Jacqueline H Smitrovich

Publications (10)33.29 Total impact

• Article: Mechanistic studies of the allylic rearrangements of alpha-silyloxy allylic silanes to silyloxy vinylic silanes.

  Angie I Kim, Kyle L Kimmel, Antonio Romero, Jacqueline H Smitrovich, K A Woerpel
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  ABSTRACT: Mechanistic evidence suggests that the Lewis acid-promoted allylic rearrangement of alpha-silyloxy allylic silanes proceeds along an ionic reaction pathway involving a contact ion pair. The driving force for this transformation is alleviation of steric congestion at the allylic position of the alpha-silyloxy allylic silane and stabilization of pi cc by hyperconjugation.
  The Journal of Organic Chemistry 09/2007; 72(17):6595-8. · 4.45 Impact Factor
• Article: Synthesis of a tetrahydropyran NK1 receptor antagonist via asymmetric conjugate addition.

  Mark A Huffman, Jacqueline H Smitrovich, Jonathan D Rosen, Geneviève N Boice, Chuanxing Qu, Todd D Nelson, James M McNamara
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  ABSTRACT: Two asymmetric syntheses of the NK(1) receptor antagonist 1-[2-(R)-{1-(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(R)-(3,4-difluorophenyl)-4-(R)-tetrahydro-2H-pyran-4-ylmethyl]-3-(R)-methylpiperidine-3-carboxylic acid (1) were developed. In both routes, the core tetrahydropyran stereochemistry was established by asymmetric conjugate addition to an alpha,beta-unsaturated ester (6), using an amide of the chiral auxiliary pseudoephedrine. Selective ester reduction then allowed formation of lactone 2 with the thermodynamically preferred trans geometry. The chiral ether side chain (3) was attached by stereoselective acetal substitution. In the first route, the chiral piperidine ester fragment was installed at the end by N-alkylation. In the shorter second synthesis, this piece was appended to the Michael acceptor at the beginning.
  The Journal of Organic Chemistry 06/2005; 70(11):4409-13. · 4.45 Impact Factor
• Article: Synthesis of a potent hNK-1 receptor antagonist via an SN2 reaction of an enantiomerically pure alpha-alkoxy sulfonate.

  Todd D Nelson, Jonathan D Rosen, Jacqueline H Smitrovich, Joseph Payack, Bridgette Craig, Louis Matty, Mark A Huffman, James McNamara
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  ABSTRACT: The concise synthesis of a stereochemically rich hNK-1 receptor antagonist is described. The synthesis is highlighted by an S(N)2 reaction of an enantiomerically pure alpha-alkoxy sulfonate (orthogonally protected butane triol), which was prepared by utilizing salen-mediated hydrolytic kinetic resolution technology. A stereocontrolled acetalization was employed to connect two enantiomerically pure fragments with a high degree of diastereoselectivity.
  Organic Letters 02/2005; 7(1):55-8. · 5.86 Impact Factor
• Article: Effective use of preparative chiral HPLC in a preclinical drug synthesis.

  Todd D Nelson, Christopher J Welch, Jonathan D Rosen, Jacqueline H Smitrovich, Mark A Huffman, James M McNamara, David J Mathre
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  ABSTRACT: Access to a key 3-aryl-delta-lactone intermediate in enantiopure form using preparative chiral chromatography allowed expedited preparation of an important drug discovery target. A preclinical drug discovery strategy that combines rapid route discovery with effective use of preparative chiral chromatography can result in significant savings of both time and labor.
  Chirality 12/2004; 16(9):609-13. · 2.35 Impact Factor
• Article: Michael reactions of pseudoephedrine amide enolates: effect of LiCl on syn/anti selectivity.

  Jacqueline H Smitrovich, Lisa DiMichele, Chuanxing Qu, Geneviève N Boice, Todd D Nelson, Mark A Huffman, Jerry Murry
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  ABSTRACT: The stereochemical outcome of the asymmetric Michael reaction of pseudoephedrine amide enolates changes dramatically in the presence of LiCl. Reaction of the enolate in the absence of LiCl results in formation of the anti Michael adduct with high selectivity, whereas in the presence of lithium chloride the syn adduct is favored. This method provides access to enantiomerically enriched trans-3,4-disubstituted delta-lactones from the anti Michael adducts by a two step reduction/lactonization sequence. Information obtained from NMR studies indicates that, under both enolization conditions, the (Z)-enolate is formed. A model to explain the turnover in selectivity based on NMR evidence is presented.
  The Journal of Organic Chemistry 04/2004; 69(6):1903-8. · 4.45 Impact Factor
• Article: Catalytic C-H functionalization driven by CO as a stoichiometric reductant: application to carbazole synthesis.

  Jacqueline H Smitrovich, Ian W Davies
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  ABSTRACT: [reaction: see text] A palladium-catalyzed regioselective C-H bond functionalization driven by CO as the stoichiometric reductant is described. Nitrogen heterocycles, e.g., carbazoles, are accessible in good to excellent yields with use of palladium acetate and 70 psig of carbon monoxide at 140 degrees C.
  Organic Letters 03/2004; 6(4):533-5. · 5.86 Impact Factor
• Article: Pseudoephedrine as a chiral auxiliary for asymmetric Michael reactions: synthesis of 3-aryl-delta-lactones.

  Jacqueline H Smitrovich, Geneviève N Boice, Chuanxing Qu, Lisa DiMichele, Todd D Nelson, Mark A Huffman, Jerry Murry, James McNamara, Paul J Reider
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  ABSTRACT: [reaction: see text] The asymmetric Michael reaction of pseudoephedrine amides is reported. The 1,5-dicarbonyl products are converted to 3-aryl-delta-lactones in a two-step reduction/lactonization sequence. This method provides access to enantiomerically enriched trans-3,4-disubstituted delta-lactones.
  Organic Letters 06/2002; 4(11):1963-6. · 5.86 Impact Factor
• Article: Copper-Mediated Substitution Reactions of Alkylmagnesium Reagents with Allylic Carbamates:  (Z)-Selective Alkene Synthesis

  Jacqueline H. Smitrovich, K. A. Woerpel
  11/1998;
• Article: Oxidation of Sterically Hindered Alkoxysilanes and Phenylsilanes under Basic Conditions

  Jacqueline H. Smitrovich, K. A. Woerpel
  08/1996;
• Article: An efficient synthesis of a highly functionalized 4-arylpiperidine

  Geneviève N. Boice, Cécile G. Savarin, Jerry A. Murry, Karen Conrad, Louis Matty, Edward G. Corley, Jacqueline H. Smitrovich, Dave Hughes
  Tetrahedron. 60(50):11367-11374.