Cationic cyclisation

The application of this procedure to the fused polycyclic compound E, which already has a linear dual and only the last two steps (iii-iv) apply to it, leads to a linear acyclic structure F which may be traced back to the biogenetic cyclisation of squalene to lanosterol via cationic intermediates, as well as to the stereospecific cationic cyclisation of polyolefins studied by Johnson [18]. 

It is worthwhile remembering once more that the cationic cyclisation of 48 yields, by contrast, the six-membered rings of compound 49 [27] (Scheme 7.18) ... 

Strategies based on very particular and specific reactions, such as Diels-Alder addition, either inter- or intramolecular (see also cycloeliminations), cationic cyclisations (important in the "biomimetic synthesis" of steroids), Pauson-... 

Caryophyllenes, as an example of two naturally occurring isomeric sesquiterpenes containing a medium-sized ring, in which the success of the total syntheses lies in the stereoselective control of a chiral centre, in a common synthetic key intermediate, which governs the configuration (JE or Z) of the double bonds present in each one of the two isomers. In this context, a brief reference to Cecropia Juvenile Hormone synthesis by the Syntex group, as well as to Johnson s cationic cyclisation of unsaturated polyolefins to fused polycyclic compounds, is made. 

The Wharton-Grob fragmentation and the cationic cyclisation of polyolefins. Synthesis o/Cecropia juvenile hormone and d, -progesterone. 

Cyclisation of unsaturated elastomers has been the subject of interesting research. Cyclisation yields hard resinous products which have commercial importance and are designated as cyclised rubber [49, 50]. Cyclisation can be carried out with cationic, radiation induced, photo-induced or by thermal methods. Among all these methods cationic cyclisation has been extensively reported probably because there are less side reactions. The generally accepted mechanism of cyclisation of 1,3 diene elastomers is shown in Scheme 4.3a. 

Phenols and naphthols are converted to chromans in a one-pot reaction with isoprene. The specific catalyst AgOTf promotes tandem alkylation, via a 1,4-addition, and cyclisation by O-C bond formation (Scheme 10). With other dienes, 2-naphthol preferentially forms dihydronaphthofurans <06JOC6705>. The Bi(OTf)3-catalysed [1,3] rearrangement of (4-substituted aryl) 3-methylbut-2-enyl ethers to 2-prenylphenols is spontaneously followed by a cationic cyclisation to chromans <06S3963>. 

Reports of examples of arylphosphonates include those of water-soluble phosphinic-polyphosphonic acids, e.g. 132, and the phosphonate 133 which when coupled to alcohols, to give e.g. 134, act as linkers to proteins in experiments intended to generate antibodies to catalyse cationic cyclisation reactions.Novel water-soluble phosphonate-substituted phthalocyanines have been prepared.The phosphonate esters 135 are insoluble in water but can be hydrolysed by hydrochloric acid to give the water-soluble phosphonic acids 136. Aromatic phosphonate-phosphines 137, and their air-stable complexes, have been obtained from the reaction of 4-halogeno-substituted phenylphosphonates with lithium diphenylphosphide. ... 

This compound proved to be the most powerful odorant agent in polyether polyols. Even in trace amounts, this substance confers an unpleasant odour to polyether polyols. The formation of this compound takes place in the purification step, in acidic media, involving the terminal propenyl-ether groups (in fact vinyl ether groups are very sensitive to acidic attack). The probable mechanism is the following cationic cyclisation ... 

Cationic cyclisation of an hydroxyalkene produced by way of 3-methoxyhydrodnnamaldehyde and its Wittig reaction Mith the... 

Finally, Maikov and coworkers used terpene-derived IV,IV -dioxide 21.22 in a total synthesis of marine serrulatane diterpene (—)-elisabethadione 21.67 (Scheme 21.9) exhibiting potent anti-inflammatory activity. Asymmetric crotylation of cinnamaldehyde 21.65 on a 5 mmol scale afforded syn-homoallylic alcohol 21.66 in 82% yield, 94% enantiomeric excess and with complete distereoselectivity. Other key reactions to install the stereogenic centres of the target molecule included anionic ory-Cope rearrangement and cationic cyclisation. ... 

