Substrates diastereoselective protonation

Thus, for aspartase (aspartate ammonia-lyase) the reaction direction is L-aspartate - fumarate + NH 3. The enzyme uses L-aspartate but not the D-enantiomer the product is fumarate not maleate. Hence, this enzyme has strict substrate and product selectivity. For greater detail, this could read strict substrate enantioselectivity and product diastereoselectivity. If necessary, information concerning prochirality could be conveyed in the same way for this same enzyme there is substrate diastereoselectivity for the protons at C-3. 

For weak acids, the proton is directly transferred from the acid to the substrate in a reagent-controlled manner and, in order to increase the selectivity, extremely shielded 2 -substituted m-terphenyls have been developed as concave protonating reagents inspired by the geometry of enzymes. Thus, the diastereoselective protonation by a series of substituted phenols of endocyclic keto enolates, obtained by the stereocontrolled 1,4-addition of lithiocuprates onto substituted cyclohexenones, was reported by Krause and coworkers354 355 and applied to the synthesis of racemic methyl dihydroepijasmonate356. 

Ketenes also serve as starting materials to NHC-bound enolate equivalents. Ye reported that enantiomerically enriched dihydropyranones bearing quaternary chiral centers could be generated from aryl-substituted ketenes (Scheme 14.22). Likewise, these substrates underwent diastereoselective protonation, presumably via the intermediacy of acyl triazoliums, to give chiral a-arylesters with good... 

The diastereoselectivity of protonation of enolate anions has been studied by H/D exchange.156 /i-Substituted ethyl butanoates were chosen as substrates, with conditions that rigorously excluded ion-pairing and aggregation effects. Stereoelectronic effects were found typically to produce higher stereoselection than purely steric effects, hi the specific case of H/D exchange in 3-ethoxybutanoate in ethanol-4 protonation of the enolate of 3-fluorobutanoate was chosen as a computational model.157 Similar... 

The addition of a hydride donor to a /i-hydroxyketo ne can also be conducted in such a way that the opposite diastereoselectivity is observed. However, the possibility previously discussed for additions to a-chiral carbonyl compounds is not applicable here. One must therefore use a different strategy as is shown in Figure 10.22, in which the OH group at the stereocenter C-/i of the substrate is used to bind the hydride donor before it reacts with the C=0 double bond. Thus, the hydridoborate A reacts intramolecularly. This species transfers a hydride ion to the carbonyl carbon after the latter has been protonated and thereby made more electrophilic. The hydride transfer takes place via a six-membered chair-like transition state,... 

Bennett has shown that sugar-derived substrates can also be used for the preparation of highly functionalised cyclopentanes.82,83 For example, treatment of iodide 75 with Sml2 initiated a highly diastereoselective construction of cyclopentane 76 (Scheme 5.50). These reactions require the presence of HMPA and a proton source to avoid competing 1,4-reduction of the a,p-unsaturated ester and cleavage of the allylic C-O bond.82,83... 

The rate of epimerization of an a-stereogenic centre within a carbonyl-containing compound with several stereogenic centres depends on the acidity of the enolizable proton. Diastereoselectivity depends on kinetic and/or thermodynamic effects (reagent and substrate control)... 

In many cases various proton sources, solvents, auxiliaries, and conditions have been applied in order to obtain different diastereoselectivites from the protonation of nonstereogenic car-banion centers. However, only the tw o extreme diastereomeric product ratios are given in this section. In most experiments kinetically controlled protonation can be assumed. However, since the anionic substrate already carries one (or more) stereogenic center, selective equilibration at the newly formed stereogenic carbon - hydrogen center could increase the diastereoselec-tivity. Indeed, epimerization of this center is a valuable tool for diastereoselective synthesis, provided that the carbon-hydrogen bond is acidic enough (see enolates, Section 2.1.3.1). 

Deprotonation of the (S)-phenylalaninol derivative (S)-181 in the presence of the achiral Hgand TMEDA produces the diastereomers 182 and 183 in a ratio of 90 10 [Eq. (47,see Sect 2.4) [68]. Here,due to internal substrate-inherent induction, the pro-R-H is removed preferentially ( / induction [ 118]). In the presence of (-)-sparteine, which has a high preference for the pro-S protons Ik induction), the diastereomer 183 is formed with an opposite 90 10 diastereoselectivity obviously the substrate-inherent diastereoselectivity is overridden by the reagent-induced selectivity. 

The product formation as well as the high diastereoselectivity observed in the rearrangement of the six- and seven-membered allyUc esters can be explained by rearrangement via a boat-like transition state A, which is discussed frequently for cyclic allyUc substrates [Ig]. Steric interactions between the axial proton of the cycloalkenyl ring and the probably solvated chelating metal obviously disfavor the chair-Uke transition state B (Fig. 5.2.5). 

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