Directing the Stereoselectivity of the Claisen Rearrangement to Form Cyclic Ketones with Full Substitution at the α-Positions.

We report an enantioselective synthesis of cyclic ketones with full substitutions at the α-positions in a highly diastereoselective manner. Our method is achieved by subjecting substrate motifs in 2-allyloxyenones to chiral organomagnesium reagents, which trigger the Claisen rearrangement upon direct 1,2-carbonyl addition. The observed diastereoselectivity of the allyl migration is proposed to originate from the intramolecular chelation of the magnesium alkoxide to the allyloxy moiety.

Copper(I)-Catalyzed Synthesis of Unsymmetrical All-Carbon Bis-Quaternary Centers at the Opposing α-Carbons of Cyclohexanones.

We describe a new synthetic reaction that generates all-carbon bis-quaternary centers at the opposing side of α-carbons in cyclohexanone with four different substituents in a controlled manner. Catalyzed by Cu(MeCN)4BF4 salt, this chemistry is proposed to proceed via an intermediacy of unsymmetrical O-allyl oxyallyl cations, which undergo a sequence of regioselective nucleophilic addition with substituted indoles and diastereoselective Claisen rearrangement in a single synthetic operation. The stereochemical outcome of the products features the cis diastereorelationship between the two aryl groups at the α,α'-positions.

Correction: Synthesis of functionalized tetrahydropyrans via cascade cycloaddition involving silyloxyallyl cation intermediates.

Correction for 'Synthesis of functionalized tetrahydropyrans via cascade cycloaddition involving silyloxyallyl cation intermediates' by Fatimat O. Badmus et al., Chem. Commun., 2020, 56, 5034-5037, DOI: .

Synthesis of functionalized tetrahydropyrans via cascade cycloaddition involving silyloxyallyl cation intermediates.

An expedient synthesis of highly substituted tetrahydrobenzofuran via an unsymmetrical silyloxyallyl cation is reported. Conveniently generated under catalytic Brønsted acid conditions, nucleophilic capture of this reactive intermediate by silylenolate, followed by Paal-Knorr cascade cyclization in the presence of tosic acid monohydrate effectively constructed the tetrahydrobenzofuran core in a single synthetic step.

Mechanistic Perspectives in the Regioselective Indole Addition to Unsymmetrical Silyloxyallyl Cations.

Our investigations on the reaction mechanism to account for regioselectivity on the addition of indoles to unsymmetrical silyloxyallyl cations are reported. Using both experimental and computational methods, we confirmed the significance of steric effects from the silyl ether group toward directing the inward approach of indoles, leading to nucleophilic attack at the less substituted electrophilic α'-carbon. The role of residual water toward accelerating the rate of reaction is established through stabilization of the participating silyloxyallyl cation.

Brønsted Acid-Catalyzed Formal [2 + 2 + 1] Annulation for the Modular Synthesis of Tetrahydroindoles and Tetrahydrocyclopenta[ b]pyrroles.

An expedient synthesis of tetrahydroindoles and tetrahydrocyclopenta[ b]pyrroles, highlighted by Brønsted acid catalyzed formal [2 + 2 + 1] annulation reaction, is reported. Using three readily accessible reaction components, i.e., an electrophilic species in silyloxyallyl cations and two distinct nucleophiles in silylenol ethers and amines, our chemistry enables the assembly and functionalization of these biologically important N-heterocycles in a highly modular manner.

Brønsted Acid Catalyzed Synthesis of Functionalized 1,4- and 1,6-Dicarbonyl Monosilyl Enol Ethers under Operationally Practical Conditions.

Herein, we report an improved protocol for the concise synthesis of functionalized 1,4- and 1,6-dicarbonyl-derived monosilyl enol ethers via ionization of α'-hydroxy silyl enol ethers to generate unsymmetrical silyloxyallyl cations that were subsequently captured by TBS silyl enolates. These transformations were efficiently performed in acetonitrile at room temperature by employing pyridinium triflate as a catalyst. Our new reaction conditions are operationally more practical and broaden the accessibility of various 1,4- and 1,6-dicarbonyl groups, which include diketone, ketoester, and ketothioester functionalities.

Regioselective Functionalization of Enamides at the α-Carbon via Unsymmetrical 2-Amidoallyl Cations.

A new method to functionalize enamides via an intermediacy of unsymmetrical 2-amidoallyl cations is reported. Generated under mild Brønsted acid catalysis, these reactive species were found to undergo addition with various nucleophiles at the less substituted α-carbon to produce highly substituted enamides in high yields with complete control of regioselectivity.

Effects of Solvent and Residual Water on Enhancing the Reactivity of Six-Membered Silyloxyallyl Cations toward Nucleophilic Addition.

A new strategy for the generation of six-membered unsymmetrical silyloxyallyl cations using catalytic mild Brønsted acid is reported. These reactive intermediates were found to readily undergo direct nucleophilic addition with a broad range of nucleophiles to produce various α,α'-disubstituted silyl enol ether structural motifs. The findings also highlight the significance of the solvent effect and residual water in enhancing the reaction rate.

Structures and Energetics of Four Adjacent G·U Pairs That Stabilize an RNA Helix.

Consecutive G·U base pairs inside RNA helices can be destabilizing, while those at the ends of helices are thermodynamically stabilizing. To determine if this paradox could be explained by differences in base stacking, we determined the high-resolution (1.32 Å) crystal structure of (5'-GGUGGCUGUU-3')2 and studied three sequences with four consecutive terminal G·U pairs by NMR spectroscopy. In the crystal structure of (5'-GGUGGCUGUU-3')2, the helix is overwound but retains the overall features of A-form RNA. The penultimate base steps at each end of the helix have high base overlap and contribute to the unexpectedly favorable energetic contribution for the 5'-GU-3'/3'-UG-5' motif in this helix position. The balance of base stacking and helical twist contributes to the positional dependence of G·U pair stabilities. The energetic stabilities and similarity to A-form RNA helices suggest that consecutive G·U pairs would be recognized by RNA helix binding proteins, such as Dicer and Ago. Thus, these results will aid future searches for target sites of small RNAs in gene regulation.