Dinesh Nath

Defense Date

3-1-2013

Graduation Date

Spring 2013

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

Committee Chair

Fraser Fleming

Committee Member

Bruce Beave

Committee Member

Tomslav Pintauer

Committee Member

Paul Sampson

Keywords

Alkylation, Arylation, Catalysis, Chemoselectivity, Cu-Catalysis, Metalated Nitrile

Abstract

This thesis describes new methods of carbon-carbon bond formation using metalated nitriles generated via metal exchange reactions. Sulfinylnitriles undergo a sulfinyl-metal exchange to yield lithiated, magnesiated and zincated nitriles, which can trap a range of electrophiles. The sulfinyl-metal exchange is effective with vinylic, quaternary and tertiary substitution patterns and addresses the long-standing problem of alkylating secondary nitriles. This method was then further extended to other oxidation states of sulfur, namely sulfonyl-metal exchange and relatively unknown sulfide-metal exchange. The sulfide metal exchange overcomes the problem related to the propensity of highly substituted sulfinylnitriles to eliminate. Sulfide-metal exchange is synthetically attractive because of the numerous methods for generating arylsulfides and the high tolerance of arylsulfides to numerous reagents.

A copper-catalyzed arylation reaction of aryl iodides and metalated nitriles was developed using catalytic Cu (I) and an amine ligand. A proof of principle has been established, providing a sound basis for developing the reaction. A new strategy has been developed for alkylation of alkenenitrile using LDA as base in presence of catalytic CuCN. Subsequent trapping with an electrophile, affords alkylated alkenenitriles in which the olefin is no longer in conjugation with the nitrile.

The distinct structural differences between N- & C-metalated nitriles have been harnessed in a series of chemoselective alkylations. Lithiated nitriles are found to be particularly reactive toward alkyl halides whereas magnesiated nitriles react selectively with oxygenated electrophiles. Using this strategy allows chemoselective alkylation of metalated nitriles.

Format

PDF

Language

English

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