Selective Synthesis of 6′‐Arylidene‐1‐aryl‐3‐aryl‐spiro[pyrrolizidine‐2,2′‐cyclohexanone] by Cycloaddition of Azomethine Ylides to Dibenzylidene Cyclohexanone

Azomethine ylides derived in situ from l ‐proline and aryl aldehydes underwent regioselective and stereoselective cycloadditions with diaryl cycloahexanone to form a series of spiro‐pyrrolizidine compounds. By using equimolar proportions of the reactants in DMF, only a single mono‐adduct, namely 6′‐arylidene‐1‐aryl‐3‐aryl‐spiro[pyrrolizidine‐2,2′‐cyclohexanone], was formed, the second double bond in the dipolarophile remaining unaffected. Structure elucidation was achieved by detailed spectroscopic analyses and XRD studies. Interesting solid‐state structural characteristics were revealed by XRD analysis.     

A new highly efficient three-component domino Heck-Diels-Alder reaction with bicyclopropylidene: rapid access to spiro[2.5]oct-4-ene derivatives

Bicyclopropylidene (1) was found to surpass even methyl acrylate (17 a) in its rate of undergoing carbopalladation with aryl- or alkenylpalladium species, leading to substituted allylidenecyclopropanes 5, 7 and 10, mostly in high yields (37-78 %). These dienes and cross-conjugated trienes react in a Diels-Alder mode with dienophiles to give spiro[2.5]octenes 18 a-Ph, 18 b-Ph and 18 a-Vin, respectively, in good yields (89, 69 and 65 %). The overall transformation can be achieved as a one-pot three-component reaction with a variety of dienophiles to furnish the domino Heck-Diels-Alder products 18 regioselectively in most cases in good to very high yields (49-100 %). The reaction of 1 with iodobenzene (2-Ph) and 17 a gave 18 a-Ph in virtually quantitative yield-also on a gram scale-using only 1 mol % of catalyst, and even bromobenzene (22) gave 18 a-Ph in 59 % yield. Bicyclopropylidene (1), in the presence of palladium acetate/triphenylphosphane underwent rearrangement to allylidenecyclopropane (5-H), which in turn dimerized (73 %) in the absence of other reaction partners, or could be trapped by diethyl fumarate (17 c) to give the Diels-Alder adduct 18 c-H in 45 % yield. The coupling of oligoiodobenzenes with 1 and subsequent cycloaddition could be extended to a multicomponent reaction. In this way, 1,4-diiodobenzene (37), 1 and an alkyl acrylate gave the products 38 of a twofold Heck-Diels-Alder reaction in up to 87 % yield, 1,3,5-triiodobenzene (39) reacted in up to 72 % yield and ultimately 1,2,4,5-tetraiodobenzene (41) gave the fourfold domino Heck-Diels-Alder product 42 in 47 % isolated yield, in a single operation in which 12 new carbon-carbon bonds were formed.     

Catalytic asymmetric synthesis of spirooxindoles by a mannich-type reaction of isothiocyanato oxindoles

Easy access: a strontium/Schiff base complex as catalyst for the title reaction provided straightforward access to enantiomerically enriched spiro[imidazolidine-4,3'-oxindole] compounds, as well as a spiro[imidazoline-4,3'-oxindole] through a two-step conversion from the Mannich adduct.     

Metal atoms collinear with the spiro carbon of 6,6-open adducts, M2@C80(Ad) (M = La and Ce, Ad = adamantylidene)

The photochemical reaction of M2@C80 (M = La and Ce) with 2-adamantane-2,3'-[3H]-diazirine (1) affords the corresponding adducts by carbene addition. The adducts were characterized by spectroscopic and single-crystal X-ray structure analyses. Crystallographic data for the adduct La2@C80(Ad) (2, Ad = adamantylidene) reveal that the two La atoms are collinear with the spiro carbon of the 6,6-open adduct. It is noteworthy that the La-La distance is highly elongated by the addition of carbene. Paramagnetic 13C NMR spectral analysis of the adduct Ce2@C80(Ad) (3) indicates that the two Ce atoms are also collinear with the spiro carbon at room temperature in solution. The unique metal positions were confirmed by density functional calculations.     

A facile regioselective construction of spiro epoxy-bridged tetrahydropyranone frameworks

Investigations on the reactivity profile of the transient five-membered-ring cyclic carbonyl ylides, generated from α-diazo ketones, in the presence of the CO group of various simple ketones and symmetrical/unsymmetrical 1,2-diones were carried out. The reaction of α-diazo ketones with 1,2-naphthoquinone furnished interesting diastereomeric cycloadducts in which both the CO groups acted as dipolarophilic sites. The similar reaction in the presence of several isatin derivatives afforded novel spiro dioxa-bridged indole derivatives as a mixture of diastereomers. The single crystal X-ray structure analysis manifestly revealed the mode of cycloaddition and the stereochemistry of two of the diastereomers. A diverse set of novel spiro epoxy-bridged tetrahydropyranone frameworks have been constructed in good yield via the tandem cyclization-cycloaddition of α-diazo ketones with the CO group as heterodipolarophile in a regioselective manner.     

