Electronic and chelation effects on the unusual C2-methylation of N-(para-substituted)phenylaziridines with lithium organocuprates

Density functional theory calculations with the B3LYP functional were performed for the title ring‐opening reaction to understand the intrinsic activating and directing effects of the N‐substituents, as well as the electron donating effect of the para‐substituted (Y = Cl, H, Me) phenyl group at the more hindered benzylic C2 atom. The N‐tosyl group (i.e., N‐Tos) or the N‐(2‐pyridyl)sulfonyl group (i.e., N‐Py) was introduced to activate the ring nitrogen atom (N1) and the para‐substituted (Y = Cl, H, Me) phenyl group for the activation of the C2 atom. Conformational searches and geometry optimizations were performed for the N‐(para‐substituted)phenylaziridines ( 1 ～ 6 ). Calculations indicate that the aziridine 6 (i.e., Py/Me) has the most elongated C2? N1 bond intrinsically due to the electronic activating effects, implying the aziridine 6 to be the most potent candidate for the more‐hindered C2 opening. Transition states (TSs) were investigated for the prospective ring‐opening paths (I～IV), considering the types of intermolecular push–pull interactions between the N‐activated phenylaziridines and the cuprate. The N‐Py group provides an unique C2‐favored TS along the path IV, which the N‐Tos group cannot afford, due to the less charge transfer from the nucleophilic CH of the cuprate into the electrophilic C2 atom. Furthermore, the e‐donating effect of the para‐substituents (Y = Cl, H, Me) enhances the C2 opening for the path IV. This study enables us to understand the unusual ring‐opening phenomena in terms of electronic and directing effects and hence may serve as a tool to design substrates for highly regioselective ring openings. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Synthesis and characterization of novel aliphatic polycarbonates

A new six‐membered cyclic carbonate monomer, 5‐benzyloxy‐trimethylene carbonate, was synthesized from 2‐benzyloxy‐1,3‐propanediol, and the corresponding polycarbonate, poly(5‐benzyloxy‐trimethylene carbonate) (PBTMC), was further synthesized by ring‐opening polymerization in bulk at 150 °C using aluminum isobutoxide [Al(OⁱBu)₃], aluminum isopropoxide, or stannous octanoate as an initiator. The results showed that a higher molecular weight polycarbonate could be obtained in the case of Al(OⁱBu)_3. The protecting benzyl group was removed subsequently by catalytic hydrogenation to give a polycarbonate containing a pendant hydroxyl group (PHTMC). The polycarbonates obtained were characterized by Fourier transform infrared spectroscopy, ¹H NMR,¹³C NMR, gel permeation chromatography, and DSC. NMR results of PBTMC offered no evidence for decarboxylation occurring during the propagation. The pendant hydroxyl group in PHTMC resulted in an enhancement of the hydrophilicity of the polycarbonate. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 70–75, 2002     

A Straightforward Approach towards Cyclic Photoactivatable Tubulysin Derivatives

The development of a new photolabile protecting group containing an additional allyl functionality allows the synthesis of cyclic photoactivatable natural products. Cyclization occurs between the allyl moiety in the protecting group and a second double bond in the target molecule by means of ring‐closing metathesis. Cyclization should increase the metabolic stability towards proteases. On the other hand, the conformational change should cause diminished biological activity. As illustrated for tubulysin derivatives, cyclic and photoactivatable drug candidates can easily be obtained in only two steps from simple building blocks through Ugi reaction and ring‐closing metathesis. The photolabile protecting group is introduced by means of the isocyanide component during the Ugi reaction.     

Computational evaluation of radical ring‐opening polymerization

The tendencies of ring‐opening processes in radical ring‐opening polymerizations were evaluated by AM1 and PM3 semi‐empirical calculations and 6‐31G*‐level calculations based on the density functional theory (DFT) B3LYP models. Sixteen cyclic monomers bearing vinyl or exomethylene groups were categorized into ring‐opening and no‐ring‐opening monomers by the evaluation of the differences of the internal energies and the lengths of the cleaving bonds between the ground states of the initial radicals and the activated states in the ring‐opening processes. Although the semi‐empirical calculations not parameterized to radical reactions resulted in the moderate categorization of the ring‐opening monomers, the DFT calculation clearly distinguished the ring‐opening and no‐ring‐opening monomers. The ring‐opening tendencies were also evaluated with the changes in the internal energies throughout the ring‐opening processes, but this method could not group the ring‐opening and no‐ring‐opening monomers clearly. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2827–2834, 2007     

ABA and Star Amphiphilic Block Copolymers Composed of Polymethacrylate Bearing a Galactose Fragment and Poly(ε‐caprolactone)

Novel ABA and star amphiphilic block copolymers of poly(vinyl sugars) with biodegradable hydrophobic poly(ε‐caprolactone) segments are presented. They were prepared by a combination of ring‐opening polymerization of ε‐caprolactone and atom‐transfer radical polymerization of methacrylate‐bearing isopropylidene‐protected galactose. Subsequently, the protecting groups of the sugar fragments were removed by treatment with 80% formic acid.     

