Facial discrimination

Intramolecular Sm(n)-mediated coupling of ketones with distal vinylepoxides results in the corresponding carbocydic derivatives with good to excellent diaster-eoselectivity [125], When the reaction was conducted with enantioenriched substrates the products were obtained with poor ees, indicating low it-facial discrimination in this reaction. 

In the synthesis of six-membered cyclic nitronates (35) by the (42 + 43) cycloaddition, facial discrimination can be achieved by introducing enantiomerically pure chiral fragments into nitro olefin (42) (147, 157) enamine (117), or enol (134). In addition, Prof. Seebach (96) and postgraduate students supervised by Prof. Denmark (158) successfully used chiral LA for facial discrimination. 

Silyl nitronates containing chiral inductors have not been as yet used in intermolecular [3 + 2]-cycloaddition reactions. In this case, the facial discrimination was generally created by introducing chiral nonracemic fragments into dipolarophiles (see review 433). 

Organoaluminum reagents have been used in the copper-catalyzed conjugate addition to enones with some success. Iwata and co-workers (182) demonstrated that dimethoxyphenyl oxazoline (247) provides modest selectivities in the copper-catalyzed conjugate addition of trimethylaluminum to 3,4,4-trimethylcyclohexadi-enone to provide the adduct in 68% ee, Eq. 145. The use of TBSOTf is crucial to attain high conversion and selectivity in this process. Woodward and co-workers (183) subsequently reported that a Cu(I) complex of thiocarbamate 248 provides modest facial discrimination in the addition of trimethylaluminum to a linear enone to afford 245b in 51% ee, Eq. 146. The authors note that this catalyst system decomposes under the reaction conditions at ambient temperature. 

The reaction of vinyl ethers and enamines with nitroalkenes is highly regiose-lective, with only the head-to-head adduct observed. The endo approach of the dienophile is preferred in the thermal cycloaddition, however, the mode of approach can be controlled by the choice of the Lewis acid promoter (214). Facial discrimination has been obtained by the use of chiral groups on the both the nitroalkene (215,216) and the enamine (217) or vinyl ether (218), as well as with chiral Lewis acids (46,66,94,219,220). 

Other brain regions are undoubtedly involved in affi-liative behaviors. For example, the ventral temporal area of the cortex appears to be involved in facial discrimination in humans, and abnormalities in the activation of this area during facial discrimination tasks are present in individuals with autism (Schultz et ah, 2000). In rats and other mammals, the olfactory bulb and entorhinal cortex also appear to be involved in affiliative behaviors, including maternal behaviors (Numan, 1994). 

In this fourth part we outline some aspects of the reaction of lithium enolates with electrophilic reagents and their nucleophilic addition onto saturated carbonyl groups. Two significant problems associated with these reactions are (i) the site (C/O) selectivity due to the ambident character of enolates, and (ii) the facial discrimination which controls the stereochemistry of the overall process. 

The [2+2] cycloaddition of this chiral enol ether 63 with in situ generated dichloroketene proceeded with a high level of facial discrimination (95 5) to afford dichlorocyclobutanone 64 (Greene... 

These findings suggest that a substituent R at the d-position is more effective than one at the e-position in controlling facial discrimination toward the aldehyde carbonyl (Fig. 15). The origin of this effect has not been determined. 

This is the most common form of substrate control in asymmetric aldol reactions. In general, Ti-facial discrimination arises from the n-stereocenter of the enolate component however, there are many cases where a / -oxygen substituent plays an important role. 

The next milestone appeared in the 1950s in the context of the development of asymmetric reactions. Various stereochemical reactions induced by facial discrimination of the carbonyl group have always been pivotal in this field. Cram s rule inspired an explosion of studies on diastereoselective reactions followed by enan-tioselective versions. The recent outstanding progress in the non-linear effect of chirality or asymmetric autocatalysis heavily relies on the carbonyl addition reactions. Thanks to these achievements, natural products chemistry has enjoyed extensive advancement in the synthesis of complex molecules. It is no exaggeration to say that we are now in a position to be able to make any molecules in as highly selective a manner as we want. 

Highly acid sensitive a-siloxy epoxides (108 R1 = R2 = Me) are available in good to excellent yields through the epoxidation of silyl enols ethers (107) with jV-sulfonyloxaziridine (63b) <87JOC954>. Hydrolysis of (108) gave the a-hydroxy carbonyl compound (109) in good-to-excellent yield (55-95%) and represents an alternative to peracids usually used to effect this transformation known as the Rubottom reaction. With chiral nonracemic TV-sulfonyloxaziridines the ees of (109) were low (7-11% ee) because of the poor facial discrimination between the re and si faces of the silyl enol ether (Scheme 20). 

The reaction of the simplest diene derived from a carbohydrate (Scheme 7) with acrolein leads to a total endo selectivity furthermore, water increases the facial discrimination. This might be interpreted by considering the hydrophobi-city of the two faces, the attack on the more hydrophobic face (anti to hydrophilic functions) being favored in water [56]. 

The course of these reactions was studied by ab initio SCF calculations using the 3-21G basis set (49). Although several pathways were found to be energetically accessible, the authors preferred a chair like transition state such as 23.8. The facial discrimination was reasoned to arise from a preferred conformation of the enamine where the C-H bond of the phenethylamine lies in the nodal plane of the conjugated system. In this configuration, selective attack occurs on the face occupied by the smaller methyl group, away from the phenyl ring. 

N, P ] and [P, P ] Aldehydes with an a-stereocenter exhibit unusually high diastereofacial preferences for the addition of silyl enol ethers and ketene acetals with Lewis acid assistance (81). Heathcock and Uehling found good levels of facial discrimination in the addition of silyl enol ethers to chiral enones (Scheme 38, Table 11) (82). With the more substituted silyl enol ether, only one diastereomeric addition product is obtained (Eq. [1], Scheme 38). Use of a prostereogenic silyl enol ether allows control over the relative... 

The facial discrimination of the asymmetric epoxidation of allyl alcohols follows die empirical rule given in Figure 7 JO in nearly all die cases examined. However, exceptions have been observed with dialkenyl glycols [1382, 1383]. Due to the efficiency of the Sharpless epoxidation, the use of chiral auxiliaries for the epoxidation of allylic alcohols is not generally required. However, Charette and Cdte performed the epoxidation of carbohydrate ethers of allyl alcohols with MCPBA and observed a good stereoselectivity (80%) [369],... 

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