Synthesis and rearrangement of [1,1′-bicyclobutyl]-1-ols and spiro[3.4]octan-5-ols: a general access to bicyclo[3.3.0]octenes (hexahydropentalenes)

Several new Grignard reagents based on substituted cyclobutanes have been generated and added to cyclobutanones to yield mono- to trimethylated [1,1′-bicyclobutyl]-1-ols. Mono- to trimethylated spiro[3.4]octan-5-ols have been prepared from the parent ketone via alkylation and/or addition reactions. Upon treatment with acid, all [1,1′-bicyclobutyl]-1-ols and spiro[3.4]octan-5-ols rearrange to yield a single bicyclo[3.3.0]octene.     

Synthesis and characterization of a bisadduct of La@C82

A bisadduct of La@C82 has been synthesized in a good yield by a Bingel-Hirsch reaction. Its structure has been well-defined by X-ray crystallographic analysis. A pair of enantiomers of the adduct form a dimer in the single crystal.     

XY-ZH compounds as potential 1,3-dipoles. Part 63: Silver catalysed azomethine ylide cycloaddition—the synthesis of spiro homoserine lactone analogues

A range of room temperature 1,3-dipolar cycloaddition reactions of imines of 2-amino-γ-lactone and thiolactone, catalysed by a combination of AgOAc or Ag₂O with NEt₃ or DBU, are described. The spiro lactones/thiolactones are formed regio- and stereoselectively as single cycloadducts in good yield via the syn dipoles and an endo-transition states.     

Simplified synthesis of spiro‐bridged ladder‐type poly(p‐phenylene)

In this study, a simplified route to synthesize soluble, spiro‐bridged ladder‐type poly(p‐phenylene)s (spiro‐LPPP) was developed. The new, simplified synthesis route for spiro‐LPPP involves two reaction steps: a single‐stranded precursor polymer containing diaryloylbenzene building blocks was obtained by the Suzuki reaction, followed by a subsequent twofold cyclization cascade using methanesulfonic acid to form the target spiro‐LPPP. Spiro‐LPPP shows a well‐defined chemical structure, high molecular weight (M_n of 17,500 g/mol with a polydispersity index of 2.0), excellent thermal stability (5% weight loss at 370 °C), and good solubility in common organic solvents. Spiro‐LPPP emits blue light (λ_max,em = 455 nm) with the high solution PL quantum yield (94%). The spectral properties of spiro‐LPPP in the solid state are very similar to the solution properties, thus indicating a low degree of intermolecular aggregation. After annealing a thin film of spiro‐LPPP to 120 °C in air for 3 to 24 h, its emission spectrum is unchanged, reflecting excellent thermooxidative stability. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5137–5143, 2009     

A novel reaction of cyclic ketene acetals with phenyl isocyanate through zwitterion

A novel reaction of cyclic ketene acetals with phenyl isocyanate through zwitterion was found to yield the corresponding spiro compounds in good yields.     

Synthesis and characterization of poly(cyclohexane 2,2-dipropargyl-1,3-propylene ketal) containing double spiro structure

The Polymerization was carried out by MoCl₅ and WCl₆ associated with various organo-metallic cocatalysts. MoCl₅-based catalysts were found to be more effective. Polymerization of monomer containing a spiro structure proceeded rapidly to reach 80% yield within 2 h at 30°C. Polymerization of monomer led to a soluble, purple colored polymer with number average molecular weight (M_n) of 50000. Elemental analysis, ¹H-NMR, ¹³C-NMR, IR, and UV-visible spectra of the resulting polymer indicated that the polymer contains alternating double and single bonds along the polymer backbone and a cyclic recurring unit with a double spiro structure. In addition, the polymer had good oxidative and thermal stability and good solubility in common organic solvents. © 1995 John wiley & Sons, Inc.     

Total synthesis of (+/-)-gleenol and (+/-)-axenol via a functionalized spiro[4.5]decane

Total synthesis of the biologically important axane sesquiterpenes, gleenol (1) and axenol (2), was accomplished through a readily available spiro[4.5]decane. The key features of the synthesis of 1 and 2 include Claisen rearrangement to afford the multi-functionalized spiro[4.5]decane 4 as a single diastereomer in excellent yield, installation of the C7 isopropyl group via ketene dithioacetal instead of direct alkylation and a diastereoselective reduction of ketone under the Birch conditions.     

2-azabicyclo[2.2.2]octa-3,5-dione via a nitrile Diels-Alder reaction

The hetero-Diels-Alder reaction of an electron-deficient nitrile, p-toluenesulfonyl cyanide, with the silyl enol ether of cyclohexenone produced a hydrolytically sensitive [4 + 2] adduct in good yield. Use of Mander's reagent, ethyl cyanoformate, with the same diene, produced an unstable adduct. Hydrolysis of the tosyl cyanide adduct resulted in the isoquinuclidinone 2-aza[2.2.2]octa-3,5-dione as a crystalline compound in excellent yield from the nitrile.     

