James M. Takacs

The Wacker Reaction and Related Alkene Oxidation Reactions

The objective of this review is to survey the current state of the Wacker and related alkene oxidation reactions focusing on the reactions of higher alkenes and emphasizing the mechanistic pictures that have evolved, the current understanding regarding issues of selectivity, recent applications of the chemistry in synthesis, and the use of other transition metal catalysts to effect related oxidation reactions. The Wacker oxidation reaction has been extensively studied over the years. There are a number of excellent reviews published on various aspects of the reaction (1), with a series of reviews by Tsuji deserving particular note for their special insight into the development of this reaction (2-4).

Amide-directed catalytic asymmetric hydroboration of trisubstituted alkenes

Rhodium-catalyzed hydroborations of trisubstituted alkenes are generally slow and often suffer from competing alkene isomerization. In contrast, the trisubstituted alkene moieties contained within the framework of a beta,gamma-unsaturated amide undergo facile reaction, perhaps facilitated by carbonyl directing effects and two-point binding of the substrate to the rhodium catalyst. Stereoisomeric substrates, for example, (E)- and (Z)-3, cleanly give rise to diastereomeric products, and thus the rhodium-catalyzed reaction is stereospecific. In addition, simple TADDOL-derived phenyl monophosphite ligands in combination with Rh(nbd)(2)BF(4) afford highly enantioselective catalysts (seven examples, 91-98% ee). These catalysts provide an alternative methodology to prepare Felkin or anti-Felkin acetate-aldol products and related derivatives that are obtainable from the intermediate chiral organoboranes.

Rhodium-catalyzed asymmetric hydrogenation using self-assembled chiral bidentate ligands*

The chirality-directed self-assembly of bifunctional subunits around a structural metal - typically, zinc(II) - is used to form a heteroleptic complex in which a second set of ligating groups are suitably disposed to bind a second metal, forming a heterobimetallic catalyst system. We find that subtle changes in the structural backbone (i.e., ligand scaffold) of such chiral bidentate self-assembled ligands (SALs) can be used to manipulate the ligand topography and chiral environment around catalytic metal; thus, the scaffold can be optimized to maximize asymmetric induction. Using this combinatorial strategy for ligand synthesis, a preliminary study was carried out in which a library of 110 SALs was evaluated in the rhodium-catalyzed asymmetric hydrogenation of a simple N-acyl enamide. The level of enantioselectivity obtained varies from near racemic to greater than 80 % ee as a function of the ligand scaffold, with the possibility of further improvement yet to be explored.

The selective formation of neutral, heteroleptic zinc(II) complexes via self-discrimination of chiral bisoxazoline racemates and pseudoracemates

The reversible metal-directed multi-component self-assembly of chiral bisoxazolines proceeds with a high level of chiral self-discrimination and thus defines a simple strategy for the preparation of neutral, heteroleptic zinc(II) complexes.

Click-connected ligand scaffolds: macrocyclic chelates for asymmetric hydrogenation.

Click chemistry is used to construct ligand scaffolds for a series of chiral diphosphites. Enantioselectivity as high as 97% ee is obtained using these click ligands in rhodium-catalyzed asymmetric hydrogenation. Control experiments and spectroscopic data suggest that a 16-membered P,P-macrocyclic Rh(I) chelate is formed.

ENANTIOSELECTIVE DIELS-ALDER REACTIONS : ROOM TEMPERATURE BIS(OXAZOLINE)-ZINC, -MAGNESIUM, AND -COPPER TRIFLATE CATALYSTS

Abstract A series of chiral bis(oxazoline) ligands, differing in the length of the chain connecting the chiral oxazoline subunits and in the nature of the substituent at the chiral center, were examined in the room temperature Zn(OTf) 2 , Mg(OTf) 2 catalyzed reaction of N-crotonyloxazolidinone with cyclopentadiene. A 1,4-bis(oxazoline) ligand proved best for Zn(OTf) 2 and afforded product consistent with reaction via an octahedral model, while 1,3-bis(oxazoline) ligands were best for Mg(OTf) 2 and Cu(OTf) 2 .

Targeting methanopterin biosynthesis to inhibit methanogenesis.

ABSTRACT This paper describes the design, synthesis, and successful employment of inhibitors of 4-(β-d-ribofuranosyl)aminobenzene-5′-phosphate (RFA-P) synthase, which catalyzes the first committed step in the biosynthesis of methanopterin, to specifically halt the growth of methane-producing microbes. RFA-P synthase catalyzes the first step in the synthesis of tetrahydromethanopterin, a key cofactor required for methane formation and for one-carbon transformations in methanogens. A number of inhibitors, which are N-substituted derivatives of p-aminobenzoic acid (pABA), have been synthesized and their inhibition constants with RFA-P synthase have been determined. Based on comparisons of the inhibition constants among various inhibitors, we propose that the pABA binding site in RFA-P synthase has a relatively large hydrophobic pocket near the amino group. These enzyme-targeted inhibitors arrest the methanogenesis and growth of pure cultures of methanogens. Supplying pABA to the culture relieves the inhibition, indicating a competitive interaction between pABA and the inhibitor at the cellular target, which is most likely RFAP synthase. The inhibitors do not adversely affect the growth of pure cultures of the bacteria (acetogens) that play a beneficial role in the rumen. Inhibitors added to dense ruminal fluid cultures (artificial rumena) halt methanogenesis; however, they do not inhibit volatile fatty acid (VFA) production and, in some cases, VFA levels are slightly elevated in the methanogenesis-inhibited cultures. We suggest that inhibiting methanopterin biosynthesis could be considered in strategies to decrease anthropogenic methane emissions, which could have an environmental benefit since methane is a potent greenhouse gas.

Comparison of the electronic structure of two polymers with strong dipole ordering

Two different polymers, with large local electric dipoles, are compared: copolymers of polyvinylidene fluoride with trifluoroethylene [P(VDF-TrFE, 70%:30%)] and polymethylvinylidenecyanide (PMVC). While the different local point group symmetries play a key role, both crystalline polymers exhibit intra-molecular band structure, though the Brillouin zone critical points differ.

Enantioselective Diels-Alder reactions: novel constrained bis(oxazoline) ligand-metal triflate catalysts

Abstract Five chiral 1,4-bis(oxazoline) ligands, each bearing a bicyclic backbone, were prepared and examined in Mg(OTf)2-, Zn(OTf)2-, and Cu(OTf)2-catalyzed Diels-Alder reactions. The cycloadditions were carried out at room temperature and afforded enantiomeric excess up to 88%. Surprisingly, a non-C2-symmetric bis(oxazoline) bearing a meso backbone was among the more efficient ligands examined.

Catalytic iron-mediated ene carbocyclizations of trienes : enantioselective syntheses of the iridoid monoterpenes (-)-mitsugashiwalactone and (+)-isoiridomyrmecin

Abstract The iron-catalyzed cycloisomerization of a chiral (2E,7E) 2,7,9-decatriene derivative bearing a methyl substituent adjacent to the 1,3-diene subunit proceeds with high levels of 1,2-stereoinduction relative to the resident methyl-bearing stereocenter. The stereochemistry of the chiral cyclopentane product is proven by conversion to (−)-Mitsugashiwalactone ( 1 ) and to (+)-Isoiridomyrmecin ( 2 ).