Stereochemistry double bond additions

This process accounts for most of the observations relating to product stereochemistry, double bond isomerism, deuterium exchange and other features encountered in the hydrogenation and deuteration of olefins. 140-142,144 addition of hydrogen to the double bond proceeds in... 

Intermolecular Cycloaddition at the C=C Double Bond Addition at the C=C double bond is the main type of 1,3-cycloaddition reactions of nitrile oxides. The topic was treated in detail in Reference 157. Several reviews appeared, which are devoted to problems of regio- and stereoselectivity of cycloaddition reactions of nitrile oxides with alkenes. Two of them deal with both inter- and intramolecular reactions (158, 159). Important information on regio-and stereochemistry of intermolecular 1,3-dipolar cycloaddition of nitrile oxides to alkenes was summarized in Reference 160. 

Comments The diene A is symmetrical so it doesn t matter which double bond is attacked by the carbene. On the other hand, it may be difficult to stop carbene addition to the second double bond. The only control over the stereochemistry will be that the trans compound we want is more stable. Japanese chemists have recently synthesised optically active trans chrysanthemic acid by this route (Tetrahedron Letters. 1977, 2599). 

The term syn addition describes the stereochemistry of reactions such as this m which two atoms or groups add to the same face of a double bond When atoms or groups add to opposite faces of the double bond the process is called anti addition... 

The stereochemistry of the most fundamental reaction types such as addition, substitution, and elimination are described by terms which specify the stereochemical relationship between the reactants and products. Addition and elimination reactions are classified as syn or anti, depending on whether the covalent bonds which are made or broken are on the same face or opposite faces of the plane of the double bond. 

Entries 1 and 2 in Scheme 2.9 are typical of concerted syn addition to alkene double bonds. On treatment with peroxyacetic acid, the Z-alkene affords the cis-oxirane, whereas the -alkene affords only the iraws-oxirane. Similarly, addition of dibromocarbene to Z-2-butene yields exclusively l,l-dibromo-cw-2,3-dimethylcyclopropane, whereas only 1,1-dibromo-/ra 5-2,3-dimethylcyclopropane is formed from -2-butene. There are also numerous stereospecific anti additions. Entiy 3 shows the anti stereochemistry typical of bromination of simple alkenes. 

A significant modification in the stereochemistry is observed when the double bond is conjugated with a group that can stabilize a carbocation intermediate. Most of the specific cases involve an aryl substituent. Examples of alkenes that give primarily syn addition are Z- and -l-phenylpropene, Z- and - -<-butylstyrene, l-phenyl-4-/-butylcyclohex-ene, and indene. The mechanism proposed for these additions features an ion pair as the key intermediate. Because of the greater stability of the carbocations in these molecules, concerted attack by halide ion is not required for complete carbon-hydrogen bond formation. If the ion pair formed by alkene protonation collapses to product faster than reorientation takes place, the result will be syn addition, since the proton and halide ion are initially on the same side of the molecule. 

Reactions of alkynes with electrophiles are generally similar to those of alkenes. Because the HOMO of alkynes (acetylenes) is also of n type, it is not surprising that there IS a good deal of similarity between alkenes and alkynes in their reactivity toward electrophilic reagents. The fundamental questions about additions to alkynes include the following. How reactive are alkynes in comparison with alkenes What is the stereochemistry of additions to alkynes And what is the regiochemistry of additions to alkynes The important role of halonium ions and mercurinium ions in addition reactions of alkenes raises the question of whether similar species can be involved with alkynes, where the ring would have to include a double bond ... 

Benzene-sensitized photolysis of methyl 3-cyclohexene-1-carboxylate in acetic acid leads to addition of acetic acid to the double bond. Only the trans adducts are formed. What factor(s) is (are) responsible for the reaction stereochemistry Which of the two possible addition products, A or B, do you expect to be the major product ... 

A number of groups have criticized the ideas of Dauben and Noyce, especially the concept of PDC. Kamernitzsky and Akhrem, " in a thorough survey of the stereochemistry of addition reactions to carbonyl groups, accepted the existence of SAC but not of PDC. They point out that the reactions involve low energies of activation (10-13 kcal/mole) and suggest that differences in stereochemistry involve differences in entropies of activation. The effect favoring the equatorial alcohols is attributed to an electrostatic or polar factor (see also ref. 189) which may be determined by a difference in the electrostatic fields on the upper and lower sides of the carbonyl double bond, connected, for example, with the uncompensated dipole moments of the C—H bonds. The way this polar effect is supposed to influence the attack of the hydride is not made clear. 

