The β-Silyl Effect on the Memory of Chirality in Friedel–Crafts Alkylation Using Chiral α-Aryl Alcohols

Abstract

Iron salt-catalyzed Friedel-Crafts alkylation of chiral α-aryl alcohols with a trimethylsilyl group was found to proceed with retention of the configuration of the hydroxyl group as a leaving group. The memory of chirality of this system stems from the β-silyl effect of the trimethylsilyl group on the carbocation intermediate.

Mechanistic insights on the Pd-catalyzed addition of C–X bonds across alkynes – a combined experimental and computational study

“…This result is in agreement with the known effect of silyl groups to be able to stabilize carbocations in α, 59 β 60,61 and γ 62 positions. In addition, analyzing the changes in bond lengths during the isomerization from cis - to trans -Pd( ii ) intermediate ( VIa to Va ) shows a slight elongation of the double bond and concomitant shortening of both C–Si and C–Pd bonds in the TS, suggesting a delocalization of positive charge between Pd, C and Si.…”

Recent Progress in Memory Of Chirality (MOC): An Advanced Chiral Pool

“…Recently, Itoh reported Friedel-Craft alkylation reactions of indole using α-aryl-β-silyl alcohols as alkylating agents (Scheme 16). 41 Starting from enantioenriched alcohols 61 and 63, the corresponding alkylated compounds 62 and 64 were obtained with retention of configuration retaining a high level of chirality transfer. Similar treatment of enantiopure alcohol 65 gave the corresponding alkylated product in almost racemic form (3% ee).…”

Memory of Chirality in a Flow‐Based System: Enantioselective Synthesis of Quaternary α‐Amino Acids Using Flow Microreactors

“…The principle relies on a memorization of the initial chirality by a global chiral conformation of the intermediate. Therefore this strategy is very sensitive to reaction conditions in particular reaction rate and temperature, and many MOC reactions are either intramolecular or performed at low temperature or both , . We have already developed a 3‐step asymmetric synthesis of quaternary α‐amino acids based on MOC .…”