Cis-Addition to double bonds

The stereochemistry of cathodic hydrogenation is thus far not predictable or explainable. There is a preponderance for trans addition in the reduction of al-kynes, while cis addition occurs predominantly with cis- and trans-stilbene and maleic acid derivatives. On the other hand, dimethylmaleic acid and dimethyl-fumaric acid are exclusively hydrogenated to the trans products, meso- and dl-di-methylsuccinic acid 302 With a silver-palladium cathode in 5% aquous sulfuric acid triple bonds are reduced in a specific cis addition to double bonds 303 ... 

Photolytically generated carbene, as mentioned above, undergoes a variety of undiscriminated addition and insertion reactions and is therefore of limited synthetic utility. The discovery (3) of the generation of carbenes by the zinc-copper couple, however, makes carbene addition to double bonds synthetically useful. The iodo-methylzinc iodide complex is believed to function by electrophilic addition to the double bond in a three-center transition state giving essentially cis addition. Use of the... 

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

Butene-2. The experimental results for the reaction of methylene with cis and trans butene-2 are summarized in Table III. In the liquid phase and in the gas phase at high pressures (>200 mm.) the major products are 1,2-dimethylcyclopropane (addition to double bond), pentane-2, and 2-methylbutene-2 (insertion products), and the steric configuration of the butene-2 is predominantly retained in the products... 

Preparation of cis-trans Isomers by Physical and Chemical Methods Stereochemistry of Addition to Double Bonds... 

Addition of an A1—C bond in tri-1-alkyl alanes to the C=C triple bond of acetylene and 1-alkynes occurs as a rule under substantially milder conditions than the addition to double bonds of alkenes. Alkenyl alanes are formed from triethylalane and acetylene or 1-butyne at 40°-50°C with cis addition ... 

Although the addition of carbene to a double bond to make a cyclopropane is well known, it is not particularly useful synthetically because of the tendency for extensive side reactions and lack of selectivity for thermally or photochemically generated carbenes. Similar processes involving carbenoids (species that are not free carbenes) are much more useful from the preparative standpoint [91,92]. For example, metal catalyzed decomposition of diazoalkanes usually results in addition to double bonds without the interference of side reactions such as C-H insertions. Consider the possible retrosynthetic approaches to a 1,2-disubstituted cyclopropane shown in Figure 6.8. Disconnection a entails the addition of a methylene across a double bond, a conversion that is often stereospecific e.g., the Simmons-Smith reaction [93]). Disconnections b and c are more problematic, since the issue of cis/trans product isomers (simple diastereoselection) arises. 

Boron-hydrogen bonds undergo addition to double bonds readily. The well-known hydroboration reaction has been extensively studied and thoroughly reviewed 180). It involves a cis addition of b—H to the C=C... 

The initial reactions of NO3 and alkenes are the addition to double bonds as seen in Chap. 5, Sect. (5.5.3). As shown in Table 7.2, the reaction rate constants increase with carbon number, but for the same carbon number species those for the internal alkenes are much larger. The reaction mechanisms of the NOs-alkene reactions are similar to those with OH and alkenes and an example for cis-2-butene can be illustrated as below. 

In the case of cis-l,4-polyisoprene three different additions to double bonds are possible ... 

It is usually assumed that the epoxidation reaction proceeds initially by cis addition to the double bond. 

Tliis hydroxylation gives cis addition to the double bond (see Norman p.502-3 or Tedder vol. 1, p.61-2 if you re not sure about this). How then could you make TM 152 ... 

Woodworth, based on the common reaction of addition of carbenes to double bonds to form cyclopropane derivatives (15-50). If the singlet species adds to cis-2-butene, the resulting cyclopropane should be the cis isomer since the movements of the two pairs of... 

A variety of long-chain hydrocarbons have been found to be tolerated in this position as well as the parent hydrocarbon. In general, a minimum of one double bond located near or at the mid-point of the carbon chain is required for activity. In addition, the double bond must be cis configured (Table 6.1) [33]. 

The larger (Z,Z)-l,5-cyclononadiene (169) reacts141 stereoselectively with PhSeCl in AcOH to give the substituted hydrindan 170 (equation 138). In consideration of the anti addition mode of selenenyl reagents to double bonds, the transannular reactions of 169 have been rationalized on the basis of the two reaction intermediates, 171 or 172, which are liable to place the PhSe- and AcO- groups in a cis- 1,4-relationship and trans to the bridgehead hydrogen (equation 139). The preferential formation of 170 has thus been attributed to the fact that the pathway via 172 should involve a boat transition state. 

Gawron et al. (13,14) determined the stereochemistry of natural isocitric acid by chemical means. The results require the rrons-addition of water across the cis-aconitate intermediate double bond to produce either citrate or 2R,3S-isodtrate. Mass and NMR analyses of isotopically labeled citrate and isocitrate in the early 1960 s (15-17), defined the stercospedficities of the dehydration steps. These results led Gawron to propose the binding of cis-aconitate to the active site in two orientations differing by a 180° rotation about the double bond, as shown in Equation 2. This allows for the protonation by a base (-BH) and hydroxylation of the double bond to occur on aconitase at single, separate loci for the formation of either citrate or isocitrate. 