The accessibility of nonracemic allyl acetoacetates makes the Carroll rearrangement an attractive strategy to assemble molecular complexity with adjacent tertiary and quaternary stereocenters. In the late 1950s, researchers at Hoffmann-La Roche utilised propargylic acetoacetate 194 to synthesise pseudoinone 195. Pyrolysis in the presence of Bronsted acid initiated the Carroll rearrangement to yield allenyl ketone 198 which tautomerised to pseudoinone 195. The minor product 196 resulted from Bronsted acid-mediated r-cation cyclisation of 199. 

Frebault, F.C. and Simpkins, N.S. (2010) A cationic cyclisation route to prenylated indole alkaloids synthesis of malbrancheamide B and brevianamide B, and progress towards stephacidin A. Tetrahedron, 66, 6585-6596. 

The formation of the c -annulated hexahydrothioxanthene (34) from thiophenol and hept-6-enals may also result from a [ +2] cycloaddition, although the minor stereoisomers probably arise from a cationic non-concerted cyclisation <96SL396>. 

Cyclopenta[fc]dioxanes (44) are accessible from the reaction of the dioxenylmolybdenum carbene complex (43) with enynes <96JOC159>, whilst an intramolecular and stereoselective cyclisation of (Ti5-dienyl)tricarbonyliron(l+) cations affords chiral frans-2,3-disubstituted 1,4-dioxanes <96JOC1914>. 2,3-Dimethylidene-2,3-dihydro-1,4-benzodioxin is a precursor of the 3,8-dioxa-lff-cyclopropa[i]anthracene, which readily dimerises to dihydrotetraoxaheptacene (45) and the analogous heptaphene <96AJC533>. 

Finally, intramolecular hydroamination/cyclisation of M-alkenyl ureas was catalysed by the well-defined [AuCl(IPr)] complex (Schane 2.16), in the presence of AgOTf (5 mol%, rt, methanol, 22 h). The cationic Au(lPr)+ is presumably the active species [83]. 

The postulated mechanism for the reaction involves activation of the alkyne by jt-coordination to the cationic (IPr)Au% followed by direct nucleophilic attack by the electron-rich aromatic ring to form product 111. Alternatively, two 1,2-acetate migrations give the activated aUene complex, which can be cyclised to product 110 by nucleophilic attack of the aromatic ring on the activated aUene (Scheme 2.21) [92]. 

The two saturated rings of the cannabinoid nucleus are formed with the correct stereochemistry at C-6, C-6a and C-lOa but without selectivity at C-9 in a single acid-catalysed cyclisation step from the phenol 51. Stabilisation of a cationic intermediate by the alkyne group is proposed to account for the facile cyclisation . 

As Skinner has pointed out [7], there is no evidence for the existence of BFyH20 in the gas phase at ordinary temperatures, and the solid monohydrate of BF3 owes its stability to the lattice energy thus D(BF3 - OH2) must be very small. The calculation of AH2 shows that even if BFyH20 could exist in solution as isolated molecules at low temperatures, reaction (3) would not take place. We conclude therefore that proton transfer to the complex anion cannot occur in this system and that there is probably no true termination except by impurities. The only termination reactions which have been definitely established in cationic polymerisations have been described before [2, 8], and cannot at present be discussed profitably in terms of their energetics. It should be noted, however, that in systems such as styrene-S C/4 the smaller proton affinity of the dead (unsaturated or cyclised) polymer, coupled, with the greater size of the anion and smaller size of the cation may make AHX much less positive so that reaction (2) may then be possible because AG° 0. This would mean that the equilibrium between initiation and termination is in an intermediate position. 

