30948-27-7

Upstream product

• 55739-56-5 α-acetamido-3-methoxy-4-acetoxycinnamic acid 
• 7636-26-2 3-methoxy-DL-tyrosine 

Downstream Products

• 113948-38-2 (-)-(R)-3-methoxytyrosine methyl ester hydrochloride 
• 15402-76-3 (+)-(R)-3-methoxytyrosine 

Relevant academic research and scientific papers

Cobalt-Catalyzed Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic Acids by Homolytic H2 Cleavage

The asymmetric hydrogenation of α,β-unsaturated carboxylic acids using readily prepared bis(phosphine) cobalt(0) 1,5-cyclooctadiene precatalysts is described. Di-, tri-, and tetra-substituted acrylic acid derivatives with various substitution patterns as well as dehydro-α-amino acid derivatives were hydrogenated with high yields and enantioselectivities, affording chiral carboxylic acids including Naproxen, (S)-Flurbiprofen, and a d-DOPA precursor. Turnover numbers of up to 200 were routinely obtained. Compatibility with common organic functional groups was observed with the reduced cobalt(0) precatalysts, and protic solvents such as methanol and isopropanol were identified as optimal. A series of bis(phosphine) cobalt(II) bis(pivalate) complexes, which bear structural similarity to state-of-the-art ruthenium(II) catalysts, were synthesized, characterized, and proved catalytically competent. X-band EPR experiments revealed bis(phosphine)cobalt(II) bis(carboxylate)s were generated in catalytic reactions and were identified as catalyst resting states. Isolation and characterization of a cobalt(II)-substrate complex from a stoichiometric reaction suggests that alkene insertion into the cobalt hydride occurred in the presence of free carboxylic acid, producing the same alkane enantiomer as that from the catalytic reaction. Deuterium labeling studies established homolytic H2 (or D2) activation by Co(0) and cis addition of H2 (or D2) across alkene double bonds, reminiscent of rhodium(I) catalysts but distinct from ruthenium(II) and nickel(II) carboxylates that operate by heterolytic H2 cleavage pathways.

Asymmetric hydrogenation of C=C double bonds using Rh-complex under homogeneous, heterogeneous and continuous mode conditions

A green process for enantioselective hydrogenation of dehydroamino acid derivatives and dimethyl itaconate with a rhodium catalyst modified by a new phosphine-phosphoramidite has been developed providing 97.7-99.8% enantioselectivity in green solvents such as ethylene carbonate and propylene carbonate. The l-DOPA precursor was obtained by simple filtration in 71% yield with 99.5% ee. Dimethyl itaconate was hydrogenated under solvent-free condition at 50 °C with 98.7% ee. The new rhodium complex was heterogenized on a mesoporous Al2O3 support using phosphotungstic acid (PTA) as an anchoring agent and tested in heterogeneous batch and flow reaction modes. The supported catalyst was reused eight times in the batch mode with over 97% ee and used over 12 hours in the flow reaction mode with an average of 97% ee in the asymmetric hydrogenation reaction of (Z)-α-acetamidocinnamic acid methyl ester.

Optically pure 1,2-bis[(o-alkylphenyl)phenylphosphino]ethanes and their use in rhodium-catalyzed asymmetric hydrogenations of α-(acylamino)acrylic derivatives

Optically pure (S,S)-1,2-bis[(o-alkylphenyl)-phenylphosphino]ethanes 1a-d were prepared in four steps from phenyldichlorophosphine via phosphine-boranes as the intermediates. The rhodium complexes 5a-d of these diphosphines were used for the asymmetric hydrogenations of α-(acylamino)-acrylic derivatives including β-disubstituted derivatives. Markedly high enantioselectivity (78→99%) was observed for the reduction of β-monosubstituted derivatives. β-Disubstituted derivatives were also reduced in considerably high enantioselectivity (up to 90%). The single crystal X-ray analysis of the rhodium complex 5c of (S,S)-1,2-bis[phenyl(5′,6′,7′,8′- tetrahydronaphthyl)phosphino]ethane (1c) revealed its δ-type structure with face orientation of the two tetrahydronaphthyl groups and edge orientation of the two phenyl groups. This conformation corresponds to that of the rhodium complex of 1,2-bis[(o-methoxyphenyl)phenylphosphino]ethane (DIPAMP); the rhodium complex of (R,R)-DIPAMP, whose chirality at phosphorus is opposite that of 5c, exhibits a λ-type structure with the face orientation of the two o-methoxyphenyl groups and the edge orientation of the two phenyl groups. The conformational similarity of these rhodium complexes as well as the stereochemical outcome in the asymmetric hydrogenations means that the coordinative interaction of the methoxy group of DIPAMP with rhodium metal is not the main factor that affects asymmetric induction.

