Cyclization double

Reactions involving quinoline hydrazide derivatives have been noted in the pyridazino-[4,3-c]- (64MI21500), -[4,5-f ]- (31M(58)238) and -[4,5-c]-quinoline (71CB3341) series, whilst the double cyclization of (358) to the pyridazino[4,5-f ]quinoline (359) (80CPB3457) and related cyclizations in the same series (80H(14)267) are of a basically similar type. A lone cyclization of this type from cinnoline intermediates involves the o-acetonylcarboxamide type formation of the pyridine ring to give the pyrido[3,4-c]cinnoline (360) (76JCS(Pl)592). 

The double cyclization to. the pyrazino[2,3-f ]quinoline (423) referred to above must also involve a [6 + 0 (y)] cyclization step. 

In general, fluorinated sulfonic acids can be used as eatalysts for various cationic cyclizations Typical examples are the triflic acid catalysis in the double cyclization of A,VV-dibenzylpropynylamine [82] (equation 30) and the fluorosulfonic acid catalyzed condensation of phenylacetaldehyde [<5J] (equation 31)... 

In a recent communication, the parent system 2 has been obtained in poor yields (16% and 10%, respectively) from the double cyclization of N-diphenyl-1,3-phenylenediamine either by using two equivalents of palladium acetate in refluxing acetic acid or by irradiation in methanol in the presence of a catalytic amount of iodine (00SC3651). All the available approaches sununarized so far were marred by harsh reactioi conditions or troublesome-to-prepare starting materials, leading to low overall yields of the desired products and difficulty in introducing sensitive substituents. 

Double cyclization of the phenylglycine o-carboxylic acids 611 (R = H) with acetic or benzoic anhydride by heating gave the mesoionic oxazolones 612 and 613, respectively, which upon treatment with BF3 Et20 gave 615... 

The successful implementation of this strategy is shown in Scheme 4. In the central double cyclization step, the combined action of palladium(n) acetate (10 mol %), triphenylphosphine (20 mol %), and silver carbonate (2 equiv.) on trienyl iodide 16 in refluxing THF results in the formation of tricycle 20 (ca. 83 % yield). Compound 20 is the only product formed in this spectacular transformation. It is noteworthy that the stereochemical course of the initial insertion (see 17—>18) is guided by an equatorially disposed /-butyldimethylsilyl ether at C-6 in a transition state having a preferred eclipsed orientation of the C-Pd a bond and the exocyclic double bond (see 17). Insertion of the trisubstituted cycloheptene double bond into the C-Pd bond in 18 then gives a new organopal-... 

An impressive achievement of this strategy has been the construction of three-dimensional structures. Utilizing branched phenylacetylene sequences, double cyclization yielded macrobicyclic arrays 54 and 55 [43]. The zenith of Moore s approach is macrotricycle 56, a freely hinged system with a sizable 36xl2xl2A molecular cavity [44]. 

Scheme 92. Synthesis of cu-alpinigenine (445) and alpinigenine (441) by photochemical double cyclization. Reagents a, Mel b, IRA-400 c, A d, NBS, 1 N HO e, HI04, H2S04 f, Av, /-BuOH.

The formation of the indole moiety has found immense attention, since it exists in many bioactive compounds such as the indole alkaloids [302]. Whilst the Fischer indole synthesis remains the most important procedure, during the past few years several transition metal-catalyzed syntheses have been developed. Recently, a Cu11-catalyzed cyclization of anilines containing an ortho-alkynyl group was published by Hiroya and coworkers [303], which allows a double cyclization in domino fashion to provide annulated indoles. Thus, reaction of 6/4-92 in the presence of... 

Double cyclizations can occur one interesting example is the formation of the thieno[2,3-c]isothiazole (97) from the cyano-substituted ketoester... 

With alkenes bearing two suitably placed nucleophilic groups, the two mechanisms may even occur in sequence, leading to a double cyclization product, as depicted in Scheme 7 [44-48]. 

Paracrystallinity, Cu/ZnO/AIjOj, 31 295 2"-Paracyclophanes, 32 453 Paracyclophanes, macrocycles, 29 206-208 Paraffin, see also Alkanes alkylation, 10 165, 27 98 carbon selectivity, bed residence time effects, 39 249-250 cracking, 39 283 cyclization, 28 295 rates, 28 301, 302 double cyclization, 28 312-314 in exhaust gases, 24 66, 67 hydrogenolysis, 30 43-44 hydroisomerization, 39 183 oxidation, 32 118-121 solubility enhanced hydrogeolysis, 39 285 Parahydrogen conversion rate correlations, 27 48-50... 

Anodic oxidation of endiamine 69 provided an example of double cyclization to an indolo-oxazoUne 70 [92]. The oxidation was carried out in CH3CN-... 

