Stereoisomers reactions

Syntheses follow a kind of bio-mimetic approach [283, 284] in building up the chain during a sequence of Wittig-type reactions or Horner-Wadsworth-Emmons olefination, adding two carbons to the chain at a time with either methyl- or ethyl-branches. As the final products need to be highly pure (E)-stereoisomers, reaction steps and purification need to be carefully controlled. 

An extensive use of (TMS)3SiH can be found in the key steps of alkaloid syntheses. The synthesis of derivative 55, as the key intermediate for the preparation of alkaloid (ih)-pancracine [67], has been obtained from the reaction of 54 under normal conditions, in an 84 % yield as a single stereoisomer (Reaction 7.56). 

Related a,p-Unsaturated Esters. Similar a,p-unsaturated esters bearing a heterocyclic chiral auxiliary of a-amino acid origin at the p-position are known and have been utilized in asymmetric synthesis. Effective asymmetric conjugate additions of cuprates to (2), (3), and (5)J epoxidations of (3), and dipolar cycloadditions of (2) have been reported. Although oxazoli-dine (4) is only obtained as an 86 14 equilibrating mixture of stereoisomers, reactions with the lithium (Z)-enolate of methyl N-benzylideneglycinate (see Ethyl N-Benzylideneglycinate) are exclusively diastereoselective. 

Compounds such as PhCHBr-CHBrPh have two asymmetric centres, each of which can have the R or the S configuration. There will be three stereoisomers (reactions 3.18 and 3.19), which can be designated S,S (14), R,R (15), and R,S (12) (S,R will be the same as R,S because of the symmetry of the molecule). The R,R and S,S forms will be optically active and rotate polarized light in opposite directions by an equal amount. Synthesis will normally give a 50/50 mixture of the two isomers, the racemic or ( + ) mixture. The R,S or nteso isomer will be optically inactive since it is identical with its mirror image (the mirror plane in 12 can be seen in the eclipsed conformation obtained by rotation of the front of the molecule clockwise by 60° round the central C-C bond). 

Scheme XL, Synthesis of dl-perhydrogephyrotoxin 207). The last step of reaction B yields a 1 1 mixture of stereoisomers. Reaction C yields a 3 2 mixture of stereoisomers. A i) 110°. B i) Formylmethylenetriphenylphosphorane, ii) Pyridinium toluenesulphonate, CH3OH, iii) Pd/C, H2, iv) 2-Methoxy-2-methylbutenal, v) NaBHt. C i) 80°. D i) C6H5CH2Br, ii) NaOH. E i) NaBH4, ii) CH3C(OC2H5)3, F i) C2H5SH, BF3, (C2H5)20, ii) Tosyl chloride, pyridine, iii) Lithiodibutylcuprate, iv) CICO2CH2CCI3. G i) O3, ii) NaBHt, hi) LiOH, iv) NaH, v) CH2N2. H i) a. LiN(i-Pr)2,...

Here we will illustrate the method using a single example. The aldol reaction between an enol boronate and an aldehyde can lead to four possible stereoisomers (Figure 11.32). Many of these reactions proceed with a high degree of diastereoselectivity (i.e. syn anti) and/or enantioselectivity (syn-l syn-Tl and anti-l anti-lT). Bernardi, Capelli, Gennari,... 

The Julia-Lythgoc olefination operates by addition of alkyl sulfone anions to carbonyl compounds and subsequent reductive deoxysulfonation (P. Kocienski, 1985). In comparison with the Wittig reaction, it has several advantages sulfones are often more readily available than phosphorus ylides, and it was often successful when the Wittig olefination failed. The elimination step yields exclusively or predominantly the more stable trans olefin stereoisomer. 

Asymmetric cyclization using chiral ligands has been studied. After early attempts[142-144], satisfactory optical yields have been obtained. The hexahy-dropyrrolo[2,3-6]indole 176 has been constructed by the intramolecular Heck reaction and hydroaryiation[145]. The asymmetric cyclization of the enamide 174 using (S j-BINAP affords predominantly (98 2) the ( )-enoxysilane stereoisomer of the oxindole product, hydrolysis of which provides the ( l-oxindole aldehyde 175 in 84% yield and 95% ec. and total synthesis of (-)-physostig-mine (176) has been achieved[146]. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

When a bidentate phosphine is used as a ligand for the reaction of J-keto esters or /i-diketones, no dimerization takes place. Only a 2-butenyl group is introduced to give 68[49,62], Substituted dienes such as isoprene, 1,3-cyclohexa-diene, and ocimene react with carbon nucleophiles to give a mixture of possible regio- and stereoisomers of 1 1 adducts when dppp is used as a ligand[63,64]. 

You have seen that measurements of heats of reaction such as heats of combustion can pro vide quantitative information concerning the relative stability of constitutional isomers (Section 2 18) and stereoisomers (Section 3 11) The box in Section 2 18 described how heats of reaction can be manipulated arithmetically to generate heats of formation (AH ) for many molecules The following material shows how two different sources of thermo chemical information heats of formation and bond dissociation energies (see Table 4 3) can reveal whether a particular reaction is exothermic or en dothermic and by how much... 

