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Degree

PHD, Kent State University, College of Arts and Sciences / Department of Chemistry, 2005.

Abstract

1-Bromo-1-lithioethene has proven to be a useful practical reagent for the selective introduction of the 1-bromoethenyl group into various organic and organometallic substrates. The conditions for 1-bromo-1-lithioethene synthesis were optimized and reasons for published erratic yields of 1-halo-1-lithioethenes were revealed. An inexpensive all glass low temperature reactor was designed to allow a reproducible synthesis of 1-bromo-1-lithioethene and perform routine chemical transformations at -100 to -125 °C. Experimental observations along with computational evidence suggest that 1-bromo-1-lithioethene exists in a crystalline form while its bromine atom remains non-chelated. At -110 to -115 °C, 1-bromo-1-lithioethene affords clean 1,2-addition to carbonyl compounds. It possesses low basicity and is compatible with acetate, allyl ether and tosylate protecting groups. Several dichlorosilanes, tributyltin chloride and iodine proved to be efficient electrophiles for trapping 1-bromo-1-lithioethene providing one-step access to potentially useful small 1,1-difunctionalized ethene building blocks. Esters of a-bromoallylic alcohols undergo Ireland-Claisen rearrangement under mildly basic enolization conditions. Esters of tertiary bis-allylic alcohols (originating from trapping of 1-bromo-1-lithioethene with a,b-unsaturated ketones) provided the best yields of rearranged products under Li(NSiMe3)2 / MnCl2 conditions with preparatively useful levels (ca 1:10) of alkene E/Z selectivity and good regioselectivities. According to ab initio calculations and the experimentally observed trends, the rearrangement of (Z)-silyl ketene acetals of these tertiary a-bromoallylic esters is faster and much more selective than the rearrangement of the corresponding (E)-silylketene acetals. For other substrates, trialkylsilyl triflate / triethylamine enolization conditions proved to be optimal but, in some cases, observed alkene E/Z selectivities were lower (1 : 4 to 2 : 3) and no regioselectivity was observed for secondary bis-allylic alcohols (originating from trapping of 1-bromo-1-lithioethene with a,b-unsaturated aldehydes). 1-Bromo-1-lithioethene was successfully applied in partially developed synthetic approaches toward Physalin and VM55599, showing its potential as a building block in natural products syntheses.

Keywords

organolithiums; Felkin-Anh diastereoselectivity; low temperatures; cryogenic reactor; carbohydrates; building blocks

Advisor

Paul Sampson

Pages

215p.

Document number: kent1135388929
Permalink: http://rave.ohiolink.edu/etdc/view?acc_num=kent1135388929

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