Stereo selectivity

Whereas the three possible selectivities, stereo-, regio- and chemo-selectivity, of bromine addition are determined in steps posterior to the formation of the ionic intermediate. Bromine addition is, therefore, more complex than bromine substitution, as regards the variety of the selectivities and as regards the mechanistic aspects which determine the product formation. 

As you have been reminded of these definitions, you have also seen several important concepts related to chemical selectivity that will inform any discussion and debate around what is green. We can readily see, for example, that when working with chiral molecules we not only have to worry about reacting with a particular type of bond or functional group, but we also have to do it in such a way that only the bond of interest forms that preserves or creates the desired isomer. As any synthetic organic chemist knows, there remains a considerable amount of chiral chemistry that suffers from a lack of selectivity (stereo-, regio-, and enantioselectivity) and in many cases more than 50% of the starting material ends up as waste. 

Some years ago, we started a project aimed at the development of simple and efficient enzymatic methods for the synthesis of biologically-active carbohydrates on a preparative scale. The use of enzymes as catalysts for the synthesis of carbohydrates has many potential advantages, such as enabling selective, stereo specific syntheses with a minimum of reaction steps under mild conditions and in aqueous solutions in which carbohydrates are highly soluble. Moreover, many enzymes now can be produced in quantity by fermentation and can be immobilized and reused. 

The hypothetical glycosidation shown in Scheme 1 entails three of the four modes of selectivity, stereo, chemo and regio that, according to Trost (7), confront organic synthesis in general. The fourth, enantioselectivity, is usually not encountered in oligosaccharide synthesis since the chiralities of die donor and acceptor are usually specified by nature. 

The potential of enzymes as practical catalysts is well described, and their activity and selectivity (stereo-, chemo-, and regioselectivity) for catalyzed reactions cover a broad range. Enzymes clearly constitute very powerful green tools for catalyzing synthetic chemical processes. In this context, the continuous increase of the market for enantiopure fine chemicals places enzymes as suitable catalysts for green synthetic processes. Catalytic promiscuity of enzymes in nonaqueous environments has been widely described and is related to the ability of a single active site to catalyze more than one chemical transformation for example, lipase B from Candida antarctica (CALB) is able to catalyze aldol additions, Michael-type additions, and so on [4]. 

The symposium was held at Hoshi University in Tokyo. Due to the multidisciplinary nature of the subjects treated, the scope and subjects were grouped into two parts. In the first group, the chemistry of cyclodextrins, synthetic organic hosts, inorganic and metal complex hosts and layered hosts were treated. In the second group applications in various fields, biomimetic aspects, physicochemical aspects, selectivity, stereo-specificity and other aspects were discussed. The scientific sessions were carried out in a really vivid atmosphere. The number of participants viz 50 from 19 overseas countries and 253 domestic participants exceeded our expectation. 

Stereochemical strategies The transform selection is guided by stereocenters that have to be removed in retrosynthesis. The user has to select strategic stereo-centers. 

Alkali alkaline earth metal enolates tend to be aggregates- complicates stereo selection models. 

Svntliesis The reactions were actually carried out like tliis (Stereo- and regio-selectivity turn out all right, J. Amer. Chem. Soc.. 1924, 4, 783). 

The hydroxyl groups of glucose (and, of course, other saccharides) must be regio- and stereo-selectively attacked, if this most abundant natural carbon compound is to be used as starting material. We shall first show with a few selected examples, how this can be achieved (A.H. Haines, 1976 J. Lehmann, 1976 L. Hough, 1979). 

A conceptually surprising and new route to prostaglandins was found and evaluated by C.R. Johnson in 1988. It involves the simple idea to add alkenylcopper reagents stereo-selectively to a protected chiral 4,5-dihydroxy-2-cyclopenten-l-one and to complete the synthesis of the trisubstituted cyclopentanone by stereoselective allylation of the resulting enolate. 

