Enantioselective lateral lithiation-substitution of o-ethyl- and o-benzyl-N-pivaloylanilines: Studies of a pathway of stereoinformation transfer
Basu, Amit
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/21964
Description
Title
Enantioselective lateral lithiation-substitution of o-ethyl- and o-benzyl-N-pivaloylanilines: Studies of a pathway of stereoinformation transfer
Author(s)
Basu, Amit
Issue Date
1996
Doctoral Committee Chair(s)
Beak, Peter
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Language
eng
Abstract
The secondary amides o-ethyl-N-pivaloylaniline and o-benzyl-N-pivaloylaniline are laterally lithiated by sec-butyllithium to generate a dilithio intermediate. Electrophilic substitution of the organolithium in the presence of ($-$)-sparteine provides the products with enantiomeric excesses close to 80% for reactions with most electrophiles. The absolute configuration at the benzylic carbon is the same regardless of whether stannyl or stannyl chlorides, alkyl halides, or aldehydes and ketones are used as the electrophile.
Lithio-destannylation of the enantioenriched organostannane in the presence of ($-$)-sparteine followed by electrophilic substitution provides the products with configurations opposite to that obtained by the deprotonation sequence. It is found that highly enantioenriched products from the deprotonation sequence are obtained only after a warm/cool sequence, where the ($-$)-sparteine is incubated with the organolithium for 45 minutes at $-25\sp\circ$C prior to carrying out electrophilic substitution at $-78\sp\circ$C. The effects of solvent and temperature on the stereoselectivity of the reaction have also been studied.
The use of substoichiometric amounts of TMSCl as an electrophile is found to provide the product with higher enantiomeric excess than when excess TMSCl is used. This is suggested to arise as a consequence of kinetic resolution of non-equilibrating diastereomeric ligand/organolithium complexes. We have utilized this observation to amplify the enantioselectivity of the reaction sequence by using the electrophile as the limiting reagent and recycling the unwanted diastereomeric complex. An energy diagram for the reactions of the diastereomeric complexes is presented, and the stereoinformation transfer is suggested to occur via a dynamic thermodynamic resolution.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
