Mukaiyama Aldol Reactions Catalyzed By Lewis Acidic Mg(Ⅱ)

This thesis aims at the studies of Lewis acidic Mg (â…¡) -catalyzed Mukai-yama-type aldol reactions and consists of the following parts: Chapter 1 summarized synthetic applications of magnesium (â…¡) species and its complexes in various functional transformations and C?C bond-forming reactions. High Lewis acidity, high oxophilicity, and high coordination numbers (up to 5 or 6) are critical factors for the unique reactivity of Mg (â…¡) catalyst. Results and mechanistic discussions on the systematic studies of Mukaiyama-type aldol coupling of typical silyl enolatesⅠ～Ⅲwith various carbonyl substrates catalyzed by MgI₂ etherate [MgI₂·(OEt₂)_n (1)] are documented in chapter 2. We have revealed in this chapter the unique catalytic reactivity of MgI₂ etherate (1) in the chemoselective Mukaiyama-type aldol coupling of aryl aldehydes and acetals with silyl enolates: (1) Aromatic and vinyl aldehydes are reactive substrates towardⅠ～Ⅲ; Both aliphatic and aromatic ketones are inert; Aliphatic aldehydes are unreactive toward enol silanes â…¡and â…¢, reacting with silyl ketene acetal â… sluggishly; (2) Aryl aldehydes with electron-donating substituent (i.e., o-or p-OMe, -Me, -NMe2) reacted much faster than benzaldehyde and electron-withdrawing substituent (i.e., -Cl, -Br, -NO₂, -CF₃) deactivated aryl aldehyde remarkably; (3) Both aliphatic and aryl (or vinyl) aldehyde acetals are reactive substrates, while ketone acetals are inert; (4) Acetals are generally more reactive than the parent aldehydes and acetalization activates unreactive aliphatic aldehydes. This magnesium-catalyzed silyl enolate addition is mild, efficient and operationally simple. Iodide counterion, weakly coordinating peripheral ethereal ligands for Mg (â…¡), and a non-coordinating reaction media (i.e., CH2Cl2) are critical factors for the unique reactivity of this catalytic system. Scheme 1 OTMSOMePhOTMSOTMSOTMSR CO2MeOXROX OPhROX OTMSORCHO or RCH(OMe)2MgI2.(OEt2)nCH2Cl2(1-5 mol %)X = TMSX = H(1)X = Meâ… â…¡â…¢Synthetic application of this novel catalytic aldol reaction was demonstrated in chapter 3 on the novel approach for the total synthesis of styryllactone natural products. Starting from cinnamaldehyde, (±)-5-hydr-oxygoniothalamin (3-1) was synthesized through 8 steps in an overall yield of 34% and thus the formal total synthesis of (±)-isoaltholactone (3-7), a representative styryllactone natural product, was achieved. The key step is Mukaiyama-type aldol coupling of cinnamaldehyde with 1,2-bis(trimethyl-siloxy)-1-cyclobutene ( â…¢) catalyzed by MgI2 etherate (1). This novel synthetic approach is short and efficient, which represents a novel and more general methodology for the synthesis of the styryllactone natural products from readily available starting materials. Scheme 2 Ph CHO TMSOTMSO+PhOOOHOOPhHOOIsoaltholactonesteps5-Hydroxy goniothalamin...