eprintid: 6354 rev_number: 5 userid: 6 dir: disk0/00/00/63/54 datestamp: 2011-11-10 19:31:31 lastmod: 2016-11-15 13:36:27 status_changed: 2011-11-10 19:31:31 type: thesis_degree metadata_visibility: show contact_email: rai6@pitt.edu item_issues_count: 0 eprint_status: archive creators_name: Ivanov, Roman Aleksandrovich creators_email: rai6@pitt.edu creators_id: RAI6 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. ispublished: unpub divisions: sch_as_chemistry full_text_status: public keywords: г-SELECTIVE ALKYLATION; ALLYL HALIDES; METALLO-ENE CYCLIZATIONS; ALKYLZINC HALIDES; AROMATIC RADICAL-ANIONS abstract: 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 date_type: completed institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Cohen, Theodore etdcommittee_name: Wilcox, Craig etdcommittee_name: Mokotoff, Michael etdcommittee_name: Wipf, Peter etdcommittee_email: cohen@pitt.edu etdcommittee_email: daylite@pitt.edu etdcommittee_email: moagie@pitt.edu etdcommittee_email: pwipf@pitt.edu etdcommittee_id: COHEN etdcommittee_id: DAYLITE etdcommittee_id: MOAGIE etdcommittee_id: PWIPF etd_defense_date: 2008-02-25 etd_approval_date: 2008-06-12 etd_submission_date: 2008-02-14 etd_access_restriction: immediate etd_patent_pending: FALSE assigned_doi: doi:10.5195/pitt.etd.2011.6354 thesis_type: dissertation degree: PhD committee: Theodore Cohen (cohen@pitt.edu) - Committee Chair committee: Craig Wilcox (daylite@pitt.edu) - Committee Member committee: Michael Mokotoff (moagie@pitt.edu) - Committee Member committee: Peter Wipf (pwipf@pitt.edu) - Committee Member etdurn: etd-02142008-151714 other_id: http://etd.library.pitt.edu/ETD/available/etd-02142008-151714/ other_id: etd-02142008-151714 citation: 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) document_url: http://d-scholarship-dev.library.pitt.edu/6354/1/roman_ivanov_2008_etd_v3.pdf