Dibenzyl Azodicarboxylate Research Articles

Benign synthesis of terpene-based 1,4-p-menthane diamine

Terpenes represent a promising renewable feedstock for the substitution of fossil resources in the synthesis of renewable platform chemicals, like diamines. This work describes the synthesis and full characterization of 1,4-p-menthane diamine (1,4-PMD) obtained from α-terpinene (1). A two-step procedure using dibenzyl azodicarboxylate (DBAD) and H2 as rather benign reagents was employed under comparatively mild conditions. Both C–N bonds were formed simultaneously during a visible-light mediated Diels–Alder reaction, which was investigated in batch or flow, avoiding regioselectivity issues during the amination steps that are otherwise typical for terpene chemistry. Heterogeneously catalyzed quadruple hydrogenation of the cycloadduct (2a) yielded 1,4‑PMD (3). While the intermediate cycloadduct was shown to be distillable, the target diamine can be sublimed, offering sustainable purification methods.

Chiral Calcium Phosphate-Catalyzed Enantioselective Amination of 3-Aryl-2-oxindoles with Dibenzyl Azodicarboxylate.

A chiral calcium phosphate-catalyzed enantioselective amination of 2-oxindoles with dibenzyl azodicarboxylate has been developed, affording the products in consistently high yields and excellent enantioselectivity. This synthetic method features low catalyst loading and a high catalytic efficiency. Moreover, the practical value of this process is well demonstrated by a scale-up experiment and a trial of catalyst recovery and reuse.

Chiral Calcium Phosphate Catalyzed Enantioselective Amination of 3-Aryl-2-benzofuranones.

A 4-tert-butyl-phenyl substituted (R)-[H8]-BINOL chiral calcium phosphate catalyzed enantioselective amination of 3-aryl-2-benzofuranones with dibenzyl azodicarboxylate is described. The catalyst loading of the reaction is 1 mol %. This transformation is facile and has a high degree atom economy, which gave products with good yields and high enantioselectivities (79% to 99%). This reaction has excellent ee and a broad substrate scope with mild reaction conditions.

Efficient Synthesis of Sulfenamides through Mitsunobu‐type Coupling Reaction of Thiols with Amines using Dibenzyl Azodicarboxylate

AbstractS−H activation reaction of thiols employing dibenzyl azodicarboxylate (DBAD) has been developed for the preparation of sulfenamides. The dehydrogenation of thiols and amines under these reaction conditions involved the formation of dibenzyl hydrazine‐1,2‐dicarboxylate (5 a), which led to the S−N bond formation reaction. The reaction proceeds efficiently with the release of 5 a and affords various sulfenamides in good to excellent yields.

Organocatalyst Efficiency in the α‐Aminoxylation and α‐Hydrazination of Carbonyl Derivatives in Aqueous Media or in a Ball‐Mill

Pyrrolidine‐derived organocatalysts have been tested in two types of α‐heterofunctionalization reactions in aqueous media or under solvent‐free ball‐milling conditions. The best results in terms of both activity and enantioselectivity were obtained with O‐silylated 4‐hydroxyproline derivatives in the α‐aminoxylation reaction between n‐butyraldehyde and nitrosobenzene (83 % yield in water, 86 % yield by ball milling and ee > 99 %). A very good yield (82 %) and excellent optical purity (ee > 99 %) were also achieved in the α‐hydrazination reaction of 3‐phenylpropanal with dibenzyl azodicarboxylate by the ball‐milling technique.

Enantioselective Three-Component Amination of Enecarbamates Enables the Synthesis of Structurally Complex Small Molecules.

The control of asymmetric synthesis tools represents a major challenge, especially when it comes to the synthesis of bioactive molecules. In this context, the asymmetric synthesis of 1,2-diamines through amination of enecarbamates has been proposed as a highly efficient and tunable approach. Indeed, reactivity of the latter species could be exploited to realize a double functionalization via an electrophilic amination followed by nucleophilic trapping. Herein, we describe a chiral phosphoric acid catalyzed electrophilic amination of enecarbamates with dibenzyl azodicarboxylate and oxygenated or thiol-containing nucleophiles affording stable precursors of α-hydrazinoimines in high yields and with almost complete enantioselectivities (up to >99%). These precursors were successfully functionalized with various silylated nucleophiles without epimerization of the stereogenic center, giving access to a wide range of 1,2-disubstituted 1,2-diamines. We also show that the thiolated precursors were successfully engaged in a Friedel-Crafts reaction against a variety of aromatic and heteroaromatic nucleophiles, leading to various 1-(hetero)aryl-1,2-diamines without loss of enantioselectivity and with complete diastereoselectivity. Reductive N-N bond cleavage provided the N,N-diprotected 1,2-diamines with no loss in diastereo- or enantioselectivity. The protocol was successfully scaled up to a multigram scale and the catalyst was successfully recovered, demonstrating the potential applications of this new methodology.

