Formal (3+3) Cycloaddition of Silyl Enol Ethers Catalyzed by Trifric Imide: Domino Michael Addition-Claisen Condensation Accompanied with Isomerization of Silyl Enol Ethers

Abstract

Silyl enol ethers are of enormous importance in synthetic chemistry as isolable enolate equivalents. They are frequently employed in carbon-carbon bond forming reactions such as Mukaiyama-aldol reactions, Mukaiyama-Michael reactions, Diels-Alder reactions and so on. Interaction of silyl enol ether A with an electrophile (E ϩ ) gives the corresponding silyloxonium cation B. When the intermediate B is quenched with the counter anion or an appropriate nucleophile, desilylated product C will be obtained (Fig. 1, path a). On the other hand, if the silicon-oxygen bond of the siloxonium cation B is strong enough, deprotonation of B at the adjacent position of the carbonyl carbon can occur to generate silyl enol ether D (or DЈ). [1][2][3][4][5][6] If the newly formed silyl enol ether D successively reacts with another electrophile (E' ϩ ), a,aЈ-disubstituted ketone E will be obtained in a one step (path b). To the best of our knowledge, only limited studies of domino reactions consisting of two bondformation reactions based on the concept have been reported. 7-10)We have reported on a catalytic (2ϩ2) cycloaddition, in which silyl enol ethers 1 react with a,b-unsaturated esters 2 in the presence of triflic imide (Tf 2 NH) at Ϫ78°C giving siloxycyclobutanes 4. [11][12][13][14] In the process, the siloxonium intermediate 3 bearing a ketene silyl acetal moiety, which is formed as a transient intermediate by Mukaiyama-Michael addition, would undergo successive intramolecular aldol reaction (nucleophilic attack) at low temperatures to form a 4-membered ring (Fig. 2, path a).15) It was made clear that the cycloaddition is activated by silyl triflic imide (SiNTf 2 ), which would be in situ generated from Tf 2 NH with a substrate silyl enol ether. 11,14) We envisaged that a,b-unsaturated carbonyl compounds which possess two electrophilic carbons (one is the b-carbon and another is the ester carbonyl function) may act as dual electrophilic species under appropriate conditions. Namely, if deprotonation of 3 giving silyl enol ether 5 and successive cyclization occur, 6-membered product 6 would be created (path b). In this paper, we wish to report on the intermolecular and intramolecular formal (3ϩ3) cycloadditions of silyl enol ethers with a,b-unsaturated esters in the presence of Tf 2 NH.At the outset of this study, we examined (3ϩ3) cycloaddition of 2-methyl-1-(t-butyldimethylsilyloxy)cyclohexene (1a) with various a,b-unsaturated carbonyl compounds 2a-e in We describe here a Tf 2 NH-catalyzed formal (3؉ ؉3) cycloaddition of silyl enol ethers with acrylates as a new domino reaction. In the domino sequence, the catalyst activates Michael addition, deprotonation of the resulting silyloxonium cation and intramolecular Claisen condensation. It was found that reaction modes significantly depend on the reaction temperature. We also examined the mechanistic detail of the reaction by 1 H-NMR experiment.

Stronger Brønsted Acids: Recent Progress

“…They also reported a formal [3 + 3] cycloaddition of silyl enol ethers 32 , which involved the domino Michael addition–Claisen condensation accompanied by the isomerization of silyl enol ether (Scheme ). The desired reaction occurred to afford tricyclic skeleton 33 in moderate chemical yield (45%), which is the same as the core skeleton of clovane …”

“…The desired reaction occurred to afford tricyclic skeleton 33 in moderate chemical yield (45%), which is the same as the core skeleton of clovane. 68 Allylsilane bearing a bulky silyl moiety also participated in the formation of cyclobutane in the presence of Tf 2 NH. 69−72 Allylsilanes 34 bearing a triisopropylsilyl or a t-BuMe 2 Si moiety efficiently underwent the [2 + 2] cycloaddition to furnish corresponding cyclobutane 35 in good yield accompanied by the formation of cyclopentane 36 (Scheme 10).…”

Facile isomerization of silyl enol ethers catalyzed by triflic imide and its application to one-pot isomerization–(2 + 2) cycloaddition

“…The obtained compound 6 is identical to the product in the reaction of 2a with 5 [10,13]. It is noteworthy that two different reactions, isomerization and (2 + 2) cycloaddition, are catalyzed by Tf 2 NH [14–18]. By contrast, when 1a reacted with 5 in the presence of Tf 2 NH at −78 °C, (2 + 2) cycloaddition directly proceeded to give 2-methylbicyclo[4.2.0]octane 7 in 66% yield along with the formation of two diastereomers (Scheme 2).…”

Triflimide (HNTf2) in Organic Synthesis

“…The reaction gave a moderate yield at refluxing chloroform (Scheme ). In retrospect, this is a very unusual observation, because the same reactants and catalyst provided a [2 + 2] cycloadduct, as shown in Scheme . The difference is reaction temperature.…”