Project description:In continuation of our recent studies on group 14 rings with exocyclic silicon-carbon double bonds, we report here on the synthesis and reactivity of previously unknown acyl-substituted 1,4-disilacyclohexa-2,5-dienes. 1,1,4,4-Tetrakistrimethylsilyl-1,4-disilacyclohexa-2,5-diene 1 cleanly afforded the silyl anion 1-K after addition of 1 equiv of KO t Bu. 1-K subsequently could be reacted with various electrophiles to the expected substitution products including compounds 4 and 5. When photolyzed with λ > 300 nm radiation, 4 and 5 undergo Brook-type 1,3-Si → O migration reactions to generate the corresponding 1,4-disilacyclohexadienes with exocyclic Si=C bonds as the primary products. These metastable silenes only could be characterized in form of appropriate quenching products. The reaction of compound 4 with KO t Bu followed by the addition of 1 equiv of PhMe2SiCl surprisingly gave the silylated 1,4-disilanorbornadiene cages 8 and 9 instead of the expected exocyclic silene. The responsible sila-Peterson-type mechanism could be elucidated by density functional theory calculations at the conductor-like polarizable continuum model (THF) B3LYP-GD3/6-31 + G(d) level and by the isolation and characterization of unstable intermediate products after proper derivatization.
Project description:A catalytic regio- and stereoselective 1,4-hydroboration of 1,3-dienes was accomplished with pinacolborane in the presence of Ni(cod)(2) and PCy(3). This reaction exhibits broad substrate scope operating on a range of substituted dienes and occurs with generally high levels of selectivity and efficiency. Reactivity patterns suggest that the reactive conformation of the diene is the S-cis form. The intermediate allylboronate can be oxidized to stereodefined allylic alcohols or can be used in stereoselective carbonyl addition reactions.
Project description:The first nickel-catalyzed enantioselective allylic alkylation of lactone and lactam substrates to deliver products bearing an all-carbon quaternary stereocenter is reported. The reaction, which utilizes a commercially available chiral bisphosphine ligand, proceeds in good yield with a high level of enantioselectivity (up to 90% ee) on a range of unactivated allylic alcohols for both lactone and lactam nucleophiles. The utility of this method is further highlighted via a number of synthetically useful product transformations.
Project description:Titanium-mediated cross-coupling of allenic alcohols with alkynes has been investigated. Divergent reaction pathways were discovered that provide either stereodefined 1,4-dienes or substituted cross-conjugated trienes. In short, allene substitution plays a critical role in the determination of reaction pathway.
Project description:We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give gem-disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-rich p-anisoyl lactam protecting group and the use of a nonpolar solvent proved crucial to obtaining high enantioselectivity in most cases. Additionally, we demonstrate the use of our methodology in the synthesis of a gem-disubstituted analogue of the FDA-approved anti-insomnia drug suvorexant.
Project description:The first iridium-catalyzed enantioselective vinylogous allylic alkylation of coumarins is presented. Using easily accessible linear allylic carbonates as the allylic electrophile, this reaction installs unfunctionalized allyl groups at the γ-position of 4-methylcoumarins in an exclusively branched-selective manner generally in high yields with an excellent level of enantioselectivity (up to 99 : 1 er).
Project description:Benzyl phosphonate esters often serve as reagents in Horner-Wadsworth-Emmons reactions. In most cases, they can be prepared from benzylic alcohols via formation of the corresponding halide followed by an Arbuzov reaction. To identify a more direct synthesis of phosphonate esters, we have developed a one-flask procedure for conversion of benzylic and allylic alcohols to the corresponding phosphonates through treatment with triethyl phosphite and ZnI(2).
Project description:The first enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted acyclic enol carbonates providing linear α-quaternary ketones is reported. Investigation into the reaction revealed that the use of an electron-deficient phosphinooxazoline ligand renders the enolate geometry of the starting material inconsequential, with the same enantiomer of product obtained in the same level of selectivity regardless of the starting ratio of enolates. As a result, a general method toward acyclic all-carbon quaternary stereocenters has been developed.
Project description:N-alkyl amino acids find widespread application as highly valuable, renewable building blocks. However, traditional synthesis methodologies to obtain these suffer from serious limitations, providing a major challenge to develop sustainable alternatives. We report the first powerful catalytic strategy for the direct N-alkylation of unprotected α-amino acids with alcohols. This method is highly selective, produces water as the only side product leading to a simple purification procedure, and a variety of α-amino acids are mono- or di-N-alkylated, in most cases with excellent retention of optical purity. The hydrophobicity of the products is tunable, and even simple peptides are selectively alkylated. An iron-catalyzed route to mono-N-alkyl amino acids using renewable fatty alcohols is also described that represents an ideal green transformation for obtaining fully bio-based surfactants.
Project description:Regioselective anti-allylindation of alkynes was achieved using InBr₃ and allylic silanes. Various types of alkynes and allylic silanes were applicable to the present allylindation. This sequential process used the generated 1,4-dienylindiums to establish novel synthetic methods for skipped dienes. The 1,4-dienylindiums were characterized by spectral analysis and treated with I₂ to stereoselectively give 1-iodo-1,4-dienes. The Pd-catalyzed cross coupling of 1,4-dienylindium with iodobenzene successfully proceeded in a one-pot manner to afford the corresponding 1-aryl-1,4-diene.