Bulky Secondary Amines Research Articles

Coplanar Atropochiral 5H‐Cyclopenta[2,1‐b:3,4‐b′]dipyridine Ligands: Synthesis and Applications in Asymmetric Ring‐Opening Reaction

AbstractBipyridines represent a class of ligands renowned for their versatility and efficacy in numerous transition metal‐catalyzed reactions. Chiral bipyridine ligands are noted for their distinctive reactivity and stereoselectivity. In this work, we have designed and synthesized a class of bipyridine ligands endowed with an axially chiral scaffold. These ligands feature: (a) a precisely aligned coplanar bipyridine framework that is beneficial for metal chelation; (b) a spacious environment around the metal‐bipyridine complexes, capable of hosting substrates with substantial steric bulk; (c) a chiral pocket induced by the axially chiral architecture. These atropochiral planar bipyridine ligands were successfully applied in copper‐catalyzed ring‐opening reactions of cyclic diaryliodoniums with bulky secondary amines, achieving high efficiency and stereoselectivity that were unsuccessful in our previous efforts.

Coplanar Atropochiral 5H-Cyclopenta[2,1-b:3,4-b']dipyridine Ligands: Synthesis and Applications in Asymmetric Ring-Opening Reaction.

Bipyridines represent a class of ligands renowned for their versatility and efficacy in numerous transition metal-catalyzed reactions. Chiral bipyridine ligands are noted for their distinctive reactivity and stereoselectivity. In this work, we have designed and synthesized a class of bipyridine ligands endowed with an axially chiral scaffold. These ligands feature: (a) a precisely aligned coplanar bipyridine framework that is beneficial for metal chelation; (b) a spacious environment around the metal-bipyridine complexes, capable of hosting substrates with substantial steric bulk; (c) a chiral pocket induced by the axially chiral architecture. These atropochiral planar bipyridine ligands were successfully applied in copper-catalyzed ring-opening reactions of cyclic diaryliodoniums with bulky secondary amines, achieving high efficiency and stereoselectivity that were unsuccessful in our previous efforts.

Organic bases, carbon dioxide and naphthenic acids interactions. Effect on the stability of petroleum crude oil in water emulsions

Understanding the mechanisms that lead to the formation of petroleum crude oil in water emulsion is fundamental for the development of sustainable exploitation procedures and efficient oil spills remediation technologies. In this study we surveyed the effectiveness of different nitrogen-containing organic bases in promoting emulsification through the interaction with the naphthenic acid fraction present in crude oil. It was found that bulky secondary amines were the most effective, able to stabilize the emulsion at 10 wt% of oil content for more than 20 min, and the emulsion at 40 wt% for more than 5 h. Interfacial tension measurements indicated that the interaction was effective even when naphtenic acids were dosed at very low levels (total acid number lass than 0.3). It was also observed that a successive addition of carbon dioxide to the system readily induced the breaking of the emulsion, probably by affecting the equilibrium involved in the formation of the naphthenates stabilizing species. In the light of these findings, we tested polyethylene glycols bearing a terminal amino moiety as a new class of CO2 responsive emulsifiers suitable for the petroleum industry.

Selective synthesis of functionalized allyl amines and ethers from (E)-2,3-bisphosphonated allyl bromide

An efficient and straightforward approach toward functionalized allylic amines and ethers is disclosed starting from tetraethyl (3-bromoprop-1-ene-1,2-diyl)bisphosphonate (E)- 1 and secondary and tertiary amines. The coupling reaction of allyl bromide (E)- 1with less bulky secondary amines provides a new family of allylamines 3, while, its reaction with more bulky secondary and tertiary amines, in methanol at reflux, led to functional allyl ethers 4 and 5.

Allylic aminations with hindered secondary amine nucleophiles catalyzed by heterobimetallic Pd-Ti complexes.

Phosphinoamide-scaffolded heterobimetallic palladium-titanium complexes are highly effective catalysts for allylic aminations of allylic chlorides with hindered secondary amine nucleophiles. Three titanium-containing ligands are shown to assemble active catalysts in situ and enable catalysis at room temperature. A variety of sterically bulky secondary amines are efficiently allylated in high yields with as little as 1 mol % palladium catalyst. Piperidine and pyrrolidine products are also efficiently generated via intramolecular aminations with hindered amine nucleophiles.

Extremely bulky secondary phosphinoamines as substituents for sterically hindered aminosilanes.

The synthesis of a series of extremely bulky secondary amines with a phosphine function, Ar(†)(PR2)NH (Ar(†) = C6H2{C(H)Ph2}2Pr(i)-2,6,4; R = Ph, NEt2, NPr(i)2) is described. Deprotonation with either n-BuLi or KH yields the respective alkali metal amides in some cases. Their reaction with the chlorosilanes SiCl4, HSiCl3, Cl2SiPh2, Cl3Si-SiCl3 and Si5Cl10 allows access to monomeric molecular compounds bearing the extremely bulky amino substituents via salt elimination. The products obtained may serve as precursors for subsequent reduction reactions to access sterically protected low valent and low coordinate silicon compounds.

