Stereospecific trans-double bond formation

The behavior in the larger systems in which stereospecific trans-double bond formation in rings takes place from solvolysis of exo-derivatives has been used successfully for syntheses of trans-cyclooctenyl derivativescyclooctadienyl derivatives and cyclotridecenyl derivatives. ... 

Substituent effects on the rates of elimination of aryl-substituted 1,2-diphenyl-1,2-dihaloethanes are small, suggesting that double bond formation is advanced in the transition structure and that most of the charge is localized on the departing halide ion. ° The debromination of 2,3-dibromobutane with iodide ion is highly stereospecific, with the meso diastereomer giving almost exclusively trans-2-butene, and the racemic diastereomer producing mostly a s-2-butene (Figure 10.38). The results were taken as evidence for a... 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

Taking 1,2-disubstituted cyclopropane as an example, retro synthesis analysis shows that there are three possible ways to disconnect the three-membered ring—a, b, and c as shown in Figure 5-11. Route a involves the addition of methylene across a double bond, and this is often a stereospecific conversion or Simmons-Smith reaction.92 One can clearly see that route b or c will encounter the issue of cis/trans-product formation. 

In the course of mechanistic studies it was established that aniline does not react with the cyclopropenones (153 and 154) even under reflux conditions. It was therefore assumed that the formation of (158) involves initial nucleophilic attack by the aminopyridine ring nitrogen on the electrophilic cyclopropenone ring. In this way 155 is formed, which is then transformed via the reactive intermediates (156, 157, and/or 161) to the prodticts. Kascheres et al. noted that the formation of 157 is formally a stereospecific trans addition of the 2-aminopyridines to the double bond of the cyclopropenone (153). Such sterospecificity has been observed in kinetically controlled Michael additions. 

Orfanopoulos et al. studied the photochemical reaction of alkenes, aryalkenes, dienes dienones, and acyclic enones with [60]fullerene to obtain various substituted cyclobutylfullerenes [240,241,243,247], For example, the photocycloaddition of cis- and Irans-1 -(p-mcthoxyphenyl)-1 -propenc 68 to C6o gives only the trans [2 + 2] adducts (Scheme 27), thus the reaction is stereospecific for the most thermodynamically stable cycloadduct. A possible mechanism includes the formation of a common dipolar or biradical intermediate between 3C o and the arylalkene. Subsequent fast rotation of the aryl moiety around the former double bond leads exclusively to the trans-69 [2 + 2] adduct. Irradiation of this product, yielded 90% trans-68,10% cis-68 and cycloreversion products. Thus, a concerted mechanism can be excluded because the photocycloreversion is expected to give the trans-68 as the only product. These results can be explained by the formation of a common dipolar or diradical intermediate. Similarly, cycloreversion products from C6o and tetraalkoxyethylene... 

Aziridine formation can therefore never be a proof for the involvement of a nitrene. Addition of carbethoxy nitrenes to carbon-carbon double bonds is observed in solution 35,79-83) as weu as in the gas phase 84,85), in these reactions the singlet and the triplet species are involved, the former add stereospecific-ally 80,81,83) an(j the latter nonstereospecifically. The addition of singlet and triplet carbethoxynitrene 29 to cis- and trans-4-methylpentene-2 37 has been studied very carefully 80,83,86) Both adducts 38 and 39 were formed — showing that the reaction was not stereospecific. 

Stereoselectivity. Epoxidation involves an electrophilic yyn-addition of the oxygen moiety of the peroxy acid to the double bond. The concerted formation of two new C-0 bonds ensures that the reaction is stereospecific cA-alkenes furnish the corresponding cA-epoxides and trans-alkenes the corresponding trans-isomers (racemic). 

For the competitive epoxidation of cis- and fra s-2-octenes with 4a, the ratio of the formation rate of czs-2,3-epoxyoctane to that of the trans isomer is >3x10 , which is much larger than the ratios (1.3-11.5) reported for other stereospecific epoxidation systems. The epoxidation of 3-substituted cyclohexenes, such as 3-methyl-l-cyclohexene and 2-cycIohexen-l-ol, showed an unusual diastereoselectivity the corresponding epoxides were formed highly diastereoselectively with the oxirane ring trans to the substituents anti configuration) (Eq. 4.6). In addition, the more accessible but less nucleophilic double bonds in noncon-jugated dienes, such as frfl is-l,4-hexadiene, (R)-(-F)-limonene, 7-methyl-l,... 

