Stereochemistry and orientation

It is substantially unquestioned that thermal Diels-Alder reactions are strictly cis additions, configurations of both diene and dienophile being retained in the adduct . 

Dienes cannot react with an unsaturated bond unless they are in a cisoid conformation the latter is fixed in some cyclic dienes such as cyclopentadiene and cyclohexadiene. but is equilibrated with other conformations in open-chain dienes, the transoid being usually more favoured, viz- 

This is certainly one of the reasons why cyclic cisoid dienes react faster than open-chain dienes (see Section 4.1.3.). 

The stereochemical course of the Diels-Alder reaction, with olefins as dienophiles, follows trends that can be better specified separating different kinds of additions as follows. 

STEREOCHEMICAL COURSE OF SOME DIELS-ALDER REACTIONS 

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Sunderwirth, S. G., Wood, J. K. Stereochemistry and orientation in bimolecular elimination reactions. Trans. Kans. Acad. Sci. 1967, 70, 17-32. 

When topological strategies are used concurrently with other types of strategic guidance several benefits may result including (1) reduction of the time required to find excellent solutions (2) discovery of especially short or convergent synthetic routes (3) effective control of stereochemistry (4) orientational (regiochemical) selectivity (5) minimization of reactivity problems and (6) facilitation of crucial chemical steps. 

Makriyannis A, Banijamali A, Van der Schyf C, Jarrell H. The role of cannabinoid stereochemistry and absolute configuration and the orientation of A9-THC in the membrane bilayer. Structure-activity relationships of cannabinoids. In Rapaka RS, Makriyannis A, eds. Interactions of Cannabinoids with Membranes. National Institute on Drug Abuse Research Monograph 79. Rockville, MD US Department of Health and Human Services, 1987. 

Currently, only a handful of examples of unique protein carboxylate-zinc interactions are available in the Brookhaven Protein Data Bank. Each of these entries, however, displays syn coordination stereochemistry, and two are bidentate (Christianson and Alexander, 1989) (Fig. 5). Other protein structures have been reported with iyw-oriented car-boxylate-zinc interactions, but full coordinate sets are not yet available [e.g., DNA polymerase (Ollis etal., 1985) and alkaline phosphatase (Kim and Wyckoff, 1989)]. A survey of all protein-metal ion interactions reveals that jyw-carboxylate—metal ion stereochemistry is preferred (Chakrabarti, 1990a). It is been suggested that potent zinc enzyme inhibition arises from syn-oriented interactions between inhibitor carboxylates and active-site zinc ions (Christianson and Lipscomb, 1988a see also Monzingo and Matthews, 1984), and the structures of such interactions may sample the reaction coordinate for enzymatic catalysis in certain systems (Christianson and Lipscomb, 1987). 

Monosaccharides can be assembled into an almost limitless variety of oligosaccharides, which differ in the stereochemistry and position of glycosidic bonds, the type and orientation of substituent groups, and the number and type of branches. Oligosaccharides are far more information-dense than nucleic acids or proteins. 

Both enzymes have the Asp-His-Ser catalytic side chains, the same as in the serine proteases. The active atoms of this catalytic triad have essentially identical stereochemistry in the serine proteases and in these lipases. The amino acids themselves, however, have quite different conformations and orientations. 

This section will demonstrate the first sergeants and soldiers-type helix command surface experiment, in which thermo-driven chiroptical transfer and amplification in optically inactive polysilane film from grafted (or spin-coated) optically active helical polysilane onto quartz substrate [92]. Although helix and optical activity amplification phenomena based on the sergeants and soldiers principle was mainly investigated in polymer stereochemistry, the orientation and physical properties of a thick layer deposited onto a solid surface and controlled by a monolayer command film based on command surface principles was established in photochemical material and surface science [93,94]. Both sergeants and soldiers and command surface experiments appear to have been developed independently. 

Parker, D.H., Jalink, H. and Stolte, S. (1987). Dynamics of molecular stereochemistry via oriented molecular scattering, J. Phys. Chem., 91, 5427-5437. 

Figure 11.5 shows a mechanism that has been postulated for this reaction. First, an electrophilic mercury species adds to the double bond to form a cyclic mercurinium ion. Note how similar this mechanism is, including its stereochemistry and regiochemistry, to that shown in Figure 11.4 for the formation of a halohydrin. The initial product results from anti addition of Fig and OH to the double bond. In the second step, sodium borohydride replaces the mercury with a hydrogen with random stereochemistry. (The mechanism for this step is complex and not important to us at this time.) The overall result is the addition of H and OH with Markovnikov orientation. 

The Markovnikov orientation observed in halohydrin formation is explained by the structure of the halonium ion intermediate. The two carbon atoms bonded to the halogen have partial positive charges, with a larger charge (and a weaker bond to the halogen) on the more substituted carbon atom (Figure 8-5). The nucleophile (water) attacks this more substituted, more electrophilic carbon atom. The result is both anti stereochemistry and Markovnikov orientation. 

Show how we can control the stereochemistry and regiochemistry (orientation) of Problems 8-46, 47, 59, and 65 additions to alkenes to obtain the products we want. 

Lythgoe, Kocienski and their coworkers investigated the scope, stereochemistry and mechanism of the classical Julia olefination (also called the Juha-Lythgoe olefination) and paved the way for its broad application in target-oriented synthesis [87-90]. The bias towards fi-olefins, with the isomer ratio being typically in the range 7/3 to 9/1 for primary unhindered sulfones and aldehydes, marks a distinctive stereochemical feature of the reaction. 

S)-Naproxen is the aaive ingredient in the widely used pain relievers Naprosyn and Aleve. The three-dimensional orientation of two atoms at a single carbon in naproxen determines its therapeutic properties. Changing the position of these two atoms converts this anti-inflammatory agent into a liver toxin. In Chapter 5 we learn more about stereochemistry and how small structural differences can have a large effect on the properties of a molecule. 

Substrate and/or intermediate species absorb on an electrode surface and orient themselves so that their least hindered sides face the electrode unless there is another effect, such as a polar one. This may be the simplest steric factor governing the stereochemistry of reactions. There may also be more complicated steric effects that result in conformational or configurational change of the species, since the electrode on which the species adsorb strongly may behave as if it were a very bulky substituent. For example, visualize a substituted cyclohexane molecule (Fig. 1). The substituent must be preferentially in the equatorial position in a free state (I), but it may be in the axial position in an adsorbed state (II), if the electrode effectively gives more steric hindrance than the substituent. 

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