ChemInform Abstract: Base‐Catalyzed Asymmetric α‐Functionalization of 2‐(Cyanomethyl)azaarene N‐Oxides Leading to Quaternary Stereocenters.

AbstractA highly enantioselective α‐functionalization of 2‐(cyanomethyl)pyridine N‐oxides and pyrazine N‐oxides via conjugate addition of 4‐hydroxy‐4‐methylpent‐1‐en‐3‐one or α‐amination with di(tert‐butyl) or dibenzyl azodicarboxylate is developed.

Heterogeneous Dipeptide‐Catalyzed α‐Amination of Aldehydes in a Continuous‐Flow Reactor: Effect of Residence Time on Enantioselectivity

AbstractA solid‐supported dipeptide‐catalyzed continuous‐flow process was developed for the direct enantioselective α‐amination of aldehydes with dibenzyl azodicarboxylate as the electrophilic nitrogen source. With residence time control as an efficient tool for the fine‐tuning of the enantioselectivity, synthetically useful α‐hydrazino alcohols were achieved with excellent ees. The packed‐bed system proved to be highly robust: no decrease in catalyst activity or selectivity was detected throughout 20 h of continuous‐flow operation.magnified image

ChemInform Abstract: Synthesis of Bis‐α‐amino Acids Through Proline Catalyzed Asymmetric α‐Amination of Higher Homologues of Garner′s Aldehyde.

AbstractThe convenient synthesis of bis‐α‐amino acid esters involves the proline catalyzed highly diastereoselective α‐hydrazination of aldehydes (I) with dibenzyl azodicarboxylate as the key step.

Toward the optimization of continuous-flow aldol and α-amination reactions by means of proline-functionalized silicon packed-bed microreactors

The activity and stability under flow conditions of covalently and non-covalently silica supported proline and proline-like organocatalysts is herein described. The slow aldol reaction of cyclohexanone with p-nitro benzaldehyde and the fast α-amination of isovaleraldehyde with dibenzyl azodicarboxylate have been selected as model reactions for this study. Prospects and limitations of the disclosed continuous-flow organocatalytic approach are widely discussed.

ChemInform Abstract: Efficient Methodology for the Preparation of β-Aminotetralin Derivatives via Electrophilic Amination.

Abstract A mild and efficient method for the construction of β-aryl amines from the corresponding α-aryl ketones is presented. The key steps of the synthesis involve an electrophilic amination by dibenzyl azodicarboxylate followed by a stereoselective LiHBEt 3 reduction. The reaction sequence is applied to the synthesis of the tricyclic ergoline analogue 4 .

ChemInform Abstract: Synthesis of Amines and Amino Alcohols by Electrophilic Amination and Highly Stereoselective Reduction.

A practical and selective method for the synthesis of the β-arylamines 5 and the cis- or trans-amino alcohols 8 or 11 is reported. The reaction sequence starts from α-tetralones 1 which readily react with dibenzyl azodicarboxylate to afford the protected α-hydrazino ketones 2. Then, depending on the reduction conditions, the trans-hydrazino alcohols 10 or the cis isomers 7 are formed predominantly. The stereoselectivities which range between 18:1 and 1:67 (trans/cis) are explained by stereoelectronic effects (σ,σ interactions) and steric hindrance. Depending on the workup procedure, we can control, whether the cis-hydrazino alcohols 7 or the oxazolidinone derivatives 3 are isolated. Subsequent hydrogenolyses of 4, 7 and 10 lead to the target molecules 5, 8 and 11, respectively.

General Synthesis of C-Glycosyl Amino Acids via Proline-Catalyzed Direct Electrophilic α-Amination of C-Glycosylalkyl Aldehydes

Non-natural axially and equatorially linked C-glycosyl alpha-amino acids (glycines, alanines, and CH2-serine isosteres) with either S or R alpha-configuration were prepared by D- and L-proline-catalyzed (de >95%) alpha-amination of C-glycosylalkyl aldehydes using dibenzyl azodicarboxylate as the electrophilic reagent.

Total Synthesis of LFA-1 Antagonist BIRT-377 via Organocatalytic Asymmetric Construction of a Quaternary Stereocenter

A catalytic route for enantioselective total synthesis of cell adhesion inhibitor BIRT-377 is described. The quaternary stereocenter was constructed through l-proline-derived, tetrazole-catalyzed direct asymmetric alpha-amination of 3-(4-bromophenyl)-2-methylpropanal with dibenzyl azodicarboxylate. In the course of these studies, a one-pot trifluoro acetylation/selective benzyloxycarbonyl deprotection method was developed. [structure: see text]

Enantioselective Organocatalytic Diels Aminations: α‐Aminations of Cyclic β‐Keto Esters and β‐Keto Lactones with Cinchonidine and Cinchonine.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cu‐ and Pd‐Catalyzed Asymmetric One‐Pot Tandem Addition—Cyclization Reaction of 2‐(2′,3′‐Alkadienyl)‐β‐keto Esters, Organic Halides, and Dibenzyl Azodicarboxylate: An Effective Protocol for the Enantioselective Synthesis of Pyrazolidine Derivatives.

