Sulfone Group as a Versatile and Removable Directing Group for Asymmetric Transfer Hydrogenation of Ketones.

The sulfone functional group has a strong capacity to direct the asymmetric transfer hydrogenation (ATH) of ketones in the presence of [(arene)Ru(TsDPEN)H] complexes by adopting a position distal to the η6 -arene ring. This preference provides a means for the prediction of the sense of asymmetric reduction. The sulfone group also facilitates the formation of a range of reduction substrates, and its ready removal provides a route to enantiomerically enriched alcohols that would otherwise be extremely difficult to prepare by direct ATH of the corresponding ketones.

Squeezing formaldehyde into C60 fullerene.

The cavity inside fullerene C60 provides a highly symmetric and inert environment for housing atoms and small molecules. Here we report the encapsulation of formaldehyde inside C60 by molecular surgery, yielding the supermolecular complex CH2O@C60, despite the 4.4 Å van der Waals length of CH2O exceeding the 3.7 Å internal diameter of C60. The presence of CH2O significantly reduces the cage HOMO-LUMO gap. Nuclear spin-spin couplings are observed between the fullerene host and the formaldehyde guest. The rapid spin-lattice relaxation of the formaldehyde 13C nuclei is attributed to a dominant spin-rotation mechanism. Despite being squeezed so tightly, the encapsulated formaldehyde molecules rotate freely about their long axes even at cryogenic temperatures, allowing observation of the ortho-to-para spin isomer conversion by infrared spectroscopy. The particle in a box nature of the system is demonstrated by the observation of two quantised translational modes in the cryogenic THz spectra.

Enantioselective Synthesis of Bicyclopentane-Containing Alcohols via Asymmetric Transfer Hydrogenation.

Compounds a containing bicyclo[1.1.1]pentane (BCP) adjacent to a chiral center can be prepared with high enantiomeric excess through asymmetric transfer hydrogenation (ATH) of adjacent ketones. In the reduction step, the BCP occupies the position distant from the η6-arene of the catalyst. The reduction was applied to the synthesis of a BCP analogue of the antihistamine drug neobenodine.

Asymmetric Transfer Hydrogenation of α-Keto Amides; Highly Enantioselective Formation of Malic Acid Diamides and α-Hydroxyamides.

The asymmetric transfer hydrogenation (ATH) of α-keto-1,4-diamides using a tethered Ru/TsDPEN catalyst was achieved in high ee. Studies on derivatives identified the structural elements which lead to the highest enantioselectivities in the products. The α-keto-amide reduction products have been converted to a range of synthetically valuable derivatives.

Combining Electronic and Steric Effects To Generate Hindered Propargylic Alcohols in High Enantiomeric Excess.

Tethered ruthenium-TsDPEN complexes have been applied to the catalysis of the asymmetric transfer hydrogenation of a range of aryl/acetylenic ketones. The introduction of an ortho- substituent to the aryl ring of the substrate results in a reversal of the enantioselectivity, while the introduction of two o-fluoro substituents results in an improvement to the reduction enantioselectivity, as does the replacement of a phenyl ring on the alkyne with a trimethylsilyl group. These effects are rationalized as resulting from a change in the steric properties of the aryl ring and the electronic properties of the alkyne which, when matched in the reduction transition state, combine within a "window" of substrate/catalyst matching to generate products of high ee.

Highly Enantioselective One-Pot Synthesis of Chiral ß-Heterosubstituted Alcohols via Ruthenium-Prolinamide-Catalyzed Asymmetric Transfer Hydrogenation.

The utility of a chiral Ru-prolinamide catalytic system has been demonstrated in one-pot synthesis of optically active ß-triazolylethanol and ß-hydroxy sulfone derivatives. The said methodology proceeds through asymmetric transfer hydrogenation of in situ formed ketones of the corresponding chiral products. Various chiral prolinamide ligands were screened, and ligand L6 with isopropyl groups substituted at the ortho position has shown excellent activity at 60 °C in aqueous medium producing up to 95% yield and 99.9% enantioselectivity.

Kinetic resolution of 1,2-diols using immobilized Burkholderia cepacia lipase: A combined experimental and molecular dynamics investigation.

Kinetic resolution of rac-1,2-diols using the biocatalyst Burkholderia cepacia lipase (BCL) immobilized on a biodegradable binary blend support of hydroxypropyl methyl cellulose(HPMC)/polyvinyl alcohol (PVA) has been investigated. The immobilization technique improved enzyme activity significantly and it has excellent recyclability with good yield and enantiomeric excess values up to the studied range of nine cycles. At optimum reaction conditions, conversion of 45-50% with excellent enantiomeric excess (up to 99% ee) were obtained. It was observed that BCL shows enantio-preference to R form of primary hydroxyl group for acylation, whereas S form is preferred for diacetate formation. The resultant products were characterized with the help of different analytical techniques such as 1H and 13C NMR, chiral HPLC, IR and GC-MS. In order to understand the effect of solvent as well as various derivatives of substrates, combined molecular dynamics and docking simulations were carried out. Explanation related to experimentally observed enantio-selectivities have been provided based on transition state structures of acylated complexes.

Kinetic Resolution Driven Diastereo- and Enantioselective Synthesis of cis-ß-Heteroaryl Amino Cycloalkanols by Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation.

The utility of tethered Ru-TsDPEN catalyst has been demonstrated for the asymmetric transfer hydrogenation of rac-α-heteroaryl amino cycloalkanones to construct biologically important cis-ß-heteroaryl amino cycloalkanols with two contiguous chiral centers via dynamic kinetic resolution. The stated (R,R)-Teth-TsDPEN-Ru-catalyzed transformation is carried out under mild conditions using formic acid/triethylamine as a hydrogen source with excellent diastereo- and enantioselectivities. Further, this methodology has been applied for the synthesis of an antileishmanial agent and chiral ionic liquid.