Alkenes enantiotopic

In this example addition to the double bond of an alkene converted an achiral mol ecule to a chiral one The general term for a structural feature the alteration of which introduces a chirality center m a molecule is prochiral A chirality center is introduced when the double bond of propene reacts with a peroxy acid The double bond is a prochi ral structural unit and we speak of the top and bottom faces of the double bond as prochiral faces Because attack at one prochiral face gives the enantiomer of the com pound formed by attack at the other face we classify the relationship between the two faces as enantiotopic... 

The double bond m 2 methyl(methylene)cyclohexane is prochiral The two faces however are not enantiotopic as they were for the alkenes we discussed m Section 7 9 In those earlier examples when addition to the double bond created a new chirality cen ter attack at one face gave one enantiomer attack at the other gave the other enantiomer In the case of 2 methyl(methylene)cyclohexane which already has one chirality center attack at opposite faces of the double bond gives two products that are diastereomers of each other Prochiral faces of this type are called diastereotopic... 

There are three main criteria for design of this catalytic system. First, the additive must accelerate the cyclopropanation at a rate which is significantly greater than the background. If the additive is to be used in substoichiometric quantities, then the ratio of catalyzed to uncatalyzed rates must be greater than 50 1 for practical levels of enantio-induction. Second, the additive must create well defined complexes which provide an effective asymmetric environment to distinguish the enantiotopic faces of the alkene. The ability to easily modulate the steric and electronic nature of the additive is an obvious prerequisite. Third, the additive must not bind the adduct or the product too strongly to interfere with turnover. 

Enantiotopic (NMR), 455 Endergonic. 153 Endergonic reaction, Hammond postulate and, 197-198 Endo stereochemistry, Diels-Alder reaction and, 495 Endothermic, 154 -ene, alkene name ending, 176 Energy difference, equilibrium position and, 122... 

Asymmetric induction has also been achieved in the cyclization of aliphatic alcohol substrates where the catalyst derived from a spirocyclic ligand differentiates enantiotopic alcohols and alkenes (Equation (114)).416 The catalyst system derived from Pd(TFA)2 and (—)-sparteine has recently been reported for a similar cyclization process (Equation (115)).417 In contrast to the previous cases, molecular oxygen was used as the stoichiometric oxidant, thereby eliminating the reliance on other co-oxidants such as GuCl or/>-benzoquinone. Additional aerobic Wacker-type cyclizations have also been reported employing a Pd(n) system supported by A-heterocyclic carbene (NHC) ligands.401,418... 

Epoxides are interesting starting materials for further derivatisation. In most instances the reaction will lead to the formation of mixtures of enantiomers (that is when the alkenes are prochiral, or when the faces are enantiotopic). Four important reactions should be mentioned in this context ... 

This in accordance with the mechanism shown in Figure 14.5. In a preequilibrium two 2-propoxide anions are replaced by a tertiary-butylperoxy anion and an allyloxy anion, as follows clearly from the kinetic equation. This intermediate has a very low concentration and has not been observed directly. From here on we can only speculate on the interactions leading to a preferred attack on either of the enantiotopic faces of the alkene. 

The catalytic desymmetrization shown in Scheme 5 involves a meso-tetraene substrate optically pure unsaturated siloxane 23 is obtained in >99% ee and 76% yield [16]. The unreacted siloxy ether moiety is removed to afford optically pure 24. Mo-alkylidenes derived from both enantiotopic terminal alkenes in 22 are likely involved. Since the initial metal-alkylidene generation is rapidly reversible, the major product arises from the rapid RCM of the matched segment of the tetraene. If any of the mismatched RCM takes place, a subsequent and more facile matched RCM leads to the formation of meso-bicycle. Such a byproduct is absent from the unpurified mixture containing 23, indicating the exceptionally high degree of stereodifferentiation induced by the chiral Mo com-... 

