relation: http://d-scholarship-dev.library.pitt.edu/6354/
title: GENERALIZATION OF HIGHLY ã-REGIOSELECTIVE SUBSTITUTIONS IN ALLYL HALIDES BY ALKYLZINCS AND APPLICATIONS TO ZINC-ENE CYCLIZATIONS AND THE SYNTHESIS OF (R)-(+)-DIHYDRO-ALPHA-IONONE.
creator: Ivanov, Roman Aleksandrovich
description: Allyl phenyl sulfides have proven to be extremely versatile and widely used reagents in organic chemistry. There are thousands of publications that relate their uses in synthesis. However, the conventional method of preparing ã-substituted allyl phenyl sulfides by alkylation of deprotonated commercially available allyl phenyl sulfides, only allows electrophilic groups to be introduced. This method fails if the alkylating agent is tertiary, secondary, vinylic, or arylic. In this work a new method, in which a nucleophilic group can be introduced at the carbon atom bearing the phenylthio group, referred to as ã-allylic substitution, is thoroughly studied and used in several examples to demonstrate its significance for synthesis. This procedure should vastly increase access to a wide variety of allyl phenyl sulfides. In this work, copper mediated ã-allylic substitution reactions of organozinc reagents with allyl chlorides bearing a ã-phenylthio group are reported and the best reaction conditions for mono- and dialkylzincs are revealed. The scope and limitations of ã-allylic substitutions of organozincs with a variety of different allyl chlorides were thoroughly investigated and an important temperature effect was observed and used to expand the scope of these reactions.Furthermore, this work deals with an important aspect of the preparation of the organometallic nucleophiles required for these ã-substitutions. Many of these can be prepared by reductive lithiation of readily available alkyl phenyl thioethers by aromatic radical-anions. However, large-scale preparations suffer from the requirement of separation of the desired product from the aromatic byproduct using either slow column chromatography or vacuum sublimation. An improved procedure for reductive lithiation of phenyl thioethers with 1-(N,N-dimethylamino)naphthalenide was developed to overcome this drawback. Reductive lithiation was then used not only as a preliminary step in the preparation of organozincs for copper mediated ã-regioselective substitution reactions but also as a key step in the enantioselective synthesis of (R)-(+)-dihydro-á-ionone. It was demonstrated that the combination of reductive lithiations, zinc-ene reactions and copper mediated organozinc ã-regioselective substitutions can be used for efficient syntheses of ring-fused intermediates in an iterative and stereoselective fashion from inexpensive commercially available starting compounds
date: 2008-06-12
type: University of Pittsburgh ETD
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/6354/1/roman_ivanov_2008_etd_v3.pdf
identifier:   Ivanov, Roman Aleksandrovich  (2008) GENERALIZATION OF HIGHLY ã-REGIOSELECTIVE SUBSTITUTIONS IN ALLYL HALIDES BY ALKYLZINCS AND APPLICATIONS TO ZINC-ENE CYCLIZATIONS AND THE SYNTHESIS OF (R)-(+)-DIHYDRO-ALPHA-IONONE.  Doctoral Dissertation, University of Pittsburgh.    (Unpublished)