Imides Research Articles

Chain and Step Growth Polymerizations of Cyclic Imino Ethers: From Poly(2‐oxazoline)s to Poly(ester amide)s

Cyclic imino ethers (CIEs), such as 2-oxazolines and 2-oxazines are a unique class of monomers, which because of their manifold reactivities can be polymerized via multiple techniques. Most prominent, the living cationic ring-opening polymerization (CROP) of CIEs enables the synthesis of well-defined tailor-made poly(CIEs), which have tremendous importance as functional and biocompatible polymers. On the other hand, CIEs are also powerful monomers in polyadditions resulting in the formation of a variety of biodegradable polyamide-based systems. In this contribution, the enormous potential of CIEs as functional building blocks is discussed, which goes well beyond the CROP. Besides trends in the CROP of CIEs, recent developments in step-growth polymerizations of CIEs are highlighted, including the spontaneous zwitterionic copolymerization (SZWIP) which provides access to functional alternating N-acylated poly(amino ester)s (NPAEs) and polyadditions of multifunctional CIEs which give main-chain poly(ester amide)s (PEAs).

Diastereoselective construction of spirocyclic pyrrolidines bearing two quaternary centers via CuII-P, N-Ligand catalyzed 1,3-dipolar cycloaddition

Here, we report a convenient access to diastereoselective synthesis of polysubstituted pyrrolidines bearing a unique spiro quaternary center at the C-2 position and another quaternary center at C-4. The synthesis system, CuII/P, N-Ligand-catalyzed 1, 3-dipolar cycloaddition, by employing homoserine lactone derived cyclic imino esters as the dipoles and α, α, β-trisubstituted olefins as the dipolarophlies, provides exo-spiro-pyrrolidines with good yields, high diastereoselectivities (up to >98:2 dr) and performs well for a broad scope of substrates.

ChemInform Abstract: Gold‐Catalyzed Povarov‐Type Reaction of Fluorinated Imino Esters and Furans.

A gold-catalyzed Povarov-type reaction of fluorinated imino esters and furans is described. The process, which takes place in dichoromethane at room temperature, gives rise to novel fluorinated tetrahydrofuran-fused tetrahydroquinolines in good yields and moderate levels of diastereoselectivity in a very simple manner. The reported examples expand the versatility of the Povarov reaction to unprecedented fluorinated substrates, generating scaffolds that contain quaternary α-amino acid units.

Thiourea-Quaternary Ammonium Salt Catalyzed Asymmetric 1, 3-Dipolar Cycloaddition of Imino Esters To Construct Spiro[pyrrolidin-3,3'-oxindoles

A highly enantioselective 1,3-dipolar cycloaddition of imino esters with methyleneindolinones has been realized by using readily available thiourea-quaternary ammonium salts as phase-transfer catalysts, enabling efficient construction of a range of chiral spiro[pyrrolidin-3,3'-oxindoles] in good yields with excellent enantioselectivities under mild conditions.

ChemInform Abstract: Bifunctional AgOAc/ThioClickFerrophos Catalyzed Asymmetric 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylides to Nitroalkenes

Abstract18 examples

Straightforward and Highly Stereoselective Synthesis of 3,3,4‐Trifluoropyrrolidines Involving 1,3‐Dipolar Cycloaddition with 2,3,3‐Trifluoroacrylate

The reactions of benzyl 2,3,3‐trifluoroacrylate with azomethine ylides, generated by the treatment of imino esters with lithium diisopropylamide, took place smoothly to give the corresponding 1,3‐dipolar cycloadducts, fluorine‐containing pyrrolidines, in good yields and with high diastereoselectivities (>95:<5). When the fluorinated acrylate bore a chiral auxiliary as a substituent, for instance (l)‐(–)‐menthyl ester, the 1,3‐dipolar cycloaddition reaction was found to give the corresponding fluorinated pyrrolidine derivatives in not only a diastereoselective but also an enantioselective manner.

Gold-Catalyzed Povarov-Type Reaction of Fluorinated Imino Esters and Furans.

A gold-catalyzed Povarov-type reaction of fluorinated imino esters and furans is described. The process, which takes place in dichoromethane at room temperature, gives rise to novel fluorinated tetrahydrofuran-fused tetrahydroquinolines in good yields and moderate levels of diastereoselectivity in a very simple manner. The reported examples expand the versatility of the Povarov reaction to unprecedented fluorinated substrates, generating scaffolds that contain quaternary α-amino acid units.

Taniaphos·AgF-catalyzed enantioselective 1,3-dipolar cycloaddition of stabilized azomethine ylides derived from 2,2-dimethoxyacetaldehyde

The enantioselective Taniaphos·silver fluoride-catalyzed enantioselective 1,3-dipolar cycloaddition using 2,2-dimethoxyacetaldehyde derived imino esters and maleimides is described. The employment of this complex allows the reaction in the absence of an extra base giving high yields and ee of the corresponding endo-cycloadducts. Calculations performed at B3LYP/6-31G*&LANL2DZ level of theory predicted the expected absolute stereochemistry for both BINAP and Taniaphos·silver fluoride-mediated cycloadditions, as well as the enantioselectivity and mild conditions of the reaction.

