ChemInform Abstract: SILYL KETENE ACETAL CHEMISTRY: STERIC LIMITATIONS IN LEWIS ACID‐PROMOTED ADDITION OF KETONES

Abstract

Die Umsetzung der Ketone (I) mit dem: silylierten Ketenacetal (II) führt zu Hydroxycarbonsäureestern (III) mit quartärem Kohlenstoff.

Total Synthesis of (±)-Aspergilline A

“…Recognizing the potential for retro-aldol reaction in the cyclization of compound 15 , we focused our efforts on Mukaiyama Aldol conditions so as to capture the cyclized product in situ as the corresponding trimethylsilyl ether ( 16 ). As illustrated in Scheme , we were delighted to find that conversion of 15 to the corresponding silyl ketene acetal followed by treatment with TiCl 4 produced 16 in good to excellent yields (75–90%) as a single diastereomer . Subsequent cleavage of the 2,4-dimethyoxybenzyl (DMB) protecting group with DDQ provided amide 17 and set the stage for introduction of the tetramic acid .…”

Chemistry of Fluorinated Carbon Acids: Synthesis, Physicochemical Properties, and Catalysis

“…The notable catalysis of Tf 2 CHCH 2 CHTf 2 3 was observed not only in the VMM reaction but also in the Mukaiyama aldol reaction. 28) Rhodes pointed out that the reaction of sterically bulky undecan-6-one 8a with a ketene silyl acetal did not yield the corresponding aldol product under classical titanium tetrachloride (TiCl 4 )-mediated conditions 29) (Chart 8). On the other hand, only 1.0 mol% of 3 was sufficient to complete this reaction, giving rise to 9.…”

Carbon Acid Induced Mukaiyama Aldol Type Reaction of Sterically Hindered Ketones

“…This fact supports the idea that strong electrophilic activation of carbonyl substrates by silicon Lewis acids makes the effective nucleophilic addition to sterically hindered carbonyl electrophiles possible. Since the reactivity of ketones is lower than that of aldehydes due to steric and electronic reasons, the Mukaiyama aldol reaction of ketones often required the use of stoichiometric or substoichiometric amounts of suitable Lewis acids such as TiCl 4 and BF 3 to obtain the corresponding aldol products in good to excellent yield. , Meanwhile, the required catalyst loading of highly active silicon Lewis acids to complete the reaction is relatively low . As an elegant example according to this concept, Sawamura and co-workers reported that the Mukaiyama aldol reaction of acetophenone and dimethylketene silyl acetal smoothly proceeds in the presence of only 1 mol % of toluene-coordinated silylium borate [Et 3 Si(toluene)]B(C 6 F 5 ) 4 , which shows a strong cationic silicon character .…”

“…The present conditions using carbon acid 1 was also effective in the C−C bond formation between acyclic ketone with dimethylketene silyl acetal. It is known that, in the presence of 1 molar equiv of TiCl 4 , the reaction of highly hindered undecan-6-one 2g with dimethylketene silyl acetal does not give the desired aldol product . In contrast, the use of 1 realized the clean formation of aldol adduct 5a (Scheme , also see Supporting Information).…”