Triple bonds in side chains of aromatics can be reduced to double bonds or completely saturated. The outcome of such reductions depends on the structure of the acetylene and on the method of reduction. If the triple bond is not conjugated with the benzene ring it can be handled in the same way as in aliphatic acetylenes. In addition, electrochemical reduction in a solution of lithium chloride in methylamine has been used for partial reduction to alkenes trans isomers, where applicable) in 40-51% yields (with 2,5-dihydroaromatic alkenes as by-products) [379]. Aromatic acetylenes with triple bonds conjugated with benzene rings can be hydrogenated over Raney nickel to cis olefins [356], or to alkyl aromatics over rhenium sulfide catalyst [54]. Electroreduction in methylamine containing lithium chloride gives 80% yields of alkyl aromatics [379]. 

It is of interest to note that the addition of nitrosyl chloride to a molecule such as cis,trans, trans-1,5,9-cyclododecatriene takes place only at one of the trans bonds [72], It would appear from this that, in a competitive reaction between cis and trans double bonds, the reaction at the trans bond is favored. However, further work is required to substantiate this generalization, particularly in view of the fact that in an experiment involving both cis- and trans-stilbene the nature of the nitrosyl chloride adduct was not fully determined [55]. 

The two nonbonded electrons of a carbene can be either paired or unpaired. If they are paired, the species is spectrally a singlet, while, as we have seen (p. 193), two unpaired electrons appear as a triplet. An ingenious method of distinguishing between the two possibilities was developed by Skell,202 based on the common reaction of addition of carbenes to double bonds to form cyclopropane derivatives (5-50), If the singlet species adds to cis-2-butene, the resulting cyclopropane should be the cis isomer since the movements of... 

Additional statistical weight matrices are required to describe interactions which occur near the cis carbon-carbon double bond in oleic acid. If the rth bond in branch j is a cis carbon-carbon double bond, interactions can be taken into account using the following matrices ... 

Fatty acid chains may contain no double bonds—that is, be satu rated, or contain one or more double bonds—that is, be mono- or polyunsaturated. When double bonds are present, they are nearly always in the cis rather than in the trans configuration. (See p. 362 for a discussion of the dietary occurrence of cis and trans unsatu- rated fatty acids.) The introduction of a cis double bond causes the I tfatty acid to bend or "kink" at that position (Figure 16.3). If the fatly acid has two or more double bonds, they are always spaced at three carbon intervals. [Note In general, addition of double bonds decreases the melting temperature (Tm) of a fatty acid, whereas j increasing the chain length increases the Tm. Because membrane lipids typically contain LCFA, the presence of double bonds in some fatty acids helps maintain the fluid nature of those lipids.]... 

Hafner, Kaiser, and Puttner have observed that the addition of carbomethoxynitrene to cis- and /ra/ts-butene-2 at —30° yielding an aziridine proceeds in a stereospecific manner.327 They concluded that the nitrene reacts preferentially in the singlet state. Indeed, it is generally assumed that singlet nitrenes (118) add to double bonds by a one-step, concerted mecha-... 

As the name anaerobic implies, the double bond of the fatty acid is inserted in the absence of oxygen. Biosynthesis of monounsaturated fatty acids follows the pathway described previously for saturated fatty acids until the intermediate /3-hydroxydecanoyl-ACP is reached (fig. 18.15). At this point, a new enzyme, /3-hydroxydecanoyl-ACP dehydrase, becomes involved. This dehydrase can form the a-j8 trans double bond, and saturated fatty acid synthesis can occur as previously discussed. In addition, this dehydrase is capable of isomerization of the double bond to a cis /3-y double bond as shown in figure 18.15. The /3-y unsaturated fatty acyl-ACP is subsequently elongated by the normal enzymes of fatty acid synthesis to yield pal-mitoleoyl-ACP (16 1A9). The conversion of this compound to the major unsaturated fatty acid of E. coli, cA-vacccnic acid (18 1A11), requires a condensing enzyme that we have not previously discussed, /3-ketoacyl-ACP synthase II, which shows a preference for palmitoleoyl-ACP as a substrate. The subsequent conversion to vaccenyl-ACP is cata-... 

It must be noted that the approach of the monomer to the reactive metal-carbon bond should occur from the less hindered side. The greater stability of the trans complex should arise because the substituted carbon atom of the last unit is involved in the formation of the four-membered ring, so that reaction is hindered. The structure of copolymers of deuteropropylene from cis- and trans-(U,)-propylene proved that, even in syndiotactic polymerization, cis-addition to the double bond occurs, because with 1,2-disubstituted monomers, structures of ery-thro and threo di-syndiotactic polymers degenerate (see Fig. 4). 

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