Ethers cyclisation

Molecular oxygen inserts into substituted cyclopentadienes under acidic conditions producing pyrylium salts a hydroperoxide rearrangement is proposed <05JOC5768>. In a further development of the use of benzotriazole (Bt) in synthesis, P-lithiation of the vinyl ether 16 and quenching of the anion with chalcone affords an enol ether. Cyclisation with PCI5 produces 2,4,6-triarylpyrylium salts <05S245>. 

Hydroxyquinoline-2-one with 3-chioro-3-methylbutyne refluxed in acetone containing potassium iodide and carbonate during 20 hours gave the butynyl ether, cyclisation of which in hot dimethylaniline at 200X for 2 hours furnished 3,3-dimethyl-3H-pyrano[3,2-f]quinoline-8(7H)-one (ref. 153). 

This lithiated epoxysulfone cyclisation strategy has been iteratively applied in the total synthesis of hemibrevitoxin B, a polycyclic ether marine toxin from the red tide organism Gymnodinium breve (Scheme 5.41) [64]. 

Stabilised sulphur ylides react with alkenylcarbene complexes to form a mixture of different products depending on the reaction conditions. However, at -40 °C the reaction results in the formation of almost equimolecular amounts of vinyl ethers and diastereomeric cyclopropane derivatives. These cyclopropane products are derived from a formal [2C+1S] cycloaddition reaction and the mechanism that explains its formation implies an initial 1,4-addition to form a zwitterionic intermediate followed by cyclisation. Oxidation of the formed complex renders the final products [30] (Scheme 8). 

Similar results are obtained from incineration of polymeric materials with octabromo- and pentabromodiphenyl ether (refs. 11,12). The temperature with the maximum PBDF-yield depends on the kind of polymeric matrix. All three bromo ethers 1-2 give the same isomer distribution pattern with preference for tetrabrominated dibenzofiirans. The overall yield of PBDF is lower for incineration of pentabromobiphenyl ether 2, 4 % at 700°C compared to 29 % for ether 1 at 500 °C (ref. 12). The preferred formation of tetrabrominated fiirans observed at all temperatures cannot be a result of thermodynamic control of the cyclisation reaction it is likely due to the special geometry of the furnaces. One explanation is that a spontaneous reaction occurs at approximately 400°C while the pyrolysis products are transferred to the cooler zones of the reactor details can be found elsewhere (ref. 12). 

The cyclisation of naphthyl propargyl ethers occurs efficiently under microwave irradiation leading to naphthopyrans, but naphthofurans are formed in the presence of base <96JCR(S)338>. The thermal rearrangement of naphthyl 3-trimethylsilylprop-2-ynyl ethers yields the 4-trimethylsilyl derivatives of naphthopyrans <96H(43)751>. 

In other cyclisations to functionalised oxepanes, Rychnovsky and Dahanukar have shown that the epoxide 36 cyclises with BF3 etherate and TMSCN to form the oxepane 37 as single product <96TL339>, and Evans and Roseman have prepared a series of cyclic ethers by radical cyclisation of the acylselenides 38 (Scheme 8) <96JOC2252>. The major product was always the cw-isomer and the best yields were obtained with (TMSjaSiH. 

On page T 54 we use disconnection (a) to devise a synthesis of morpholines e.g. 14), Since cyclisation is so easy, we might consider the alternative double C-N disconnection (b) and use the bis-chloro ether (15), made on page... 

This time the cyclisation was more successful, the five membered cyclic ether (25) being formed in excellent yield in acid. 

An oxidative Prins cyclisation of the allylsilane-tethered a-stannyl ethers offers a route to tetrahydropyrans avoiding the need for catalysis by a Lewis acid (Scheme 17) . 

The product 46 from the Rh(I)-catalysed [2+2+2] cycloaddition of the diynyl ether 44 to the substituted iodobenzene 45 undergoes a Pd-catalysed cyclisation to the fused chromans 47 <00TL3003>. 

A tandem enolate-arylation-allylic cyclisation, in which an essential z-butyldimethylsilyl ether protecting group delays the cyclisation step until the Pd-catalysed arylation is complete, enables 1-vinyl-l//-[2]benzopyrans 54 to be prepared from 2-bromobenzaldehyde (Scheme 32) <00CC1675>. 4-Substituted isochromans 55 are formed from aldehydes by a Pd-catalysed termolecular queuing cascade. The sequence involves cyclisation of an aryl iodide onto a proximate alkyne followed by an allene insertion. Transmetallation with indium then allows addition to the aldehyde (Scheme 33) . 

A deeper insight into the operation of the oxygen-atom effect as well as a further assessment of its dependence on chain length is provided by an investigation of Illuminati et al., (1981) on the kinetics of formation of benzo-crown ethers (54a) and of the analogous non-cyclisation reaction (54b)... 

An interesting alternative intramolecular cyclisation was discovered by Jprgensen and co-workers [187]. Although not strictly exploiting an enamine intermediate, the transformation represents a secondary amine catalysed Morita-Baylis-Hillman reaction leading to a series of highly functionalised cyclohexene products. Reaction of the Nazarov reagent 137 with a,P-unsaturated aldehydes in the presence of the diarylprolinol ether 30 led to the cyclohexene products 138 (49-68% yield 86-96% ee) via a tandem Michael/Morita-Baylis-Hillman reaction (Scheme 54). 

The enol ethers generated in situ by the addition of ethanol to l,4-pentadiyn-3-ones are cyclised to the 4/f-chalcogenopyran-4-ones on treatment with disodium chalcogenides (Scheme 40) <99JHC707>. The 2,6-diphenyl derivatives are useful catalysts for the Baylis-Hillman reaction <99TL3741>. 

N. Moufid, Y. Chapleur, and P. Mayon, Radical cyclisation of some unsaturated carbohydrate-derived propargyl ethers and acetals, J. Chem. Soc. Perkin Trans, p. 999 (1992). 

The propargyl ether 1 was heated in refluxing dimethylaniline for 5 hours in the expectation that Claisen rearrangement followed by cyclisation would lead to the linear tricyclic system. The only product - isolated in only 12.5% yield - was, however, the angular tricyclic ketone 2. 

The radical reductive cyclisation of diesters to acyloins (see also Section 5.9.1, p. 628) is an important method of synthesis for ring sizes from four-membered upwards. The example selected here is 2-hydroxy-3-methylcyclopent-2-enone ( corylone ) (29) (Expt 7.10), which is an important perfumery and flavouring material.53 In the first step (i), methyl acrylate is converted into its dimer with tris(cyclohexyl)phosphine in pyridine solution.5b Step (ii) is the protection of the double bond by conversion into the dimethylamino adduct. The acyloin reaction is step (iii), and the product is trapped as its bis(trimethylsilyl)ether. Finally, in step (iv), the protecting dimethylamino and trimethylsilyl groups are removed by passage down a column of silica gel. 

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