Stereospecific processes

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. 

A method for achieving net anti hydroxylation of alkenes combines two stereospecific processes epoxidation of the double bond and hydrolysis of the derived epoxide. 

Scheme 8 presents the sequence of reactions that led to the synthesis of the B-ring of vitamin B12 by the Eschenmoser group. An important virtue of the Diels-Alder reaction is that it is a stereospecific process wherein relative stereochemical relationships present in the diene and/or the dienophile are preserved throughout the course of the reaction.8 Thus, when the doubly activated dienophile 12 (Scheme 8) is exposed to butadiene 11 in the presence of stannic chloride, a stereospecific reaction takes place to give compound 27 in racemic form. As expected, the trans relationship between... 

In an approach to FR182877, Sorensen and co-workers generated allenoate intermediate 289 from an ce-bromo-ce,/j-unsaturated lactone and effected an intramolecular acylation to afford a-alkylidene-/3-keto-y-lactone 290 as a single stereoisomer (Scheme 19.52) [61]. Evidence for the allenoate intermediate was established by the treatment of a-bromoenoate 291 with tBuLi, which afforded the cydized compound 292 as a single stereoisomer. Treatment of the isomeric bromoenoate of compound 291 also gave 292. Hence this demonstrated a stereoselective but not stereospecific process. 

For aliphatic ketones, although intersystem crossing is fast, the singlet (njjt ) state will react by a stereospecific process with alkenes that have electron-withdrawing groups in their molecules ... 

The stereoselectivity of the reaction can be rationalized in terms of the relative stabilities of the products 133 and 134. The stereoselectivity was more pronounced in the cyclohexane series. The stereoselectivity increases with increasing size of substituent R, and the reaction becomes a stereospecific process for the rert-butyl derivatives. The equatorial position of a bulkier substituent is preferred, and thus in the phenyl series the steric requirement of the phenyl group is smaller than that of the methyl group. 

Polymerizations that yield tactic structures (either isotactic or syndiotactic) are termed stereoselective polymerizations. The reader is cautioned that most of the literature uses the term stereospecific polymerization, not stereoselective polymerization. However, the correct term is stereoselective polymerization since a reaction is termed stereoselective if it results in the preferential formation of one stereoisomer over another [IUPAC, 1996]. This is what occurs in the polymerization. A reaction is stereospecific if starting materials differing only in their configuration are converted into stereoisomeric products. This is not what occurs in the polymerization since the starting material does not exist in different configurations. (A stereospecific process is necessarily stereoselective but not all stereoselective processes are stereospecific.)... 

C-3 as determined by mass spectral analysis.(55) In a mechanism involving ketone hydration prior to bindTrTg, incorporation in recovered inhibitor should be at least 50%, a value corresponding to that expected for a single cycle of nonstereospecific addition/nonstereospecific elimination of water to the ketone carbonyl. The actual results then indicate that addition-elimination is a highly stereospecific process and thus enzyme-catalyzed. 

Stereochemical studies were carried out using cis- and trans- 1-propen-1-yl propionate. It was found that each of these esters exchanged to give mixtures of cis- and trans- 1-propen-l-yl acetates. As shown by Equation 15, this result is unexpected if acetoxypalladation were a stereospecific process. Further evidence was provided by the fact that 1-cyclopen ten-1-yl propionate exchanged to give the corresponding acetate. Again, as shown by Equation 16, this result is unexpected if acetoxypalladation were stereospecific. 

It was shown [43] that reactions of E and Z isomers of 21-24 proceed as stereospecific processes. Depending on the configuration of the starting cyclic a,(3-unsaturated ketone, the reaction yields either trans isomers 25-28 (E configuration of 21-24) or their cis forms (Z configuration of 21-24). 

An isotactic stereospecific polymerization arises essentially from the favored complexation of one prochiral face of the a-olefin, followed by a stereospecific process. The stereospecific insertion process and the stereospecific polymerization of racemic a-olefins giving isotactic polymers may be expected to be stereoselective whenever the asymmetric carbon atom is in an a- or /3-position relative to the double bond, and when the interaction between the chirality center of the olefin and the chiral catalytic site is negligible. 

For condensed-phase reactions, Kirmse (1964) has used SS as a criterion of cyclic (singlet) versus acyclic (triplet) transition states and/or intermediates in these cases. When insertion is stereospecific with retention, a cyclic species is assumed when insertion is unselective the acyclic species is assumed. We can, in fact, associate the singlet with a one-step, stereospecific process. On the other hand, one or more products could be formed from a triplet intermediate. 

A detailed study14 of the stereochemistry of fluoro-desilylation (Table 5) showed that the removal of silicon is a stereospecific process occurring with retention of configuration. Accordingly, from the E-isomers of thioacylsilane 5-oxides 30, the Z-thioaldehyde 5-oxides 40 were obtained. The myrtanyl derivative (entry 9) is the first enantiomerically pure thioaldehyde 5-oxide ever prepared. In contrast, loss of stereochemical integrity was observed during the desilylation of tert-butyl trimethylsilyl sulfine (entries 4 and 5) and mesityl-trimethylsilylsulfine (entries 10, 11, and 12). It was demonstrated that the loss of stereospecificity results from a fluoride-induced equilibration of thioaldehyde 5-oxides after the desilylation. 

