Re-face attack

Q Chiral racemic y-alkyl-substituted enones the titanium(IV) chloride mediated addition of enol silanes and silylketene acetals to 7 shows high induced diastereoselection (diastereomeric ratios from 89 11 to more than 97 3) and the major isomer 8 results from addition of the enolsilane with ul topicity288. Re face attack on the S enantiomer of 7.)... 

NeuA, has broad substrate specificity for aldoses while pyruvate was found to be irreplaceable. As a notable distinction, KdoA was also active on smaller acceptors such as glyceraldehyde. Preparative applications, for example, for the synthesis of KDO (enf-6) and its homologs or analogs (16)/(17), suffer from an unfavorable equilibrium constant of 13 in direction of synthesis [34]. The stereochemical course of aldol additions generally seems to adhere to a re-face attack on the aldehyde carbonyl, which is complementary to the stereoselectivity of NeuA. On the basis of the results published so far, it may be concluded that a (31 )-configuration is necessary (but not sufficient), and that stereochemical requirements at C-2 are less stringent [71]. 

Ti-BINOL-catalyzed reactions have been well established. When the Ti is replaced by Zr,92 the resulting complex 140 can also catalyze the addition of allyl-tributyltin to aldehydes (aldehydes allyl-tributyltin 140 = 1 2 0.2 mol ratio) in the presence of 4 A MS. Product l-alken-4-ols are obtained in good yield and high ee. The, Sz-face of the aldehyde is attacked if (S)-BINOL is used, and Re-face attack takes place when (K)-BINOL is used as the chiral ligand. For Zr complex-catalyzed reactions, the reaction proceeds much faster, although the... 

In methanol at room temperature, the re-face attack of CN" to the intermediate imine 4 is preferred. 

The most representative results of these additive systems are (1) allyl alcohol seems to inhibit the Si-face attack of the hydride, and (2) allyl bromide inhibits the. Re-face attack. In this system, if it is assumed that CF3 is sterically less demanding than the CH2COCH3 substituent, Prelog s rule holds for the yeast-allyl bromide additive reduction system, whereas it is not followed when the additive is allyl alcohol [26]. 

Concerning the substrate oct-1-ene 99, the normal products 100 and 101 could be formed via [2a + 2S] transition states, however, in the event of re-face attack, more severe interactions of R with the environment could open an alternative radical pathway leading to N-alkylation. 

Scheme 2. Mechanistic analysis of reaction pathways for NeuA catalysis that considers the crucial influences of C-3 and anomeric configurations and of chair conformations on the three-point attachment of aldoses as acceptor substrates, Si-face attack leads to regular (4S)-configurated adducts while re-face attack leads to inverted stereochemistry (abbreviations anm = anomerization, inv = ring inversion)...

The stereochemical course of aldol additions generally seems to adhere to a re-face attack on the aldehyde carbonyl, a facial selection complementary to that of sialic acid aldolase. On the basis of the results published so far it may further be concluded that a (3J )-configuration is necessary (but not sufficient), and that stereochemical requirements for C-2 are less stringent. 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0- 2,6-dnsopropoxybenzoyl)tartanc acid and BH3 THF complex in propiomtnle solution at 0°C Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution The relative stereochemistry of the major adducts was assigned as Fischer-r/treo, and predominant Re-face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (R,R)-enanttomer of the tartanc acid catalyst (K Furuta, 1991). 

R,2S configuration of the Michael adduct resulting from the reaction of cyclohexanone with /3-nitrostyrcnc indicates the. Re-face attack on /3-nitrostyrcne by an enamine intermediate. The enantioselectivities observed (<70% ee) were rather modest.154... 

The Cp() ,f )-Ti[All] and Cp(S,S)-Ti[All] reagents have been condensed with a variety of aldehydes always with good enantios-electivities (eqs 4-11). The degree of enantioface discrimination of these allyltitanium reagents is very high. The Si face attack is preferred for the Cp(/f,/f)-Ti[All] reagent and the Re face attack is preferred for the Cp(S,S)-Ti[All] reagent. 

Cycloadditions (Athene Five-Membered Cyclo-adduct) The levels of selectivity found for 1,3-dipolar cycloaddition reactions are not as high as those obtained for Lewis acid-catalyzed Diels-Alder reactions. However, the 10,2-camphorsultam auxiliary can achieve synthetically useful levels of induction in these reactions, and this has been attributed to efficient enoyl conformational control by the sultam moiety leading to preferred C(a)-re face attack even in the absence of metal complexation. ... 

Analogous with the previous results of enol silyl ethers of ketones, nonsubstituted ketene silyl acetals are found to exhibit lower levels of stereoregulation, while the propionate-derived ketene silyl acetals display a high level of asymmetric induction. The reactions with aliphatic aldehydes, however, resulted in a slight reduction in optical and chemical yields. With phenyl ester-derived ketene silyl acetals, syn adducts predominate, but the selectivities are moderate in most cases in comparison with the reactions of ketone-derived silyl enol ethers. Exceptions are a,p-unsaturated aldehydes, which revealed excellent diastereo- and enantioselectivities. The observed syn selectivity and re-face attack of nucleophiles on the carbonyl carbon of aldehydes are consistent with the aforementioned aldol reactions of ketone-derived enol silyl ethers. 

The relative stereochemistry of the major adducts is assigned to be syn, and the predominant re face-attack of enol ethers at the aldehyde carbonyl carbon has been confirmed when a natural tartaric acid derivative is used as a Lewis acid ligand. The use of an unnatural form of tartaric acid as a chiral source gives the other enantiomer, as expected. Almost perfect asymmetric induction are achieved with the syn adducts. 

A successful approach to exploit the chelating ability of MeMgBr to control addition to the hydrazone 31 was discovered when the Grignard reaction was carried out in toluene solvent. Since toluene is a noncoordinating and nonpolar solvent, the magnesium coordinates with the substrate to activate the hydrazone and control the facial selectivity, as shown. A 94 6 selectivity for Re face attack to give 32 was observed after 1 hr at 20 C. There was no reaction after 48 hr at reflux temperature in THF [50]. 

---