Date of Award

Spring 1995

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)



First Advisor

Brebick, Robert F.

Second Advisor

Seitz, Martin A.

Third Advisor

Fournelle, Raymond


The purpose of this work was to explore efficient synthetic pathways to mono and bicyclic phosphonates (phostones) and to study their reactions and associated mechanistic and stereochemical behavior. The work was divided into two main parts. The first focused on the synthesis of the five- and six-membered ring phostones, 2-oxo-2-ethoxy-1,2-oxaphosphorinane 1 and 2-oxo-2-ethoxy-1,2-oxaphospholane 2. New and improved methodologies for the synthesis of phostones 1 and 2 are presented. The related 3-alkylated derivatives of 1 (R = Me 13, Et 14, nPr 15, iBu 16, PhCH$\sb2$ 17, HOCH$\sb2$CH$\sb2$ 20, HOCH$\sb2$CH$\sb2$CH$\sb2$ 21, PhCH(OH) 22, Ph$\sb2$C(OH) 23, Ph$\sb2$CH 36) were prepared by the reaction of 1 with LDA in THF at low temperature, followed by treatment with a variety of alkyl halides or appropriate carbonyl compounds.

A study on the stereoselective alkylation of 1 and a mechanistic discussion of these reactions is presented. In addition, the X-ray crystal structures of the cis isomer 22a, and the cis and trans isomers 23a and 23b were determined. The crystal structure of 23a showed an interesting intramolecular hydrogen bonding of the form O-H$\cdots$O = P that was not present in 23b. Compound 23 also underwent a series of unusual intramolecular rearrangements to form a phosphorylated tetrahydropyran ring.

The second part of this work was devoted to the synthesis of 1-phospha-2,10-dioxabicyclo (4.4.0) decane-1-oxide 3, 1-phospha-2,9-dioxabicyclo (4.3.0) nonane-1-oxide 4, and analogues of bicyclic phostone 3 with substituents at carbon six. These compounds were obtained by two different methods. The first method was effected by the ring closure of alcohols 20 and 21 under basic reaction conditions (LiH/benzene, EtONa/DME). Substituted bicyclic phostones were obtained by alkylation of the ylide derived from 3. The second method involved tandem formation of two consecutive C-C bonds from bis-(3-bromopropyl) alkylphosphonates in the final, key step. All the synthetic approaches to these bicyclic phostones led to the same cis stereoisomer. This was confirmed by an X-ray crystal structure and comparison of the spectroscopic data of the compounds. The trans isomer 3b was obtained from equilibration of 3a by deprotonation-reprotonation of the acidic $\alpha$-proton. A discussion of the mechanism and possible causes for the exclusive formation of the cis isomer 3a is presented. All new compounds have been fully analyzed and characterized by $\sp1$H, $\sp{13}$C, $\sp{31}$P NMR, IR, MS spectroscopy and combustion analysis.