Bifunctional Furfuryl Cations Strategy: Three‐Component Synthesis of Enamidyl Triazoles

A new multicomponent synthesis of functionalized enamidyl triazoles starting from simple and readily available starting materials is described. A simple treatment of a dichloromethane solution of an azide, amine, and 5‐bromo‐2‐furylcarbinol with a Lewis acid provides the enamidyl triazole in good to high yield. A triple domino sequence, formal [3+2] cycloaddition/ring‐opening/amidation, is involved in this new skeleton‐generating reaction.     

Catalytic Ring Expansion of Cyclic Hemiaminals for the Synthesis of Medium‐Ring Lactams

A mild and efficient intermolecular ring‐expansion approach was developed for the synthesis of medium‐ring lactams by using siloxy alkynes. Key to success is the suitable combination of a superior catalyst and an exceptional nitrogen‐protecting group. Control experiments indicated that the reaction is remarkably selective toward the desired lactam formation, even with many possible non‐productive pathways.     

Synthesis of polyphosphodiesters by ring‐opening polymerization of cyclic phosphates bearing allyl phosphoester protecting groups

The allyl phosphoester group is shown to be a protecting group for the synthesis of anionic polyphosphodiesters. Our strategy relies on the synthesis of a cyclic phosphate monomer bearing a pendant allyl phosphoester group, its easy purification by fractional distillation, its organocatalyzed ring‐opening polymerization by 1,8‐diazobicyclo[5.4.0]undec‐7‐ene (DBU) and 1‐[3,5‐bis(trifluoromethyl)phenyl]‐3‐cyclohexyl‐thiourea (TU). Finally, the deprotection of the allyl phosphoester group is carried out by reaction with sodium benzenethiolate in the absence of any detectable degradation. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2642–2648     

Synthesis of a new 2‐amino‐glycan,poly‐(1→6)‐α‐D‐mannosamine,by ring‐opening polymerization of 1,6‐anhydro‐mannosamine derivatives

A stereoregular 2‐amino‐glycan composed of a mannosamine residue was prepared by ring‐opening polymerization of anhydro sugars. Two different monomers, 1,6‐anhydro‐2‐azido‐mannose derivative ( 3 ) and 1,6‐anhydro‐2‐(N, N‐dibenzylamino)‐mannose derivative ( 6 ), were synthesized and polymerized. Although 3 gave merely oligomers, 6 was promptly polymerized into high polymers of the number‐average molecular weight (M_n) of 2.3 × 10⁴ to 2.9 × 10⁴ with 1,6‐α stereoregularity. The differences of polymerizability of 3 and 6 from those of the corresponding glucose homologs were discussed. It was found that an N‐benzyl group is exceedingly suitable for protecting an amino group in the polymerization of anhydro sugars of a mannosamine type. The simultaneous removal of O‐ and N‐benzyl groups of the resulting polymers was achieved by using sodium in liquid ammonia to produce the first 2‐amino‐glycan, poly‐(1→6)‐α‐D ‐mannosamine, having high molecular weight through ring‐opening polymerization of anhydro sugars.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Thietane ring as a novel protecting group

A novel protecting group for NH functionality of heterocycles, a thietane ring, was proposed. It can be readily introduced by alkylation of NH-heterocycles with 2-chloromethylthiirane. Removal of the thietane protecting group is performed via oxidation to thietane 1,1-dioxide with hydrogen peroxide in acetic acid and subsequent treatment with sodium alkoxide.     

