Mark J. Burk

New chiral phospholanes; Synthesis, characterization, and use in asymmetric hydrogenation reactions

Abstract We describe the practical synthesis of enantiomerically pure trans-2,5-disubstituted-1-phenylphospholanes which are then employed in the preparation of a new series of C2-symmetric bis- and C3-symmetric tris(phospholane) ligands. A versatile three-step route to the important chiral 1,4-diol intermediates, used in the phosphine syntheses, is outlined. Rhodium complexes bearing the new phosphine ligands were prepared and shown to act as efficient catalyst precursors for the enantioselective hydrogenation of various unsaturated substrates.

Beyond Nature's Chiral Pool: Enantioselective Catalysis in Industry.

Enantioselective catalysts produce organic compounds in enantiomerically enriched form. They are highly efficient tools for the synthesis of biologically active materials, such as pharmaceuticals and crop-protection chemicals, in which enantiomeric purity can be critical. The design of chiral ligands is the key to developing new enantioselective catalysts. Three unusual families of ligands have been used to develop practical technology for enantioselective hydrocyanation of olefins, ring-opening of epoxides, and hydrogenation of various compounds.

Practical Access to 2-Alkylsuccinates through Asymmetric Catalytic Hydrogenation of Stobbe-Derived Itaconates

Enantiomerically pure 2-alkylsuccinates are obtained on a 500-g scale after hydrogenation with the cationic rhodium complexes with tetraalkyl-substituted 1,2-bis(phospholanyl)ethane or -benzene ligands [R′-DuPHOS; Eq. (a)]. The catalysts allow smooth hydrogenation of mixtures of the prochiral E and Z isomers of itaconate derivatives with very high enantioselectivities and catalytic efficiencies; even tetrasubstituted itaconates were hydrogenated with 96% ee.

Asymmetric intramolecular hydrosilylation of hydroxyketones

Abstract A procedure for the catalytic asymmetric intramolecular hydrosilylation of α- and β-hydroxyketones has been developed. A cationic rhodium (I) catalyst bearing the new chiral diphosphine (R,R)-i-Pr-DuPHOS affords the product diols in up to 93% ee.

The stereochemistry of enamide intermediates in DuPHOS-Rh(I) catalysed asymmetric hydrogenation

Abstract Stereochemical aspects of the title reaction were investigated for the (S,S)-Me-DuPHOS ligand 5a , largely by NMR examination of Ir complexes. They were found to behave in an analogous fashion to that established for P-aryl diphosphine-rhodium(I) complexes.

Oxidatively induced reductive elimination. A novel titanium complex resulting from C–F bond activation

Reaction between bis(cyclopentadienyl)titanacyclobutanes (1) and tetrakis(trifluoromethyl)cyclopentadienone (2) results in formal reductive elimination of cyclopropanes and activation of an sp3 C–F bond in (2) to afford the novel organometallic product (3)(structurally characterized by X-ray crystallography).

Asymmetric hydrogenation reactions mediated by a new class of bicyclic bisphosphinites

Abstract The bicyclic alcohol (−)- 4 was prepared from (−)-bicyclo[3.2.0]hept-2-en-6-one (−)- 1 in 50% yield. The diol (−)- 4 was coupled to selected chlorophosphines 6 – 12 to produce a series of bisphosphinites 13 – 19 in 89–95% yield. From these bisphosphinites were prepared the rhodium complexes 20 – 26 which were characterised by 31 P NMR and used in situ for the asymmetric hydrogenation of α-enamides 27 – 29 . Complexes 21 , 23 – 25 proved to be the superior catalysts for the production of ( R )- N -acetylphenylalanine (91, 84, 90 and 87.5% ee) from 27 and ( S )- N -acetylalanine methyl ester (70, 72, 68 and 71% ee) from 28 .

Einfacher Zugang zu 2‐Alkylsuccinaten durch asymmetrische katalytische Hydrierung von durch Stobbe‐Kondensation erhaltenen Itaconaten

Im 500-g-Masstab sind enantiomerenreine 2-Alkylsuccinate leicht zuganglich, wenn bei der Hydrierung kationische Rh-Komplexe mit tetraalkylsubstituierten 1,2-Bis(phospholanyl)ethan- oder -benzol(R′-DuPHOS)-Liganden verwendet werden [Gl. (a)]. Selbst Gemische der prochiralen (E)- und (Z)-Isomere von Itaconaten werden hocheffizient und enantioselektiv umgesetzt, z. B. auch tetrasubstituierte Itaconate mit 96% ee. R′ = H, Alkyl, Aryl.

Asymmetric synthesis of β-amino alcohols and 1,2-diamines through DuPHOS-Rh catalysed hydrogenation

Abstract A novel enantioselective synthesis of β-amino alcohols and 1,2-diamines is reported which incorporates the first description of the asymmetric hydrogenation of dehydro-β-amino alcohols and dehydro-α-amino aldoximes.