Two new methods have been developed employing silicon-containing molecules in novel organic transformations. The first strategy utilizes Lewis base-activation of triethoxysilylalkynes to deliver mild acetylide nucleophile equivalents. The second approach involves the use of enolate additions to acylsilanes to generate β-silyloxy homoenolate intermediates. Lewis base-catalyzed activation of triethoxysilylalkynes promotes the addition of alkynyl units to aldehydes and ketones. The resulting propargyl alcohols are isolated in high yields. The use of Lewis base catalysis in this reaction allows for the mild acetylide generation. This facet allows for the addition of alkynyl units to base-sensitive functionality (e.g. aliphatic aldehydes and ketones) and for the selective addition to aldehydes and ketones in the presence of other carbonyl functionality (e.g. esters). Mechanistic studies indicate that the reaction is proceeding by an auto-catalytic cycle. Additionally, the Lewis base-activated pentavalent intermediate can be visualized by low temperature 29Si NMR spectroscopy. Furthermore, the developed reaction has been applied to the diastereoselective Lewis base-promoted addition of alkynes to N-tert-butanesulfonyl imines, affording chiral propargyl amines in exceptional yield and selectivity. Amide enolate additions to acylsilanes generate stable β-silyloxy homoenolate intermediates. These homoenolates have been shown to undergo addition to a variety of electrophiles, including alkyl halides, aldehydes, ketones, and imines in good yields. Intramolecular cyclization of the β-silyloxy homoenolate intermediate onto the amide carbonyl is not observed. Additionally, the addition to imines leads to the formation of γ-amino-β-hydroxy amides with excellent diastereoselectivities. Importantly, these products can be efficiently cyclized under microwave-assisted conditions to form biologically valuable highly substituted γ-lactams. The use of chiral amide auxiliary control in the process permits the stereoselective formation of the homoenolate addition products, through a mechanistically investigated thermodynamic equilibration pathway.

Last modified

• 08/27/2018

Creator

• Robert B. Lettan ii

DOI

• https://doi.org/10.21985/N2QB0G

Subject

• Chemistry

Keyword

• Organic Chemistry

Date created

• 2007-07-17

Resource type

• Dissertation

Rights statement

• In Copyright