In addition to being regioselective alcohol dehydrations are stereoselective A stereo selective reaction is one m which a single starting material can yield two or more stereoisomeric products but gives one of them m greater amounts than any other Alcohol dehydrations tend to produce the more stable stereoisomer of an alkene Dehydration of 3 pentanol for example yields a mixture of trans 2 pentene and cis 2 pentene m which the more stable trans stereoisomer predominates... 

Although both stereoisomers yield 4 tert butylcyclohexene as the only alkene they do so at quite different rates The cis isomer reacts over 500 times faster than the trans The difference in reaction rate results from different degrees of rr bond develop ment in the E2 transition state Since rr overlap of p orbitals requires their axes to be parallel rr bond formation is best achieved when the four atoms of the H—C—C—X unit he in the same plane at the transition state The two conformations that permit this are termed syn coplanar and anti coplanar... 

Reactions such as catalytic hydrogenation that take place at the less hindered side of a reactant are common m organic chemistry and are examples of steric effects on reactivity Previously we saw steric effects on structure and stability m the case of CIS and trans stereoisomers and m the preference for equatorial substituents on cyclo hexane rings... 

Step 2 of the mechanism m Figure 6 12 is a nucleophilic attack by Br at one of the carbons of the cyclic bromonium ion For reasons that will be explained m Chapter 8 reactions of this type normally take place via a transition state m which the nude ophile approaches carbon from the side opposite the bond that is to be broken Recall mg that the vicinal dibromide formed from cyclopentene is exclusively the trans stereoisomer we see that attack by Br from the side opposite the C—Br bond of the bromonium ion intermediate can give only trans 1 2 dibromocyclopentane m accordance with the experimental observations... 

Two factors combine to determine which stereoisomers are actually formed m the reaction... 

A common misconception is that a stereospecific reaction is simply one that is 100% stereoselective The two terms are not synonymous however A stereospecific reac tion IS one which when carried out with stereoisomeric starting materials gives a prod uct from one reactant that is a stereoisomer of the product from the other A stereo selective reaction is one m which a single starting material gives a predominance of a... 

Wnte the organic products of each of the following reactions If two stereoisomers are formed show both Label all chirality centers / or 5 as appropriate... 

Cyclic diols give dicarbonyl compounds The reactions are faster when the hydroxyl groups are cis than when they are trans but both stereoisomers are oxidized by periodic acid... 

The intermediate m hydrogenation formed by reaction of the unsaturated ester with the hydrogenated surface of the metal catalyst not only can proceed to the saturated fatty acid ester but also can dissociate to the original ester having a cis double bond or to its trans stereoisomer Unlike polyunsaturated vegetable oils which tend to reduce serum cholesterol levels the trans fats produced by partial hydrogenation have cholesterol raising effects similar to those of saturated fats... 

Before leaving this biosynthetic scheme notice that PGE2 has four chirality cen ters Even though arachidomc acid is achiral only the stereoisomer shown m the equa tion IS formed Moreover it is formed as a single enantiomer The stereochemistry is controlled by the interaction of the substrate with the enzymes that act on it Enzymes offer a chiral environment m which biochemical transformations occur and enzyme catalyzed reactions almost always lead to a single stereoisomer Many more examples will be seen m this chapter... 

Enantiomers (Section 7 1) Stereoisomers that are related as an object and its nonsupenmposable mirror image Enantioselective synthesis (Section 27 4) Reaction that converts an achiral or racemic starting material to a chiral product in which one enantiomer is present in excess of the other... 

Chlorine and bromine add to benzene in the absence of oxygen and presence of light to yield hexachloro- [27154-44-5] and hexabromocyclohexane [30105-41-0] CgHgBr. Technical benzene hexachloride is produced by either batch or continuous methods at 15—25°C in glass reactors. Five stereoisomers are produced in the reaction and these are separated by fractional crystallization. The gamma isomer (BHC), which composes 12—14% of the reaction product, was formerly used as an insecticide. Benzene hexachloride [608-73-17, C HgCl, is converted into hexachlorobenzene [118-74-17, C Clg, upon reaction with ferric chloride in chlorobenzene solution. 

The widespread use of cinnamic derivatives has led to the pursuit of reUable methods for thek dkect synthesis. Commercial processes have focused on condensation reactions between ben2aldehyde and a number of active methylene compounds for assembly of the requisite carbon skeleton. The presence of a disubstituted carbon—carbon double bond in the sidechain of these chemicals also gives rise to the existence of two distinct stereoisomers, the cis or (Z)- and trans or (E)- isomers ... 

Some stereospecific reactions are listed in Scheme 2.9. Examples of stereoselective reactions are presented in Scheme 2.10. As can be seen in Scheme 2.9, the starting materials in these stereospecific processes are stereoisomeric pairs, and the products are stereoisomeric with respect to each other. Each reaction proceeds to give a single stereoisomer without contamination by the alternative stereoisomer. The stereochemical relationships between reactants and products are determined by the reaction mechanism. Detailed discussion of the mechanisms of these reactions will be deferred until later chapters, but some comments can be made here to illustrate the concept of stereospecificity. 

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