Regio- and stereo-selectivity

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). 

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]. 

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). 

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). 

Sulfinyldiene 40 reacts, regio- and stereo selectively, with methylacrylate in the presence of a catalyst, affording carbomethoxycyclohexene derivatives [45]. Among the catalysts examined, the best was lithium perchlorate used as a suspension in DCM it gave only endo isomers in 70% yield in a 96 4 d.e. ratio (Equation 3.11). 

Scheme 8-18 Regio- and stereo-selectivity in hydrozirconation of terminal alkynes...

Figure 8.14 Preparation of (S)-3-cyano-5-methyl hexanoic acid from isobutylsuccinonitrile using a regio- and stereo-selective nitrilase from AtNitl Arabidopsis thaliana...

Chemical synthesis, an approach limited by complex synthetic sequences using protection of hydroxyl groups to achieve regio- and stereo-selectivity... 

Sucrase-type (non-Leloir-type) enzymes that operate both regio- and stereo-selectively, using sucrose as a cheap substrate, or, in some cases (such as cyclodextrin (CD) transferases) starch these enzymes are, however, limited to the transfer of only glucose or fructose... 

This report surveys new routes for the synthesis of oligosaccharides, with emphasis on enzymatic reactions, since they offer unique properties, proceeding highly regio-and stereo-selectively in water solution, and generally afford high yields. Summarized... 

Cycloaddition of the azomethine ylides 79, readily produced from 78 which is available in two steps from clavulanic acid, opens a route to a range of P-lactam based heterocycles, e.g. 80, through a regio- and stereo-selective reaction <99JHC1365,00T5579>. 

Cycloaddition reactions (see Table I) involving unsaturated carbohydrates are regio- and stereo-selective. These selectivities can be understood by assuming that the photochemical interaction between the two 7r-systems results in formation of the more stable 1,4-diradical. The reaction between 3,4,6-tri-O-acetyl-D-glucal (1) and acetone pro-... 

The use of stannylcuprate reagents is well established.112,113 The reactions occur under mild conditions. They are reversible, and the reactivity and regio- and stereo-selectivity are sensitive to the structure and reaction conditions, as illustrated by the reaction of allene with the lower-order cuprate Bu3SnCuCNLi and, more readily, with the higher order cuprate (Bu3Sn)2CuCNLi (Equation (29)).114... 

The regio- and stereo-selective functionalization of aldonolactones yields optically active lactones, which are important precursors in natural product synthesis. Concepts such as chiral templates and chirons, derived from carbohydrates, have been ingeniously and widely applied in synthesis (233). Among the commercially available aldonolactones, D-ribono-1,4-lactone is... 

It has long been known that unsaturated compounds containing a delocalized system of 71 electrons can rearrange into cyclic compounds or other n systems. Such reactions were only incidentally studied until 1930. 0. Diels and K. Alder published their first paper on diene synthesis (which was later given the name Diels-Alder reaction) in 1928. Subsequent work of K. Alder and G. Stein (1933 and 1937) proved the generality of the reaction and its high regio and stereo selectivity. This led to the interest on thermal transformations in unsaturated compounds. 

DISFAVOURED REGIO- AND STEREO-SELECTIVITY Reversal of kinetic control in a ring closure reaction... 

Oxiranes undergo ring-opening with cerium(VI) ammonium nitrate and an excess of a quaternary ammonium halide to yield haloethanols [34], The reaction occurs with high regio- and stereo-selectivity, for example, / (+)-styrene oxide produces S(+)-2-chloro-2-phenylethanol in 85% yield with 96% ee. 

In another case, the anion radical species undergoes regio- and stereoselective in-termolecular coupling reactions with carbon-carbon double bonds (Scheme 34) or triple bonds [74]. This reaction is useful for the regio- and stereo-selective formation of cyclic alcohols having a 5-membered ring [75, 76]. 

The coupling reaction is very fast because unstable cyclopentadienols resulting from the decomposition of ferrocenium cations can be trapped, in good yields (80%), by triazoline diones [73]. The cycloadduct is obtained with totally regio and stereo selectivities (Scheme 51). 

Figure 2.2 Regio- and stereo-selective steroid hydroxylation...

Anh, N. T. Regio- and Stereo-Selectivities in Some Nucleophibc Reactions. 88, 145-612 (1980). 

A range of addition reactions of (TMS)3GeH with alkynes, alkenes, ketones, azines, and quinones has been studied using EPR. In addition, synthetic studies of hydrogermylation of alkynes have shown that the reaction proceeds regio- and stereo-selectively, whereas reactions with alkenes do not take place (presumably owing to the reversibility of the germyl radical addition) (Scheme 29). 

The C-glycosylation of pentose glycals with silylacetylenes or allylsilanes through oxocarbenium ion intermediates proceeds with high regio- and stereo-selectivity, giving the 1,4-anti compounds as the main products. ... 

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