Stereoselectivity ligand control

P. Denis, A. Jean, J. F. Crcizy, A. Mortreux, and F. Petit, J. Am. Chem. Soc., 112, 1292 (1990) A. Mortreux, Ligand Controlled Catalysis Chemo to Stereoselective Syntheses from Olefins and Dienes over Nickel Catalysts, in A. F. Noels, M. Graziani, and A. J. Hubert, eds., Metal Promoted Selectivity in Organic Synthesis, p. 47, Kluwer Academic, Dordrecht, 1991. 

These results, obtained with chiral substrates, agree with the general sense of enantioselective hydrogenation of prochiral 3-oxo carboxylic esters. Obviously, the chirality of the BINAP ligand controls the facial selectivity at the carbonyl function, whereas cyclic constraints determine the relative reactivities of the enantiomeric substrates. Sterically restricted transition states that lead to the major stereoisomers are shown in Scheme 66. Overall, one of four possible diastereomeric transition states is selected to afford high stereoselectivity by dynamic kinetic resolution that involves in situ racemization of the substrates. 

This type of additive (or ligand) control of stereoselectivity has three advantages. First of all, after the reaction has been completed, the chiral additive can be separated from the product with physical methods, for example, chromatographically. In the second place, the chiral additive is therefore also easier to recover than if it had to be first liberated from the product by means of a chemical reaction. The third advantage of additive control of enantioselectivity is that the enantiomerically pure chiral additive does not necessarily have to be used in stoichiometric amounts catalytic amounts may be sufficient. This type of catalytic asymmetric synthesis, especially on an industrial scale, is important and will continue to be so. 

In 1981, a stereoselective palladium-catalyzed 1,4-diacetoxylation of conjugated dienes was reported [51-53]. By ligand control it was possible to direct the reaction to either 1,4-trans- or 1,4-cw-diacetoxylation (Scheme 8-7). 

The Pd-catalyzed, LiHBEt3-mediated reductive desulfonylation of allylic sulfones is also used in the ligand-controlled stereoselective synthesis of dienes191 where it is possible to control the geometry of the diene by a proper selection of the palladium ligand as shown by the distribution of products 1 and 2 (Eq. 115). The method described herein is also applicable to the so-called integrated chemical processes , which allow the preparation of a wide variety of alkenes by combining alkylation of allylic sulfones and reductive desulfonylation in one pot.192,193... 

Chiral samarium (II) complexes have also been applied towards the hydrodimerization of acrylic acid amides [16]. Such reactions involve the ligand-controlled dimerization of conjugated ketyl radicals in the enantioselective formation of 3,4-tra .y-disubstituted adipamides (Eq. 11). Yields were mainly low, often under 40% and enantiocontrol was modest with selectivities ranging from around 50-85% ee. A nine-membered chelated transition state 37 is used to rationalize the stereoselectivity of the dimerization where the ligand-bound conjugated ketyl radicals are oriented cis to each other on the metal assuming an octahedral geometry. 

The hydroxide-promoted exchange of the a-proton of amino acids is catalyzed by metal ions [326]. If the amino acid is coordinated to a chiral complex fragment, the ratio of the two enantiomeric forms of the amino acid is controlled by a chiral intermediate [3]. One of the chiral fragments presented above in the discussion of the stereoselective ligand exchange reactions, [Co(S),(S)-ppm)j (see Table 8.2), was used to promote the epimerization of optically pure a-alanine [327]. The proposed mechanism is shown in Figure 8.10. 

A practical route to a highly syndiotactic poly(3-hydroxybut-yrate) (PHB) using a one-pot reaction has been presented (12). The stereoselective and controlled polymerization of racemic -butyro-lactone can be achieved by an initiator that is prepared in situ from yftrium(III) isopropoxide and a bisphenoxide ligand. 

Ananikov VP, Orlov NV, Kabeshov MA, Beletskaya IP, Starikova ZA. Stereoselective synthesis of a new t)fpe of 1, 3-dienes by ligand-controlled carbon-carbon and carbon-heteroatom bond formation in nickel-catalyzed reaction of diaryldichalcogenides with alkynes. Organometallics 2008 27 4056 061. 

The following C2-symmetric bis-sulfonamide is a more efficient controller of stereoselectivity in aldol additions. The incorporation of this ligand into the bromodiazaborolane, subsequent generation of the boron enolate derived from 3-pentanone, and addition to achiral aldehydes preferentially leads to the formation of ijn-adducts (synjanti 94 6 to >98 2) with 95-98% ee. Chemical yields of 85-95% are achieved51. 

There are very few examples of asymmetric synthesis using optically pure ions as chiral-inducing agents for the control of the configuration at the metal center. Chiral anions for such an apphcation have recently been reviewed by Lacour [19]. For example, the chiral enantiomerically pure Trisphat anion was successfully used for the stereoselective synthesis of tris-diimine-Fe(ll) complex, made configurationally stable because of the presence of a tetradentate bis(l,10-phenanthroline) ligand (Fig. 9) [29]. Excellent diastereoselectivity (>20 1) was demonstrated as a consequence of the preferred homochiral association of the anion and the iron(ll) complex and evidence for a thermodynamic control of the selectivity was obtained. The two diastereoisomers can be efficiently separated by ion-pair chromatography on silica gel plates with excellent yields. 

An interesting way to control the stereoselectivity of metathesis-reactions is by intramolecular H-bonding between the chlorine ligands at the Ru-centre and an OH-moiety in the substrate [167]. With this concept and enantiomerically enriched allylic alcohols as substrates, the use of an achiral Ru-NHC complex can result in high diastereoselectivities like in the ROCM of 111-112 (Scheme 3.18). If non-H-bonding substrates are used, the selectivity not only decreases but proceeds in the opposite sense (product 113 and 114). 

Summary of Facial Stereoselectivity in Aldol and Mukaiyama Reactions. The examples provided in this section show that there are several approaches to controlling the facial selectivity of aldol additions and related reactions. The E- or Z-configuration of the enolate and the open, cyclic, or chelated nature of the TS are the departure points for prediction and analysis of stereoselectivity. The Lewis acid catalyst and the donor strength of potentially chelating ligands affect the structure of the TS. Whereas dialkyl boron enolates and BF3 complexes are tetracoordinate, titanium and tin can be... 

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