Stereochemistry of the Reactions

The initial trigonal bipyramid (TBP) can be formed in two ways from the tetrahedral phosphorus atom either by nucleophilic attack of the hydroxide ion at any of the six edges of the tetrahedron, leaving the nucleophile 1 in an equatorial position (equatorial attack), or by attack at any of the four faces of the tetrahedron, which would set the nucleophile in an apical position (apical attack). Because apical bonds are longer, and therefore weaker, than equatorial bonds, apical attack is favoured since the formation energy of the initial TBP is then lower. In the same way, since apical bonds are weaker they should be more easily broken than their equatorial counterparts, hence the apical departure of the leaving group 2 is favoured. 

SCHEME 3. Formation, isomerization and decomposition of the hydroxyphosphoranes from the chiral salt 31 

TABLE 15. Stereochemistry of alkaline hydrolysis of phosphonium salts with a good leaving group 

The stereochemical outcome of the reactions in question is determined by 1) the direction of approach of the attacking nucleophile to the carbonyl plane at the stage of formation of the tetrahedral intermediate and 2) the relation of the character of dissociation of this intermediate to its conformation. 

---

This is exactly what we have done [21], For each reaction the constitution and stereochemistry of the reaction partners, the coenzymes, and regulators were stored as connection tables (as far as they were known), and the enzymes by name and EC number. 

The mechanism and the stereochemistry of the reaction was studied using borodeuteride andfor deuterium oxide (480) and a reaction pathway was suggested (Scheme 93). 

Attack by a nucleophile or the solvent can occur at either of the ion pairs. Nucleophilic attack on the intimate ion pair would be expected to occur with inversion of configuration, since the leaving group would still shield the fiont side of the caibocation. At the solvent-separated ion pair stage, the nucleophile might approach fiom either fece, particularly in the case where solvent is the nucleophile. Reactions through dissociated carbocations should occur with complete lacemization. According to this interpretation, the identity and stereochemistry of the reaction products will be determined by the extent to which reaction occurs on the un-ionized reactant, the intimate ion pair, the solvent-separated ion pair, or the dissociated caibocation. 

The order of reactivity of the hydrogen halides is HI > HBr > HCl, and reactions of simple alkenes with HCl are quite slow. The studies that have been applied to determining mechanistic details of hydrogen halide addition to alkenes have focused on the kinetics and stereochemistry of the reaction and on the effect of added nucleophiles. The kinetic studies often reveal complex rate expressions which demonstrate that more than one process contributes to the overall reaction rate. For addition of hydrogen bromide or Itydrogen... 

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. 

A complete mechanistic description of these reactions must explain not only their high degree of stereospecificity, but also why four-ir-electron systems undergo conrotatory reactions whereas six-Ji-electron systems undergo disrotatory reactions. Woodward and Hoifinann proposed that the stereochemistry of the reactions is controlled by the symmetry properties of the HOMO of the reacting system. The idea that the HOMO should control the course of the reaction is an example of frontier orbital theory, which holds that it is the electrons of highest energy, i.e., those in the HOMO, that are of prime importance. The symmetry characteristics of the occupied orbitals of 1,3-butadiene are shown in Fig. 11.1. 

One interesting phenomenon was the effect of the boron substituent on enantioselectivity. The stereochemistry of the reaction of a-substituted a,/ -unsatu-rated aldehydes was completely independent of the steric features of the boron substituents, probably because of a preference for the s-trans conformation in the transition state in all cases. On the other hand, the stereochemistry of the reaction of cyclopentadiene with a-unsubstituted a,/ -unsaturated aldehydes was dramatically reversed on altering the structure of the boron substituents, because the stable conformation changed from s-cis to s-trans, resulting in production of the opposite enantiomer. It should be noted that selective cycloadditions of a-unsubsti-tuted a,/ -unsaturated aldehydes are rarer than those of a-substituted a,/ -unsatu-... 

Show the product of the Diels-Alder reaction of the following diene with 3-buten-2-one, H2C=CHCOCH3. Make sure you show the full stereochemistry of the reaction product. 

Treatment of cyclic vinylaziridine 105 with organocuprates of the R2CuLi type proceeds in a highly syn-selective manner (Scheme 2.29) [46], The syn stereochemistry of the reaction reflects the effect of the acetonide group, which directs the nucleophilic attack to the less hindered a-face. The formation of SN2 products 109 from the cyclic (chlorovinyl)aziridine 107 can be explained by assuming a syn-SN2 ... 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

Stereochemistry of the reactions of optically active organometallic transition metal compounds. H. Brunner, Top. Curr, Chem., 1975,56, 68-90 (74). 

