Stereoselective Synthesis of N-Propargyl Alkynes and Axial Chiral N-Allenes with Epimeric Imidazolone Auxiliaries
|Sechi, Maria Laura
|This thesis describes the synthesis of an N-propargyl pyrroloimidazolone chiral auxiliary/directing group with syn or anti stereochemistry derived from L-proline hydantoin and its diastereoselective lithiation for the synthesis of central chiral alkynes and axial chiral allenamides. Lithiation followed by quench with alkylating electrophiles or aldehydes/ketones gives access to chiral propargyl or allene derivatives respectively, both in high diastereomeric ratio (>95:5 dr). Use of the anti epimer of the aforementioned imidazolone chiral auxiliary results in the reversal of stereochemistry at the propargyl position of the products, again with high diastereoselectivity. This conclusion was confirmed by the synthesis and comparison of the solely central chiral alkynes from both the syn and anti series, obtained via acid-induced elimination of the labile silyloxy protecting group. Therefore, this method allows for the preparation of both enantiomeric propargyl products without the need to prepare additional starting materials from more expensive unnatural D-proline. X-Ray analysis of an allene derivative confirmed that lithiation of the syn pyrroloimidazolone followed by direct quench with prochiral benzaldehydes led to axial chiral allenamides in high selectivity (>95:5 dr) with atypical stereochemistry of the resulting benzylic alcohol. Lithiation followed by transmetalation to a titanium triisopropoxide intermediate before benzaldehyde quench gave epimeric allenamides with opposite stereochemistry at the benzylic alcohol. Density Functional Theory (DFT) computational modelling explained this reversal of stereochemistry at the benzylic position as arising from stereofacial attack in 6,5-bicyclic or 6-membered transition states in the lithium or titanium series, respectively.
|allenamides, pyrroloimidazolones, lithiation, diastereoselective
|Stereoselective Synthesis of N-Propargyl Alkynes and Axial Chiral N-Allenes with Epimeric Imidazolone Auxiliaries
|Electronic Thesis or Dissertation
|Department of Chemistry
|Faculty of Mathematics and Science