Stereochemistry stereospecificity

Irradiation of 26 in cyclohexane solution containing either cis- or trans-4-methyl-2-pentene forms aziridines with complete (>98%) retention of olefin stereochemistry.Stereospecific aziridine formation is usually considered as evidence of a concerted, singlet nitrene addition reaction. 

Corey E J and J C Bailar ]t 1959. The Stereochemistry of Complex Inorganic Compounds. XXII. Stereospecific Effects in Complex Ions. Journal of the American Chemical Society 81 2620-2629. 

Note that the stereochemistry comes out right. H s a and b are cis because they were cis in the starting quinone and the Diels-Alder reaction is stereospecific in this respect. H is also cis to and H " because the Diels-Alder reaction is stereoselectively endo. These points are described in more detail in Norman p.284-6 and explained in Ian Fleming Frontier Orbitals and Organic Chemical Reactions, Wiley 1976, p. 106-109. How would you make diene A ... 

The diacetoxylation of E,E)- and ( ,Z)-2.4-hexadiene (351 and 353) is stereospecific, and 2,5-dimethylfurans (352 and 354) of different stereochemistry have been prepared from the isomers. Two different carboxylates are introduced with high cis selectivity by the reaction of 1,3-cyclohexadiene and... 

The regioselective and stereospecific construction of C-20 stereochemistry is explained by the following mechanism. The Pd(0) species attacks the ( )-/3-carbonate 616 from the a-side by inversion to form the Tr-allylpalladium species 620, which has a stable syn structure[392]. Then concerted decarboxylation-hydride transfer as in 621 takes place from the a-side to give the unnatural configuration in 617. On the other hand, the Tr-allylpalladium complex 622... 

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. 

The hydrolysis of sulfonate esters of 2 octanol is stereospecific and proceeds with complete inversion of configuration Write a structural formula that shows the stereochemistry of the 2 octanol formed by hydrolysis of an opti cally pure sample of (S) (+) 1 methylheptyl p toluenesulfonate identify the prod uct as / or S and deduce its specific rotation... 

Thermal decomposition of cis- and frans-3,6-dimethyl-3,4,5,6-tetrahydropyridazines affords propene, cis- and frans-l,2-dimethylcyclobutanes and 1-hexene. The stereochemistry of the products is consistent with the intermediacy of the 1,4-biradical 2,5-hexadienyl. The results indicate that thermal reactions of cyclic azo compounds and cyclobutanes of similar substitution proceed with similar stereospecificity when compared at similar temperatures 79JA2069). 

When the reaction of acetaldehyde with a 6-diazopenicillanate is catalyzed by BFs-EtiO, an epoxide of unknown stereochemistry is obtained (79H( 13)227). With ZnCh catalysis, however, the 6a-acetyl derivative is obtained, which can be stereospecifically reduced as the Mg chelate to the 6a-(/ -l-hydroxyethyl) derivative as part of an elegant synthesis of the carbapenem thienamycin (Scheme 40) (8UA6765). 

Entries 1 and 2 in Scheme 2.9 are typical of concerted syn addition to alkene double bonds. On treatment with peroxyacetic acid, the Z-alkene affords the cis-oxirane, whereas the -alkene affords only the iraws-oxirane. Similarly, addition of dibromocarbene to Z-2-butene yields exclusively l,l-dibromo-cw-2,3-dimethylcyclopropane, whereas only 1,1-dibromo-/ra 5-2,3-dimethylcyclopropane is formed from -2-butene. There are also numerous stereospecific anti additions. Entiy 3 shows the anti stereochemistry typical of bromination of simple alkenes. 

The stereochemistry of both chlorination and bromination of several cyclic and acyclic dienes has been determined. The results show that bromination is often stereo-specifically anti for the 1,2-addition process, whereas syn addition is preferred for 1,4-addition. Comparable results for chlorination show much less stereospeciftcity. It appears that chlorination proceeds primarily through ion-pair intermediates, whereas in bromina-hon a stereospecific anfi-l,2-addition may compete with a process involving a carbocation mtermediate. The latter can presumably give syn or anti product. 

