Stereo chemical selectivity

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. 

A mechanistic rationale for the observed cw-selectivity has been proposed based on preorganisation of the Breslow-type intermediate and imine through hydrogen bonding 253, with an aza-benzoin oxy-Cope process proposed. Reaction via a boat transition state delivers the observed cw-stereochemistry of the product (Scheme 12.57). Related work by Nair and co-workers (using enones 42 in place of a,P-unsaturated sulfonylimines 251, see Section 12.2.2) generates P-lactones 43 with fran -ring substituents, while the P-lactam products 252 possess a cw-stereo-chemical relationship. 

His research program focuses on the asymmetric synthesis of biologically active, stereo-chemically complex, natural products. Target molecules are selected which pose unique challenges in asymmetric bond construction. A complex multistep synthesis endeavour... 

This work reveals that an antibody can selectively deliver a single regio- and stereo-chemically defined product for a reaction in which multiple, alternative transition states are accessible and can also selectively lower the energy of the higher of two alternative transition states. 

By definition, it is necessary to recognize geometric isomers, isotopomers and stereoisomers as distinct species. Moreover, there is the pragmatic issue that regio-selectivity, isotopic labeling and stereo-chemical investigations are three very important avenues of mechanistic enquiry. 

There is an increasing number of areas where bioreactors are serious alternatives to conventional chemical reactors, particularly when their mild conditions and high selectivity can be exploited. In the pharmaceutical industry micro-organisms and enzymes can be used to produce specific stereo-isomers selectively, a very desirable ability since it can be that only the one isomer (possibly an optical isomer) may possess the required properties. In such applications the limitations of bioreactors are clearly outweighed by the advantages in their use. The fact that the products are formed in rather dilute aqueous solution and at relatively low rates may be of secondary importance and it may then be economically feasible to employ multiple separation stages in their purification. 

Similar transformations using diphenylphosphine oxide and diethyl thio-phosphite have also been performed. Rhodium prolinate second generation complex Rh2(S-TISP)2 has been used as a very effective catalyst promoting conversion of dimethyl aryldiazomethyl phosphonates (192) into the stereo-chemically defined donor/acceptor substituted rhodium carbenoid intermediates. The latter are capable of cyclopropanation of various styrene derivatives affording cyclopropylphosphonates (193) in high yields (85-96%), diastereo-selectivity (>98% de), and enantioselectivity (76-92% ee) ( Scheme 52). A... 

The reduction of intermediately formed, isolable unsaturated nitriles opens up an easy route to regio- and stereo-chemically pure unsaturated aldehydes. The overall reaction is a regio- and stereo-selective hydroformylation of alkynes [61]. 

Several ketone lithium enolates and dianions of jS-dicarbonyl substrates similarly undergo highly selective 1,4-addition to a variety of a-enones. Thus, tandem inter- and intramolecular Michael addition using the enolates of a,/l-unsaturated ketones as Michael donors was achieved successfully (Scheme 6.88) [111] treatment of 111-ATPH complex in toluene with a THF solution of the benzalacetone lithium enolate at -78 °C, then heating under reflux for 13 h gave the stereo-chemically homogeneous annulation product in 50% yield almost exclusively. 

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. 

A plausible mechanism of several possibilities for the formation of this ring system, is via face-selective epoxidation followed by ring-opening and dehydration. Since this isoprene unit is introduced without loss of. stereochemical integrity, it was deemed unlikely that the Penicillia sp. has a mechanism for scrambling the DMAPP via a dimethyl vinyl carbinol-type intermediate which would necessarily provide stereo chemically scrambled isoprene equivalents to the cell s cytosolic pool of DMAPP. 

Elworthy TR, Kertesz DJ, Kim W, Roepel MG, Quattrocchio-Setti L, Smith DB, Tracy JL, Chow A, Li F, Brill ER, Lach LK, McGee D, Yang DS, Chiou S-S (2004) Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1 2-pyrrolidinones - stereo-chemical and lower side-chain optimization. Bioorg Med Chem Lett 14 1655-1659... 

Metal-Catalyzed Reactions The metal-catalyzed bisthiolations are currently limited to Pd, Ni, and Rh complexes, where the stereoselective formation of alkenes 40 with high (Z)-selectivity was observed. For the Ni-catalyzed reaction, it is possible to prepare stereo-chemically defined 1,4-bisthio substituted conjugate dienes 41 through sequential alkyne insertions to Ni—S and Ni—C bonds 42 (Scheme 46.7). The use of silyldisulfides" followed by one-pot desilyation and electrophilic addition... 

The second hierarchy results along the endpoints path Ic-IIb-III, see Figure 3.16. This tells us that, by some subsidiary, slower action, the stereo-specificity selection is the first stage of the chemical-biological interaction analyzed, followed by membrane transport and only then by the stabilization of chemical bonds through polarizability. 

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... 

Enzymes are proteins catalyzing all in vivo biological reactions. Enzymatic catalysis can also be utilized for in vitro reactions of not only natural substrates but some unnatural ones. Typical characteristics of enzyme catalysis are high catalytic activity, large rate acceleration of reactions under mild reaction conditions, high selectivities of substrates and reaction modes, and no formation of byproducts, in comparison with those of chemical catalysts. In the field of organic synthetic chemistry, enzymes have been powerful catalysts for stereo- and regioselective reactions to produce useful intermediates and end-products such as medicines and liquid crystals. ... 

This chapter will briefly survey some basic physical and chemical properties of water as well as the possible relevance of these properties to aqueous organic chemistry in terms of reactivity, selectivity (chemo-, regio-, and stereo-), and phase-separations. 

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