Date of Award

Fall 1996

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)



First Advisor

Cremer, Sheldon E.

Second Advisor

Donaldson, William A.

Third Advisor

Steinmetz, Mark G.


The goal of this study was to induce asymmetry into a prochiral phosphorus atom from a directly bonded carbon-based chiral auxiliary. The project was divided into two parts, intermolecular and intramolecular transfer of chirality. For the intermolecular study a bicyclo (2.2.1) heptyl group was chosen as the chiral auxiliary. Several of these bicyclo (2.2.1) heptyl phosphonates were synthesized. The intermolecular transfer of chirality study employed a prochiral diphenoxyphosphoryl substituent. Treatment of exo-2-(diphenoxyphosphoryl)bicyclo (2.2.1) heptane 28 with the nucleophiles t-BuO$\sp-$ and $\rm Ph\sb3CO\sp-$ gave diastereomeric ratios of 98:2 and 92:8, respectively. Treatment with eight other nucleophiles gave favorable diastereomeric ratios, but because of secondary reactions this system is more difficult to evaluate. For the intramolecular study a series of 4-alkyl and 4-aryl substituted 4-(diethoxyphosphoryl)butanols were synthesized. The substituents at position 4 include: R = Et 96, Me 97, Ph 98, Cy 99, t-Bu 100. The alcohols were treated with base to form an alkoxide which subsequently gave ring closure to form 3-alkyl and 3-aryl substituted 2-oxo-2-ethoxy-1,2-oxaphosphorinanes (phostones). The highest diastereomeric ratio that was observed was for 100 R = t-Bu where an exclusive diastereomer was observed. The diastereomeric ratio was the result of kinetic, not thermodynamic control as indicated by independent $\rm CD\sb3CD\sb2O\sp-$ incorporation experiments. In all cases the preferred diastereomer was cis. Cis:trans ratios of the diastereomers ranged from 70:30 to 100:0 in THF. When the phostones were allowed to react with an excess of base, epimerization at phosphorus occurred by an $\rm S\sb{N}2P$ process. A series of 3-alkyl and 3-aryl 3-(diethoxyphosphoryl)propanols were also prepared. Substituents at carbon 3 included Me, Et, and Ph. Treatment of these alcohols with base gave five-membered ring phostones with diastereomeric ratios close to 50:50 in most cases. The highest ratio observed was 80:20 (R = Me 113). Diastereomeric ratios slightly greater than 50:50 were observed when heat was used to initiate the ring closure to form 3-alkyl and 3-aryl substituted 2-oxo-2-ethoxy-1,2-oxaphospholanes (five-membered ring phostones). In addition to the stereochemical investigation, effective methods for improved synthesis of phostones were explored.