Pro-chiral

The isomerization of an allylic amine to an enamine by means of a formal 1,3-hydrogen shift constitutes a relatively small structural change. However, this transformation could be extremely valuable if it could be rendered stereoselective. In important early studies, Otsuka and Tani showed that a chiral cobalt catalyst, prepared in situ from a Co(ii) salt, a chiral phosphine, and diisobutylaluminum hydride (Dibal-H), can bring about the conversion of certain pro-chiral olefins to chiral, isomeric olefins by double bond migra-... 

Pro-chiral pyridine A-oxides have also been used as substrates in asymmetric processes. Jprgensen and co-workers explored the catalytic asymmetric Mukaiyama aldol reaction between ketene silyl acetals 61 and pyridine A-oxide carboxaldehydes 62 <06CEJ3472>. The process is catalyzed by a copper(II)-bis(oxazoline) complex 63 which gave good yields and diastereoselectivities with up to 99% enantiomeric excess. 

In the presence of a chiral promoter, the asymmetric aldol reaction of pro-chiral silyl enol ethers 71 with prochiral aldehydes will also be possible (Table 3-6). In this section, a chiral promoter, a combination of chiral diamine-coordinated tin(II) triflate and tributyl fluoride, is introduced. In fact, this is the first successful example of the asymmetric reactions between prochiral silyl enol ethers and prochiral aldehyde using a chiral ligand as promoter. 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

Predictable absolute stereochemistry Thus far, when dealing with a pro-chiral allylic alcohol substrate, no exception to the rules laid down in Figure 4-1 has been observed. 

Ru(II)-BINAP complexes (1) can effect enantioselective hydrogenation of pro-chiral ally lie and homoallylic alcohols, without hydrogenation of other double bonds in the same substrate.1 The alcohols geraniol (2) and nerol (3) can be reduced to either (R)- or (S)-citronellol (4) by choice of either (R)- or (S)-l. Thus the stereochemical outcome depends on the geometry of the double bond and the chirality... 

Deracemization of lj-diols.1 Ketalization of (-)-menthone (1) with a pro-chiral 1,3-diol (2) results in formation of only two of the four possible diastereomers (3 and 4), which can be separated by chromatography and then hydrolyzed to provide (S)- and (R)- 2 in 92-98% ee. 

The prochirality concept is not necessarily an expression of a precursor-product relationship because there exist stereoselective reactions at pro-chiral elements that do not generate elements of chirality. An illustration of this is the reversible enzymatic dehydration of citric to cu-aconitic acid. In this process two prochiral centers of citric acid disappear and we obtain an achiral line of stereoisomerism that physically coincides with a prochiral plane of prostereoisomerism. 

The conjugate addition of organometallic reagents R M to an electron-deficient alkene under, for instance, copper catalysis conditions results in a stabilized car-banion that, upon protonation, affords the chiral yS-substituted product (Scheme 7.1, path a). Quenching of the anionic intermediate with an electrophile creates a disubstituted product with two new stereocenters (Scheme 1, path b). With a pro-chiral electrophile, such as an aldehyde, three new stereocenters can be formed in a tandem 1,4-addition-aldol process (Scheme 1, path c). 

Isomerizations may take place over some catalysts more than over others. Regio- as well as stereoisomers may be formed [13, 49. Such side reactions are undesirable in the reduction of pro-chiral alkenes, and especially in the hydrogenation of some cycloalkenes. 

As a consequence of the wide choice of hydride reagents the classical methods such as reduction with sodium in ethanol almost fell into oblivion [579, 520]. Nevertheless some old reductions were resuscitated. Sodium di-thionite was found to be an effective reducing agent [262], and the reduction by alcohols [309] was modified to cut down on the temperature [755] or the time required [527], or to furnish chiral alcohols ( in good yields and excellent optical purity ) by using optically active pentyl alcohol and its aluminum salt [522]. Formation of chiral alcohols by reduction of pro-chiral ketones is... 

Where possible, it may be most economical to effect a chiral transformation on a pre-formed, pro-chiral ring. Ben Feringa of the University of Groningen prepared (Chem Commun. 2005, 1711) the enone 2 from 4-methoxypyridine 1. Cu -catalyzed conjugate addition of dialkyl zincs to 2 proceeded in up 96% . Pd-mediated allylation of the intermediate zinc enolate led to 3, with the two alkyl subsituents exclusively trans to each other. 

Table I. Hydrogenation of Pro-Chiral Substrates Enantiomeric Excess vs. Reaction Variables"...

This obviously is unlikely for the given example because there is no reason for cyanide ion to have anything other than an exactly equal chance of attacking above or below the plane of the ethanal molecule, producing equal numbers of molecules of the enantiomers, 21 and 22. However, when a chiral center is created through reaction with a dissymmetric (chiral) reagent, we should not expect an exactly 1 1 mixture of the two possible isomers. For example, in an aldol-type addition (Section 18-8E) of a chiral ester to a pro-chiral ketone the two configurations at the new chiral center in the products 23 and 24 are not equally favored. That is to say, asymmetric synthesis is achieved by the influence of one chiral center (R ) on the development of the second ... 

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