Synthesis of a spirocyclic indoline lactone

Base-promoted cyclization of tert-butyl [2-(benzylideneamino)phenyl]acetate (13a) and subsequent C3-alkylation with allyl bromide affords 3-allyl-2-phenyl-2,3-dihydro-1H-indole-3-carboxylic acid, tert-butyl ester (15b) in high yield as a single diastereomer. This result is contrary to prior publications that describe failed cyclization of an analogous ethyl ester (ethyl [2-(4-methoxybenzylideneamino)phenyl]acetate) under strongly basic conditions. N-Acylation, olefin dihydroxylation, and tert-butyl ester cleavage affords the spirocyclic lactone 18 as a pair of diastereomers. Isolation and characterization of individual diastereomers 18a and 18b are described.     

Synthesis of the spirocyclic alkaloid nitramine

The alkaloid nitramine was prepared in a four operation process using reductive cyclization of a γ-cyano ester to a spirolactam as a key step.     

Synthesis of spirocyclic butenolides by ring closing metathesis

Spirocyclic butenolides were efficiently prepared by a ring closing metathesis strategy.     

Synthesis of block and star copolymers by photoinduced radical coupling process

The general design for the synthesis of AB diblock, and A₂B and AB₂ star copolymers based on the statistical coupling of poly(styrene) (PSt) and poly (methyl methacrylate) (PMMA) macromolecules containing photoreactive benzophenone is presented. For this purpose, mono- and bifunctional initiators for Atom Transfer Radical Polymerization (ATRP) bearing benzophenone group were synthesized and characterized. End- and mid-chain benzophenone functional PSt and PMMA with low molecular weights were obtained by ATRP using these initiators in the presence of CuBr/N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) catalytic complex. Poly(styrene-block-methyl methacrylate) (PSt-b-PMMA) copolymers were prepared by photolysis of the solutions containing end functional PSt and PMMA in THF at λ = 350 nm for 60 min in the presence of a hydrogen donor such as N-methyldiethanolamine (NMDEA). The proposed mechanism assumes hydrogen abstraction of photoexcited benzophenone moiety by NMDEA. Ketyl radicals resulting from abstraction reaction undergo radical-radical coupling to form benzpinacol structure at the core. Formation of A₂B and AB₂ type star copolymers upon irradiation of solutions containing appropriate combinations of end- and mid-chain functional polymers was also demonstrated. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2938–2947, 2009     

Synthesis of diarylcyclopropyl spirocyclic ketones

A facile one-pot synthetic route for preparing a series of functionalized diarylcyclopropyl spirocyclic ketones 4 is developed. The efficient cyclopropanation route of the conjugated cyclic ketones 2 with sulfones 1 in the presence of NaH shows interesting molecular diversities. The reaction mechanism of the stereocontrolled cyclopropanations has been discussed.     

Synthesis of bifluorenes via cobalt halide radical coupling

Reaction of in situ generated lithium fluorenide salts with cobalt chloride results in formation of the corresponding bifluorenes. The scope of fluorenes that can be coupled include those containing substituents amenable to polymerization for application to poly(bifluorene) synthesis and alkyl substituted fluorenes for use in the preparation of bimetallic transition metal complexes. Based on experiments using a radical trap, the reaction mechanism involves reduction of cobalt and subsequent fluorenyl radical coupling. Overall, this study demonstrates a simple and effective method for preparation of hindered tertiary and quaternary C-C bonds using a readily available and inexpensive coupling agent.     

Synthesis of O-glycolyl-linked neuraminic acids through a spirocyclic intermediate

[reaction: see text] The neuraminic acid derivative 5 is readily converted in several steps to the neuraminic acid dimer 12, linked through the hydroxyl of a 5-N-glycolyl group in an alpha-2,5 glycosidic linkage. The sequence is shown to proceed through a spirocyclic intermediate 9 by in situ NMR experiments. Similar derivatives of N-glycolylneuraminic acid (Neu5Gc), including polymers, have been identified from marine sources, including starfish and sea urchins, often as sulfated derivatives and are thought to mediate sperm-egg recognition.     

Synthesis of novel angular spirocyclic azetidines

The syntheses of a variety of novel angular azaspiro[3.3]heptanes are reported. gem-Difluoro and gem-dimethyl variants of the angular 1,6-diazaspiro[3.3]heptane module were prepared in high yields using efficient sequences. Additionally, a practical one-pot synthesis of 5-oxo-2-azaspiro[3.3]heptanes and subsequent conversions into functionalized derivatives are described. The methods reported are amenable to the synthesis of these building blocks for drug discovery as members of a library or individually on a preparative scale.     

Synthesis of dihydrobenzoxazine pyrrolidone spirocyclic compounds

A simple and efficient synthetic strategy for the preparation of dihydrobenzoxazine spirocyclic compounds was reported via the cycloaddition reaction of o-succinimide-substituted benzaldehyde with nitrobenzene. The reactions can be conducted under very mild reaction conditions (room temperature) using 10?mol% of Cs₂CO₃ as catalyst. A series of dihydrobenzoxazine pyrrolidone spirocyclic compounds were afforded in moderate to good yields. This strategy provides a new direction for the synthesis and study on biological activities of dihydrobenzoxazine pyrrolidone spirocyclic compounds.     

Synthesis of spirocyclic C-arylribosides via cyclotrimerization

[reaction: see text] Spirocyclic C-arylribosides were synthesized from the known gamma-ribonolactone derivative. Lithium acetylide addition followed by glycosylation with 3-(trimethylsilyl)propargyl alcohol converted the ribonolactone to silylated diynes. After desilylation or iodination, subsequent ruthenium-catalyzed cycloaddition of resultant diynes with alkynes or chloroacetonitrile gave spirocyclic C-arylribosides.     