The stereochemistry of addition is usually anti for alkyl-substituted alkynes, whereas die addition to aryl-substituted compounds is not stereospecific. This suggests a termo-iecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation mtermediate in the aryl case. Aryl-substituted alkynes can be shifted toward anti addition by including bromide salts in the reaction medium. Under these conditions, a species preceding the vinyl cation must be intercepted by bromide ion. This species can be presented as a complex of molecular bromine with the alkyne. An overall mechanistic summary is shown in the following scheme. 

Electrocyclic reactions of 1,3,5-trienes lead to 1,3-cyclohexadienes. These ring closures also exhibit a high degree of stereospecificity. The ring closure is normally the favored reaction in this case, because the cyclic compound, which has six a bonds and two IT bonds, is thermodynamically more stable than the triene, which has five a and three ir bonds. The stereospecificity is illustrated with octatrienes 3 and 4. ,Z, -2,4,6-Octatriene (3) cyclizes only to cw-5,6-dimethyl-l,3-cyclohexadiene, whereas the , Z,Z-2,4,6-octa-triene (4) leads exclusively to the trans cyclohexadiene isomer. A point of particular importance regarding the stereochemistry of this reaction is that the groups at the termini of the triene system rotate in the opposite sense during the cyclization process. This mode... 

A complete mechanistic description of these reactions must explain not only their high degree of stereospecificity, but also why four-ir-electron systems undergo conrotatory reactions whereas six-Ji-electron systems undergo disrotatory reactions. Woodward and Hoifinann proposed that the stereochemistry of the reactions is controlled by the symmetry properties of the HOMO of the reacting system. The idea that the HOMO should control the course of the reaction is an example of frontier orbital theory, which holds that it is the electrons of highest energy, i.e., those in the HOMO, that are of prime importance. The symmetry characteristics of the occupied orbitals of 1,3-butadiene are shown in Fig. 11.1. 

The stereochemistry of the 1,3-dipolar cycloaddition reaction is analogous to that of the Diels-Alder reaction and is a stereospecific syn addition. Diazomethane, for example, adds stereospecifically to the diesters 43 and 44 to yield the pyrazolines 45 and 46, respectively. 

The di-TT-methane rearrangement is a stereospecific reaction. There are several elements of stereochemistry to be considered. It is known that the double bond that remains uncyclized retains the E or Z configuration present in the starting material. This result excludes any intermediate with a freely rotating terminal radical. The concerted... 

Catalytic hydrogenation has been utilized extensively in steroid research, and the method has been found to be of great value for the selective and stereospecific reduction of various functional groups. A number of empirical correlations concerning selectivity and product stereochemistry compiled for steroid hydrogenations has been listed in a previous review. ... 

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. 

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

Although the emphasis in this chapter has been on tbe synthesis and mechanism of formation of simple enamines, brief mention will be made of the addition of amines to activated acetylenes to indicate the interest and activity in this area of substituted enamines. Since such additions tend to be stereospecific, inclusion in this section seems apropos. The addition of amines to acetylenes has been much studied 130), but the assigning of the stereochemistry about the newly formed double bond could not be done unequivocally until the techniques of NMR spectroscopy were well developed. In the research efforts described below, NMR spectroscopy was used to determine isomer content and to follow the progress of some of the reactions. 

The first objective was the conversion of L-tryptophan into a derivative that could be converted to pyrroloindoline 3, possessing a cis ring fusion and a syn relationship of the carboxyl and hydroxyl groups. This was achieved by the conversions shown in Scheme 1. A critical step was e. Of many variants tried, the use of the trityl group on the NH2 of tryptophan and the t-butyl group on the carboxyl resulted in stereospecific oxidative cyclization to afford 3 of the desired cis-syn stereochemistry in good yield. 

Addition of hydrogen halides to alkenes is not stereospecific. In contrast, addition of Br2 proceeds exclusively with anti stereochemistry. 

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