Asymmetric enantiotopic olefins

In order to achieve asymmetric hydrogenation, we need to incorporate a chiral phosphine that is capable of distinguishing between the enantiotopic faces of the prochiral olefin, so that one of these faces is coordinated preferentially to the rhodium atom. (It should be noted that the attachment of a prochiral olefin to a metal atom produces a chiral system irrespective of what else is attached to the metal.) Thus the catalyst solution will contain two diastereomeric species, each having the same phosphine chirality but with opposite chiralities of the metal olefin center. Such an equilibrium is shown as Kx in Figure 3. 

The potential utility of an asymmetric addition to a prochiral carbonyl can be seen by considering how one might prepare 4-octanol (to take a structurally simple example) by asymmetric synthesis. Figure 4.16 illustrates four possible retro-synthetic disconnections. Note that of these four, two present significant challenges asymmetric hydride reduction requires discrimination between the enantiotopic faces of a nearly symmetrical ketone a), and asymmetric hydroboration-oxidation requires a perplexing array of olefin stereochemistry and regiochemical issues h). In contrast, the addition of a metal alkyl to an aldehyde offers a much more realistic prospect (c) or (d). 

For achiral metallocene-based catalysts Czv and achiral Q metallocenes in Chart 2) the chain-end control is present as the only stereocontrol mechanism. It derives from the presence of an asymmetric carbon atom on the last inserted monomer. The chirality R or 5) of this atom is related to the enantiotopic face of the olefin where the insertion took place (Scheme 34). In the NMR spectrum of the polymer we lose this kind of information, as two successive insertions of the re olefin face and two successive insertions of the si face produce the same m diad (see section II.G). As a consequence, we can observe only the relative chirality between consecutive inserted monomer units (5,5 or R,R as m diads and S,R or R,S as r diads) disregarding the absolute configuration of tertiary atoms. We prefer to use the re and si nomenclature indicating the stereochemistry of the methines in the polymer chain (Scheme 35), bearing in mind that the insertion of the re propene enantioface will produce an 5 configuration on the methine. 

In addition to simple asymmetric hydroacylation of alkenes, highly efficient desymmetrization of alkenes has also been achieved by Wu and co-workers. Interestingly, the catalyst system (Rh(I)-BINAP) differentiated the enantiotopic faces of the olefins and thus the cyclopentanone products were obtained with excellent ee s. The authors also showed that neutral and cationic Rh(I)-BINAP complexes furnished dififerent products. The neutral catalyst system preferentially fiunished the cw-3,4-disubstituted cyclopentanone, and the cationic catalyst afforded the trans isomer. 

A key step in metal-induced olefin polymerization has the olefin tt face complexing to the metal center. The two faces of the propylene double bond are enantiotopic. Isotactic polypropylene forms when only one face of the propylene monomer consistently reacts to make polymer. Thus, a chiral catalyst is needed to distinguish enantiotopic faces of an olefin. But, how do we ensure that only one face reacts It is a complicated problem, because when an olefin like propylene complexes to a metal center in a typical chiral environment, not only will both faces complex to some extent, but many orientations are possible for each complex. This leads to many different reaction rates, and a mixture of Stereochemistries. A key to the solution, then, was to develop a catalyst that is chiral but not asymmetric. In particular, the C2-symmetric metallocene shown below was prepared. The metal is chirotopic but non-... 

As shown in Table I, when styrene in the a-CD complex was brominated at 0°C for 2 h, the levorotatory dibromide (2) ([a] -47.0 ) and racemic bromohydrin (3) were isolated in 90% yield (2 3 = 96 4). Bromination of the olefin in the -CD complex gave no 3 but 2 ([a] f -5.5°) in 95% yield at the same reaction condition. The chiral induction for the reaction of the a-CD complex rose to 9 times that of the fi-CD complex. The same sign of the specific rotations of 2 shows that styrene forms complexes with a- and y5-CDs such that the access of bromine to the olefinic plane occurs into the same enantiotopic face in the two cases, and this face may be slightly less blocked by the inclined plane in both the asymmetric cavities of CDs. A detailed mechanism, however, cannot be described at the present time, because neither crystalline nor molecular structures were determined for the solid CD complexes. No bromination of styrene in the CD complexes occurred at a temperature of —10 °C or below because the vapor pressure of bromine is not enough to sustain the reaction bromine solidifies at -7.3 °C. 

The ability of the catalyst to form asymmetric epoxides led Jacobsen to ask whether the same chiral salen ligands that discriminate between the enantiotopic faces of an approaching olefin also create an effective dissymmetric environment for nucleophilic attack at a bound epoxide. Indeed, Jacobsen et al. were also able to use very similar salen catalysts for the asymmetric ring opening of epoxides by nucleophilic attack on an epoxide activated by binding to a chiral, Lewis acidic Cr(III) metal salen complex. 

Most optically active olefinic products possess axial or planar chirality, which can be easily converted into central chirality by further appropriate chemical transformation without any serious loss of optical purity. The products obtained by the discrimination of enantiotopic carbonyl groups or kinetic resolution already have central chirality as well as reactive functional groups such as olefinic or unsaturated carbonyl systems. Consequently, asymmetric olefination provides an efficient methodology for the construction of useful chiral synthons applications along these lines in the asymmetric construction of useful and complex chiral molecules have just started and will be extensively investigated in the future. 

The asymmetric cyclisation of achiral olefinic organohthium reagents by a stereogenic alkah metal centre can be modulated by ( )-sparteine, which confers enantiofacial selectivity on the reaction such that the anionic cyclisation process discriminates between the enantiotopic faces of an unactivated C=C bond. Recently, modifications have been made to the well known hthium-ene cyclisation reaction whereby the subsequent expulsion of a thiophenoxide group yields a fused vinylcyclopropane. Moreover, allylic lithium oxyanion-induced reactivity and stereoselectivity in this intramolecular carbometallation has been demonstrated in the highly stereoselective synthesis of a natural bicyclo[3.1.0] hexane. ... 

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