Re-facial

This catalyst induces preferential re facial attack on simple aldehydes, as indicated in Ligure 2.2. The enantioselectivity appears to involve the shielding of the si face by the indole ring through a ir-stacking interaction. 

A proposed mechanism is shown in Scheme 1. The re-facial attack of CN to the intermediate imine 4 appears to be preferred, forming (R,S)-3. (R,S)-3 is less soluble and precipitates out of solution (R,R)-3 is more soluble and epimerizes in solution via the imine 4. 

Substituted norsnoutanes (61) have been introduced as substrates with sterically unbiased re-faces, which allow electronic effects in re-facial selectivity of nucleophilic additions to be evaluated.96 Examples indicate how this system allows separation of long-range electronic effects into orbital and electrostatic contributions. 

The enzyme-catalysed cyclization of (A)-[9-2 H i. H i ]gcranyl diphosphate to (45)-limonene has been found to terminate predominately by re-facial, anti proton elimination at tire cis methyl group of the intermediate (35)-l inalyl diphosphate.80... 

Mechanism and transition states The basic principles of the proline-catalyzed direct aldol reaction are summarized in Section 6.2.1.1 [93, 94a], The preferred diastereo- and enantioselectivity were explained in terms of the potential transition states for the aldol reaction using hydroxyacetone shown in Scheme 6.38 [93], Thus, re-facial attack of the aldehyde at the si face of hydroxyacetone leads to the... 

The six-membered transition-state is stabilized by hydrogen-bonding between the nitrogen of the imine and the carboxyl group of proline. Switching of the facial selectivity is disfavored, because of to steric repulsion between the PMP group of the imine and the pyrrolidine moiety of the enamine. This is opposite to similar direct asymmetric aldol reaction in which re-facial attack occurs [27, 30, 36]. 

Cyclopropanation and Aziridination (Alkene Three-Membered Cycloadduct) - Cyclopropanation of various trans-N-enoyl derivatives using diazomethane with Pd(OAc)2 as catalyst affords cyclopropyl products with good C(a)-re -facial control (eq 8). Similarly, aziridination with N-aminophthalimide-lead tetraacetate affords N-phthalimidoaziridines with variable but generally good jr-face selectivity (33-95% de). ... 

The re facial preference displayed by the reagent is enhanced in reactions proceeding through Lewis acid-catalyzed open transition states. Thus, when reacted with the ketene silyl acetal (eq 5) under zinc iodide catalysis, a 96 4 ratio of products was obtained. The corresponding uncatalyzed reaction led to an 85 15 mixture of the same products in similar yield. ... 

There are also several catalysts that can effect enantioselective aldol addition. The reactions generally involve enolate equivalents, such as silyl enol ethers, that are unreactive toward the carbonyl component alone, but can react when activated by a Lewis acid. The tryptophan-based oxaborazolidinone 7 has proven to be a useful catalyst 2i that induces preferential re facial attack on simple aldehydes. 

Subsequently, the one-pot organocatalytic [C+NC+CC] coupling reaction between aldehydes 204, dialkyl-2-aminomalonate 205 and a,p-unsaturated aldehydes 28 was achieved with highly chemo-and enantioselectivity by Cordova, et al Scheme 3.66 [83]. The mechanism involved the 1,3-dipolar cycloaddition of azomethine yhde and chiral iminium intermediate, via re-facial and endo-addition to give the pyrroUdine derivatives. Later, the authors reported a similar approach to 5-hydroxypyrrolidme 208 from acylaminomalonates 207 and a,P-unsaturated aldehydes 28, Scheme 3.67 [84]. 

The opposite configuration notation of the product alcohols are due to the CIP sequence rules. The directions of the asymmetric induction are consistent to afford (R)- isomers by si facial addition of hydride for both aliphatic and al-kylaromatic ketones. However, for a-haloketone and a-ketoester, re facial addition of hydride provides (S)-isomeric alcohols. The direct comparison of K-xylide asymmetric reductions reveals that the reagent resembles very closely to that of K-glucoride. 

It is proposed that efficient shielding of the 5t-face of the chiral iminium intermediate by the bulky aryl groups of the catalyst leads to a stereoselective Re-facial nucleophilic conjugate attack on the electrophilic P-carbon by the amino group of 163 (Scheme 1.70). Then the chiral enamine intermediate generated performs a 3-exo-tet nucleophilic attack on the now electrophilic nitrogen atom, and acetic acid is released. The intramolecular ring closure pushes the equilibrium in the forward direction and makes this step irreversible. 

We propose six-membered chair-like closed transition states for the reaction at the higher temperatures (-45 C and -20 C) as shown in Scheme 3 (57). The reaction proceeds exclusively with Re facial enantioselection to the aldehyde. The anti selectivity may be caused by the predominant formation of the ( )-boron enolate 11 and/or by its higher reactivity than the (Z)-isomer 10. From the ( )-isomer, the corresponding anti-Mol should be obtained via the cyclic h ansition state 13. 

In the lanthanoid-lithium-( )-BINOL-catalyzed nitroaldol reaction of 2,2-difluoroaldehydes, the nitronates were found to preferentially react on the Si face of the aldehydes. On the contrary, (/1)-LLB generdly causes attack with the Re facial selection as ahown in Figure 2 (39,40,42). Therefore, the enantiotopic face selection for 2,2-difluoroaldehydes is opposite to that for nonfluorinated aldehydes. This stereoselectivity is identical with that of jS-oxaaldehydes, suggesting that fluorine atoms at the a position exert a significant influence on the enantioface selection. The fluorine atoms may coordinate with the rare earth or the lithium of LLB complexes. 

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