Diastereoface-differentiation

Diastereoface-differentiating reactions of a carbenoid with an alkene bearing an easily removable, chiral substituent have been used only ocassionally for the enantioselective production of a cyclopropane 216). A recent example is given by the cyclopropanation of the (—)-ephedrine-derived olefin 223 with CH2N2/Pd(OAc)2 after removal of the protecting group, (1/ , 2R )-2-phenylcyclopropane carbaldehyde was isolated with at least 90% e.e. 37). 

This approach sets the stage for an enantiotopos-differentiating olefin metathesis which would allow the enantioselective synthesis of 258. However, the realization of such an approach has not yet been successful [132]. The second building block (259) containing the A ring was synthesized diastereoselectively by a diastereoface-differentiating intramolecular Heck-Mizoroki reaction of the enantiomerically enriched furan 260 [120]. 

A complete set of examples is given in Section 1.2.4.2. Occasionally, an ambiguity can arise when the starting material is not clearly defined. For instance, the following reaction" may be classified as diastereotopos- or diastereoface-differentiating depending on whether the lactone or the enolate is considered to be the starting material ... 

To avoid this difficulty the words single-step and reactant are used. Clearly, the lactone is considered to be a starting material, but the enolate to be the reactant and therefore a diastereoface-differentiating reaction is said to have occurred. This example may illustrate another point, i.c.. that the product-based classification according to types of stereoselectivity and the Izumi-Tai classification (stereodifferentiation) are independent to a certain extent. Thus, the example can be classified as a diastereoface-differentiating, diastereoselective reaction. 

Quite obviously, this is simultaneously an enantiotopos- and diastereoface-differentiating (enantio- and diastereoselective) reaction3. Similar combinations can be found in Table 15. Section 1.2.2.3 (p 54). Thus, the transformation of 12 into 13 is a diastcreotopos-diastereoface-... 

Most stereoselective reactions are enantio- or diastereoface-differentiating reactions. Seebach and Prelog condensed their rules into a small but concise table1 that is reproduced here in a very slightly modified manner (Table 16). 

The same models as for intermolccular processes are applied for intramolecular diastereoface differentiating double-bond additions. However, there are some advantages in the intramolecular version. Firstly, the entropy factor lowers the barrier of activation and allows reactions to proceed at lower temperatures, which increases the selectivity. Secondly, the cyclic transition states introduce the elements of ring strain and transannular interactions, which lead to enhanced differences between two diastereomorphous geometries. Both of these factors cooperate to increase the selectivity of the intramolecular reaction. For example, halolactonization, by definition, is an intramolecular process. 

A more sophisticated level ofdiastereoselection is obtained by combining various diastereoface differentiating effects in one addition step. This can be done in an additive or a multiplicative manner. 

When the configuration at (at least) one chiral unit is known in a nonracemic product, then the relative configuration needs to be determined. This situation occurs in substrate-induced reactions with many classical examples in steroid, terpene, and carbohydrate chemistry, such as the reduction of a carbonyl group (diastereoface-differentiating reaction), the transformation —CH2------> —CHBr— by radical bromination (diastereotopos-differentiating reaction), or dif-... 

Examples to show some other types of diastereoface-differentiating reactions. Here, the configuration was again established using chemical methods. 

Modern synthetic chemistry has taken up the challenge of acyclic substrate-induced stereoselection302, including auxiliary-directed stereoselectivity. The main principles are 1,2-in-duction, the formation of cyclic intermediates, and intramolecular reactions. Many aspects, rules , and examples of diastereoface-differentiating reactions, both in cyclic and in acyclic systems, are summarized in Section 2.3.5.2. 

In addition to simple diastereoselectivity, high levels of induced diastereoselectivity may be obtained, for example, with racemic 2-phenylpropanal, where the induced diastereoselectivity due to diastereoface differentiating attack of the organometallic reagent on the aldehyde is 82 18. 

The classification of stereo-differentiation (63) (see Section VII) is as follows enantiomer-differentiation includes enantioface-difTerentiation, enantiotopos-dilferentiation, and enantiomer-differentiation diastereo-differentiation includes diastereoface-differentiation, diaster-eotopos-differentiation, and diastereomer-differentiation. 

In this section the diastereoface-differentiatings ability and the enantiomer-differentiating6 ability of MRNi will be introduced as examples. 

By modification with an optically active compound, RNi can acquire both enantiomer-differentiating ability and diastereoface-differentiating ability in addition to the enantioface-differentiating ability. The diastereoface- and enantiomer-differentiating abilities of MRNi can be observed when a substrate containing both chiral and sp2-prochiral centers is used, because such a compound has a diastereoface and a chirality. 4-Hydroxy-2-pentanone is one of the substrates with a chiral and sp2-prochiral center, as shown in Fig. 17. 

A diastereoface-differentiating reaction is a reaction in which one diastereomer is produced more than the other from the substrate containing both chirality and sp2-prochirality, as shown in Fig. 17. Both sides of the molecular plane of such a molecule are called diastereofaces. One of the diaslereomers could be produced more than the other when the catalyst or reagent differentiates one of the diastereofaces and performs an addition reaction. Thus, we call this type of reaction a "diastereoface-differentiating reaction."... 

Diastereoselective transfer hydrogenation of the chiral ketone (S)-A with (R,/ )-43 in 2-propanol gives (3S.4S)-B in >97% yield (Scheme 1.87) [327). Reaction with (S,5)-43 affords the 3R.4S alcohol predominantly. The degree and sense of diastereoface differentiation are mostly controlled by the chirality of the Ru catalyst. 

An example of diastereoface differentiation is provided in an asymmetric synthesis of the dipeptide Ala-Ala [70]. The element of chirality is that of one of the alanine groups, and the faces are those of a Schiff base, > C=N—. The material undergoing a catalytic reduction is the isobutyl ester of the benzylamine Schiff base of N-pyruvoyl-(5)-alanine, 54. The ratio of R S (55) to S S dipeptide was 82 18 for an optical purity of 64%. 

The report includes details for asymmetric a-alkylation of a symmetrical ketone (97% ee) via the SAMP hydrazone and references to other stereoselective reactions of SAMP (or RAMP) hydrazones. Under standard conditions (LDA, 0°), deprotonation takes place regioselectively at the less substituted a-position with uniform diastereoface differentiation. 

Lodge, E. R Heathcock, C. H. Acyclic stereoselection. 40. Steric effects, as well as (T -orbital energies, are important in diastereoface differentiation in additions to chiral aldehydes, J. Ant Chem. Soc. 1987,109, 3353-3361. 

Electron-deficient allylic systems, such as -/-hydroxy- or y-alkoxy-a,/J-unsalurated esters 1R-23, show a peculiar behavior. ( )-Alkenes afford the normal sense of diastereoface differentiation 16d 29 which dramatically increases in the presence of an additional silyloxy-substituted stereocenter at the <5 position22. On the contrary, (Z)-configurated alkenes give low or unpredictable selectivities8 20 37. 

A similar effect is observed in the osmylation of allylamides bearing a bis-homoallylically located sulfoxide group94. In this case the asymmetric 1,5-induction of the stereogenic sulfur atom totally overwhelms the weak bias of the allylic chirality. The concomitant sulfoxide-to-sulfone transformation suggests sulfoxide involvement in the oxidation mechanism. In this example, as well as in the previous one, replacement of the sulfur-based directing group by a sulfone moiety leads to a drop in diastereoface differentiation. 

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