ChemInform Abstract: Selected Reactions of Diethyl (E)‐1‐(Bromomethyl)‐2‐cyanovinylphosphonate with Secondary and Tertiary Amines.

AbstractThe reaction of phosphonate (I) with less bulky secondary amines leads to phosphonates of type (III)/(IV) after substitution and rearrangement.

Sequential Ruthenium(II)-Acetate Catalyzed C–H Bond Diarylation in NMP or Water and Hydrosilylation of Imines

Ruthenium(II)-acetate catalysts are shown to promote sp2 C–H bond activation/diarylation of arylimines with aryl bromides selectively at ortho positions in both organic solvent (N-methylpyrrolidone, NMP) and in water. Water allows to produce a more active ruthenium catalyst for diarylation of ketimines. Furthermore, the diarylation of imines in water in basic media allows the access to diarylated aldehyde. Sequential catalytic C–H arylation/reduction using either a stoichiometric amount of NaBH3CN or via a ruthenium(II) catalytic hydrosilylation of the resulting imines offers a direct route to bulky secondary amines.

Formation of Tertiary Amides and Dihydrogen by Dehydrogenative Coupling of Primary Alcohols with Secondary Amines Catalyzed by Ruthenium Bipyridine‐Based Pincer Complexes

AbstractDehydrogenative coupling of primary alcohols with secondary amines to form tertiary amides and dihydrogen (H2) is efficiently catalyzed by bipyridyl‐based ruthenium pincer complexes (0.2–1 mol%) under neutral conditions (in case of the dearomatized complexes), or with added catalytic amount of base. The reaction is sensitive to steric hindrance; in the case of amidation of bulky secondary amines a less sterically hindered complex is more efficient. Selective acylation of primary amines in the presence of secondary amines was also demonstrated.magnified image

Selected Reactions of Diethyl (E)‐1‐(bromomethyl)‐2‐cyanovinylphosphonate with Secondary and Tertiary Amines

ABSTRACTAn easy regio‐ and stereoselective synthesis of new nitrogenous molecules 2a–e was successfully realized via an effective coupling reaction of diethyl (E)‐1‐(bromomethyl)‐2‐cyanovinylphosphonate 1 with various secondary amines in methanol. Hence, the use of less and more bulky secondary amines gives rise, respectively, to the successive (SN2′) substitution–isomerization and (SN2) substitution derivatives 2a–c and 2d–e. Moreover, the addition of tertiary amines to 1 in the same reaction conditions, leads exclusively to the rearranged vinyl ether 3 in good yields.

Extremely bulky amido-group 14 element chloride complexes: Potential synthons for low oxidation state main group chemistry

The preparation of a series of extremely bulky secondary amines, Ar*N(H)SiR(3) (Ar* = C(6)H(2){C(H)Ph(2)}(2)Me-2,6,4; R(3) = Me(3), MePh(2) or Ph(3)) is described. Their deprotonation with either LiBu(n), NaH or KH yields alkali metal amide complexes, several monomeric examples of which, [Li(L){N(SiMe(3))(Ar*)}] (L = OEt(2) or THF), [Na(THF)(3){N(SiMe(3))(Ar*)}] and [K(OEt(2)){N(SiPh(3))(Ar*)], have been crystallographically characterised. Reactions of the lithium amides with germanium, tin or lead dichloride have yielded the first structurally characterised two-coordinate, monomeric amido germanium(II) and tin(II) chloride complexes, [{(SiR(3))(Ar*)N}ECl] (E = Ge or Sn; R = Me or Ph), and a chloride bridged amido-lead(II) dimer, [{[(SiMe(3))(Ar*)N]Pb(μ-Cl)}(2)]. DFT calculations on [{(SiMe(3))(Ar*)N}GeCl] show its HOMO to exhibit Ge lone pair character and its LUMO to encompass its Ge based p-orbital. A series of bulky amido silicon(IV) chloride complexes have also been prepared and several examples, [{(SiR(3))(Ar*)N}SiCl(3)] (R(3) = Me(3), MePh(2)) and [{(SiMe(3))(Ar*)N}SiHCl(2)], were crystallographically characterised. The sterically hindered group 14 complexes reported in this study hold significant potential as precursors for kinetically stabilised low oxidation state and/or low coordination number group 14 complexes.