The more reactive furan (139a) undergoes thermal Diels-Alder reaction [52] with reactive dienophiles such as maleic anhydride and maleimide (Scheme 5.21). Whereas the cycloaddition with the maleic anhydride afforded the exoadduct at room temperature, the stereochemistry of the reaction of maleimide depends on the reaction temperature. 

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 ... 

Diels-Alder reaction is one of the most fundamental reactions for organic synthesis. Its synthetic utility is unquestioned. The stereochemistry of the reactions has attracted much attention. The retention of stereochemistry in the diene and the dienophile, the predominant formation of endo-attack products in the reactions of cyclic dienes, and highly controlled regioselectivity in the reactions of substimted dienes and... 

Compound (22) was used to synthesise some central nervous system stimulants, the others mostly in i nvestiga Lions of the stereochemistry of the reaction. Vihat generalisation can you make on the stereochemistry of the organo-copper additions ... 

We know which two groups are adding to the double bond, and we know the regiochemistry of the addition. But in order to draw the products correctly, we also need to know the stereochemistry of the reaction. To better explain this, we will redraw the alkene in a different way. 

EXERCISE 11.16 Given the following information, determine if the stereochemistry of the reaction is relevant, and draw the expected prodnets ... 

Answer If we compare the starting material and product, we see that we must add H and OH. We look at the regiochemistry, and we see that OH is ending up at the more substituted carbon—so we need a Markovnikov addition. Then, we look at the stereochemistry and we see that we are not creating two stereocenters in this reaction (in fact, we are not even creating one stereocenter). Therefore, the stereochemistry of the reaction will be irrelevant. So we need to choose reagents that will give a Markovnikov addition of H and OH. We can accomplish this with an acid-catalyzed hydration ... 

The conversion of long-chain alkanoate CoA esters into the alkenoate CoA esters by acyl-CoA oxidase involves an anti elimination reaction. The stereochemistry of the reaction in Candida lipolytica was established using stearoyl-CoA-labeled with H at the 2 R)-, 3(R)-, and 3(5)-positions (Kawaguchi et al. 1980). 

The improvements in MNi so far achieved were mostly due to our efforts to eliminate the N site from MNi by changing preparation variables of the catalyst, while the other important factor i has not been satisfactorily considered. In the present study, hydrogenation of various prochiral ketones with TA-MNi almost freed from the N site were carried out in order to gain insight into the mode of stereo control on MNi, which was expected to determine the stereochemistry of the reaction and to take part in the origin of the factor i. 

Reaction with the hindered secondary alcohol menthol stops at the dialkyl sulfite ester. The examples reported do not establish the stereochemistry of the reaction. 

Give the structure, including stereochemistry, of the expected products of the following reactions. Identify the critical factors that determine the regio- and stereochemistry of the reaction. 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

Mechanistic studies have been designed to determine if the concerted cyclic TS provides a good representation of the reaction. A systematic study of all the E- and Z-decene isomers with maleic anhydride showed that the stereochemistry of the reaction could be accounted for by a concerted cyclic mechanism.19 The reaction is only moderately sensitive to electronic effects or solvent polarity. The p value for reaction of diethyl oxomalonate with a series of 1-arylcyclopentenes is —1.2, which would indicate that there is little charge development in the TS.20 The reaction shows a primary kinetic isotope effect indicative of C—H bond breaking in the rate-determining step.21 There is good agreement between measured isotope effects and those calculated on the basis of TS structure.22 These observations are consistent with a concerted process. 

The hydroxy group in Zi-cycloocten-3-ol determines the stereochemistry of the reaction with the Simmons-Smith reagent. By examining a model, predict the stereochemistry of the product. 

The stereochemistry of the reaction depends on the Lewis acid. Protic acids favor retention of configuration, as does TMSOTf. Most metal halides give mixtures of inversion and retention, but A1(CH3)3 gives dominant inversion.142 Inversion is suggestive of direct carbonyl group participation. 

The stereochemistries of the reactions between 0-aryl 0-methyl phosphonochloridothioates and nucleophiles have been studied in relation to the synthesis of 1,3,2-oxazaphospholidines. No displacement of chlorine takes place on treatment of O-methyl 0-4-nitrophenyl phosphonochloridothioate with 2-methoxyethanol, and in the presence of 1-phenylethylamine, it is only the latter which reacts. In addition, when the same phosphonochloridothioate is treated with sodium ethoxide, it is the 4-nitrophenoxy group, rather than chlorine, which is displaced. Both displacements were shown to occur with inversion of configuration at phosphorus. The use of such an acid chloride as a two-step 1cyclophosphorylating1 agent of 2-aminoalcohols to give 1,3,2-oxazaphospholidines (209), is illustrated. ... 

---