H8-MonoPhos and its application in catalytic enantioselective hydrogenation of α-dehydroamino acids

H8-MonoPhos, a new stable and readily soluble monodentate phosphoramidite ligand, has been facilely prepared from H8-BINOL. The ligand achieved up to 99.9% ee and 96.7% ee in hydrogenation of dehydroalanine and dehydrohomophenylalani

Asymmetric Hydrogenation Catalyzed by (S,S)-R-BisP*-Rh and (R,R)-R-MiniPHOS Complexes: Scope, Limitations, and Mechanism

A new class of chiral C2-symmetric bis(trialkyl)phosphine ligands has been prepared and used in Rh(I)-catalyzed asymmetric hydrogenation reactions. The ligands, 1,2-bis(alkylmethylphosphino)ethanes 1 a-g (abbreviated as BisP*, alkyl = t-butyl, 1-adamantyl, 1-methylcyclohexyl, 1,1-diethylpropyl, cyclopentyl, cyclohexyl, isopropyl) and 1,2-bis(alkylmethylphosphino)methanes 2 a-d (abbreviated as MiniPHOS, alkyl = t-butyl, cyclohexyl, isopropyl, phenyl) are prepared by a simple synthetic approach based on the air-stable phosphine-boranes. These new ligands give the corresponding Rh(I) complexes, which are effective catalytic precursors for the asymmetric hydrogenation of a representative series of dehydroamino acids and itaconic acid derivatives. Enantioselectivities observed in these hydrogenations are universally high and in many cases exceed 99%. X-Ray characterization of four precatalysts, study of the pressure effects, deuteration experiments, and characterization of the wide series of intermediates in the catalytic cycle are used for the discussion of the possible correlation between the structure of the catalysts and the outcome of the catalytic asymmetric hydrogenation.

Asymmetric hydrogenation - Influence of the structure of carbohydrate derived catalysts on the relative enantioselectivity Q(H/Me) regarding acid and ester substrates and its inversion - Selectivity increase in water by amphiphiles

4,6-O-Benzylidene protected 2,3-bis(O-diphenylphosphino)-D-glycopyranoside rhodium(I) chelate precatalysts 1-4 e,f showed for the hydrogenation of methyl (Z)2-N-acylamidoacrylates 6-8 a stepwise decrease of the enantioselectivity with increasing number of axially oriented hexopyranoside substituents. The decrease is even stronger for the analogous substrate acids 6h-8h resulting in an unusual low relative enantioselectivity Q = q(H)/q(Me) of 0.3 for the precatalysts 4e and 4f. Deprotected, 4,6-OH-group bearing catalysts 1-4 g,h generally show smaller differences of %ee in methanol or benzene, however, not in water. Under addition of amphiphiles a in comparison with blanks b the relative enantioselectivity Q = q(a)/q(b) clearly increases for both groups of catalysts in most cases to Q-values between 3 up to 8 - independent of a neutral or ionic nature of the amphiphile.

A new P-chiral bisphosphine, (S,S)-1,2-bis[(o-ethylphenyl)phenylphosphino]ethane, as an effective ligand in catalytic asymmetric hydrogenation of α-(acylamino)acrylic acids

(S,S)-1,2-Bis[(o-ethylphenyl)phenylphosphino]ethane has been prepared via optically active phosphine-boranes. Asymmetric hydrogenation of α-(acylamino)acrylic acids by a rhodium complex with this ligand affords N-acylamino acids in 86-93% ee.