Oxidative cyclisation, alkenes

For large-scale oxidations of carbohydrates (> Ig) cf. the first column of Table 2.3. For synthesis of carbohydrates by alkene cyclisation cf. 3.1.3.3. 

Steroids Carbonyl Compounds Cycloaddition Enone and Dienone Rearrangements Alkenes Isomerisation and Rearrangement Alkenes Cycloaddition Alkenes Photo-oxidation Terpenoids Aromatic Compounds Isomerisation and Cycloaddition Practical Photochemistry Scale-up Aromatic Compounds Substitution and Cyclisation Alkaloids Photoinitiated Free-radical Chain Reactions. 

Thallium compounds, especially in the form of thallium(i) and thallium(iii) salts, are ahle to mediate a great numbers of reactions, including oxidative rearrangements of ketones and alkenes, cyclisation reactions, a-oxidation of ketones, aromatic thallations, oxidative couplings, oxidations of phenols and nitrogen compounds and disulfide bond formation, thus, constituting a useful tool in synthetic organic chemistry. However, their application as catalysts has been less explored and there are only a few successful examples reported in the literature. 

The photochemical cyclisation of p.y-unsaturated ketoximes to 2-isoxazolines, e.g., 16—>17, has been reported <95RTC514>. 2-Isoxazolines are obtained from alkenes and primary nitroalkanes in the presence of ammonium cerium nitrate and formic acid <95MI399>. Treatment of certain 1,3-diketones with a nitrating mixture generates acyl nitrile oxides, which can be trapped in situ as dipolar cycloadducts (see Scheme 3) <96SC3401>. 

Methoxatin 267 is a bacterial co-enzyme that allows the oxidation of methane to more useful one-carbon compounds. The 1,2-dione in the middle ring is the powerhouse of the molecule and can be made from the simpler aromatic compound 268 by oxidation. Oxidative cyclisation of the Z-alkene 269 might give 268. 

Finally the remaining alkene is dihydroxylated with catalytic Os04and stoichiometric iV-methyl-morpholine (NMO) as oxidant to give the diol 56 that cyclises to the THF 57 stereospecifically. The aldehyde 58 was used to make (-)-dysiherbane. 

Halolactonisation works well because bromine and iodine form three-membered ring intermediates when they attack an alkene. Sulfur (II) and selenium (II) electrophiles form even better defined intermediates of this kind and similar cyclisation reactions occur with impressive control over selectivity.27 A simple example would be the formation of the bicyclic lactone 181. As the carboxylic acid is tethered to the five-membered ring, it can cyclise only to the intermediate with S(e) on the other face 180. The mechanism is similar to that of iodolactonisation and the stereochemical points are the same. The products are useful for the generation of radicals as Bu3SnH removes a PhSe group and leaves a radical behind while oxidation and elimination leaves a new alkene (chapter 33). 

This may look like a rather specialised method but the biomimetic inspiration applies to much simpler compounds. Taxodione 261 is an antitumour compound from the swamp cypress Taxo-dium distichum. It has an extended quinone-like enone system and two trans fused six-membered rings. Livinghouse42 realised that the extended quinone might be derived by oxidation of a simpler aromatic compound 262 where X is an oxidisable group. He then saw a possible polyolefin cyclisation in which a tertiary cation derived from a simple alkene 263 starts the reaction and the aromatic ring terminates the sequence. 

Brown s crotyl borane 158 (chapter 24) provides reagent control through a chair-like six-membered ring in the formation of 159. Oxidation of the alkene (ozone with oxidative workup) gives the free acid marked in 160 and on removal of the benzylic group the freed amine (circled) cyclises to it to give the pyrrolidone required (147 as its methyl ester). The synthesis can easily be completed from there. 

Thiadiazoles can be prepared by the oxidative cyclisation of 1,2-diamines or aminocarboxamides. Condensation of snlfamide (S02(NH2)2) with 1,2-diketones gives 1,2,5-thiadiazole 1,1-dioxides. A good general method is the reaction of trithiazyl trichloride with activated alkenes and alkynes this method is also useful for the fusion of a 1,2,5-thiadiazole onto other heterocycles, such as pyrroles. The reaction possibly proceeds via cycloaddition to an N-S-N unit in the trithiazine ring. "... 

A radical cation is involved in the direct synthesis of chromans by an intramolecular oxidative cyclisation of 3-arylpropanols 32 brought about by a hypervalent iodine(III) reagent <04TL2293> and iodonium species catalyse the intramolecular arylation of alkenes which yields iodo-substituted chromans 33 <04JA3416>. 3-Allenylchroman-4-ols result from a one-pot reaction between salicylaldehydes and 1,4-dibromobut-2-yne in which the intramolecular cyclisation of the intermediate ether is mediated by In metal <04SL45>... 

The combination of Ni(COD)2 and l,3-di-ferf-butylimidazol-2-ylidene (ItBu) was demonstrated to effectively catalyse an intramolecular alkene hydroacylation to construct five- and six-membered benzocyclic ketones in good to excellent yields (Scheme 14.71). Al-aryl-substituted NHCs are not effective for this transformation. The reaction is proposed to proceed via a process as shown in Scheme 14.72. Thus, 2-allylbenzaldehyde coordinates to Ni(0)/ItBu to form complex A. The oxidative cyclisation of A gives a nickelacycle intermediate B. B undergoes p-hydride elimination and reductive elimination to produce final product C, along with regeneration of the catalyst. ... 

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