14380-85-9

Upstream product

• 67-56-1 methanol 
• 21946-94-1 (S)-2-(1,3-dioxoisoindolin-2-yl)-3-phenylpropanamide 
• 5123-55-7 Nα-phthaloyl-L-phenylalanine 
• 98654-98-9 (S)-N-methyl-2-(1,3-dioxoisoindolin-2-yl)-3-phenylpropanamide 
• 85-44-9 phthalic anhydride 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 39739-09-8 methyl (S)-2-(1,3-dioxoisoindolin-2-yl)-3-(4-hydroxyphenyl)propanoate 
• 1080-06-4 L-Tyr-OMe 
• 1582806-47-0 (S)-3-phenyl-2-phthalimido-N-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)propanamide 
• 1582806-46-9 (S)-2-phthalimido-N-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)propanamide 
• 1403251-25-1 (S)-2-(1,3-dioxoisoindolin-2-yl)-N-methoxypropanamide 
• 591-50-4 iodobenzene 
• 4306-25-6 (S)-2-phthalimidopropionyl chloride 
• 22509-74-6 N-ethoxycarbonylphthalimide 

Downstream Products

• 132785-20-7 (2R,3R)-3-bromo-N-phthaloylphenylalanine methyl ester 
• 132785-21-8 (2R,3S)-3-bromo-N-phthaloylphenylalanine methyl ester 
• 132785-26-3 (2S,3R)-3-hydroxy-N-phthaloylphenylalanine methyl ester 
• 33551-75-6 (2R)-N-phthaloyl-3-fluorophenylalanine methyl ester 
• 33551-74-5 (2S,3S)-3-hydroxy-N-phthaloylphenylalanine methyl ester 
• 6254-48-4 (2S,3R)-3-phenylserine 
• 136918-14-4 phthalimide 
• 19713-73-6 methyl (2Z)-3-phenylprop-2-enoate 
• 103-26-4 Methyl cinnamate 

Relevant academic research and scientific papers

Stereoselective synthesis of chiral α-amino-β-lactams through palladium(II)-catalyzed sequential monoarylation/amidation of C(sp 3)-H Bonds

Give Me an Ar, give Me an N! Arylation of the methyl group in a simple derivative of readily available alanine under palladium catalysis was followed by intramolecular amidation at the same position to give chiral α-amino-β-lactams with a wide range of aryl substituents (see scheme; Phth=phthaloyl). The α-amino-β-lactams were obtained in moderate to high yields with good functional-group tolerance and high diastereoselectivity. Copyright

A Simple Aliphatic Diamine Auxiliary for Palladium-Catalyzed Arylation of Unactivated β-C(sp3)-H Bonds

Palladium-catalyzed β-C(sp3)-H arylation of aliphatic acid derivatives was achieved by means of 2-dimethylaminoethylamine auxiliary as a directing group. The β-C(sp3)-H arylation reactions with aryl and heteroaryl iodides efficiently afforded the corresponding arylated hydrocinnamic acid derivatives. Direct β-C(sp3)-H alkynylation, and arene C?H arylation and alkynylation were also realized under the same or slightly modified conditions. The aliphatic diamine auxiliary in the products could be readily removed by methanol in the presence of BF3 ? OEt2. In comparison with the widely used bidentate nitrogen-containing directing groups, 2-dimethylaminoethylamine is a simple, cheap, readily available and removable, and atom-economical directing group for C?H functionalization. (Figure presented.).

Ligand-Enabled β-C–H Arylation of α-Amino Acids Without Installing Exogenous Directing Groups

Herein we report acid-directed β-C(sp3)-H arylation of α-amino acids enabled by pyridine-type ligands. This reaction does not require the installation of an exogenous directing group, is scalable, and enables the preparation of Fmoc-protected unnatural amino acids in three steps. The pyridine-type ligands are crucial for the development of this new C(sp3)-H arylation.

LIGAND-CONTROLLED C(SP3)-H ARYLATION AND OLEFINATION IN SYNTHESIS OF UNNATURAL CHIRAL ALPHA AMINO ACIDS

The use of ligands to tune the reactivity and selectivity of transition metal-catalysts for C(-sp3)-H bond functionalization is a central challenge in synthetic organic chemistry. Herein, we report a rare example of catalyst-controlled C(sp3)-H arylation using pyridine and quinoline derivatives: the former promotes exclusive monoarylation, whereas the latter activates the catalyst further to achieve diarylation. Successive application of these ligands enables the sequential diarylation of a methyl group in an alanine derivative with two different aryl iodides, affording a wide range of β-Ar-p-Ar ' -cc-amino acids with excellent levels of diastereoselectivity (d.r. > 20:1). Both configurations of the β-chiral center can be accessed by choosing the order in which the aryl groups are installed. The use of a quinoline derivative as a ligand also enables C(sp3)-H olefination of a protected alanine.