Many stereoselective reactions have been most thoroughly studied with steroid examples because the rigidity of the steroid nucleus prevents conformational changes and because enormous experience with analytical procedures has been gathered with this particular class of natural products (J. Fried, 1972). The name steroids (stereos (gr.) = solid, rigid) has indeed been selected very well, if one considers stereochemical problems. We shall now briefly point to some other interesting, more steroid-specific reactions. 

Hard carbon nucleophiles of organometallic compounds react with 7r-allyl-palladium complexes. A steroidal side-chain is introduced regio- and stereo-selectively by the reaction of the steroidal 7T-allylpalladium complex 319 with the alkenylzirconium compound 320[283]. 

In addition to being regioselective alcohol dehydrations are stereoselective A stereo selective reaction is one m which a single starting material can yield two or more stereoisomeric products but gives one of them m greater amounts than any other Alcohol dehydrations tend to produce the more stable stereoisomer of an alkene Dehydration of 3 pentanol for example yields a mixture of trans 2 pentene and cis 2 pentene m which the more stable trans stereoisomer predominates... 

In addition to being regioselective dehydrohalogenation of alkyl halides is stereo selective and favors formation of the more stable stereoisomer Usually as m the case of 5 bromononane the trans (or E) alkene is formed m greater amounts than its cis (or Z) stereoisomer... 

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance The best examples are found m biochemical processes Most bio chemical reactions are catalyzed by enzymes Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment m which chemical reaction can take place Ordinarily enzyme catalyzed reactions occur with such a high level of stereo selectivity that one enantiomer of a substance is formed exclusively even when the sub strate is achiral The enzyme fumarase for example catalyzes hydration of the double bond of fumaric acid to malic acid m apples and other fruits Only the S enantiomer of malic acid is formed m this reaction... 

The hydrogenation of 2 methyl(methylene)cyclohexane is an example of a stereo selective reaction meaning one m which stereoisomeric products are formed m unequal amounts from a single starting material (Section 5 11)... 

A common misconception is that a stereospecific reaction is simply one that is 100% stereoselective The two terms are not synonymous however A stereospecific reac tion IS one which when carried out with stereoisomeric starting materials gives a prod uct from one reactant that is a stereoisomer of the product from the other A stereo selective reaction is one m which a single starting material gives a predominance of a... 

Select reaction conditions that would allow you to carry out each of the following stereo specific transformations... 

Preformed Carbocationic Intermediates. Propargyl cations stabilized by hexacarbonyl dicobalt have been used to effect Friedel-Crafts alkylation of electron-rich aromatics, such as anisole, /V, /V- dim ethyl a n il in e and 1,2,4,-trimethoxybenzene (24). Intramolecular reactions have been found to be regio and stereo-selective, and have been used ia the preparatioa of derivatives of 9JT- uoreaes and dibenzofurans (25). 

Another anticonvulsant, formerly used as a hypnotic, is 5-ethyl-5-phenyIhydantoin [631 -07-2] (Nirvanol, Mephenytoin). Its S isomer is stereo-selectively eliminated in most subjects, a fact having clinical consequences with both desired and untoward effects (119). 

Under conditions similar to those already outlined, stable aziridin imine derivatives, e.g. (422) and (423), can be prepared in excellent yields (70-80%) by treating the appropriate a-bromoamidines (easily accessible from the amide precursor) with potassium t-butoxide in ether <70AG(E)38l). At low temperatures the elimination proceeds with high regio- and stereo-selectivity at -40 °C (421) yields predominantly (422). 

It is hoped that these volumes will be useful not only to the chemist who wishes to carry out synthesis in the steroid field, but also to the broader group of organic chemists who are interested in carrying out selective and stereo-chemically defined reactions, as well as protective chemistry on extraneous functional groups, during a broad range of synthetic applications. The chapter on the introduction of deuterium and by inference tritium into steroids was included because of the importance of this technique in mechanistic and metabolic studies both in the steroid and nonsteroid field. 

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

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