Dehydroamino Esters Research Articles

Design and Synthesis of Spirochroman‐2‐on‐4,1'‐indan‐7'‐ol and Its Application for Synthesizing Chiral Monophosphinite Ligands†

Comprehensive SummaryThe design and synthesis of spirochroman‐2‐on‐4,1'‐indan‐7'‐ol (SCIOL) and its application for synthesizing chiral monophosphinite ligands are reported. The synthesis features a tandem double Friedel‐Crafts reaction/lactonization to construct the spiro framework and the desired racemic SCIOL was obtained via 6 steps with a total yield of 44.5%. Using an inclusion resolution with N‐benzylcinchonidinium chloride, the optical SCIOL could be obtained in good yields on a gram scale. The preliminary studies indicated that the corresponding chiral spiro monophosphinite ligands exhibit high catalytic activity and enantioselectivity (up to 94% ee) in the rhodium‐catalyzed asymmetric hydrogenation of N‐acetyl dehydroamino esters. These outcomes highlight the significant potential of SCIOL as a useful framework for the development of chiral spiro ligands.

Pt/Al2O3 Catalyzed Diastereoselective Hydrogenation of β-Dehydro-amino Esters Induced by a Chiral Prosthetic Group

A chiral prosthetic group induced heterogeneous diastereoselective asymmetric hydrogenation of β -dehydroamino esters, catalyzed by Pt/Al 2 O 3 , has been developed. A series of β -dehydroamino esters were successfully hydrogenated in high yields with good diastereoselectivities ( dr up to 5.2:94.8). This method provides a convenient and efficient synthetic way for the preparation of chiral β- amino acid derivatives, which are key intermediates for bioactive compounds and pharmaceuticals.

Rhodium‐Catalyzed Asymmetric Hydrogenation of Olefins with PhthalaPhos, a New Class of Chiral Supramolecular Ligands

A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (PhthalaPhos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2-acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1-yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3-phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.

Modular optimization of enantiopure epoxide-derived P,S-ligands for rhodium-catalyzed hydrogenation of dehydroamino acids

The optimization of P,S-ligands derived from enantiopure (2S,3S)-phenylglycidol for asymmetric rhodium-catalyzed hydrogenation of dehydroamino esters is described. The exceptionally high modular character of the (2S,3S)-phenylglycidol platform is demonstrated by systematic modification of the ether and thioether moieties, the skeletal aryl substituent and the stereo and regiochemistry of the ligands. An experimentally useful method for the monitoring of hydrogenation reactions is also described and used for obtaining relevant data of the catalytic systems studied.

Expedient Pathway into Optically Active 2‐Oxopiperidines

AbstractThe piperidine ring system is one of the most common structural subunits and is found in many natural products. Moreover, piperidine alkaloids and derivatives thereof are of great interest for the pharmaceutical industry since they exhibit a wide range of biological activities. Consequently, short and valuable routes to highly functionalized building blocks for this important ring system are of general interest. A ring‐closing metathesis (RCM)‐mediated approach based on linear (substituted) dehydroamino esters was developed to provide cyclic dehydroamino esters. These structures represent valuable intermediates en route to highly substituted pipecolic acids as well as more elaborate heterocycles.

Enantioselective Rh-catalyzed hydrogenation of N-acyl dehydroamino esters and enamides with monodentate phosphoramidite ligands

Chiral monodentate phosphoramidite ligands were conveniently prepared from 1,1′-bi-2-naphthol (BINOL) and (S)-pyrrolidine in good yields, which were effective chiral ligands in the enantioselective rhodium-catalyzed hydrogenation of dehydroamino esters and enamides at low hydrogenation pressure. High conversion rate (up to 99% for dehydroamino esters and enamides) and good enantioselectivity (up to 96.3% ee for dehydroamino esters and 91.7% ee for enamides) were obtained.

Enantiomerically pure bicyclo[3.3.1]nona-2,6-diene as the sole source of enantioselectivity in BIPHEP-Rh asymmetric hydrogenation

In situ resolution of the rapidly racemising diphosphine BIPHEP and its relatives with the cationic Rh complex of (S,S)-bicyclonona-2,6-diene permits the asymmetric hydrogenation of dehydroamino esters.

The Synthesis of Spirobitetraline Phosphoramidite Ligands and their Application in Rhodium‐Catalyzed Asymmetric Hydrogenation

AbstractA racemic 1,1′‐spirobitetralin‐8,8′‐diol (SBITOL) was conveniently synthesized from 3‐methoxybenzaldehyde in 26 % yield over 9 steps and resolved via its bis‐(S)‐camphorsulfonates. The corresponding chiral spirobitetraline monophosphoramidite ligands have been prepared and their rhodium complexes were applied in the asymmetric hydrogenation of dehydroamino esters with good to excellent enantioselectivities (up to 99.3 % ee).

Enantioselective Rh-Catalyzed Hydrogenation of N-Formyl Dehydroamino Esters with Monodentate Phosphoramidite Ligands

Enantioselectivities up to >99% ee were achieved in the rhodium-catalyzed asymmetric hydrogenation of N-formyl dehydroamino esters using monodentate phosphoramidites as chiral ligands. The substrates were synthesized by condensation of methyl isocyanoacetate with a range of aldehydes and with cyclohexanone. A highly convenient multigram scale one step synthesis of methyl 2-(formamido)acrylate was developed. This compound was used in the synthesis of methyl 2-(formamido)cinnamate via a solvent free Heck reaction. Moreover, full conversion and >99% ee were obtained in 1 h in the hydrogenation of methyl 2-(formamido)acrylate with 0.2 mol % catalyst and 2 bar hydrogen pressure. The versatility of the formyl protection was established by its removal under mild conditions.

The Application of Monodentate Secondary Phosphine Oxide Ligands in Rhodium‐ and Iridium‐Catalyzed Asymmetric Hydrogenation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The application of monodentate secondary phosphine oxide ligands in rhodium- and iridium-catalyzed asymmetric hydrogenation

Enantiopure secondary phosphine oxides have been tested as ligands in the rhodium- and iridium-catalyzed asymmetric hydrogenation of functionalized olefins. tert-Butylphosphinoyl benzene turned out to be a versatile ligand in the iridium-catalyzed hydrogenation of β-branched dehydroamino esters and in the rhodium-catalyzed hydrogenation of an enol carbamate.

Efficient Access to Alanine Derivatives by 1,4‐Additions of Potassium Trifluoro(organo)borates

AbstractPotassium trifluoro(organo)borates, highly stable and easily prepared organoboron derivatives, were able to react with a great variety of dehydroamino esters. This reaction, catalyzed by rhodium complexes, allowed the formation of alanine derivatives bearing a great variety of amino protecting groups in good to high yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Tandem radical cyclisations leading to indolizidinones and pyrrolizidinones

Reaction of various dehydroamino esters with tin hydrides resulted in 5- endo-5- exo or 5- endo-6- endo tandem cyclisation reactions. The preferred pathway was dependent on alkene substitution and the bicyclic products have potential application in indolizidine and pyrrolizidine alkaloid synthesis.

Facile Synthesis of α,β‐Dehydro Amino Acid Esters

Dehydro amino esters (4) are readily accessible via the reaction sequence (1)←(2)←(3)←(4). The key step (3)←(4) must be performed at low temperature.