Stereochemistry anti additions

Regioseiectivity Markovnikov s ruie is foiiowed. X bonds to the iess substituted carbon. Stereochemistry Anti addition occurs. 

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... 

A dihaloalkene is an intermediate and is the isolated product when the alkyne and the halogen are present m equimolar amounts The stereochemistry of addition is anti... 

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. 

If the addition of Br to the alkene results in a bromonium ion, the anti stereochemistry can be readily eiqilained. Nucleophilic ring opening by bromide ion would occur by backside attack at carbon, with rupture of one of the C—Br bonds, giving overall anti addition. 

The stereochemistry of chlorination can be explained in similar terms. Chlorine would be expected to be a somewhat poorer bridging group than bromine because it is less polarizable and more resistant to becoming positively charged. Comparison of the data for bromination and chlorination of E- and Z-l-phenylpropene confirms this trend (see Table 6.2). Although anti addition is dominant in bromination, syn addition is slightly preferred... 

For alkyl-substituted alkynes, there is a difference in stereochemistry between mono-and disubstituted derivatives. The former give syn addition whereas the latter react by anti addition. The disubstituted (internal) compounds are considerably ( 100 times) more reactive than the monosubstituted (terminal) ones. This result suggests that the transition state of the rate-determining step is stabilized by both of the alkyl substituents and points to a bridged intermediate. This would be consistent with the overall stereochemistry of the reaction for internal alkynes. 

The stereochemistry of addition is usually anti for alkyl-substituted alkynes, whereas die addition to aryl-substituted compounds is not stereospecific. This suggests a termo-iecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation mtermediate in the aryl case. Aryl-substituted alkynes can be shifted toward anti addition by including bromide salts in the reaction medium. Under these conditions, a species preceding the vinyl cation must be intercepted by bromide ion. This species can be presented as a complex of molecular bromine with the alkyne. An overall mechanistic summary is shown in the following scheme. 

The stereochemistry of radical addition of hydrogen bromide to alkenes has been studied with both acyclic and cyclic alkenes. Anti addition is favored.This is contrary to what would be expected if the s[p- carbon of the radical were rapidly rotating or inverting with respect to the remainder of the molecule ... 

The preferred stereochemistry of addition to cyclic alkenes is anti The additions are not as highly stereoselective as hydrogen bromide addition, however. 

An explanation for the observed anti stereochemistry of addition was suggested in 1937 by George Kimball and Irving Roberts, who proposed that the... 

How does the formation of a bromonium ion account for the observed anti stereochemistry of addition to cyclopentene If a bromonium ion is formed as an intermediate, we can imagine that the large bromine atom might "shield" one side of the molecule. Reaction with Br ion in the second step could then occur only from the opposite, unshielded side to give trans product. 

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. 

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 ... 

The stereochemistry of HX addition is varied. Examples are known of predominant syn, anti, and nonstereoselective addition. It was found that treatment of 1,2-dimethylcyclohexene (4) with HBr gave predominant anti addition, ° while addition of water to 4 gave equal amounts of the cis and trans alcohols ... 

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. 

Each reaction will be different. Some will give only syn addition, some will give only anti addition, and others will not be stereospecific. For every addition reaction, we need to know the stereochemistry of the addition, and that information is contained within the mechanism. 

In cases like this, the stereochemistry is still irrelevant (as long as the compound does not possess any other stereocenters). Why With only one stereocenter, there will only be two possible products (not four). These two products will represent a pair of enantiomers (one will be R and the other will be S). You will get both of these products whether the reaction proceeds through a syn addition or through an anti addition. If the reaction is a syn addition, the OH group can come from above the plane or from below the plane of the double bond, giving both possible products. Similarly, if the reaction is an anti addition, the OH group can come from above the plane or from below the plane of the donble bond, giving both possible products. Either way, we get the two possible products. 

A quick glance at the products indicates that we are adding H and OH across the alkene. Let s take a closer look and carefully analyze the regiochemistry and stereochemistry of this reaction. The OH is ending up on the less substituted carbon, and therefore, the regiochemistry represents an anti-Markovnikov addition. But what about the stereochemistry Are we seeing a syn addition here, or is this anti addition ... 

Answer (a) We are adding Br and Br, so the regiochemistry is irrelevant. But what about the stereochemistry We look to see whether we are creating two new stereocenters. In this case, we are. So, the stereochemistry is relevant. We have explored the mechanism and justified why the reaction must be an anti addition. So, we must draw the pair of enantiomers that we would get from an anti addition. To do this properly, it will be helpful to redraw the alkene, as we have done many times before ... 

Answer (a) We are adding OH and OH, and therefore, regiochemistry will be irrelevant. What abont stereochemistry In this case, we are creating two new stereocenters, so we mnst carefully consider the stereochemistry of this reaction in order to draw the correct pair of enantiomers. This two-step synthesis gives an anti addition of OH and OH. Therefore,... 

The stereochemistry of addition of hydrogen halides to alkenes depends on the structure of the alkene and also on the reaction conditions. Addition of hydrogen bromide to cyclohexene and to E- and Z-2-butene is anti.6 The addition of hydrogen chloride to 1 -methylcyclopentene is entirely anti when carried out at 25° C in nitromethane.7... 

Dimethylcyclohexene is an example of an alkene for which the stereochemistry of hydrogen chloride addition is dependent on the solvent and temperature. At —78° C in dichloromethane, 88% of the product is the result of syn addition, whereas at 0° C in ether, 95% of the product results from anti addition.8 Syn addition is particularly common with alkenes having an aryl substituent. Table 4.1 lists several alkenes for which the stereochemistry of addition of hydrogen chloride or hydrogen bromide has been studied. 

The stereochemistry of addition depends on the details of the mechanism. The addition can proceed through an ion pair intermediate formed by an initial protonation step. Most alkenes, however, react via a complex that involves the alkene, hydrogen halide, and a third species that delivers the nucleophilic halide. This termolecular mechanism is generally pictured as a nucleophilic attack on an alkene-hydrogen halide complex. This mechanism bypasses a discrete carbocation and exhibits a preference for anti addition. 

The stereochemistry of oxymercuration has been examined in a number of systems. Conformationally biased cyclic alkenes such as 4-r-butylcyclohexene and 4-f-butyl-l-methycyclohexene give exclusively the product of anti addition, which is consistent with a mercurinium ion intermediate.17,22... 

Mechanistically, the nucleophilic addition can occur either by internal ligand transfer or by external attack. Generally, softer more stable nucleophiles (e.g., malonate enolates) are believed to react by the external mechanism and give anti addition, whereas harder nucleophiles (e.g., hydroxide) are delivered by internal ligand transfer with syn stereochemistry.120... 

With internal alkynes, the stereochemistry of addition is anti. 

The bromination of /razw-stilbenes in methanol, trifluoroethanol and in acetic acid leads almost exclusively to the erythro adducts via a 100% anti addition, regardless the substituents and the solvent. In contrast, the stereochemistry of the reaction of c/s-stilbenes exhibits a considerable dependence on the substituents and on the solvents the reaction of p-methoxystilbenes is always stereo-convergent, that of p,p -bis(trifluoromethyl)stilbenes is stereo-specific in all investigated solvents, whereas unsubstituted stilbenes can produce variable stereochemical outcomes ranging from stereo-specific to stereo-convergent in going from methanol to trifluoroethanol as solvent. 

Mercuration usually occurs without rearrangement of the carbon skeleton and gives products arising from an almost complete Markonikov addition, with only a few exceptions. The product stereochemistry depends widely upon the structure of the alkene generally anti addition is obtained although mercuration of strained alkenes can occur by syn addition. 

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