A new synthesis, including asymmetric synthesis, of spiro[4.n]alkenones from three components: cyclic ketones, chloromethyl p-tolyl sulfoxide, and acetonitrile; and a formal total synthesis of racemic acorone

1-Chlorovinyl p-tolyl sulfoxides were synthesized from several kinds of cyclic ketones and chloromethyl p-tolyl sulfoxide in good yields. Treatment of the 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium at −78°C to room temperature gave spirocyclic enaminonitriles in high yields. Acidic treatment of the enaminonitriles afforded spiro[4.n]alkenones in good yields. By using an unsymmetrical cyclic ketone, α-tetralone, and optically active chloromethyl p-tolyl sulfoxide, this procedure afforded enantiomerically pure spiro[4.5]decenone in good yield with excellent asymmetric induction from the sulfoxide chiral center. By using this method a formal total synthesis of a racemic spirocyclic sesquiterpene, acorone, was realized.     

Efficient one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine]dione via three-component reaction

An efficient one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine] dione derivatives via three-component reaction of 5-amino-3-methylpyrazole, isatin, and thioacid is described. This new protocol produces novel heptacyclic spirooxindole derivatives in good yields in comparison to conventional pentacyclic compounds. This method proceeds through a 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindoline intermediate (Baylis-Hillman type adduct), unlike 3-indolylimine (the intermediate like Shiff-Bases) as in conventional methods. The structure of one representative compound has been confirmed by X-ray diffraction analysis.     

A novel access to highly functionalised β-lactams by regio- and stereoselective 1,3-dipolar cycloaddition reaction

A highly regio- and stereoselective synthesis of novel spiro pyrrolidines/pyrrolizidines containing β-lactam and oxazolone moieties under two different conditions is achieved using [3+2] cycloaddition methodology in moderate to good yield.     

The synthesis and analgesic properties of new spiroisochromanyl acid derivatives synthesized from natural safrole

We describe in this paper the synthesis of a new spiro[2-carboxycyclopentane-1,1-(6,7-methylene-dioxy)isochroman] and a spiro[2-carboxycyclohexane-1,1-(6,7-methylenedioxy)isochroman] acids 11 and 12 , obtained from natural safrole (7) , isolated from Sassafras oil. These derivatives were obtained in high overall yield using a synthetic route in which was observed brevity and appreciable diastereoselectivity in the intramolecular regioalkylation of the 6-position of the aromatic system of the natural starting material, the key step of the synthetic route representing a variable in the well-known Friedel-Crafts reaction. The new acids, derivatives 11 and 12 , were obtained in ca. 74% and 78% overall yield. They show a good analgesic profile in the pharmacological assay, the test in mice abdominal contortion.     

Synthesis of Ketone from Alkyl Halide Using α-Chloro Nitrone as Oxidizing Reagent: A New Approach

Consecutive S_N2 reaction of α-chloronitrones were studied with isopropyl halides, and the nitrones have remarkable oxidizing properties for the conversion of isopropyl halides to ketones with good yields. In addition, the side product obtained can serve as efficient dipolarophile in 1,3-dipolar cycloaddition reaction to produce spiro cycloadduct in good yield.     

Asymmetric synthesis of spiro 2-pyrrolidin-5-ones, 2-piperidin-6-ones and 1-isoindolin-3-ones. Part 1: N-Acyliminium ion cyclisations with an internal arene nucleophile

A series of chiral non-racemic 5,5- and 5,6-bicyclic lactams is prepared from (R)-phenylglycinol. These are isomerised on treatment with aluminium trichloride in 1,2-dichloroethane to give spiro lactams in high yield and >3:1 diastereoselectivity. From four structures determined by X-ray crystallography, it follows that spiro indenes are formed preferentially with retention of configuration at the spiro carbon atom and spiro naphthalenes with inversion.     

Rapid Access for the Synthesis of 1‐N‐Methyl‐spiro[2.3′]oxindole‐spiro[3.7″] (3″‐Aryl)‐5″‐methyl‐3″,3a″,4″,5″,6″,7″‐hexahydro‐2H‐pyrazolo[4,3‐c]pyridine‐4‐aryl‐pyrrolidines Through Sequential 1,3‐Dipolar Cycloaddition and Annulation

The 1,3‐dipolar cycloaddition of an azomethine ylide, generated from isatin and sarcosine by a decarboxylative route with various p‐substituted 3,5 bis(aryl methylidene)N‐methyl‐4‐piperidinones in refluxing methanol, proceeded regioselectively to give novel dispiroheterocycles. The product on subsequent annulation with hydrazine hydrate afforded 1‐N‐methyl‐spiro[2.3′]oxindole‐spiro[3.7″](3″‐aryl)‐5″‐methyl‐3″,3a″,4″,5″,6″,7″‐hexahydro‐2H‐pyrazolo[4,3‐c]pyridine‐4‐aryl‐pyrrolidines in good yield.