A Memory of Chirality Approach to the Stereoselective Synthesis of 4-Hydroxy-α-methylprolines

Abstract

To extend the memory of chirality (MOC) methodology to structurally more diverse compounds, the synthesis of 4-hydroxy-alpha-methylprolines was undertaken. Yield and selectivity were very good, with an unexpected reversal in selectivity observed for the cyclization of one adduct with an unprotected hydroxyl.

Stereoselective Synthesis of Quaternary Proline Analogues

“…Kolaczkowski et al applied this methodology to the stereoselective synthesis of 4-hydroxy-α-methylprolines. [100] Their approach builds on the observation that epichlorohydrin reacts stereospecifically with carboxy-protected alanines to give the corresponding chiral chlorohydrins. Installation of protecting groups in the (2S,4R)-chlorohydrin and cyclization by the standard memory of chirality methodology (KHMDS, DMF, -60°C) led to the selective formation of the trans-4-hydroxy-α-methylproline (Scheme 53).…”

Synthesis of New Trifluoromethylated Hydroxyethylamine‐Based Scaffolds

“…In most of these cases, yields and the diversity of amino acids used were poor. [32][33][34][35][36][37][38][39][40][41][42][43][44][45] Currently, there are only two efficient methods for this reaction. The first one involves the use of Ca(OTf) 2 as a promoter of the reaction.…”

Principles, Concepts and Strategies of Stereoselective Synthesis

“…If at least one on those criteria mentioned during the memory of chirality process is not fulfilled, the enantioselectivity of the (S)-product will be decreased. Memory of chirality is an intriguing and powerful strategy in stereoselective organic synthesis [45][46][47][48][49][50] that has been applied to enolate chemistry, [51][52][53][54] radical and photochemical processes, [55][56][57] and reactions involving carbocation intermediates. 58,59 Several examples of MOC are provided in Scheme 1.3.…”