Recent Developments and Optimization of Lipase‐Catalyzed Lactone Formation and Ring‐Opening Polymerization

To obtain materials useful for the biomedical field, toxic catalysts should be removed from the synthetic route of polymerization reactions and of their precursors. Lipase‐catalyzed ring‐opening polymerization and the synthesis of cyclic precursors can be performed with the same catalyst under different conditions. Here, we highlight the use of lipases as catalysts and optimization of their performance for both ring‐closing and ring‐opening polymerization, via varying parameters such as ring size, concentration, substrate molar ratio, temperature, and solvent. While the conditions for ring‐closing reactions and ring‐opening polymerizations of small molecules, such as ε‐caprolactone, have been extensively explored using Candida antarctica lipase B (CALB), the optimization of macrocyclization, especially for more bulky substrates is surveyed here. Finally, recent methods and polymer architectures are summarized with an emphasis on new procedures for more sustainable chemistry, such as the use of ionic liquids as solvents and recycling of polyesters by enzymatic pathways.

     

五元氮杂环的开环反应研究进展

综述了近年来各种五元氮杂环的开环反应及其在有机合成中的应用。杂环化合物在有机合成中的作用越来越重要,五元氮杂环是其中最重要的一部分,其开环反应可以用来合成某些用其它方法难以合成的多官能团化合物,或通过开环和修饰合成其它环状化合物,还可以作为保护基以及研究仿生合成领域中各类复杂的生化反应等。     

Ring‐Opening and polymerization of 1‐[2′‐(heptaphenylcyclotetrasiloxanyl)ethyl]‐1,3,3,5,5‐pentamethylcyclotrisiloxane

1‐[2′‐(Heptaphenylcyclotetrasiloxanyl)ethyl]‐1,3,3,5,5‐pentamethylcyclotetrasiloxane ( II ) was prepared from 1‐[2′‐(methyldichlorosilyl)ethyl]‐1,3,3,5,5,7,7‐heptaphenylcyclotetrasiloxane ( I ) and tetramethyldisiloxane‐1,3‐diol. Acid‐catalyzed ring‐opening of II in the presence of tetramethyldisiloxane gave 1,9‐dihydrido‐5‐[2′‐(heptaphenylcyclotetrasiloxanyl)ethyl]nonamethylpentasiloxane ( III ) and 1,9‐dihydrido‐3‐[2′‐(heptaphenylcyclotetrasiloxanyl)ethyl]nonamethylpentasiloxane ( IV ). Both acid‐ and base‐catalyzed ring‐opening polymerization of II gives highly viscous, transparent polymers. The structures of I – IV and polymers were determined by UV, IR, ¹H, ¹³C, and ²⁹Si NMR spectroscopy. In addition, molecular weights obtained by GPC and NMR end group analysis were confirmed with mass spectrometry. On the basis of ²⁹Si NMR spectroscopy, the polymers appear to result exclusively from ring‐opening of the cyclotrisiloxane ring. No evidence for ring‐opening of the cyclotetrasiloxane ring was observed. Polymer properties were determined by DSC and TGA. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 137–146, 2006     

Hydroxylation and Ring‐Opening Mechanism of an Unusual Flavoprotein Monooxygenase, 2‐Methyl‐3‐hydroxypyridine‐5‐carboxylic Acid Oxygenase: A Theoretical Study

Hybrid meta‐GGA density functional theory (the MPWB1K functional) was used to study the hydroxylation and ring‐opening mechanism of 2‐methyl‐3‐hydroxypyridine‐5‐carboxylic acid oxygenase (MHPCO). This enzyme catalyses the conversion of 2‐methyl‐3‐hydroxypyridine‐5‐carboxylic acid (MHPC) to α‐(N‐acetylaminomethylene)succinic acid (AAMS), which is the essential ring‐opening step in the bacterial degradation of vitamin B₆. MHPCO belongs to the flavin‐containing aromatic hydroxylases family. However, MHPCO is capable of catalysing a subsequent aromatic ring‐cleavage reaction to give acyclic products rather than hydroxylated aromatic ones. Our calculations show that the re‐aromatisation of the hydroxylated intermediate occurs spontaneously in aqueous solution; this implies that the ring‐opening process occurs inside the enzyme’s active site, in which limited water is available. The instability of the hydroxylated intermediate of MHPCO is the main reason why acyclic products are formed. Previously proposed mechanisms for the ring‐opening step were studied, and were shown to be less likely to occur (ΔΔG^≠298>35 kcal mol^?1). Two new pathways with reasonable barrier heights (ΔΔG^≠298<15 kcal mol^?1) are reported herein, which are in accordance with all experimental information present to date.     