In dealing with processes where stereoisomer formation is subject to some kind of control, two terms have been used—stereoselective and stereospecific. These terms have caused some problems, and to some extent have been used synonymously. The meanings attached to these terms by chemists are unambiguous [52]. A stereospecific process is one in which a particular stereoisomer reacts to give one specific stereoisomer (or a racemate) of a product. Thus, two starting materials, differing only in stereoisomerism, must be converted into stereoisomerically different products. A classical example of chemical stereospecificity is the free radical addition of HBr to 2-bromo-2-butene. At — 78°C, the (E)-olefin, 24, forms meso-2,3-dibromobutane, 25, while the (Z)-isomer, 26, yields ( )-tAreo-2,3-dibromobutane, 27 plus 28. (Note in addition that this addition is regiospecific—2,2-dibromobutane is not formed.)... 

It will be appreciated that, with these definitions, any stereospecific process is also stereoselective however, not all stereoselective reactions are stereospecific. In some papers, the terms are modified with the prefixes, enantio- or diastereo-. 

The most definitive stereochemical studies have concerned configurational changes at the a carbon. Alexander et al. (2, 138) showed that (-I-)540-CpFe(CO)2CH(Me)Ph reacts with neat SOg at —60° or — 10°C, or with SO2 in saturated pentane at 27°C, to give the corresponding iS-sulfinate. The specific rotation of the product, [a]546, varied somewhat with the method of synthesis (—186°, —176°, and —158°, respectively). It was concluded that the insertion is a substantially stereospecific process, but whether it involves retention or inversion could not be determined. 

Racemization of the Amino Acid Substrate Deprotonation of the a-carbon of the amino acid leads to tautomerization of the Schiff base to the quinonoid ketimine, as shown in Figure 9.2. The simplest reaction that the ketimine can undergo is reprotonation at the now symmetrical a-carbon. This is not a stereospecific process therefore, displacement of the substrate by the reactive lysine residue results in the racemic mixture of d- and L-amino acid. 

From the preceding discussions, the salient features of the sulfur atom—olefin systems may be summarized as follows (a) triplet state atoms react with olefins to produce only episulfide in an almost completely stereospecific process, and (f>) the interaction of singlet state sulfur atoms with olefins produces mercaptans, and probably episulfides as well. The kinetics of the reaction is not in accord with the simple mechanism which includes one or more product-forming steps with the olefin molecule in competition with the abstraction reaction from COS, even if allowances are made for collisional relaxation of S( Z)) atoms by COS and the olefin. For this reason, the possibility should be kept in... 

The reaction of S( P) atoms with olefins is probably the first reported stereospecific triplet-state addition and as such provides experimental support for DeMore and Benson s proposal that a triplet-state addition can indeed be a stereospecific process. Clearly, therefore, at least in the... 

Radical reactions can often be rationalized on the basis of frontier orbital considerations for intermediate radical species, the reactivity and stereochemistry of which can certainly be regulated with Lewis acid additives [21-23]. The first appearance of Lewis acids in radical reactions was in polymerization reactions resulting in alternation of copolymers different from that obtained without Lewis acids [24-26]. This concept, Lewis acid-directed radical reactions, has been applied to reductions and alkylations of organic halides or olefins, and has resulted in highly stereospecific processes. 

Heine ° has pointed out that this reaction represents an example of the reverse of the reaction on pyrolysis of imido esters. Heine has recently shown that the pyrolytic isomerization of cis- and rra j-l-p-nitrobenzoyl-2,3-diphenylaziridines into 2-p-nitrophenyl-4,5-diphenyl-2-oxazolines is a stereospecific process. These results are consistent with a mechanism that involves either a four-membered transition state or a short-lived tight ion-pair intermediate that collapses to the oxazoline before racemisation can occur . The pyrolysis of l,3-diaroyl-2-aryl-aziridines results in a different kind of reaction, in which a-benzamidobenzal-acetophenones are produced, viz. 

A recent kinetic study of the extrusion of ( Bu)3Si-Si-Si( Pr)3 from a silirane suggested that the silylene was formed in a singlet state by a non-least motion, concerted, stereospecific process, but that it reacted from a triplet state via the mechanism of Scheme 7 [53]. 

As final examples of the versatility of the Ritter reaction, bridged hemiacetals react by means of their acyclic form in solution to afford amido ketones in good yield (equation 29), while halohydrins give a-amido halides, which are readily cyclized to oxazoline derivatives in an overall stereospecific process. ... 

Complications of reaction mechanism are avoided by an operational definition of a reaction. A reaction converts a compound of specifiable structure into a second of specifiable structure in a stereospecific process. The new compound possesses one new ligand not present in the starting material. For example,... 

Cyclic exponents of the same elimination type are of particular interest. Thus, numerous cyclopentanones photolytically decarbonylate to give 1,4-dienes (p. 876 ff. in Ref. 108)). With thujone (194) this [l,2,(3)4]-elimination of carbon monoxide proceeds quantitatively to give 195 109). With silver nitrate the norcaradiene 196 yields 197 (95%)110) apparently regioselectively, and the [l,2,(3)4]-elimination of methanethiol from 198 to give 199 was realized thermally (16%), acid-catalyzed (59%), and photochemiciiily (ca. 5%)105). For the acid-catalyzed reaction (acetic acid, 100 °C) a non-stereospecific process has been proved 105). 

A unique rearrangement of 2-bromophenyl allyl ethers 196 proceeds as a completely regio- and stereospecific process without any migration to the para-position and with conservation of the regiochemistry in the allyl substiments of the phenolic products 198. It was assumed that the reaction occurs via the 7r-allyl complexes 197 (equation 91) . ... 

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