Re-face

A model for the mechanism of the highly enantioselective AlMe-BINOL-cata-lyzed 1,3-dipolar cycloaddition reaction was proposed as illustrated in Scheme 6.13. In the first step nitrone la coordinates to the catalyst 11b to form intermediate 12. In intermediate 13, which is proposed to account for the absolute stereoselectivity of this reaction, it is apparent that one of the faces of the nitrone, the si face, is shielded by the ligand whereas the re face remains available... 

As another example, studies with deuterium-labeled substrates have shown that the reaction of ethanol with the coenzyme NAD+ catalyzed by yeast alcohol dehydrogenase occurs with exclusive removal of the pro-R hydrogen from ethanol and with addition only to the Re face of NAD+. 

Problem 9.25 Lactic acid buildup in tired muscles results from reduction of pyruvate. If the reaction occurs from the Re face, what is the stereochemistry of the product ... 

Problem 19.19 What is the stereochemistry of the pyruvate reduction shown in Figure 19.15 Does NADH lose its pro-R or pro-S hydrogen Does addition occur to the Si face or Re face 1 of pyruvate ... 

Assign R or S stereochemistry to the two chirality centers in isocitrate, and tell whether OH and H add to the Si face or the Re face of the double bond. 

Problem 29.6 Does the reduction of acetoacctyl ACP in step 6 occur on the Re face or the Si face of the molecule ... 

In step 2 of the citric acid cycle (Figure 29.12), c/s-aconitate reacts with water to give (2i ,35)-isocitrale. Does -OH add from the Re face of the double bond or from the Si face What about -H Does the addition of water occur with syn or anti geometry ... 

In step 8 of fatty-acid biosynthesis (Figure 29.5), reduction of fram-crotonyl ACP gives butyryl ACP. A hydride from NADPH adds to C3 of the crotonyl group from file Re face, and protonation on C2 occurs on the Si face. Is tire reduction a syn addition or an anti addition ... 

Re face (Section 9.13) One of two faces of a planar, s/ 2-hybridized atom. 

Addition of the prc-R hydrogen of NADH takes place on the Re face of pyruvate. 

For oxathiane 1, lone pair selectivity is controlled by steric interactions of the gem-dimethyl group and an anomeric effect, which renders the equatorial lone pair less nucleophilic than the axial lone pair. Of the resulting ylide conformations, 25a will be strongly preferred and will react on the more open Re face, since the Si face is blocked by the gem-dimethyl group (Scheme 1.9) [3, 15]. 

The C2 symmetry of sulfide 13 means that a single diastereomer is formed upon alkylation (Scheme 1.10). Attack from the Si face of the ylide is preferred as the Re face is shielded by the methyl group cis to the benzylidene group (28). Metzner postulates that this methyl group also controls the conformation of the ylide, as a steric clash in 27b renders 27a more favorable [16]. However, computational studies by Goodman revealed that 27a was not particularly favored over 27b, but it was substantially more reactive, thus providing the high enantioselectivity observed... 

In the case of sulfide 7 the bulky camphoryl moiety blocks one of the lone pairs on the sulfide, resulting in a single diastereomer upon alkylation. One of the conformations (29b) is rendered less favorable by non-bonded interactions such that conformation 29a is favored, resulting in the observed major isomer (Scheme 1.11). The face selectivity is also controlled by the camphoryl group, which blocks the Re face of the ylide. 

The high enantioselectivity observed was interpreted in terms of the face selectivity of the (Z)-enolate 59 (Scheme 1.20). The phenyl moiety is thought to stabilize the enolate through a n-n interaction and effectively shield its Re face such that the incoming ketone approaches preferentially from the Si face. 

Indeed, the combination of the aldehyde 1 with the (S)-enolate 2 delivers the diastereomers 3a and 3b in excellent selectivity (>100 1, matched pair ). On the other hand, a 1 30 ratio of 4 a/4 b is found in the corresponding reaction of the (2 )-enolate 2. Although the selectivity in the latter case ( mismatched pair ) is distinctly lower, the reliability of this chiral enolate 2 provides a degree of induced stereoselectivity which is sufficient for practical applications ( double diastereodifferentiation )29. The stereochemical outcome is largely determined by the chirality of the enolate in that the (S)-enolate 2 attacks the aldehyde almost exclusively from the Re-face whereas the (/ -enolate adds preferably to the Si-face of the carbonyl group in the aldehyde. 

Acyloins (a-hydroxy ketones) are formed enzymatically by a mechanism similar to the classical benzoin condensation. The enzymes that can catalyze reactions of this type arc thiamine dependent. In this sense, the cofactor thiamine pyrophosphate may be regarded as a natural- equivalent of the cyanide catalyst needed for the umpolung step in benzoin condensations. Thus, a suitable carbonyl compound (a -synthon) reacts with thiamine pyrophosphate to form an enzyme-substrate complex that subsequently cleaves to the corresponding a-carbanion (d1-synthon). The latter adds to a carbonyl group resulting in an a-hydroxy ketone after elimination of thiamine pyrophosphate. Stereoselectivity of the addition step (i.e., addition to the Stand Re-face of the carbonyl group, respectively) is achieved by adjustment of a preferred active center conformation. A detailed discussion of the mechanisms involved in thiamine-dependent enzymes, as well as a comparison of the structural similarities, is found in references 1 -4. 

Restrictions for the substrates of the transketolase-catalyzed reaction only arise from the stereochemical requirements of the enzyme. The acceptor aldehyde must be formaldehyde9,20, glycolaldehydel6,17 or a (R)-2-hydroxyaldehyde10,17. The donor ketose must exhibit a (3(7,4 R) configuration10. The enzyme selectively adds the hydroxyacetyl moiety to the Re-face of the acceptor aldehyde leading to a 3(7 configuration of the products. 

These results may be rationalized by assuming a chelation model 4. The nucleophile preferentially attacks the Re-face of the A -acylimine double bond, because the S/ -face is shielded by the phenyl group of the auxiliary9. 

J Based on polarimctry. NMR and GC analysis. These results support a uniform stereochemical course of the reaction The nucleophile attacks the Re-face of the SAMP-hydrazone. b Obtained with RAMP (2c) as auxiliary. 

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