External protonation diastereoselective

Repeated deprotonation of 278 removed due to a high H/D kinetic isotope effect the 1-proton, forming the dideuterio compound 279 with low diastereoselectivity . It is quite likely that a dynamic thermodynamic resolution is the origin. Intermediate 277 is configurationally labile, enabling an equilibration of the diastereomeric ion pairs 277 and epi-211. Similar studies were undertaken with 1-phenyl-l-pyrid-2-ylethane (280) and l-(4-chlorophenyl)-l-(pyrid-2-yl)-3-(dimethylamino)propane (281) (50% eef. An improvement of the achieved enantiomeric excesses resulted when external chiral proton sources, such as 282 or 283, were applied (84% ee for 280 with 283 and 75% ee for 281). 

Significant progress has been made towards the understanding of proton delivery 152,165 Diastereomeric silyl ethenyl ethers 145 and 148 decompose on addition of TBAF and AcOH into the corresponding enols 146 and 149, which yield with AcOH two complementary bicyclic ketones (147 and 150, respectively), in different degrees of diastereomeric purity (equations 40 and 41). Two different proton transfer processes take place Bicyclic ketone 147 is formed by external delivery of a proton to 146 on its less hindered face (equation 40) the complementary ketone 150 is formed by protonation of 149 on its more hindered face (equation 41), invoking internal proton dehvery from the intermediate pyridinium acetate 151. For a more sterically demanding and weaker acid, such as phenol, the diastereoselectivity increased for 147 but reversed for 150. ... 

To minimize this troublesome process, the concentration of the intermediate has to be kept as low as possible by means of catalytic tautomer-ization of the dienol. To make the chiral discrimination as great as possible, a strong interaction between the prochiral intermediate and the chiral environment is needed. When the chiral inductor is introduced into the starting molecule itself, diastereoselective photodeconjugations can be observed. If an external chiral inductor is used, enantioselective protonations are obtained. This approach, which may be catalytic if the chiral auxiliary is not consumed in the process, can take advantage of the acidic property of enols [27] and of the possibility of an acid- or base-catalyzed tautomer-ization of enols [28]. 

With chiral molecules, there is no need for external chiral inductors to induce a diastereoselection. For most esters made from conjugated acids and chiral alcohols, the diastereoisomeric excess (de) of the photodeconjugation process, carried out in apolar solvents containing catalytic quantities of alcohols (and/or amines), remains low. This results from the low steric interactions developed by the alkoxy group during the protonation step of the dienol, as already indicated [32]. However, if protonation of photo-dienols from one enantioface is sterically hindered, as can be observed for isobornyl derivatives 8c and 8d, values of de up to 95% can be attained [50] (Table 4 and Scheme 6). 

---