This complicated system of equations is not amenable to a general analytical solution, but it is not quite as intractable as it may seem, because there is an unusually large number of observable variables the total concentration of cations by UV-visible spectroscopy, the total concentration of Ti-C bonds by quenching with tritiated water, the concentration of monomer and of unsaturated and cyclised dimer-all as functions of reaction time Further, the system can be simplified by the use of extreme conditions, as was done by the original investigators. 

In addition to the DCTAE/DDTAV motifs, a highly conserved repetitive strand turn motif rich in aromatic amino acids (the QW motif) occurs in all OSCs and SCs and is repeated four to eight times (Table 3). These repeats are likely to be important for protein structure and stability and also for catalytic activity [55, 62-64]. The aromatic amino acids of the QW motif have been proposed to constitute sites of negative point charge that may interact with the intermediate cations during the cyclisation process [62]. 

The bornane-, camphane- and fenchane-type monoterpenes possess the [2.1.1] bicyclic skeleton formed by different cyclisation of the terpinyl cation. Important members include borneol 47, isobornyl acetate 48, camphene 49, camphor 50, fenchone 51 (Structure 4.12). 

The presence of heteroatom donors is not essential to cation-71 complexation, and indeed a number of purely hydrocarbon n—C—donor ligands have been prepared. Ligand 3.137 is synthesised in 90 % yield by cyclisation of the precursor diketone under high dilution conditions in order to minimise the formation of polymeric by-products (Scheme 3.27). 

If you don t see at once what reagent will be used for the synthon 37, you are not alone. How can we use the other OH group at C-l to make C-2 electrophilic One way to visualise the answer is to imagine what would happen if you actually made the cation 37. It would instantly cyclise 38 to form a three-membered ring 39 that could lose a proton to give the epoxide 40. Epoxides are strained ethers and react with nucleophiles such as amines 41 to give 42 and hence the aminoalcohol 33. 

Presumably the silyl enol ether of 37 adds in a conjugate fashion to the unsaturated ester 39 and the intermediate enolate then cyclises onto the cation 40 to give 38. This will happen only if the stereochemistry of 40 is the same as that of the product 38 as the 4/5 and 4/6 ring fusions must both be cis. This suggests that the first step is reversible. The formation of the cyclobutane requires that particular relationship between ketone and unsaturated ester so this kind of reaction is less versatile than photochemical cyclisation. Asymmetric versions of these reactions are also known.14 Probably the most versatile thermal method to make cyclobutanes uses ketenes and is the subject of the next chapter. 

An electrocyclic reaction is the formation of a new o-bond across the ends of a conjugated 7T-system or the reverse. They thus lead to the creation or destruction of one a-bond. Hexatrienes 1 can cyclise to six-membered rings 2 in a disrotatory fashion but we shall be more interested in versions of the conrotatory cyclisation of pentadienyl cations 3 to give cyclopentenyl cations 4. The different stereochemistry results from the different number of rt-electrons involved.1... 

The Nazarov2 is probably the most important of reactions like 3. The cation 6 is formed from a dienone 5 by protonation and cyclises to the allylic cation 7. Though this is presumably a conrotatory process, the stereochemistry is usually lost in the formation of the cyclopentenone 9. 

Thus the natural product damascenone 10, responsible in part for the smell of roses, cyclises in acid to the cation 11 that can lose a proton from one side only to give3 12. The disconnection for the Nazarov reaction is of the single bond in the five-membered ring opposite the carbonyl group 12a. 

The Robinson annelation is by no means the only ionic reaction that makes six-membered rings. Six-membered rings form easily so trapping a Nazarov intermediate (chapter 35) makes good sense. The Friedel-Crafts-like disconnection 18 suggests a most unlikely cation 19 until we realise that it would be formed in the Nazarov cyclisation of the dienone 20 whose synthesis is discussed in the workbook. 

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