Date of Award

5-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Chemistry

Advisor

Dieter, Karl R

Committee Member

Smith , Rhett

Committee Member

Bhattacharyya , Gautam

Committee Member

Pennington , Bill

Abstract

Regioselective control in allylic substitution reactions of vinylepoxides is difficult due to the competition between SN2- substitution and SN2'- allylic substitution pathway. Although excellent SN2'/SN2- and anti/syn- ratios were achieved by CuCN derived organozinc cuprates on 4,5-epoxy-2,3-enoates, application of this methodology to the vinylepoxide, trans-1-(tert-butyldimethylsilyloxy)-2,3-epoxy-4-hexene, is explored. Dialkyzinc reagents mediated by catalytic amounts of CuCN provide excellent regio-(SN2'/SN2) and diastereo-(olefinic E/Z and anti/syn-) selectivity with n-Bu, Et and t-Bu ligands, while reduced E/Z and SN2'/SN2- ratios were achieved with aromatic ligands (e.g., furyl and Ph). The assignment of regio- and stereoisomers were achieved by alternative syntheses of the authentic compounds. The epoxide opening allylic alcohol products were activated by converstion to allylic acetates or phosphates, which underwent allylic substitution reaction with lithium cyanocuprate in a highly anti-SN2'- controlled fashion. As a result of this sequential bis-allylic substitution, the synthesis of compounds with two contiguous stereogenic centers was realized.
While many methods were reported for the synthesis of 2,3-dihydro-4-pyridone derivatives, access to substituted 2-piperidones from 2-pyridones is still underdeveloped because of their low reactivity towards conjugate additions and the difficulty in control of regioselectivity. N-Boc-2-pyridone underwent conjugate addition with CuI derived lithium dialkylcuprate with modest to excellent 1,4/1,6- regioselectivities, and various ligands (n-Bu, s-Bu, t-Bu, Me and Ph) were transferred in low to modest yields. Various organolithium reagents were added to the pyridinium salt derived from N-benzyl-2-pyridone in low to modest yields, with poor to modest 1,4,/1,6- regioselectivities. One pot synthesis of 3,4-dihydro-2-pyridones was realized in excellent diastereoselectivity.
A facile (three steps) and efficient (65% over three steps) synthesis of enantiopure mono-substituted bicyclic amidines was developed. Alkylation of these mono-substituted amidines provided bis-substituted bicyclic amidines in modest yields (55%) and with decent diastereoselectivities (88:12). These chiral bicyclic amidines are potential organocatalysts for asymmetric addition such as acetoxybromination or halolactonization reactions based on our preliminary result from DBU and other literature reports. Success on DBU alkylation in high yields (up to 88%) and with various ligands (Me, Et and Bn) provides a promising methodology for synthesis of multi-alkylated (e.g., bis and tri-susbtituted) chiral cyclic amidines.

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