Development of an efficient strategy for the synthesis of the ET B receptor antagonist BQ-788 and some related analogues

BQ-788 [ N- cis-2,6-dimethylpiperidine-1-carbonyl- l-γ-methylleucyl- d-1-methoxycarbonyltryptophanyl- d-norleucine sodium salt] is a very potent and selective ET B receptor antagonist. The formation of the highly hindered trisubstituted urea functionality in the peptide chain and the carbamination on the indole nitrogen of the tryptophan side chain are major challenges in the synthesis of this particular antagonist. Furthermore, the high cost of the unnatural amino acids in the sequence of BQ-788 and its reported synthesis render this pseudopeptide very expensive to produce. In order to improve the yield and to reduce the number of steps compared to previous reported syntheses, we developed an efficient strategy involving a novel one-pot procedure for the synthesis of a highly hindered trisubstituted urea. Under very mild conditions, the urea was obtained by using triphosgene and sodium iodide. This strategy allowed us to synthesize BQ-788 in seven steps with an overall yield of 53%. We also generalized the use of this powerful methodology by creating some new structural analogues of the cis-2,6-dimethylpiperidine moiety by replacing it with other bulky secondary amines. We evaluated the antagonist properties of those three new analogues of BQ-788 in two bioassays in vitro. These new antagonists were less potent than BQ-788 in an ET B rich preparation and inactive in an ET A rich preparation.

Chemistry of Diazaphospholephosphines. 1. Preparation of Substituted 4-(Phosphino)-2,5-dimethyl-2H-1,2,3sigma(2)-diazaphospholes, Bifunctional Phosphines with Dicoordinate and Tricoordinate Phosphorus(III) Centers. Chromium(0) and Molybdenum(0) Difluorophosphine Complexes.

An improved preparation of 4-(dichlorophosphino)-2,5-dimethyl-2H-1,2,3sigma(2)-diazaphosphole (1) is described. Replacement of the two chlorine substituents with two fluorine (2), dimethylamino (3), diethylamino (4), bis(n-propyl)amine (5), pyrazole (9), 3,5-dimethylpyrazole (10), 2,2,2-trifluoroethoxy (11), phenoxy (12), pentafluorophenoxy (13), 2,6-difluorophenoxy (14), and pentafluorobenzoxy (15) substituents has been accomplished to create a large suite of potentially bifunctional phosphorus(III) ligands with two- and three-coordinate P centers spanning a range of basicity and steric bulk at the exo-phosphorus center. Bulky secondary amines (such as diisopropylamine, dibenzylamine, and iminodibenzyl) replaced only one chlorine atom to give asymmetric 4-(chloroaminophosphino)-2,5-dimethyl-2H-1,2,3sigma(2)-diazaphospholes (6, 7, and 8, respectively). The asymmetric substitution creates a diastereotopic center in both 6 and 7 which is observed as fluxional NMR behavior at room temperature. Similar diastereotopic induced behavior was observed in the substituent methylene protons of 11. Coordination studies of the fluorinated phosphole (L = 2) with Cr(0) and Mo(0) gave Cr(CO)(5)L (16), cis-Mo(CO)(4)L(2) (17), and fac-Mo(CO)(3)L(3) (18) (where L = 4-(difluorophosphino)-2,5-dimethyl-2H-1,2,3sigma(2)-diazaphosphole). The fluoro ligand displays a behavior which is similar to that of PF(3) and phosphites.

Selected Reaction of (Z)-Dimethyl α-(Bromomethyl) Fumarate with Secondary Amines

Abstract Regioselective reaction of (Z)-dimethyl α-(bromomethyl) fumarate 2 with bulky secondary amines in ether as solvent at room temperature, leads exclusively to the rearranged substitution α-(functional alkyl amino) acrylic esters 4a-i in high yields. The less and more bulky amine gives rise respectively to the two successive (SN2′) and (SN2) substitution derivatives 5j,k and 51.

Palladium-catalyzed reaction of allyl carbamates; allylation of carbonucleophiles, and protection-deprotection of amines

Allylation of carbonucleophiles with allylic carbamates under neutral conditions has been studied. The C-allylation of carbonucleophile is competitive with the N-allylation of amines, and the structure of amines is crucial for the selectivity. Bulky secondary amines gave the best results. Also a new method of protection-deprotection of amines as carbamates has been developed. Smooth deprotection is possible by the palladium-catalyzed reaction of allyl carbamates with formic acid. This method is particulary useful for primary amines, including optically active amino acids.

Reactivity of 1,3-dipoles in aqueous solution. Part 1. Stereospecific formation of Z-amidoximes in the reaction of benzonitrile oxides with amines

Nitrile oxides (3) are rapidly generated in situ on dissolution of the corresponding hydroxamoyl chlorides (1) in aqueous solution at pH > 4; reaction of (3) with the solvent is slow at pH < 10. Primary and secondary amines react stereospecifically to give only the Z-amidoximes (11), in which the nucleophile and OH groups are cis. With primary amines and ammonia the Z-isomer is also thermodynamically favoured but with the more bulky secondary amines subsequent isomerisation to the more stable E-isomer (12) occurs. Several criteria (ρ+0.53 for substituent variation in the nitrile oxide; βnuc 0.48 for primary amine variation; small enhancement shown by ‘α-effect’ amines; small steric effect of ortho-substituents in nitrile oxide) are consistent with a transition state for amidoxime formation in which there is little bond formation between the amine and the carbon of the nitrile oxide.