Fluorinative ring-expansion of cyclic ethers using p-iodotoluene difluoride. Stereoselective synthesis of fluoro cyclic ethers

Fluorinated five- to seven-membered cyclic ethers were stereoselectively synthesized from four- to six-membered cyclic ethers having an iodoalkyl substituent by fluorinative ring-expansion reaction using p-iodotoluene difluoride.     

Zinc- and indium-mediated ring-expansion reaction of alpha-halomethyl cyclic beta-keto esters in aqueous alcohol

Radical ring-expansion reaction of various alpha-halomethyl cyclic beta-keto esters and alpha-halomethyl benzocyclic beta-keto esters and chain-extension reaction of alpha-halomethyl beta-keto esters with zinc powder and indium powder in refluxing aqueous alcohol were carried out to generate the corresponding ring-expansion and chain-extension products. As the results indicate, it was found zinc powder was more effective than indium powder to give the corresponding ring-expanded products in quite good yields. Moreover, the addition of zinc bromide as Lewis acid showed an increase of the yields, depending on the substrates. The present reaction conditions are highly effective, simple, and environmentally friendly.     

Tandem conjugate additions and 3-aza-Cope rearrangements of tertiary allyl amines and cyclic alpha-vinylamines with acetylenic sulfones. Applications to simple and iterative ring expansions leading to medium and large-ring nitrogen heterocycles

Tertiary acyclic allyl amines and tertiary cyclic alpha-vinyl amines undergo conjugate additions to acetylenic sulfones to produce zwitterion intermediates, followed by 3-aza-Cope rearrangements. In the case of cyclic alpha-vinyl amines, the process results in ring-expansion, providing a novel route to 9- to 17-membered cyclic amines. The Hammett plot for the reaction of 8b with 2a- 2f shows rho = +1.19, which is consistent with formation of the proposed zwitterion in the rate-determining step, where electron-withdrawing substituents on the arylsulfonyl moiety stabilize the negative charge and enhance the rate of the reaction. Alternative pathways were observed in methanol in the case of 11, where a methoxy substituent promotes a dissociative mechanism of the corresponding zwitterion via a stabilized allyl cation, whereas the zwitterion derived from amine 12 undergoes ring-opening by direct attack of methanol upon the strained aziridinium moiety instead of by rearrangement. An iterative process was developed, where the product of one ring-expansion is converted into a new cyclic alpha-vinyl amine, followed by a repetition of the conjugate addition and [3,3] rearrangement. This protocol was illustrated by its application to the synthesis of motuporamine A and B.     

An improved catalyst system for the iron-catalyzed intermolecular ring-expansion reactions of epoxides

A considerable improvement is reported in the iron-catalyzed ring-expansion reactions of epoxides generating tetrahydrofuran derivatives by formal insertion of an alkene. Optimization of the catalyst system revealed that a preformed [Fe(salen)] complex minimizes the formation of polymerization side-products so that increased yields of intermolecular reactions were obtained. However, more importantly, the scope of the reaction could also be enlarged considerably. The iron-catalyzed ring-expansion reaction can now be applied to some styrene oxide derivatives, acting as radical donors, as well as to a wide variety of acceptor-substituted acyclic alkenes and cyclic dienes that act as radical acceptors. The use of unsymmetrical radical acceptors led to interesting questions concerning the regiochemistry of the reactions. The conservation of the stereochemistry of the starting materials in the products was investigated through a study of the reactions of E- and Z-configured acceptor-substituted double bonds. The reactions of fumaric and maleic esters were performed and the ratios of diastereomeric and regioisomeric products were determined.     

A Supramolecular Strategy for the Synthesis of Cyclic Oligomers and Polymers by Ring Expansion

Ring-opening metathesis polymerization (ROMP) of strained macrocycles is a key method to prepare diverse polymers. However, lack of ring strain in most macrocycles is an impediment to polymerization. In this paper, the polymerization/oligomerization of unstrained macrocycles was achieved using a supramolecular approach, leading selectively to cyclic products. Diphenyl thiourea and other guest molecules were used as additives to the ROMP reaction of unstrained macrocycles. An intermediate host-guest complex leads to the stabilization of the open form of the macrocycle after treatment with Grubbs catalysts, thereby favoring polymerization by inhibiting the ring-closing reaction back to the monomer. This proof-of-concept enables ring-expansion polymerization of unstrained macrocycles leading to cyclic polymers with molecular weights up to 6700 Da.     

Ring-expansion of tertiary cyclic alpha-vinylamines by tandem conjugate addition to (p-toluenesulfonyl)ethyne and formal 3-aza-Cope rearrangement

A novel ring-expansion protocol is based on the conjugate additions of cyclic alpha-vinylamines to (p-toluenesulfonyl)ethyne, followed by aza-Cope rearrangements of the resulting zwitterions, to afford medium and large-ring cyclic amines under remarkably mild conditions.     

