Stereospecificity factors

The interrelationship between the 2- and 8-positions is exemplified by 2-oxo-103 and 8-oxopurine, which are both converted by xanthine oxidase to 2,8-dioxopurine. Some unexpected results of oxidation can best be explained by assuming stereospecific factors. Thus, whereas purine, its 2-methyl, and its 2-amino derivatives give the 6-oxo derivatives, the 2-phenyl- and 2-oxopurines mentioned above oxidize at the 8-position.112... 

Since the stereochemical course of a catalytic hydrogenation is dependent on several factors, " an understanding of the mechanism of the reaction can help in the selection of optimal reaction conditions more reliably than mere copying of a published recipe . In the first section the factors which can influence the product stereochemistry will be discussed from a mechanistic viewpoint. In subsequent sections the hydrogenation of various functional groups in the steroid ring system will be considered. In these sections both mechanistic and empirical correlations will be utilized with the primary emphasis being placed on selective and stereospecific reactions. 

This reaction, now termed hydroboration, has opened up the quantitative preparation of organoboranes and these, in turn, have proved to be of outstanding synthetic utility. It was for his development of this field that H. C. Brown (Purdue) was awarded the 1979 Nobel Prize in Chemistry . Hydroboration is regiospecific, the boron showing preferential attachment to the least substituted C atom (anti-Markovnikov). This finds ready interpretation in terms of electronic factors and relative bond polarities (p. 144) steric factors also work in the same direction. The addition is stereospecific cis (syn). Recent extensions of the methodology have encompassed the significant development of generalized chiral syntheses. 

The rate of saponification of ethyl 2-thenoate, in contrast to ethyl 3-thenoate, was found to be considerably slower than predicted from the pKa of the acid, showing that the reactivities of thiophenes do not parallel those of benzene. The first explanation, that this was produced by a steric effect of the ring sulfur similar to the case in or /lo-substituted benzenes and in ethyl 1-naphthoate, could not be upheld when the same effect was found in ethyl 2-furoate. It was later ascribed to a stereospecific acid strengthening factor, involving the proper relation of the carboxylic hydrogen and the heteroatom, as the rate of saponification of 2-thienylacrylic acid was in agreement with that predicted from the acid constants. ... 

In an ionic polymerization the strong electrostatic field of the ion pairs should have a pronounced effect on the ratio of the probabilities of the two placements. Furthermore, solvation of an ion pair is much stronger than of a neutral radical, hence the influence of a solvent on stereospecificity of addition is expected to be much more pronounced in an ionic polymerization than in a radical polymerization. The nature of the gegen ion represents still another factor which is of extreme importance in determining the stereospecificity of the polymerization. 

Biotin is a member of the vitamin B famify and is an essential factor in the processes and maintenance of normal metabohsm in human beings. It is an essential growth factor for some bacteria Its chemical stmcture was estabhshed in the eady 1940s and a practical, highly stereospecific, chemical synthesis enabled D-biotin, identical to that found in yeasts and other cells, to be produced. 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

Solvent-dependent lifetimes and ion-pairing of these intermediates can be responsible for the observed variations in the stereo- and chemo-selectivity. Assuming that bromonium ions and carbocations are formed in discrete pathways, the influence of these factors can be readily understood. On the one hand, bridged ions react stereospecifically whatever the medium the... 

The trans/cis ratio of the product must, therefore, be determined at an earlier reaction stage and most probably by the ratio of species 27a and 27b. Steric or electronic factors affecting this ratio will influence the trans/cis ratio of the resulting 1,4-hexadiene. The phosphine and the cocatalyst effect on the stereoselectivity can thus be interpreted in terms of their influence on the mode of butadiene coordination. Some earlier work on the stereospecific synthesis of polybutadiene by Ni catalyst can be adopted to explain the effect observed here, because the intermediates that control the stereospecificity of the polymerization should be essen-... 

Soluble metathesis catalysts yield trans products in reactions with // / v-2-pentene, but generally are not very stereospecific with c/.v-2-pen-tene. In the latter case, the initially formed butenes and hexenes are typically about 60 and 50% cis, respectively. Basset noted (19) that widely diverse catalyst systems behaved similarily, and so it was suggested that the ligand composition about the transition metal was not a significant factor in the steric course of these reactions. Subsequently, various schemes to portray the stereochemistry have been proposed which deal only with interactions involving alkyl substituents on the reacting olefin or on the presumed metallocyclobutane intermediate. 

