Using stereoelectronic effects to explain selective reactions of 4-substituted five-membered ring oxocarbenium ions.

Department of Chemistry, University of California-Irvine, Irvine, California 92697-2025, USA.
Organic Letters (Impact Factor: 6.14). 07/2004; 6(12):2063-6. DOI: 10.1021/ol0492647
Source: PubMed

ABSTRACT [reaction: see text] The utility of the inside attack model to predict and analyze the stereoselectivities of nucleophilic additions to complex five-membered ring oxocarbenium ions is demonstrated in a systematic study of C-4-substituted acetals.

  • [Show abstract] [Hide abstract]
    ABSTRACT: While the synthesis of amide bonds is now one of the most reliable organic reactions, functionalization of amide carbonyl groups has been a long-standing issue due to their high stability. As an ongoing program aimed at practical transformation of amides, we developed a direct nucleophilic addition to N-alkoxyamides to access multisubstituted amines. The reaction enabled installation of two different functional groups to amide carbonyl groups in one pot. The N-alkoxy group played important roles in this reaction. First, it removed the requirement for an extra preactivation step prior to nucleophilic addition to activate inert amide carbonyl groups. Second, the N-alkoxy group formed a five-membered chelated complex after the first nucleophilic addition, resulting in suppression of an extra addition of the first nucleophile. While diisobutylaluminum hydride (DIBAL-H) and organolithium reagents were suitable as the first nucleophile, allylation, cyanation, and vinylation were possible in the second addition including inter- and intramolecular reactions. The yields were generally high, even in the synthesis of sterically hindered α-trisubstituted amines. The reaction exhibited wide substrate scope, including acyclic amides, five- and six-membered lactams, and macrolactams.
    Chemistry 11/2012; · 5.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of fused-bicyclic acetals containing a disiloxane ring was investigated to evaluate the source of selectivity in silyl-protected 2-deoxyribose systems. The disiloxane ring unexpectedly enables the diaxial conformer of the cation to be stabilized by an electronegative atom at C-3. This low energy conformer subsequently undergoes stereoelectronically controlled nucleophilic addition to give substituted tetrahydrofurans with high diastereoselectivity.
    The Journal of Organic Chemistry 06/2013; · 4.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two remarkable epimerization processes were uncovered during our pursuit of an enantioselective synthesis of (+)-aigialospirol featuring a cyclic acetal tethered ring-closing metathesis. Through modeling, we were able to turn these two unexpected epimerizations to our advantage via modeling to ensure a successful and concise total synthesis, thereby firmly establishing cyclic acetal tethered RCM as a powerful strategy in natural product synthesis. Most importantly, calculations allowed us to fully understand the nature and the mechanistic course of these two epimerizations that were imperative to the total synthesis efforts.
    Science in China Series B Chemistry 01/2011; 54(1):31-42. · 1.20 Impact Factor