Ring-expansion reaction of oximes with aluminum reductants

The ring-expansion reactions of heterocyclic ketoximes and carbocyclic ketoximes with several reductants such as AlHCl2, AlH3 (alane), LiAlH4, LiAlH(OtBu)3, and (MeOCH2CH2O)2AlH2Na (Red-Al) were examined. Among reductants, AlHCl2 (LiAlH4:AlCl3 = 1:3) in cyclopentyl methyl ether (CPME) has been found to be a suitable reagent for the reaction, and the rearranged cyclic secondary amines were obtained in good to excellent yields.     

Silver-Mediated Cascade Synthesis of Functionalized 1,4-Dihydro-2H-benzo-1,3-oxazin-2-ones from Carbon Dioxide

A conceptually novel catalytic domino approach is presented for the synthesis of highly functional 1,4-dihydro-2H-1,3-benzoxazine-2-one derivatives. Key to the chemoselectivity is a proper design of the precursor to override thermodynamically favored parasitic cyclization processes and empower the formation of the desired product through Thorpe–Ingold effects. The synthetic diversity of these CO₂-based heterocycles is further demonstrated, and the isolation of a reaction intermediate supports an unusual ring-expansion sequence from an α-alkylidene, five-membered cyclic carbonate to a six-membered cyclic carbamate by N-induced isomerization.     

Expanding vinyl ether monomer repertoire for ring-expansion cationic polymerization: Various cyclic polymers with tailored pendant groups

Herein, we clarified the ring-expansion cationic polymerization with a cyclic hemiacetal ester (HAE)-based initiator was versatile in terms of applicable vinyl ether monomers. Although there was a risk that higher reactive vinyl ethers may incur β-H elimination of the HAE-based cyclic dormant species to irreversibly give linear chains, the polymerizations were controlled to give corresponding cyclic polymers from various alkyl vinyl ethers of different reactivities. Functional vinyl ether monomers were also available, and for instance a vinyl ether monomer carrying an initiator moiety for metal-catalyzed living radical polymerization in the pendant allowed construction of ring-linear graft copolymers through the grafting-from approach. Furthermore, ring-based gel was prepared via the addition of divinyl ether at the end of the ring-expansion polymerization, where multi HAE bonds cyclic polymers or fused rings were crosslinked with each other. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3082–3089     

Universal cyclic polymer templates

Two unique molecular templates for generating polymeric materials with a cyclic molecular architecture were developed by combining ring-expansion metathesis polymerization and click chemistry. These two universal cyclic polymers were used in three examples to demonstrate the wide range of potential materials enabled. They include functional cyclic polymers, cyclic polymer brushes, and cyclic gels.     

New ring-expansion reactions of hydroxy propenoyl cyclic compounds under palladium(0)/phosphine-catalyzed conditions

[reaction: see text] Palladium(0)-catalyzed one-atom ring-expansion of 1-hydroxy-2,2-dialkyl-1-propenoylindan derivatives has been achieved in the presence of P(o-tolyl)(3) giving 2-hydroxy-3,3-dialkyl-2-vinyl-1-tetralone derivatives in excellent yields. This ring-expansion reaction was applied to a 17-(1-oxo-2-propenyl)-beta-estradiol derivative and furnished a similar ring-expanded product in an excellent yield.     

The direct acyl-alkylation of arynes

An efficient and mild acyl-alkylation of arynes is described. The method is used to synthesize medium-sized carbocycles by the ring-expansion of cyclic beta-ketoesters.     

Recent progress on the synthesis of cyclic polymers via ring-expansion strategies

Cyclic polymers are the simplest topological isomers of linear macromolecules, but exhibit properties that differ from linear chains in ways that remain imperfectly understood. The difficulty of synthesizing appropriately pure and high molecular weight cyclic samples has hindered experimental studies. Ring-closure methods, while versatile, are inherently limited in the range of molecular weights that can be achieved. Ring-expansion methods are a much more promising strategy toward obtaining high molecular weight cyclic polymers. The current review focuses on recent developments in ring-expansion polymerization strategies toward the synthesis of high molecular weight cyclic polymers. Significant progress in the last decade has made the synthesis of cyclic polymers possible by a variety of methods, such as ruthenium- and tungsten-catalyzed ring-expansion metathesis polymerization, organocatalytic and Lewis acid-catalyzed zwitterionic polymerization, RAFT and nitroxide-mediated radical polymerization, among many others. While the study of cyclic polymers has long been hampered by synthetic challenges, the recent resurgence of interest in this field presents an exciting opportunity for chemists. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2892–2902     

