Internal protonation, diastereoselective

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. ... 

Internal proton return to lithium enolates from secondary amines which are coordinated to the lithium ion has been used for diastereoselective (Sections 2.1.3.6. and 2.1.4.2.) and enantioselec-tive (Section 2.1.6.1.2.) protonations. A remarkable example of enantioselective internal proton return, with the exclusion of any additional proton source, occurs with racemic Naproxen amides 1l63a. 

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. 

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