Novel titanium carbenoid reagents: diversity orientated synthesis of indoles and spirocycles

Main, Calver A. (2008) Novel titanium carbenoid reagents: diversity orientated synthesis of indoles and spirocycles. PhD thesis, University of Glasgow.

Abstract

A new synthetic strategy for the preparation of a 96-member library of 2,5-disubstituted indoles involving traceless cleavage from resin is presented.
A boronate-bearing titanium alkylidene was prepared and used to convert 8 resin-bound esters into immobilised enol ethers. Cleavage from resin in mild acid with concomitant cyclisation yielded boronate-bearing indoles. Capitalising on the immobilised boronate functionality in enol ethers, Suzuki cross-coupling reactions were performed with 12 aryl iodides to give a 96-member library after cleavage from resin with mild acid. 79 members of the library were confirmed to be 2,5-disubstituted indoles.
Also reported is the use of tertiary butyllithium and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane to convert an aryl bromide into an arylboronate in the presence of a dithiane, with simultaneous reduction of an aryl azide to an amine. In a similar route, we synthesised dithiane for the attempted conversion of resin-bound esters into functionalised 7-azaindoles after cleavage from resin. Further investigation with a different ortho-nitrogen protecting group may yet prove successful.
Alkylidenation of lactones with functionalized titanium carbenoid reagents followed by acid-induced cyclisation of the resulting enol ethers constitutes a new method for the preparation of [4.4], [4.5], and [5.5] spiroacetals (1,6-dioxaspiro[4.4]nonanes, 1,6-dioxaspiro[4.5]decanes and 1,7-dioxaspiro[5.5]undecanes). The titanium carbenoids are easily generated from readily available thioacetals.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Hartley, Dr. Richard
• Date of Award: 2008
• Embargo Date: 31 April 2012
• Depositing User: Dr Calver Main
• Unique ID: glathesis:2008-730
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 10 Aug 2009
• Last Modified: 10 Dec 2012 13:25
• URI: https://theses.gla.ac.uk/id/eprint/730