SE.3.1.2. Desymmetrization of gem-Dwarboxylates An equivalent of asymmetric carbonyl addition can be achieved by the alkylation of gem-dicarboxylates (Scheme 8E.17). The alkylation of gem-dicarboxylates, which are easily prepared by the Lewis acid-catalyzed addition of acid anhydrides to an aldehyde, converts the problem of differentiating the two enantiotopic 7t-faces of a carbonyl group into that of asymmetric substitution of either enantiotopic C-O bond of the gem-dicarboxylate. Although asymmetric induction may be derived from enantio-discrimination in the ionization step or in the alkene coordination step, the fast and reversible nature of alkene coordination suggests that the ionization step is more likely to be the source of enantio-discrimination. 

The conclusion drawn from Section 3.4.1 for the hydroborations to be discussed here is this an addition reaction of an enantiomerically pure chiral reagent to a C=X double bond with enantiotopic faces can take place via two transition states that are diastereotopic and thus generally different from one another in energy. In agreement with this statement, there are diastereoselective additions of enantiomerically pure mono- or dialkylboranes to C=C double bonds that possess enantiotopic faces. Consequently, when one subsequently oxidizes all C— B bonds to C—OH bonds, one has realized an enantioselective hydration of the respective alkene. 

A highly diastereoselective oxetane formation was identified in the PB reaction of dihydropyridone with a m-hydroxybenzaldehyde derivative (Scheme 7.33). The chiral auxiliary, when bound to the aldehyde, offered a binding site to which the reaction partner could attach by two hydrogen bonds. In the hydrogen-bonded complex that was produced, the two enantiotopic faces of the alkene could be differentiated [52]... 

This is again a concerted reaction and again we know that by proton labelling. One of the two enantiotopic protons (Hs in the diagram) is lost from the bottom face of the allylic CH2 group while the new proton is added to the top face of the alkene. This is an anti rearrangement overall. 

The next step is simple—the epoxidation of one of the terminal double bonds—but it leads to two of the most remarkable reactions in all of biological chemistry. Squalene is not chiral, but enzymatic epoxidation of one of the enantiotopic alkenes gives a single enantiomer of the epoxide with just one stereogenic centre. 

In the first step the prochiral alkene entity coordinates to the cationic chiral rhodium centre with either one of the two enantiotopic faces (due to the asymmetry in the diphosphine ligand) which leads to the formation of two possible structures. Only one diastereoisomer of the intermediate alkene adduct is shown on Fig. 6.22 the second diastereoisomer can be easily imagined by taking the... 

Z)-l,2-disubstituted alkenes proved to be the most difficult class. In fact, they are not osmylated efficiently with the all purpose ligands 1F/2 F. Further studies, however, led to the discovery of the indolinyl ligands 11/21 that allowed cis dihydroxylation of these alkenes in up to 80% eel0. It should be kept in mind, however, that in the case of 1,1-disubstituted alkenes and of (Z)-l,2-disubstituted alkenes, a lowering of difference in steric requirement between the two vicinal substituents inevitably means a drop in the 7t-face discrimination since the two enantiotopic alkene 7t-faces lend to become quasi-homotopic . 

With chiral ligands the Heck reaction can be enantioselective. The amino-acid-derived phosphine ligand in the margin controls the Heck reaction of phenyl triflate with dihydrofuran. The ligand selects one enantiotopic face of the alkene (see Chapter 45 if you have forgotten this term) and the usual double bond migration and (5 elimination complete the reaction. 

The famous ligand BINAP controls an intramolecular Heck reaction to give decalin derivatives with good enantiomeric excess. BINAP is the optically pure phosphine built into the palladium catalyst. The presence of silver ions accelerates the reaction as well as preventing double bond isomerization in the original substrate. This time the chiral ligand selects which double bond is to take part in the reaction. The vinyl palladium species is tethered to the alkene and can reach only the same face. The faces of the alkenes are diastereotopic but the two alkenes are enantiotopic and you must know your right from your left to choose one rather than the other. 

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