Part 1. New Mechanistic Insights and Procedures for the Preparation of Organolithium Compounds by Reductive Lithiation. Part 2. The Stereoselective Reduction of Ketones to the Most Thermodynamically Stable Alcohols Using Lithium and Hydrated Salts of Common Transition Metals.

Kennedy, Nicole (2016) Part 1. New Mechanistic Insights and Procedures for the Preparation of Organolithium Compounds by Reductive Lithiation. Part 2. The Stereoselective Reduction of Ketones to the Most Thermodynamically Stable Alcohols Using Lithium and Hydrated Salts of Common Transition Metals. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Part 1: A widely used method of preparing organolithium compounds is by the reductive lithiation of alkyl phenyl thioethers or usually less conveniently, alkyl halides, with either aromatic radical-anions of lithium or lithium metal in the presence of a catalytic amount of an aromatic electron transfer reagent. The work presented here shows, in two parts, that (i) a catalytic amount of N,N-dimethylaniline (DMA) and lithium ribbon can achieve reductive lithiation and (ii) lithium dispersion can achieve reductive lithiation in the absence of the electron transfer agent. These procedures are more efficient and surprisingly, in both methods of reductive lithiation, the order of relative reactivity of the substrates differs from that of the method using preformed aromatic radical-anion. Moreover, DMA is significantly cheaper than alternative reductive lithiation catalysts, therefore, can be recycled during work-up, which makes this process more cost-effective. The methodology was expanded to, but may not be limited to, (i) the DMA catalyzed reductive lithiation of phenyl thioethers and alkyl chlorides and (ii) the lithium dispersion reductive lithiation of phenyl thioethers, alkyl chlorides, acrolein diethyl acetal, and isochroman.
Part 2: An operationally simple method is presented for the highly stereoselective reductions of a variety of ketones to the most thermodynamically stable alcohols. In this procedure, the ketone is treated with lithium dispersion and either FeCl24H2O or CuCl22H2O in THF at room temperature. This protocol is both more convenient and efficient than those commonly used for the diastereoselective reduction of five- and six- membered cyclic ketones.

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Details

Item Type:	University of Pittsburgh ETD
Status:	Unpublished
Creators/Authors:	Creators Email Pitt Username ORCID Kennedy, Nicole nmk28@pitt.edu NMK28 0000-0003-3920-9058
ETD Committee:	Title Member Email Address Pitt Username ORCID Committee Chair Cohen, Theodore cohen@pitt.edu COHEN Committee Member Brummond, Kay kbrummon@pitt.edu KBRUMMON Committee Member Gold, Barry goldbi@pitt.edu GOLDBI Committee Member Chapman, Toby tchapman@pitt.edu TCHAPMAN
Date:	19 January 2016
Date Type:	Publication
Defense Date:	21 August 2015
Approval Date:	19 January 2016
Submission Date:	2 September 2015
Access Restriction:	1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages:	235
Institution:	University of Pittsburgh
Schools and Programs:	Dietrich School of Arts and Sciences > Chemistry
Degree:	PhD - Doctor of Philosophy
Thesis Type:	Doctoral Dissertation
Refereed:	Yes
Uncontrolled Keywords:	Reductive Lithiation Lithium Phenylthio Ether Relative Reactivity Iron(II) Chloride Tetrahydrate Copper (II) Chloride Dihydrate Diastereoselective
Date Deposited:	19 Jan 2016 21:52
Last Modified:	19 Jan 2017 06:15
URI:	http://d-scholarship.pitt.edu/id/eprint/26105

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