William A. Nugent

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.

A ‘waterproof’ catalyst for the oxidation of secondary amines to nitrones with alkyl hydroperoxides

Abstract Catalytic oxidation of secondary amines to nitrones using alkyl hydroperoxides as primary oxidant has been demonstrated for the first time. The titanium alkoxide catalyst is protected from co-product water by the combined use of a tightly binding trialkanolamine ligand and molecular sieves. Nitrones can be obtained in high yield (up to 98%) under homogeneous, anhydrous conditions and even in the absence of solvent. The reactions are fast (2–7 h) and good selectivity can be achieved with as little as 1% catalyst.

Linear dimerization of acrylates by palladium and rhodium catalysts: effect of lewis and protic acid additives

Abstract The rates of catalytic dimerization of alkyl acrylates by PdCl 2 (NCPh) 2 and by [(C 2 H 4 )RhCl] 2 are greatly increased by the combination of a Lewis acid promoter and a proton source. For the rhodium systems, catalyst life was also enhanced and yields of up to 280 mol/mol Rh with > 98% selectivity to linear dialkyl hexenedioates have been observed. Optimal conditions involved the use of [(C 2 H 4 ) 2 RhCl] 2 , FeCl 3 and methanol in the proportions 1:5:10 at 80 °C. The isomeric composition of the product is markedly influenced by the combination of catalyst and promoter employed; either cis -Δ 2 , trans -Δ 2 , or trans -Δ 3 hexenedioate may predominate. Thus on changing the promoter from FeCl 3 to SnCl 4 in the Rh-catalyzed system, the product distribution changed from 85% trans -Δ 2 to 62% cis -Δ 2 hexene-dionate; certain Pd-catalyzed systems produced up to 60% of the isomeric Δ 3 hexenedioates.

Highly regioselective microwave-assisted synthesis of enantiopure C3-symmetric trialkanolamines

Abstract Enantiopure, C3-symmetric trialkanolamines can be efficiently and rapidly obtained on a gram scale via one pot or step-wise microwave-assisted epoxide ring opening with ammonia in high yields (up to 89%) and regioselectivity up to 100%.

Stereoselective catalytic sulfoxidations mediated by new titanium and zirconium C3, trialkanolamine complexes

Monomeric Ti(IV)/C3 trialkanolamine complexes are effective catalysts in the stereoselective sulfoxidation of alkyl aryl sulfides (ees up to 84%, 0.1% of catalyst). Such complexes were shown to have a biphilic nature, behaving as electrophilic oxidants towards sulfides while a nucleophilic pathway dominates the oxidation of sulfoxides. The analogous Zr(IV) complexes, likely dimeric, are even better and more general stereoselective sulfoxida- tion catalysts (ees up to 91%, 50 T.O.), affording sulfoxides with the opposite absolute configuration.

Homogeneous catalysis as a tool for organic synthesis

Homochiral trialkanolamines are a new class of chiral ligand for enantioselective catalysis. Mononuclear titanium complexes bearing such ligands promote the asymmetric sulfoxidation of alkyl aryl sulfides. In contrast, a dimeric zirconium species is the active catalyst in the desymmetrization of meso epoxides with azides. Mechanistic insight into the latter reaction has led to a new reaction, the enantioselective desymmetrization of meso epoxides using halides as the nucleophilic partner. HOMOCHIRAL TRIALKANOLAMINES Several years ago (ref. 1) we introduced homochiral trialkanolamines 1 as ligands for enantioselective catalysts based on early transition metals. These ligands have several advantages. They are easy to synthesize; many enantiopure epoxides react directly with ammonia according to eq. 1: H%R 60 deg C MeOH OH QH NH3 + 3 R 1 A Moreover, ligands 1 bind tightly to early transition metals in a tetradentate fashion to form robust complexes which persist even in the presence of water or silylating agents. The three asymmetric centers provide a highly asymmetric environment in coordination sphere of the transition metal. Ligands 1 displace monodentate alkoxides from group 4-6 metal alkoxides to provide the corresponding trialkanolamine(3-) complexes. An example is the reaction of homochiral triisopropanolamine with titanium(1V) isopropoxide shown in eq. 2: TH F AcCl OH Ti(OiPr)4 + N A ,LTiOiPr LTiCl (2) iPrOAc \/.a 3 iPrOH Treatment of the resultant LTiOiPr with acetyl chloride affords the LTiCl complex, 2. The x-ray crystal structure of 2 is shown in Figure 1. It can be seen that the ligand adopts a highly symmetrical C3 stereochemistry and provides a complex whose shape could be described as a “rotor” or “pinwheel”.

Structure and reactivity in the group 5B t-butylimido complexes (Me2N)3MNBut; X-ray crystal and molecular structure of N-t-butylimidotris(dimethylamido)tantalum

The novel complexes (Me2N)3MNBut(M = Nb or Ta) contain a linear MN–C unit and undergo reactions with electrophiles at the amido nitrogen; the structure of (Me2N)3MNBut has been determined by X-ray crystallography.

An unusual rotational distortion in an [(η-indenyl)RhL2] complex: molecular structures of [(η-1,2,3-Me3C9H4)Rh(η-C2H4)2] and [(η-C9H7)Rh(CO)2]

The molecular structures of [(η-1,2,3-Me3C9H4)Rh(η-C2H4)2] and [(η-C9H7)Rh(CO)2], barriers to hindered ethylene rotation in a series of indenyl rhodium bis(ethylene) complexes bearing different degrees of indenyl-ring methylation, and the barrier to hindered indenyl-ring rotation in [(η-1-MeC9H6)Rh(CO)2] are reported.

Practical Synthesis of Methyl Z-2-(N-Acetylamino) but-2-Enoate. An Intermediate to D- and L-2-Aminobutyric Acid

Abstract Treatment of inexpensive L- or DL-threonine methyl ester with acetic anhydride and either pyridine or anhydrous sodium acetate at reflux results in dehydration yielding the N,N-diacetamide of the title compound in >80% yield. Monodeacetylation of the diacetamide with 0.1 equiv of triethylamine in methanol affords the title monoacetamido derivative 1 in nearly quantitative yield.

MIB: an advantageous alternative to DAIB for the addition of organozinc reagents to aldehydes

3-exo-Morpholinoisoborneol (MIB) catalyzes the addition of organozinc reagents to aldehydes in high enantiomeric excess and provides several advantages over the venerable amino alcohol ligand DAIB.