Synthesis of α‐Ethynyl Glycines

α‐Ethynyl glycine derivatives have a high potential for functionalization by derivatization of the amino acid or acetylene moiety, and, as a result, are important intermediates in the construction of biologically active compounds, including natural products. The main methods for the synthesis of ethynyl glycines and glycinols can be divided into six different transformations: (a) homologations of serinal derivatives, (b) nucleophilic alkynylations of α‐imino esters/alcohols or their precursors α‐halo glycinates, (c) derivatizations of alkynyl imino esters, (d) electrophilic alkynylations of α‐nitro esters and azlactones by using hypervalent iodine reagents, (e) intra‐ and intermolecular aminolysis reactions of epoxides, and (f) propargylic aminations through the cyclization of bis(imidate). This microreview summarizes the methods that were published from 1996 to 2015.

ChemInform Abstract: Enantioselective Dearomative [3 + 2] Cycloadditions of Indoles with Azomethine Ylides Derived from Alanine Imino Esters.

Catalytic, enantioselective [3 + 2] cycloadditions of azomethine ylides derived from alanine imino esters with 3-nitroindoles are reported. The dearomative cycloaddition reactions occur in the presence of a catalyst generated in situ from Cu(OTf)2 and (R)-Difluorphos to form exo′-pyrroloindoline cycloadducts and establish four contiguous stereogenic centers, two of which are fully substituted. The exo′-pyrroloindoline products are formed in moderate-to-good yields (39–85%) with high diastereoselectivities (up to 98 : 1 : 1 dr) and enantioselectivities (up to 96% ee).

ChemInform Abstract: Preparation of Enantiomerically Pure Perfluorobutanesulfinamide and Its Application to the Asymmetric Synthesis of α‐Amino Acids.

AbstractPerfluorobutanesulfinamide (IV) is obtained in two steps and converted to imino ester (VI) which is used in the Rh/Ag‐catalyzed asymmetric C‐H addition to arenes bearing an ortho‐directing group to provide arylglycine derivatives.

Binap and Phosphoramidites as Privileged Chiral Ligands for the Metal-Catalyzed Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylides.

2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (binap) and phosphoramidites are privileged chiral ligands that have been tested in the coinage-metal-catalyzed 1,3-dipolar cycloadditions of metalloazomethine ylides and electrophilic alkenes. Silver(I), copper(II), and gold(I) salts have been evaluated in all of these reactions. Maleimides, acrylates, fumarates, 1,2-bis(phenylsulfonyl)ethylene, and enones reacted with imino esters to give the corresponding endo-prolinates, such as hepatitis C (HCV) inhibitors, in high diastereo- and enantioselectivity using either binap-silver and -gold(I) or phosphoramidite-silver complexes. In the case of nitroalkenes, exo-4-nitroprolinates were obtained using silver or copper(II) phosphoramidite complexes. Azlactones reacted with maleimides and acrylates to give pyrrolines only in the presence of binap-gold(I) complexes. The observed enantioselectivity and mechanism of these 1,3-dipolar cycloadditions were studied for the most relevant examples by means of DFT calculations.

Preparation of Enantiomerically Pure Perfluorobutanesulfinamide and Its Application to the Asymmetric Synthesis of α-Amino Acids.

A high yielding and practical two-step synthesis of enantiomerically pure perfluorobutanesulfinamide from Senanayake's 2-aminoindanol-derived sulfinyl transfer reagent was developed and carried out on a multigram scale. Straightforward condensation of this sulfinamide with ethyl glyoxylate provided the N-perfluorobutanesulfinyl imino ester. The utility of this activated N-sulfinyl imino ester was demonstrated for reactions that gave either no product or very low yields with the corresponding less electrophilic N-tert-butanesulfinyl derivative. Specifically, the Rh(III)-catalyzed C-H bond addition of aromatic compounds to the N-perfluorobutanesulfinyl imino ester provided arylglycines with very high diastereoselectivities for a range of directing groups including pyrrolidine amide, azo, sulfoximine, 1-pyrazole, and 1,2,3-triazole functionalities. Thermal asymmetric aza-Diels-Alder reactions also proceeded in good yields and with high selectivity, including for the substituted dienes (E)-1,3-pentadiene and (2E,4E)-2,4-hexadiene.

Synthesis of Azacyclic Nucleoside Analogues via Asymmetric [3 + 2] Cycloaddition of 9-(2-Tosylvinyl)-9H-purines.

