A New Halo Aldol Reaction: Three-Component Reaction via 1,4-Robust Activation of Ethynyl Alkyl Ketones for Stereoselective Formations of Versatile Aldol Adducts
Han-Xun Wei, Sun Hee Kim, and Guigen Li*
*Department of Chemistry and Biochemistry, Texas Tech University, Lubbock,
Texas 79409-1061, Email: guigen.li
ttu.edu
H.-X. Wei, S. H. Kim, G. Li, Org. Lett., 2002, 4, 3691-3693.
DOI: 10.1021/ol020146y
Abstract
A new, diastereoselective three-component halo aldol reaction has been discovered for the tandem formations of I-C/C-C bonds, which gives aldol adducts in good yields. The key intermediates (allenolates and 1-iodo-3-siloxy-1,3-butadienes) were directly monitored by 1H NMR.
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The document discusses a newly discovered three-component halo aldol reaction for the tandem formation of I−C/C−C bonds by activating the α',β-positions of α,β-acetylenic ketones. This reaction generates key intermediates, 1-iodo-3-siloxy-1,3-butadienes, from allenolates. The reaction achieves excellent geometric selectivity (>95%) and good yields (65−82%) across 10 examples. The process involves the conjugate addition of TMS-I to ethynyl alkyl ketones, followed by catalytic isomerization and aldol reaction in a one-pot operation. This method is useful for synthesizing biologically important compounds like brevetoxin and swinholide A. The reaction was optimized using BF3-OEt2 as a catalyst, which controlled the (E)-geometry and provided good yields. Various solvents were tested, with dichloromethane giving the best results. The reaction works with both aromatic and aliphatic aldehydes, with aliphatic aldehydes reacting slightly faster. The study aims to extend the scope of substrates and explore the asymmetric version of the reaction. The research was supported by the National Institutes of Health and the Robert A. Welch Foundation.
Key Words
Mukaiyama Aldol Addition, β-hydroxy ketones, vinyl iodides
ID: J54-Y2002-390