Recently,3 the stereochemical definitions of the addition of carbenes to C-C double bonds have been summarized. The term stereoselectivity refers to the degree of selectivity for the formation of cyclopropane products having endo vs. exo or, alternatively, syn vs. anti orientation of the substituents in the carbene species relative to substituents in the alkene substrate. The term stereospecificity refers to the stereochemistry of vicinal cyclopropane substituents originating as double-bond substituents in the starting alkene, i. e. a cyclopropane-forming reaction is stereospecific if the cis/trans relationship of the double-bond substituents is retained in the cyclopropane product. Diastereofacial selectivity refers to the face of the alkene to which addition occurs relative to other substituents in the alkene substrate. Finally, enantioselectivity refers to the formation of a specific enantiomer of the cyclopropane product. 

The usual c/i-stereospecificity observed during the hydrogenation of substituted olefins may be lowered by the formation of the trans-addition product. The inversion occurs through a migration of the double bond before saturation ... 

When Pt-olefin complexes such as PtCl3(olefin) are treated with a second olefin, replacement of the coordinated olefin by the incoming olefin does not result in either double bond migration or (Z), ( ) isomerization of the displaced olefin. However, the olefin complexes when treated at low temperature with a nucleophile such as pyridine (py) or a secondary amine undergo conversion to a or-complex by a stereospecific trans-process, i.e., frans-addition and tra s-elimination. Treatment of frans-LPtCljCZ)-ethylene-l,2-reversible formation of the carbon (7-bonded complex with slow release of pure (Z)-ethylene-l,2-[Pg.383]

The formal electrophilic addition of BrF" to a double bond proceeds stereospecifically in an anti-sense as evidenced by the formation in high yields of trans-1 -bromo-2-fluorocycloalkanes from cis-cycloalkenes or of cis-1-bromo-2-fluorocyclododecane from trans-cyclododecene, respectively.5 The addition is regioselective with the observed regiochemistry being in accordance with the Markovnikov rule. For example, the bromofluorinations of a-substituted styrenes give the 1-bromo-2-fluoro-2-phenylalkanes with virtually complete regioselectivity only traces (<1%) of the regioisomeric adducts were detectable by 19F NMR spectroscopy... 

Once candidates for key intermediates are recognized, the issues of stereochemistry must be faced. These take several forms cis-trans isomerism at carbon-carbon double bonds, stereochemistry at ring junctions, and relative configuration at chiral centers. Only those pathways that promise stereospecific or stereoselective formation of the desired compound are likely to be acceptable. For example, a molecule with one possibility for cis-trans isomerism and two chiral centers allows for 1(2 ) = 4 diastereomers. Because diastereomers usually have somewhat similar physical properties, the likelihood of obtaining a single pure stereoisomer becomes very low if the stereochemistry is not controlled adequately. 

The discussion to this point has focused on the addition of bromine to double bonds bearing alkyl substituents. There are significant differences in the addition of bromine to alkenes with aryl substituents. For example, the addition of bromine to aryl-substituted alkenes is not stereospecific. Reaction of ds-j8-methylstyrene (13) with bromine in CCI4 led to the formation of 17% of erythro- (14) and 83% of f/ireo-(l,2-dibromopropyl)benzene (15, equation 9.12). Reaction of frans-jS-methylstyrene under the same conditions yielded 88% of the erythro and 12% of the threo product, When the benzene ring in the trans reactant was substituted with a 4-methoxy group (frans-anethole), the reaction became even less stereoselective, giving 63% erythro and 37% threo product. ... 

The biosynthesis of phytoene proceeds without reduction of prephytoene. The phytoene molecule therefore contains a central double bond. Phytoene synthases from different organisms either form cis- or trans-phytoene. Formation of cis-phytoene requires the stereospecific loss of the Hb in the postulated intermediate I, whereas removal of yields irans-phytoene (Fig. 95). 

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