With 9-(2-tosylvinyl)-9H-purines as the dipolarophiles, a series of chiral azacyclic nucleosides with four continuous stereocenters were obtained in 86-99% yields, >20:1 dr, and 94 → 99% ee via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition. Both (E)- and (Z)-9-(2-tosylvinyl)-9H-purines were suitable dipolarophiles, enriching the structure diversity of azacyclic nucleosides. Furthermore, when α-methyl imino ester was explored, the corresponding azacyclic nucleoside with a chiral quaternary stereocenter could also be afforded with excellent results.

ChemInform Abstract: Rhodium‐Catalyzed Asymmetric 1,4‐Addition of α,β‐Unsaturated Imino Esters Using Chiral Bicyclic Bridgehead Phosphoramidite Ligands.

A chiral bicyclic bridgehead phosphoramidite (briphos) prepared from 1-aminoindane is a highly efficient and selective ligand for rhodium(I)-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated N,N-dimethyl-sulfamoyl imino esters at ambient temperature. This transformation provides a new class of chiral (Z)-γ,γ-diaryl-α,β-dehydroamino esters with excellent yield and enantioselectivity.

ChemInform Abstract: Synthesis of Highly Functionalized Chiral Benzopyrano[3,4‐c]pyrrolidines Bearing Five Contiguous Stereogenic Centers.

A chiral bis(imidazolidine)pyridine-Cu complex smoothly catalyzed the asymmetric [3 + 2] cycloaddition reaction of α,β-unsaturated ester-containing nitroalkenes with imino esters to give endo-pyrrolidine products in a highly enantioselective manner while maintaining the α,β-unsaturated ester functionality. Subsequent intramolecular diastereoselective cyclizations of the obtained pyrrolidine products were accomplished by treatment with KF/Al2O3 in toluene/EtOH (4:1) to give highly functionalized benzopyrano[3,4-c]pyrrolidines bearing five contiguous stereogenic centers.

Enantioselective dearomative [3 + 2] cycloadditions of indoles with azomethine ylides derived from alanine imino esters

Dearomative cycloadditions of imino esters derived from alanine with 3-nitroindoles formexo′-pyrroloindolines in good yields with high diastereo- and enantioselectivities.

High performance poly(imino imino ether ether ketone ketone) (PIIEEKK) films with intermolecular hydrogen bondings

Poly(imino imino ether ether ketone ketone) (PIIEEKK) was synthesized via palladium-catalyzed C–N cross coupling reaction of 1,4-bis(4-bromobenzoyl) benzene and 1,4-bis(4-amiophenoxy) benzene. In view of its good solubility, PIIEEKK film with high transmittance was prepared via casting method. Fourier Transform Infrared Spectrum of the PIIEEKK film revealed that in the solid state intermolecular hydrogen bonding (N–H···O=C) is present. Differential Scanning Calorimetry and Thermo Gravimetric Analysis showed that PIIEEKK film possessed high glass transition temperature (T g = 172°C) and good thermal stability with high decomposition temperature (T d,5% = 460°C). Due to intermolecular hydrogen bonding between PIIEEKK chains, the PIIEEKK film exhibited higher tensile strength.

Synthesis of Highly Functionalized Chiral Benzopyrano[3,4-c]pyrrolidines Bearing Five Contiguous Stereogenic Centers.

A chiral bis(imidazolidine)pyridine-Cu complex smoothly catalyzed the asymmetric [3 + 2] cycloaddition reaction of α,β-unsaturated ester-containing nitroalkenes with imino esters to give endo-pyrrolidine products in a highly enantioselective manner while maintaining the α,β-unsaturated ester functionality. Subsequent intramolecular diastereoselective cyclizations of the obtained pyrrolidine products were accomplished by treatment with KF/Al2O3 in toluene/EtOH (4:1) to give highly functionalized benzopyrano[3,4-c]pyrrolidines bearing five contiguous stereogenic centers.

Silver-catalysed multicomponent 1,3-dipolar cycloaddition of 2-oxoaldehydes-derived azomethine ylides

The silver-catalysed multicomponent reaction between ethyl glyoxylate, 2,2-dimethoxyacetaldehyde, or phenylglyoxal as aldehyde components with a α-amino ester hydrochloride and a dipolarophile in the presence of triethylamine is described. This domino process takes place at room temperature by in situ liberation of the α-amino ester followed by the formation of the imino ester, which is the precursor of a metalloazomethine ylide. The cycloaddition of this species and the corresponding dipolarophile affords polysubstituted proline derivatives. Ethyl glyoxylate reacts with glycinate, alaninate, phenylalaninate and phenylglycinate at room temperature in the presence of representative dipolarophiles affording endo-2,5-cis-cycloadducts in good yields and high diastereoselection. In addition, 2,2-dimethoxyacetaldehyde is evaluated with the same amino esters and dipolarophiles, under the same mild conditions, generating the corresponding endo-2,5-cis-cycloadducts with higher diastereoselections than the obtained in the same reactions using ethyl glyoxylate. In the case of phenylglyoxal the corresponding 5-benzoyl-endo-2,5-cis cycloadducts are obtained in short reaction times and similar diasteroselection.