Steric differentiation

This is the result of a steric differentiation on the basis of the approach of electrophile from the side of the enolate where the 10-position is occupied by the smaller hydrogen rather than the ring. 

The results observed in the oxidation of alkaloids which indicated something of the stereochemistry required for oxidation and prompted studies on model systems can now be interpreted more confidently. However, care must be used when basing steric differentiation on mercuric acetate oxidation studies since conditions must be employed which avoid epimerization at carbons alpha to the nitrogen. 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

For simple, conformationally biased cyclohexanone enolates such as that from 4-t-butylcyclohexanone, there is little steric differentiation. The alkylation product is a nearly 1 1 mixture of the cis and trans isomers. 

The interpretation and prediction of the relationship between the configuration of the newly formed chiral center and the configuration of the amine is usually based on steric differentiation of the two faces of the imine anion. Most imine anions that show high stereoselectivity incorporate a substituent that can engage the metal cation in a... 

Little steric differentiation is observed with either the lithium or boron enolates of 2-methyl-2-pentanone.102... 

Several enolates of 4,4-dimethyl-3-(trimethylsiloxy)-2-pentanone have been investigated.106 The lithium enolate reacts through a chelated TS with high 2,2 -anti stereoselectivity, based on the steric differentiation by the f-butyl group. 

These examples and those in Scheme 2.6 illustrate the key variables that determine the stereochemical outcome of aldol addition reactions using chiral auxiliaries. The first element that has to be taken into account is the configuration of the ring system that is used to establish steric differentiation. Then the nature of the TS, whether it is acyclic, cyclic, or chelated must be considered. Generally for boron enolates, reaction proceeds through a cyclic but nonchelated TS. With boron enolates, excess Lewis acid can favor an acyclic TS by coordination with the carbonyl electrophile. Titanium enolates appear to be somewhat variable but can be shifted to chelated TSs by use of excess reagent and by auxiliaries such as oxazolidine-2-thiones that enhance the tendency to chelation. Ultimately, all of the factors play a role in determining which TS is favored. 

In Entry 3, the trans stereochemistry arises at the stage of the protonation of the enolate. Entry 4 gives rise to a cis ring juncture, as does the corresponding carbocyclic compound.59 Models suggest that this is the result of a steric differentiation arising from the axial hydrogens on the a-face of the molecule. 

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

Table 7 Steric differentiation as a regiocontrol element in the hydrosilylation of internal alkynes...

Keywords Allylic Alkylation m Asymmetric Catalysis m C2-Symmetry m De-symmetrization m Electronic Differentiation m Heck Reaction m Hydrogenations m Metal Complexes m Modular Design m P,N-Ligands m Steric Differentiation m Respective Control... 

Enzymes, in particular peroxidases, catalyze efficiently the enantioselective oxidation of alkyl aryl sulfides and also dialkyl sulfides, provided that the alkyl substituents are sterically differentiable by the enzyme. The peroxidases HRP, CPO, MP-11, and the mutants of HRP, e. g. F41L and F4IT, were successfully used as biocatalysts for the asymmetric sulfoxidation (Eq. 14). A selection of sulfides. 

Similar chelation effects appear to be present in a-alkoxymethyl derivatives. Magnesium enolates give predominantly the Z-enolate as a result of this chelation. The corresponding trimethylsilyl enol ethers give E/Z mixtures because of a relatively weak steric differentiation between the ethyl and alkoxymethyl substituents.171... 

A selective oxidation of a primary alcohol in the presence of a secondary one in a complex substrate can be done with 88% yield with Dess-Martin periodinane. The authors comment that Selective oxidation of the primary alcohol proved to be unexpectedly straightforward. Thus, treatment with Dess-Martin periodinane afforded aldehyde with 88% yield, with complete selectivity for the primary alcohol. Despite the large number of documented applications of this mild oxidation, no study has yet addressed its potential for selective oxidations of sterically differentiated diols . 

In addition to the steric differentiation of the constants kx and k l9 the velocity of the hydride transfer steps (k2 vs. k 2) could also be different because the development of the diastereomeric transition states will require different energies. The contribution to the reaction velocity of this effect is difficult to assess. 

To examine the possibility of a more selective catalytic olefin metathesis, we first prepared chiral Mo-based complexes, 4a and 4b [10]. This approach was not without precedence related chiral Mo complexes were initially synthesized in 1993 and used to promote polymer synthesis [6], We judged that these biphen-based systems would initiate olefin metathesis with high asymmetric induction due to their rigidity and the steric differentiation imposed on the chiral complex s binding pocket. Mo complexes 4a and 4b are orange solids and indefinitely stable when kept under an inert atmosphere. 

Rate effects of the type listed in Table 6.5 make it possible to carry out chemoselective monohydrolyses of sterically differentiated chesters, for example ... 

H-3). This selective interaction suggests restricted rotation and allows steric differentiation and assignment between the diastereotopic protons. 

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