Diastereoisomers from stereospecific reactions

Apparent poor stereospecificity characterizes these 1,3-dipolar cycloaddition reactions. Formation of two diastereoisomers from fnmarate might be the result of the possible two types of endo orientation of this olefin toward the ylid, and epimerization at the 3-position, due to the high acidity of the corresponding hydrogen might be responsible for the isomerization of the expected all-ds adduct to the final product.458... 

Stereospecific reactions lead to the production of a single isomer as a direct result of the mechanism of the reaction and the stereochemistry of the starting material. There is no choice. The reaction gives a different diastereoisomer of the product from each stereoisomer of the starting material... 

The starting acid contains an E-alkene that gives a tram iodonium ion. Inversion occurs in the attack of the carboxylate anion on the iodonium ion and we have shown this by bringing the nucleophile in at 180° to the leaving group with both bonds in the plane of the paper. A single diastereoisomer of the iodolactone results from this stereospecific reaction. 

In a more polar solvent, Favorskii reactions cease to be stereospecific, and presumably take place by ionisation of the chloride to give the same cation from each diastereoisomer. Whether the reaction takes place by way of the cation or with concerted loss of the chloride ion, this reaction presented a serious puzzle before its pericyclic nature was recognised. The a overlap of the p orbital on C-2 of the enolate with the p orbital at the other end of the allyl cation 6.340 or with the orbital of the C—Cl bond 6.341 looked forbiddingly unlikely—it is 3-endo-trig at C-2. It is made possible by its pericyclic nature, where the tilt of the orbitals can begin to sense the development of overlap. The torquoselectivity in the development of overlap 6.341, however improbable it looks, corresponds to inversion of configuration at the carbon atom from which the chloride departs. 

An early report of the stereospecific reaction between (/ )(-f )-tartaric or (l )(- -)-malic acid and [Co(C03)(phen)2]Cl at ambient temperature has been refuted and both A- and A-[Co (i )L (phen)2] ions (233) are formed. The distribution ratio A(J )/A(/ ) = 0.38 for the (i )-tartrate complex. Using [Co(Cl)2(phen)2]Cl at 60 °C and Na(- -)-tartrate the ratio is 0.70, but thermodynamic distributions remain unknown. A(Ji) and A(i ) diastereoisomers of both acids have recently been isolated and characterized by CD and 360 MHz H NMR. The reaction of meso-tartaric acid results in four diastereoisomeric possibilities (depending on which asymmetric carbon is in the chelate ring) and all four have been separated (J S)R. M S)R A K)S A R)S = 26 24 27 23). From these results it appears likely that the reported stereospecific reaction of [Co(C03)(en)2]Cl with (5)(—)-tartaric acid resulting in only A-[Co (S)tart (en)2]CP is in error. The reaction of sodium citrate with [Co(Cl)2(trien)]Q also leads to a preference for the five-membered chelate involving the hydroxyl group (234) as has recently been shown by a crystal structure of )3-[Co(cit)(trien)] 5H20. ... 

When ethylenediamihe molecules in [Co(en)3p are replaced by an optically active diamine such as R(—)-propylenediamine (R-pn), the resulting two optical isomers or diastereoisomers are no longer in equal amounts. This preference for one optical isomer or one diastereoiK>mer over the other has been called ligand stereospecificity In the same se, the term stereoselectivity has been used by Dunlop and Gillard, who defined it as the behavior of molecular diastereoisomers In this chapter, the word stereoselectivity is used to mean inclination in abundance of the diastereoisomers of one geometrical isomer. This word differs from either stereoselective reaction or stereospecific reactions . ... 

These terms were introduced in Chapter 17 in connection with elimination reactions, and many of the reactions we mention will be familiar from earlier chapters (particularly Chapters 15—19, 25, and 26). A common misapprehension is that stereospecific means merely very stereoselective. It doesn t—the two terms describe quite different properties of the stereochemistry of a reaction. For the purposes of making a single diastereoisomer, you can think of stereospecific reactions as ones which simply exchange different forms of stereochemical currency (double bond geometry and three-dimensional relative stereochemistry, for example) while stereoselective reactions create additional new stereochemical value. 

Concerted cycloaddition reactions provide the most powerful way to stereospecific creations of new chiral centers in organic molecules. In a manner similar to the Diels-Alder reaction, a pair of diastereoisomers, the endo and exo isomers, can be formed (Eq. 8.45). The endo selectivity in the Diels-Alder arises from secondary 7I-orbital interactions, but this interaction is small in 1,3-dipolar cycloaddition. If alkenes, or 1,3-dipoles, contain a chiral center(s), the approach toward one of the faces of the alkene or the 1,3-dipole can be discriminated. Such selectivity is defined as diastereomeric excess (de). 

How can the Z selectivity in Wittig reactions of unstabilized ylids be explained We have a more complex situation in this reaction than we had for the other eliminations we considered, because we have two separate processes to consider formation of the oxaphosphetane and decomposition of the oxaphosphetane to the alkene. The elimination step is the easier one to explain—it is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state (as in the base-catalysed Peterson reaction). Addition of the ylid to the aldehyde can, in principle, produce two diastere-omers of the intermediate oxaphosphetane. Provided that this step is irreversible, then the stereospecificity of the elimination step means that the ratio of the final alkene geometrical isomers will reflect the stereoselectivity of this addition step. This is almost certainly the case when R is not conjugating or anion-stabilizing the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z-alkene that results reflects this. The Z selective Wittig reaction therefore consists of a kinetically controlled stereoselective first step followed by a stereospecific elimination from this intermediate. 

These epoxides react stereospecifically with nucleophiles to give single diastereoisomers of adducts. If a carbon nucleophile is used (cuprates are best), it is obvious from the structure of the products that nucleophilic attack has occurred at the end of the epoxide next to silicon. This is obviously an S>j2 reaction because it is stereospecific in any case an S>jl reaction would have occurred at the other end of the epoxide through the p-silyl cation. 

Studies have been made of the photochemical reactions of vinyloxiranes with iron carbonyl. The four diastereoisomers of 2,4-hexadienemonooxirane take part in photochemical reactions that are stereospecific. The structure of the iron complex has been determined by x-ray crystallography. Complexes formed from dienemonooxiranes with iron carbonyl can be oxidized to lactones. ... 

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