunately. A number of other transient silenes have been characterized as well with solution-phase kinetic data for a range of bimolecular silene trapping reactions, though much less extensively than 19a. These include the cyclic l,3,5-(l-sila)hexatriene derivatives 21a-c (formed by photolysis... 

The absolute rate constants for addition of methoxytrhnethylsilane (MeOTMS) to 1,1-diphenylsilene (19a) in hexane and acetonitrile solution (Table 3), which yields alkoxysi-lane 50a as the sole product (equation 43), are roughly two orders of magnitude slower than those for addition of methanol under the same conditions57. This difference is magnified to a factor of more than 1000 in the case of the less reactive (1 -sila)hexatriene derivative 21a, where only an upper limit of A MeOTMS < 105 M-1 s-1 could be established from the pseudo-first-order rate of decay of the silene in acetonitrile containing 0.6 M MeOTMS47. 

THF can also have an accelerating effect on reactivity, in cases where the weakly basic solvent can get directly involved in the reaction via a catalytic pathway and complexation with the free silene is weak. Such an effect has been observed for the reaction of alcohols with the aryldisilane-derived l,3,5-(l-sila)hexatriene derivatives 21a-c, as shown by the second-order rate constants for reaction of the three silenes by MeOH and TFE in isooctane, MeCN and THF solution (Table 11 note that the third-order rate constants for reaction of 21a-c with MeOH have been omitted)48. Table 11 also includes data for the reactions with acetone in the same three solvents, as an example of a reaction which has no catalytic component47. The rate constants for all three reactions decrease in the order isooctane > MeCN > THF for 21a, which complexes relatively strongly with the ether solvent, as demonstrated by the distinctive red shift in its UV absorption spectrum in THF (kmax = 460 nm) compared to isooctane and MeCN (kmax = 425 nm)48. Compound 21b exhibits a ca 10 nm shift of its absorption band in THF solution while none is detectable in the case of 21c, indicating that the equilibrium constant for THF complexation within this series of silenes decreases with increasing phenyl substitution at... 

The effects of substituting a phenyl group for —H or —Me at the silicon end of the Si=C bond has different effects on the rates of silene reactions depending on the substituents present at carbon. For example, the l,3,5-(l-sila)hexatriene derivatives 21a-c exhibit a significant decrease in reactivity toward methanol and acetone with increasing phenyl substitution (Table 11). This too is consistent with the stepwise mechanisms proposed for... 

A hexatriene derivative in its ground state possesses six sr-electrons distributed in pairs between the three sr-orbitals of lowest energy, and a thermal cyclisation in such a system must proceed in the dis-rotatory sense required for overlap of terminal orbital envelopes on the same side of the molecule... 

With hexene-1 and heptene-1, the yields of vinylcyclopropane derivatives are rather low (5-10 %), the main products being the corresponding hexatriene derivatives. With the other alkenes listed above, the yields of cyclopropanation products range from 55 to 7%67). 

In the presence of CuCl, exo-3-tricyclo[3.2.1.02 4]octene-6-yl-3-hexene-2-oic acid methyl ester (72) is isolated after TLC in 60% yield (Z E = 1.5 1) 67c). This is comparable to the course of the cyclopropanation of norbornadiene with both the Simmons-Smith reagent and diazomethane-CuCl. In both cases the exo-anti route is favored over the exo-syn 63). It is important to notice, that in the above mentioned nickel(O) catalyzed reactions (Eq. 11) hexatriene derivatives have never been observed. 

The basis set orbitals for conrotatory and disrotatory transition states for cyclohexadiene-hexatriene derivatives are shown below ... 

Tropone oxime 493 cannot be efficiently obtained from the reaction between 16 and hydroxylamine, because the reaction gives mainly 2-aminotropone. However, if the reaction employs tropothione 491 as the starting material, 493 is produced in good yield. The contrast of the C - 2 attack of 16 and the C -1 attack of 491 is rationalized in terms of frontier orbital theory. The tosylate 494 derived from 493 reacts quite readily with a variety of nucleophilic reagents at low temperatures to give hexatriene derivatives 495 with (Z,Z,Z)-configuration in excellent yields (Scheme 6.130) [295]. 

Correlation diagrams can be constructed in an analogous fashion for the disrotatory and conrotatory modes for interconversion of hexatriene and cyclohexadiene. They lead to the prediction that the disrotatory mode is an allowed process whereas the conrotatory reaction is forbidden. This is in agreement with the experimental results on this reaction. Other electrocyclizations can be analyzed by the same method. Substituted derivatives of polyenes obey the orbital symmetry rules, even in cases in which the substitution pattern does not correspond in symmetiy to the orbital system. It is the symmetry of the participating orbitals, not of the molecule as a whole, that is crucial to the analysis. 

With respect to aromatic substrates, the Vilsmeier formylation reaction works well with electron-rich derivatives like phenols, aromatic amines and aromatic heterocycles like furans, pyrroles and indoles. However various alkenes are also formylated under Vilsmeier conditions. For example the substituted hexatriene 6 is converted to the terminal hexatrienyl aldehyde 7 in 70% yield ... 

Scheme 11 Formation of the cyclopentenyl zwitterion derivative 55 from a l-tungsta-2-diethylamino-l,3,5-hexatriene 54 [58,59]...

The electron delocalizations in the linear and cross-conjugated hexatrienes serve as good models to show cyclic orbital interaction in non-cyclic conjugation (Schemes 2 and 3), to derive the orbital phase continuity conditions (Scheme 4), and to understand the relative stabilities (Scheme 5) [15]. 

Consider now the 1,1,6,6-tetramethylated derivative of (Z)-l,3,5-hexatriene (83), a species more properly named (Z)-2,6-dimethyl-2,4,6-octatriene and occasionally and trivially called ds-allo-ocimene . To estimate its enthalpy of formation, let us use simple olefin additivity along with ... 

To prepare the other cross-conjugated allene, 4-methylene-l,2,5-hexatriene ( 2-allenyl-1,3-butadiene ) (23), the allene alcohol 215 was first converted into the phosphate 216, that readily underwent an SN2 -type substitution with allenylmagnesium bromide to yield the target hydrocarbon as a highly reactive allene derivative (Scheme 5.32) [76],... 

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