Although the emphasis in this chapter has been on tbe synthesis and mechanism of formation of simple enamines, brief mention will be made of the addition of amines to activated acetylenes to indicate the interest and activity in this area of substituted enamines. Since such additions tend to be stereospecific, inclusion in this section seems apropos. The addition of amines to acetylenes has been much studied 130), but the assigning of the stereochemistry about the newly formed double bond could not be done unequivocally until the techniques of NMR spectroscopy were well developed. In the research efforts described below, NMR spectroscopy was used to determine isomer content and to follow the progress of some of the reactions. 

One useful feature of this reducing system is its apparent ability to allow deuteration of double bonds without scrambling. Although the precise stereochemistry of the addition remains to be established, the incorporation of only two deuterium atoms per double bond has been clearly demonstrated (7). 

The stereoisomers of olefin saturation are often those derived by cis addition of hydrogen to the least hindered side of the molecule (99). But there are many exceptions and complications (97), among which is the difficulty of determining which side of the molecule is the least hindered. Double-bond isomerization frequently occurs, and the hydrogenation product is the resultant of a number of competing reactions. Experimentally, stereochemistry has been found to vary, sometimes to a marked degree, with olefin purity, reaction parameters, solvent, and catalyst 30,100). Generalizing, it is expedient, when unwanted products arise as a result of prior isomerization, to avoid those catalysts and conditions that are known to favor isomerization. 

When the halogenation reaction is carried out on a cycloalkene, such as cyclopentene, only the trews stereoisomer of the dihalide addition product is formed rather than the mixture of cis and trans isomers that might have been expected if a planar carbocation intermediate were involved. We say that the reaction occurs with anti stereochemistry, meaning that the two bromine atoms come from opposite faces of the double bond—one from the top face and one from the bottom face. 

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

Unlike polyethylene and other simple aikene polymers, natural rubber is a polymer of a diene, isoprene (2-methyl-l,3-butadiene). The polymerization takes place by addition of isoprene monomer units to the growing chain, leading to formation of a polymer that still contains double bonds spaced regularly at four-carbon intervals. As the following structure shows, these double bonds have Z stereochemistry ... 

HC1, HBr, and HI add to alkenes by a two-step electrophilic addition mechanism. Initial reaction of the nucleophilic double bond with H+ gives a carbo-cation intermediate, which then reacts with halide ion. Bromine and chlorine add to alkenes via three-membered-ring bromonium ion or chloronium ion intermediates to give addition products having anti stereochemistry. If water is present during the halogen addition reaction, a halohydrin is formed. 

The fourth and final cyclization occurs by addition of the C13 cation to the 17,20 double bond, giving the protosteryl cation with 17jB stereochemistry. 

Subsequent dehydration of /3-hydroxybutyryl ACP by an ElcB reaction in step 7 yields trans-ciotonyl ACP, and the carbon-carbon double bond of crotonyl ACP is reduced by NADPH in step 8 to yield butyryl ACP. The doublebond reduction occurs by conjugate addition of a hydride ion from NADPH to the /S carbon of fraus-crotonyl ACP. In vertebrates, the reduction occurs by an overall syn addition, but other organisms carry out similar chemistry with different stereochemistry. 

Anti stereochemistry (Section 7.2) The opposite of syn. An anti addition reaction is one in which the two ends of the double bond are attacked from different sides. An anti elimination reaction is one in which the two groups leave from opposite sides of the molecule. 

When enantiomerically pure allyl p-tolyl sulfoxide is deprotonated and then treated with electrophilic 2-cyclopentenone, a conjugate addition occurs forming a new carbon-carbon bond with very high control of absolute stereochemistry (equation 25)65. See also Reference 48. Similarly, using more substituted enantiomerically pure allylic sulfoxides leads to virtually complete diastereocontrol, as exemplified by equations 26 and 27 the double bond geometry in the initial allylic sulfoxide governs the stereochemistry at the newly allylic carbon atom (compare equations 26 vs. 27)66. Haynes and associates67 rationalize this stereochemical result in terms of frontier molecular orbital considerations... 

In investigating the mechanism of addition to a double bond, perhaps the most useful type of information is the stereochemistry of the reaction. The two carbons of the double bond and the four atoms immediately attached to them are all in a plane (p. 8) there are thus three possibilities. Both Y and W may enter from the same side of the plane, in which case the addition is stereospecific and syn they may enter from opposite sides for stereospecific anti addition or the reaction may be nonstereospecific. In order to determine which of these possibilities is occurring in a given reaction, the following type of experiment is often done YW is added to the cis and trans isomers of an alkene of the form ABC=CBA. We may use the cis alkene as an example. If the addition is syn, the product will be the erythro dl pair, because each carbon has a 50% chance of being attacked by Y ... 

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. 

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