Cu‐ and Pd‐Catalyzed Asymmetric One‐Pot Tandem Addition—Cyclization Reaction of 2‐(2′,3′‐Alkadienyl)‐β‐keto Esters, Organic Halides, and Dibenzyl Azodicarboxylate: An Effective Protocol for the Enantioselective Synthesis of Pyrazolidine Derivatives.

Cu- and Pd-catalyzed asymmetric one-pot tandem addition-cyclization reaction of 2-(2',3'-alkadienyl)-beta-keto esters, organic halides, and dibenzyl azodicarboxylate: an effective protocol for the enantioselective synthesis of pyrazolidine derivatives.

[reaction: see text] Optically active pyrazolidine derivatives have been constructed by the Cu- and Pd-catalyzed asymmetric one-pot tandem addition-cyclization reaction of 2-(2',3'-dienyl)-beta-ketoesters, organic halides, and dibenzyl azodicarboxylate. The absolute configurations of the final products depend on the structure of the ligand.

Enantioselective Organocatalytic Diels Aminations: α-Aminations of Cyclic β-Keto Esters and β-Keto Lactones with Cinchonidine and Cinchonine

Catalytic enantioselective α-amination reactions of p-keto esters and p-keto lactones with dibenzyl azodicarboxylate are catalyzed by cinchona alkaloids, affording the products in up to 99% yield and 90% ee.

Silver-catalyzed asymmetric amination of silyl enol ethers

Catalytic amination of silyl enol ethers with azo diester compounds was investigated. It was shown that Cu(OTf)2 or AgOTf had high catalytic activity and that AgOTf was the most efficient among the catalysts tested in the reactions. In asymmetric reactions, the AgClO4-BINAP system showed high enantioselectivity. In a mixture of toluene or mesitylene and THF, silyl enol ethers reacted with dibenzyl azodicarboxylate (DBnAD) smoothly to afford the corresponding amination adducts in excellent yields with up to 86% ee.Key words: amination, amino acid, asymmetric synthesis, chiral catalyst, silver.

Asymmetric synthesis of (3S )-2,3,4,5-tetrahydropyridazine-3-carboxylic acid and its methyl ester †

Methyl (2E,4E)-5-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)penta-2,4-dienoate 16a, assembled by a Wittig condensation of tributyl(methoxycarbonylmethylene)phosphorane 19a and (2E)-3-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)propenal 20, displays excellent Re-face reactivity towards diethyl azodicarboxylate 15a, bis(2,2,2-trichloroethyl) azodicarboxylate 15b, dibenzyl azodicarboxylate 15c, diisopropyl azodicarboxylate 15d and di-tert-butyl azodicarboxylate 15e in thermal hetero-Diels–Alder reactions to give the cycloadducts 17a–e. When subjected to the action of hydrogen over palladium–carbon, the cycloadducts 17a, 17b, 17d and 17e undergo hydrogenation of their olefinic bonds to give the dihydro derivatives 18a, 18b, 18d and 18e; in the case of the cycloadduct 17c, hydrogenolysis of the benzyloxycarbonyl group also occurs to give methyl (3S)-2,3,4,5-tetrahydropyridazine-3-carboxylate 1b with an ee of 98% and 2,3,4,6-tetra-O-acetyl-β-D-glucopyranose 22. Compound 1b, with an ee of 98%, is also available from the dihydro derivative 18e by the action of trifluoroacetic acid; however, under the acidic conditions, a condensation reaction between the aglycone 1b and the glycone 22 competes to give methyl (3S)-2,3,4,5-tetrahydro-2-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl)pyridazine-3-carboxylate 25.Sodium (3S)-2,3,4,5-tetrahydropyridazine-3-carboxylate 1c, with an ee of 99%, is available from the ester 1b by a saponification reaction. The trifluoroacetic acid salt 27, with an ee of 95%, is obtained from benzyl (3S,6S)-1,2-bis(tert-butoxycarbonyl)-1,2,3,6-tetrahydro-6-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)pyridazine-3-carboxylate 17g by a hydrogenation–trifluoroacetolysis sequence. A hetero-Diels–Alder reaction involving the benzyl pentadienoate 16c and di-tert-butyl azodicarboxylate 15e provides the cycloadduct 17g.