Time-resolved resonance Raman and density functional study of an azirine intermediate in the 2-fluorenylnitrene ring-expansion reaction to form a dehydroazepine product

We report time-resolved resonance Raman spectra for the azirine intermediate produced in the 2-fluorenylnitrene ring-expansion reaction to form a dehydroazepine product. The Raman bands obtained with a 252.7 nm probe wavelength and 500 ns delay time exhibit reasonable agreement with predicted vibrational frequencies from density functional calculations for two isomers of azirine intermediates that may be formed from a 2-fluorenylnitrene precursor. The Raman bands observed for delay times of 15 ns and 10 micros were consistent with predicted vibrational frequencies from density functional calculations for the 2-fluorenylnitrene and dehydroazepine product species as well as previously reported 416 nm time-resolved Raman spectra obtained on the ns and micros time scales. Our results demonstrate that the 2-fluorenylnitrene ring-expansion reaction to produce dehydroazepine products proceeds via relatively long-lived 2-fluorenylnitrene and azirine intermediates. Substitution of a phenyl ring para to the nitrene group of phenylnitrene appears to lead to significant changes in the ring-expansion reaction so that longer lived arylnitrene and azirine intermediates can be observed. This should enable the chemical reactivity of azirine intermediates formed from arylnitrenes to be examined more readily.     

Samarium(II)-induced ring-expansion reaction of 1,2-cyclobutanedicarboxylates to produce cyclopentanones

Novel ring-expansion reaction of 1,2-cyclobutanedicarboxylates with Sm(II) in the presence of HMPA with a catalytic amount of methanol was found to provide 2-oxocyclopentanecarboxylates.     

Ring-expansion of thioacetal ring via bicyclosulfonium ylide. Effect Of protic nucleophile on ylide intermediate

The reaction of 2-(3-diazo-2-oxopropane-1-yl)-2-methyldithiolane 9a, 2-(4-diazo-3-oxobutane-2-yl)-2-methyldithiolane 9c, and 2-(3-diazo-2-oxopropane-1-yl)-2-methyl-1,3-dithiane 9b with Rh(2)(OAc)(4) gave three-carbon ring-expansion products dithiocan-2-en-1-ones 13a, 13c and dithionan-2-en-1-one 13b, respectively. 2-(5-Diazo-4-oxopentyl)-2-methyldithiolane 9e also gave the five-carbon ring-expansion products dithionan-3-en-1-one 13e and 5-methylenedithionane-1-one 13'e. On the other hand, reaction of 2-(4-diazo-3-oxobutyl)-2-methyldithiolane 9d in the presence of AcOH gave the four-carbon ring-expansion product 16d substituted by an acetoxyl group. In addition, the reaction of 2-(3-diazo-2-oxopropyl)-2-methyl-3-oxathiolane 9f in the absence of AcOH gave 4-oxa-7-thiocan-2-en-1-one 19 via a sulfonium ylide intermediate, whereas, in the presence of AcOH, an alternative regioisomer 20 was also formed competitively with 19 via an oxonium ylide intermediate.     

Enantiodivergent synthesis of both enantiomers of marine alkaloids haliclorensin and isohaliclorensin, a constituent of halitulin

Starting from (3R)-5-benzotriazolyl-3-phenylperhydropyrido[2,1-b][1,3]oxazole 9, the enantiodivergent syntheses of both enantiomers of the marine alkaloids haliclorensin 1 and isohaliclorensin 3 have been achieved. Our syntheses feature ring-expansion reactions for the formation of the aza-macrocycle ring system of 3 and sequential ring-expansion reactions (aza-Claisen rearrangement and Zip reaction) for the formation of the aza-macrocycle ring system of 1.     

Concise total synthesis of (-)-mersicarpine

A concise total synthesis of (-)-mersicarpine from a known cyclohexanone was accomplished. The azepinoindole core was constructed by a DIBAL-H-mediated reductive ring-expansion reaction of oxime.     

Eight-membered ring construction by [4 + 2 + 2] annulation involving beta-carbon elimination

Cyclobutanones underwent a formal [4 + 2 + 2] annulation reaction with 1,6- and 1,7-diynes in the presence of nickel(0) catalysts to provide bicyclic eight-membered ring ketones. The annulation reaction proceeds through a ring-expansion of oxanickelacycloheptadiene via beta-carbon elimination to form a nine-membered nickelacycle. This reaction employing cyclobutanones as a C4 unit constructs cyclooctadienone cores in one synthetic step.     

First asymmetric total synthesis of (+)-sparteine

[reaction: see text] The total synthesis of (+)-sparteine was accomplished from 2,5-norbornadione in 15 steps and 15.7% overall yield. The key steps were two ring-expansion reactions, one involving an intramolecular Schmidt reaction and one using a novel variant of the photo-Beckmann rearrangement.