Highly Stereoselective Titanium-Mediated Aldol Reaction from (S)-4-Benzyloxy-3-methyl-2-butanone

Abstract

Substrate-controlled titanium-mediated aldol reactions from (S)-4-benzyloxy-3-methyl-2-butanone provide satisfactory levels of 2,5-syn asymmetric induction if they are carried out in the presence of a second equivalent of TiCl(4). Such reactions give high yields and excellent diastereoselectivity with a wide array of achiral and chiral aldehydes without needing other sources of chirality. This procedure is thus of interest for the synthesis of natural products. Furthermore, spectroscopic studies and analyses of the reacting species have revealed a possible mechanism to account for the experimental results.

syn/anti Switching by Specific Heteroatom–Titanium Coordination in the Mannich‐Like Synthesis of 2,3‐Diaryl‐β‐amino Acid Derivatives

“…After the addition of TEA,26 titanium E / Z enolates are formed from the intermediate II . NMR experiments on 1d (see Supporting Information) confirmed the presence of the E / Z titanium enolate mixture, which by reaction with I can afford four possible dimetallic transition states (Scheme ) 26a,27. With a strongly coordinating ortho group (X = F, Cl, Br), most likely both TS‐ syn ‐A and TS‐ anti ‐B are initially formed from the E / Z enolate.…”

TiCl4/Et3N-Mediated Condensation of Acetate and Formate Esters: Direct Access to β-Alkoxy- and β-Aryloxyacrylates

“…A plausible mechanism for this condensation is outlined in Scheme . The need for a minimum of 2 equiv of TiCl 4 involves the formulation of a bimetallic intermediate, a hypothesis that has been proposed by other authors …”

Titanium Enolate Chemistry at the Beginning of the 21st Century

“…These results were optimized for α‐ tert ‐butyldimethylsilyloxy methyl ketones, which preferentially afforded 1,4‐ syn aldols 52. Similarly, titanium(IV) enolates of chiral β‐benzyloxy methyl ketones 38 reacted with numerous saturated and unsaturated aldehydes, leading predominantly to 1,4‐ syn enantiomers 40 53a. Application of an additional equivalent of TiCl 4 considerably improved both yields and diastereomeric ratios, presumably owing to the formation of a bimetallic enolate complex 39 that would be able to coordinate the aldehyde (Scheme ).…”