The first synthesis of an optically active isopavine, (—)-reframoline (29), has been achieved by the acid-catalyzed double cyclization process described previously. The properly substituted diarylamine 109 was resolved using (-t-)-di-benzoyltartaric acid to afford the (-I-) enantiomer. Conversion to the acetal 110 was accomplished without racemization. Subsequent acid-catalyzed cyclization yielded the levorotatory alkaloid 29 (Scheme 21) 112). 

A facile acid-catalyzed double cyclization of A,A-dibenzylaminoacetaldehyde dialkyl acetals of type 125 has been known to generate l-azadibenzo[c,/]bicy-clo[3.3.1]nona[3,6]dienes 126 in high yields 120,121,147). A novel and convenient synthesis of ( )-amurensinine (25) and ( )-reframine (28) (Scheme 25) proceeds from the quaternary salt 127, where proper choice of base and reaction... 

Double cyclization of iodoenynes is proposed to occur through a Rh(I)-acetylide intermediate 106, which is in equilibrium with vinylidene lOS (Scheme 9.18). Organic base deprotonates the metal center in the course of nucleophilic displacement and removes HI from the reaction medium. Once alkenylidene complex 107 is generated, it undergoes [2 + 2]-cycloaddition and subsequent breakdown to release cycloisomerized product 110 in the same fashion as that discussed previously (Scheme 9.4). Deuterium labeling studies support this mechanism. 

Scheme 9.18 Rh(l)-catalyzed double cyclization of iodoenynes - Proposed catalytic cycle.

Both single and double cyclizations of the Schiff bases 65A and 66A occur in the multicomponent tautomeric mixtures derived from as- and /ra t-cyclohexane aminodiols 69 and 70, to give monocyclized ring forms of C-2-epimeric perhydro-l,3-benzoxazines (B and G) and oxazolidines (D and E), besides 7,ll-dioxa-9-azatricyclo[7.2.1.0 °]-dodecane diastereomers 67 and 68 (Scheme 10). The tautomeric ratios are found to satisfy by Equation (1) (Table 1) and are influenced by the cis- or rra t-geometry of the cyclohexane substituents in the Schiff base (A). For the equilibria... 

A stereoselective one-pot synthesis of furo[3,2- ]pyran, 80, has been reported. The key step in the synthesis includes a double cyclization reaction along with a rearrangement (Scheme 16) <1998TL3605>. 

The pure thiacyclols incorporating the cis cyclodipeptide structure have been subsequently prepared by mild double cyclization of the corresponding linear precursors [84JCS(P1)1153] (Scheme 19). 

Azacyclols arising from amide-amide interaction have been extensively investigated. The p-nitrophenyl ester (60) of the linear tripeptide N-benzyloxycarbonyl-L-alanyl-L-phenylalanyl-L-proline undergoes a double cyclization when left in an aqueous buffer-dioxane (1 1) solution for 1 h, to produce cyclol (61) (7 ICC 1605). The hydroxyl group of the cyclol could be converted to the methyl ether by treatment with methyl iodide-silver oxide. The structure of the cyclol (61) could be confirmed by X-ray crystallography of the corresponding p-bromobenzyloxycarbonyl derivative (7 ICC 1607). 

Double cyclization was observed with siloxy enynes when a new cycloisomerization mechanism was used that involved a cascade of 1,2- alkyl shifts [154]. 

As indicated in the section describing the structures of natural dilactones, wentilactone B was wrongly assigned when the structure of 30-hydroxy-13,14,15,16-tetranorlabda-7,9(ll)-dien-(19,6(J),(12,17)-diolide was isolated. Our synthesis of this compound allows the reassignment of the structure of wentilactone B. Thus, the hydroxyl group of this natural podolactone should be relocated at C-2 with an a- configuration [87]. Two double cyclization steps were employed in this synthesis. The first involves the construction of the bicyclic skeleton via a Mn(III)-mediated... 

As demonstrated in Section IV, compounds possessing two spiroannulated cyclopropyl fragments could be successfully prepared by using double cyclopropanation or double cyclization of the corresponding bismethylene or bis(gem-dihalomethyl) precursors. 

Kazanskii and co-workers have described an interesting special case, double cyclization of -octane at 310°C over platinum-on-charcoal catalyst at 0.2 liquid hourly space velocity. The reaction product contains about 0.25% m-octahydropentalane and 2.2-4.5% alkylcyclopentanes (an approximately l lmixture of trans-l-methyl-2-ethylcyclopentane and n-pro-pylcyclopentane) (39, 40). Indirect evidence suggests that most of the octahydropentalane is formed from l-methyl-2-ethylcyclopentane, which cyclizes significantly faster than w-propylcyclopentane. 

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