A complicating factor associated with experimental application of the Skell Hypothesis is that triplet carbenes abstract hydrogen atoms from many olefins more rapidly than they add to them. Also, in general, the two cyclopropanes that can be formed are diastereomers, and thus there is no reason to expect that they will be formed from an intermediate with equal efficiency. To allay these problems, stereospecifically deuteriated a-methyl-styrene has been employed as a probe for the multiplicity of the reacting carbene. In this case, one bond formation from the triplet carbene is expected to be rapid since it generates a particularly well-stabilized 1,3-biradical. Also, the two cyclopropane isomers differ only in isotopic substitution and this is anticipated to have only a small effect on the efficiencies of their formation. The expected non-stereospecific reaction of the triplet carbene is shown in (15) and its stereospecific counterpart in (16). 

All the proposed models for syndiotactic propagation suppose that the active center is a vanadium-carbon bond and that the monomer first coordinates to the metal. Moreover, all of them attribute the stereospecificity to steric factors. However, different driving forces for the syndiospecificity have been proposed. 

In the case of TGT structures which are acyclic or which contain isolated rings, the disconnection of non-ring bonds must be examined to identify those disconnections which may be most effective on topological grounds. However, for such acyclic disconnections the topological factors may be overshadowed by other structural considerations. For instance, if a powerful stereosimplifying disconnective transform, such as stereospecific organometallic addition to carbonyl... 

Hydrogen-bonding between the 3-oxo group of 1,4,4-trisubstituted pyrrolidine-2,3,5-triones and catalytic amounts of cinchonidine controls the stereospecific hydrogenation of the system over Pt/Al203 to yield chiral 3-hydroxy compounds (-100% yield with ee >60) [21] the nature of the (V-substituent appears to be the controlling factor for the stereoselectivity with PhCH2> Et > n-Bu > cyclo-C6H . 

In the 45 years since its proposal, Frank s autocatalytic mechanism (Section 11.3, above) has spawned numerous theoretical refinements including consideration of such factors as reversibility, racemization, environmental noise, and parity-violating energy differences. [100,101] In contrast to the above examples of stereospecific autocatalysis by the SRURC, however, none of these theoretical refinements is supported by experimental evidence. While earlier attempts to validate the Frank mechanism for the autocatalytic amplification of small e.e.s in other experimental systems have generally been unsuccessful, several recent attempts have shown more promising results. [102,104]... 

Lemer and Benkovic examined the possibility of performing an intramolecular cyclisation reaction [30]. They chose the formation of a six-membered lactone ring from a hydroxy ester (12) and observed that only one single enantiomer of the 5-lactone (14) in 94% ee was formed from the corresponding 5-hydroxy ester. Moreover, the stereospecific ring closure reaction was accelerated by the antibody -elicited from the transition-state analog 15- by about a factor of 170. 

The experimental ratio of ds- to trans-cyclopropane 43 46, i.e. the stereo-specifity of the reaction cannot be considered as a simple indication of singlet or triplet percentage of RaC , since the stereochemistry of the cyclo-addition depends on many factors. Photolysis produces the exdted 5i-state of the diazoalkane 41. This compound can lose nitrogen and form the singlet carbene 42 (So-state). 42 can add directly in a stereospecific manner if ki is large. If, however, intersystem crossing 42 45 (Aisc is large) competes favorably with... 

The major factor in determining which mechanism is followed is the stability of the carbocation intermediate. Alkenes that can give rise to a particularly stable carbocation are likely to react via the ion-pair mechanism. The ion-pair mechanism would not be expected to be stereospecific, because the carbocation intermediate permits loss of stereochemistry relative to the reactant alkene. It might be expected that the ion-pair mechanism would lead to a preference for syn addition, since at the instant of formation of the ion pair, the halide is on the same side of the alkene as the proton being added. Rapid collapse of the ion-pair intermediate leads to syn addition. If the lifetime of the ion pair is longer and the ion pair dissociates, a mixture of syn and anti addition products is formed. The termolecular mechanism is expected to give anti addition. Attack by the nucleophile occurs at the opposite side of the double bond from proton addition. 

Related to these electronic factors, some examples of stereospecific coupling are known. In 7 the geminal protons on phosphorus are non-equivalent and exhibit slightly different couplings to phosphorus, both of which are temperature and solvent dependent.(1969,51) A clearer example is given by the recent work of Mikolajczyk(1969,52) on the two isomers 8 and 9. 

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