Application of copper(II)-mediated radical cross-dehydrogenative coupling to prepare spirocyclic oxindoles and to a formal total synthesis of Satavaptan

Application of radical cross-dehydrogenative coupling (CDC) procedures to prepare a range of novel spirocyclic oxindoles and to a formal total synthesis of the vasopressin V₂ receptor antagonist Satavaptan is reported. The key step involves a copper-mediated oxidative cyclisation of a simple linear anilide precursor to give the spirocyclic oxindole core. This synthetic approach was also used to prepare novel Satavaptan scaffolds and analogues.     

Synthesis of spirocyclic derivatives of azaphenanthrene containing a hydroxy-m-terphenyl fragment

The reaction of 5′-[(2-naphthylamino)methyl]-2′-hydroxy[1,1′:3′,1″]terphenyl with paraformaldehyde and 1,3-cyclohexanedione, methyl 2,2-dimethyl-4,6-dioxocyclohexanecarboxylate, dimedone, furan-2,4(3H,5H)-dione, indan-1,3-dione led to the formation of spiro derivatives of azaphenanthrene.     

Synthesis of the asperparaline core by a radical cascade

A concise access to the pentacyclic core structure of the asperparalines is described. The key step is a radical cascade sequence comprised of a 1,6-hydrogen atom transfer followed by 6-exo-trig and 5-exo-trig cyclizations.     

Synthesis of novel sulfur containing spirocyclic phosphoranes

The synthesis of new spirocyclic phosphoranes containing both sulfur and oxygen hetero atoms bonded to phosphorus is described.     

Synthesis of the spirocyclic cyclohexadienone ring system of the schiarisanrins

[structure: see text] Studies on the synthesis of the spirocyclic cyclohexadienone ring system 2 of the schiarisanrin family of natural products 1 are described and were based on the Lewis acid-promoted C-alkylation of the corresponding phenolic precursor.     

Synthesis of a well-defined polybromostyrene by living radical polymerization with a nitroxyl radical

Radical polymerization of p-bromostyrene was investigated with benzoyl peroxide (BPO) as an initiator in the presence of 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl (MTEMPO). The polymerization was performed in bulk for 3.5 h at 95°C and then continued for another 48 h at 125°C to afford the corresponding polybromostyrene with a narrow molecular weight distribution in high yield. ¹H NMR study revealed that the polymer obtained had BPO and MTEMPO moieties at its head and tail, respectively. It was confirmed that the polymerization proceeded in accordance with living mechanism, because the molecular weight linearly increased with an increase of the conversion, and it was directly proportional to the reciprocal of the initial concentration of BPO. Furthermore, the polystyrene obtained in the present study could quantitatively act as the initiator for the polymerization of p-bromostyrene in the living radical manner to afford the corresponding block copolymer, and vice versa. © 1996 John Wiley & Sons, Inc.     

Stereocontrolled [3 + 2] annulations with arene chromium tricarbonyl complexes: construction of spirocyclic compounds related to fredericamycin A

[reaction: see text] An efficient method has been developed for the stereocontrolled construction of polycyclic and spirocyclic compounds, including the spirocyclic core of the antitumor agent fredericamycin A. The strategy involves a one-pot aldol addition/Brook rearrangement/cyclization sequence beginning from arene chromium tricarbonyl complexes and can formally be described as a [3 + 2] annulation.     

Synthesis of the spirocyclic core of the prunolides using a singlet oxygen-mediated cascade sequence

[reaction: see text] A highly efficient and rapid four-step synthesis of the bis-spiroketal core of the prunolide natural products, starting from furan itself, is described. The key step and culmination of the synthesis, responsible for zipping up the spirocyclic core, is a singlet oxygen-orchestrated cascade sequence in which a double photooxygenation of a 1,2-difuryl alkene precursor precedes dehydration and spirocyclization to furnish the intact prunolide core.     

Photoinduced switching from living radical polymerization to a radical coupling reaction mediated by organotellurium compounds

An efficient and simple method for the synthesis of symmetric macromolecules by photoinduced switching from radical polymerization to a radical coupling reaction is reported. Structurally well-defined telechelic polyisoprenes and ABA-triblock copolymers were prepared by successive organotellurium-mediated living radical polymerization (TERP) under thermal conditions, followed by a polymer-end radical coupling reaction under photoirradiation.     

Synthesis of amphiphilic ABC triblock copolymers by single electron transfer nitroxide radical coupling reaction in tetrahydrofuran

A series of ABC triblock copolymers, that is, polyisoprene‐block‐polystyrene‐block‐poly(ethylene oxide) (PI‐PS‐PEO), PI‐block‐poly(tert‐butyl acrylate)‐block‐PEO (PI‐PtBA‐PEO), and PI‐block‐poly(acrylic acide)‐block‐PEO (PI‐PAA‐PEO) were obtained by combination of anionic technique, atom transfer radical polymerization (ATRP), and single electron transfer nitroxide coupling (SETNRC) reaction. Anionic polymerization of isoprene followed by end capping with ethylene oxide yielded hydroxyl‐terminated PI. After esterification, PI with Br end group was used as a macroinitiator to initiate the polymerization of styrene and tBA by ATRP that was then trapped by 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) group in PEO by SETNRC reaction rapidly with high efficiency in tetrahydrofuran at room temperature. The effect of reaction time and polymer chain length on SETNRC reaction was discussed in detail. In the presence of Cu⁰/tris[2‐(dimethylamino)ethyl]amine, SETNRC between PI‐PS‐Br and PEO‐TEMPO was carried out with the efficiency of up to 91.6% in 2 h. With the increase in polymer chain length, the efficiency decreased fleetly. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011