A facile approach for the construction of the oxetane ring from 5α-acyloxy-Δ~(4(20)) - taxoids

An oxetane ring can be constructed from 5α-acyloxy-Δ4(20)-taxoids. Hie facile intramolecular acyl migration from 5- to 20-position under slightly basic conditions enabled the construction of the oxetane ring in a convenient short cut, whereas the acyl migration from 2- to 20-position left the 2-hydroxyl accessible to a later benzoylation. An unexpected five-mem-bered 4-O, 20- O sulfite ring was formed in the attempted construction of the oxetane ring with 5α-triflate as a leaving group. After the construction of the oxetane ring, treatment with strong base LiHMDS and acetyl chloride gave the expected 4-O-acetate while treatment with acetic anhydride and DMAP gave a 4-O-acetoacetate.     

Renaissance of Ring‐Opening Chemistry of Benzotriazoles: New Wine in an Old Bottle

1,2,3‐Benzotriazoles could undergo ring cleavage to form ortho‐amino arenediazonium or α‐diazo‐imine species via a Dimroth‐type equilibrium. Historically, the synthetic potential of this unique reactivity had remained underdeveloped. Recently, some new strategies have been developed to effect the ring‐opening chemistry of benzotriazoles in more practical manners. A wide range of conceptually novel and synthetically useful reactions have been developed, which enable the access to diverse valuable heterocycles and ortho‐amino arene derivatives. As one of the players in this field, our group has also contributed a series of intriguing transition‐metal‐catalyzed denitrogenative functionalizations of benzotriazoles. In this account, we aim to provide an overview of the ring‐opening chemistry of benzotriazoles, with a focus on relevant works published in the past decade. In order to show a whole picture of the research field, some pioneering works in its developing history will also be discussed briefly.     

Samarium enolate on crosslinked polystyrene beads. III. Anionic initiator for well‐defined synthesis of poly(hydroxyethyl methacrylate) on solid support

A solid‐supported samarium enolate successfully initiated the polymerization of 2‐(trimethylsilyloxy)ethyl methacrylate (TMS‐HEMA) through the living anionic process. In addition, the silyl group was readily removed by treatment of the beads with a weak acid to afford the corresponding well‐defined poly(methacrylate) having a hydroxyethyl group in the side chain (PHEMA). The hydroxyl group of the immobilized PHEMA on the beads was successfully acetylated to give poly(2‐acetoxyethyl methacrylate), which could be quantitatively isolated from the beads by trifluoroacetic acid treatment. Moreover, the hydroxyl group of the immobilized PHEMA could be utilized as an initiator for acid promoted ring opening polymerization of lactone to yield the corresponding graft copolymer. In this method, the residual and excess reagents could be removed by filtration, which demonstrated the applicability of the present technique to a novel method for construction of functional polymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4417–4423, 2004     

Regioselection and orthogonality of the 1-phenyl-3-butenyl (PBU) protecting group in glucopyranosides

The 1-phenyl-3-butenyl (PBU) protecting group was alternatively introduced in position 4 or 6 by regioselective opening of methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-D-glucopyranose with allyltrimethylsilane in the presence of the Lewis acid promoters TMSOTf or AlCl3. The PBU group was selectively removed, in presence of t-butyldimethylsilyl, trityl or acetyl protecting groups, with acids (TFA) or using Pd(CH3CN)2Cl2.     

Highly Enantioselective Ring‐Opening Reactions of Aziridines with Indole and Its Application in the Building of C3‐Halogenated Pyrroloindolines

A magnesium‐catalyzed asymmetric ring‐opening reaction of aziridine with indole has been realized by employing commercially available chiral ligands. Both of the enantiomers of the ring‐opening product could be obtained with good yields and a high level of enantioselectivity. The corresponding ring‐opening product could be further transformed to various types of enantioenriched C₃‐halogenated‐pyrroloindolines.     

Ring‐opening polymerization of 6‐hydroxynon‐8‐enoic acid lactone: Novel biodegradable copolymers containing allyl pendent groups

This article reports the synthesis and copolymerization of 6‐hydroxynon‐8‐enoic acid lactone. The ring‐opening polymerization of this lactone‐type monomer bearing a pendant allyl group led to new homopolymers and random copolymers with ε‐caprolactone and L ,L ‐lactide. The copolymerizations were carried out at 110 °C with Sn(Oct)₂ as a catalyst. The introduction of unsaturations into the aliphatic polyester permitted us to carry out different chemical transformations on this family of polymers. For example, this article reports the bromination, epoxidation, and hydrosylilation of the allyl group in the new polyester copolymers. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 870–875, 2000