2-substituted-1, 3-dioxan-5-ones : synthesis, reactions and synthetic applications
Date
1998-01-01
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Doctoral
Abstract
This dissertation deals primarily with synthesis, reactions and synthetic applications of 2-substituted- 1,3-dioxan-5-ones. This class of compounds could be viewed as synthetic equivalents of natures building block--1,3-dihydroxyacetone and could be used in construction of many polyoxygenated natural products. A general, simple, cheap and easy to scale-up synthesis of 2-substituted-1,3dioxan-5-ones was developed. The yields of this three-step procedure, starting form commercially available tris(hydroxymethyl)nitromethane, ranged from 40 to 90%. The exploration of the chemistry of 2-substituted-1,3-dioxan-5-ones was focused on carboanion chemistry of these compounds. 2-Substituted-1,3-dioxan-5-ones were shown to easily form corresponding lithium, boron and titanium enolates. The 2-'tert'-butyl-2-methyl-1,3-dioxan-5-one was deprotonated enantioselectively in 90% e.e. with the aid of chiral lithium amide derived from (R)- or (S)-'N'-(2,2,2-trifluoroethyl)-1-phenylethylamine. This successful outcome was a result of extensive methodological studies. The enolates reacted readily with electrophiles: reactions with aldehydes provided 'anti' aldols in modest to high selectivities in cases of lithium and boron enolates and 'syn' aldols in case of titanium enolate. The enolates could be conveniently trapped as trimethylsilyl enol ethers or as enol acetates, however they failed to react with alkylating agents. The problem was solved using Enders' chiral hydrazone method. The synthetic utility of 2-substituted-1,3-dioxan-5-ones was illustrated in syntheses of (+)-frontalin and several protected ketohexoses. Additionally, the kinetics of deprotonation of a simple ketone with lithium diisopropylamide was investigated in order to shed some light on the mechanism of this type of reaction. The reaction was shown to be first order in ketone and half order in the base, and half order in the base, which suggests a monomer-based mechanism.
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Degree
Doctor of Philosophy (Ph.D.)
Department
Chemistry
Program
Chemistry