A Fluorinated Ligand Enables Room-Temperature and Regioselective Pd-Catalyzed Fluorination of Aryl Triflates and Bromides

A new biaryl monophosphine ligand (AlPhos, L1) allows for the room-temperature Pd-catalyzed fluorination of a variety of activated (hetero)aryl triflates. Furthermore, aryl triflates and bromides that are prone to give mixtures of regioisomeric aryl fluorides with Pd-catalysis can now be converted to the desired aryl fluorides with high regioselectivity. Analysis of the solid-state structures of several Pd(II) complexes, as well as density functional theory (DFT) calculations, shed light on the origin of the enhanced reactivity observed with L1.

Ligand-enabled β-C-H arylation of α-amino acids using a simple and practical auxiliary

Pd-catalyzed β-C-H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C-H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct β-C-H activation, albeit this system was not compatible with carboxylic acids containing α-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of β-arylation of carboxylic acid derivatives, especially α-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules, and chiral bis(oxazoline) ligands.

Nonnatural amino acid synthesis by using carbon-hydrogen bond functionalization methodology

Taking direction well: Substituted phenylalanine derivatives were prepared by C-H bond functionalization (see scheme). The syntheses are highly convergent and employ an N-phthaloylalanine with a 2-thiomethylaniline directing group. The use of an 8-aminoquinoline directing group allows for the diarylation of methyl and the diastereoselective arylation of methylene groups. Copyright

Chemoselective hydrogenation of imides catalyzed by Cp*Ru(PN) complexes and its application to the asymmetric synthesis of paroxetine

This work represents the first catalytic hydrogenation of imides into amides and primary alcohols, in which the unique chemoselectivity is originated from the bifunctional nature of ruthenium-NH moiety in the catalyst. Copyright

Highly efficient stereoconservative amidation and deamidation of α-amino acids

(Chemical Equation Presented) An overall stereoconservative protection and deprotection method of amino and carboxyl groups is presented. N-Phthaloyl N-alkyl secondary amides of α-amino acids can be generated from corresponding N-phthaloyl amino acids by coupling reaction of N-alkylamines using mixed anhydride method. These secondary amides can be transformed by thermal rearrangement of intermediate nitrosoamides to O-alkyl esters with retention of configuration and excellent yields.

Photochemistry of N-Phthaloyl α-Amino Acid Esters: A New Approach to β,γ-Unsaturated α-Amino Acid, Dihydrobenzazepinedione, and Pyrrolizidinone Derivatives

The N-phthaloyl-α-amino acid methyl esters of 2-aminobutyric acid (2a), valine (2b), norvaline (2c), tert-leucine (2d), isoleucine (2e), allo-isoleucine (2f), leucine (2g), methionine (2h), alanine (2i), and phenylalanine (2k) were synthesized in enantiomerically pure form via the N-phthaloyl-α-amino acids (1a-k), and their photochemistry was studied.Except 2i and 2k, which proved to be photostable, all compounds were converted into three types of products, depending on the substitution pattern: a) isomerization products (derivatives of β,γ-unsaturated α-amino acids) 3a, b, c, and e, b) ring expansion products (benzazepinedione esters) 4a and c, and c) cyclization products (5d from the tert-leucine derivative 2d).High diastereoselectivities (d.r. >95:5) were observed for all reactions except the transformations of the 2-aminobutyric acid derivative 2a.The absolute configuration of the α-stereogenic center was retained during photolysis, as proven for the isodehydrovaline (type a product) 3b.PCC oxidation (to give 7b) and hydrogenation afforded 2b with an optical rotation comparable to the starting material.Treatment of 3b with an acid or a base led to epimerization (3b') or isomerization of the C=C bond (6b), respectively.The diastereomeric dihydrobenzazepinedione esters 4a, b were formed with d.r. = 33:67 (cis:trans) and in 60percent yield during photolysis of 2a.The isoleucine derivative 2e, however, was converted into the cis isomer 4a with high diastereoselectivity (d.r. >95:5), whereas the corresponding allo substrate 2f was only converted into the trans-isomer 4b.Ethylene was extruded during irradiation of the latter substrates and during irradiation of the norvaline derivative 2c, whereas propene extrusion from the leucine derivative 2g led to the formation of the unsubstituted type b product 4c.The methionine derivative 1h was the only N-phthaloylamino acid which did not show photodecarboxylation, instead two ξ-hydrogen abstraction products were formed: the hydroxy acid 9h and the tetracylic lactone 10h.The methionine ester 2h was only converted into the ring expansion products 11h, h' presumably by a photo electron transfer step.The chronology of the double hydrogen transfer reaction (γ- followed by δ-H abstraction, leading to type a products) was determined by using the deuterium labeled compound (+/-)-2b.Key Words: Photochemistry / α-Amino acids / Amino acids, β,γ-unsaturated / Photoisomerization / Benzazepinedione esters / Selectivity, enantio-, diastereo-