Strategies oxidative cleavage

Illustrative examples of the cleavage of support-bound ethers are listed in Tables 3.30 and 3.31. Acidolytic cleavage is the most commonly used strategy, but base-mediated, photolytic, and oxidative cleavage have also been reported. Wang linker... 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

The point of this synthesis is that the workers recognised that oxidative cleavage of citronellal and citronellol would give two-ended fragments that could be used to make the core of the pheromone with the right stereochemistry. We shall see in the next chapter that this reconnection strategy is vital for the synthesis of one important group of compounds 1,6-diCOs. 

This last example makes it clear that we shall normally have to make the cyclohexenes we need for oxidative cleavage and one of the best routes to such compounds is the Diels-Alder reaction (Chapter 17). A generalised example would be ozonolysis of the alkene 21, the adduct of butadiene and the enone 20. The product 22 has a 1,6-relationship between the two carboxylic acids. Since Diels-Alder adducts have a carbonyl group outside the ring (the ketone in 21) the cleavage products 22 also have 1,5- and 1-4-diCO relationships and would be a matter for personal judgement which of these should be disconnected instead if you choose that alternative strategy. 

There is of course no need to use reconnection if you prefer another strategy but you are advised to try disconnection first. Disconnection of the 1,3-diCO relationship in the spiro-diketone 54 reveals a 1,6-diCO compound that could no doubt be made by oxidative cleavage of 58. But various authors10 preferred to ignore the 1,6-diCO relationship and simply disconnect to the enolate of cyclopentanone 56 and a bromoester 57. 

The major isomer 34 is desilylated with TBAF, and oxidative cleavage of the diol with sodium periodate generates the corresponding aldehyde 35, the racemic form of which is a known intermediate in the total synthesis of racemic CP compounds. The conversion to the indoline derivative mt-31 therefore follows the strategy of the racemic route. Circular dichroism (CD) spectroscopy verified the identity of the synthetic mt-31 as the enantiomer of the naturally derived indoline (—)-31. Synthetic ent-31 was also processed to give ent-1 and ent-2. 

The alkenyl group can also be transformed to the aldehyde function, which can hence be used in the reaction with, e.g., fullerenes (Fig. 12) [83-89], Correspondingly, two strategies have been pursued for the synthesis of such fullerene-containing Pcs. One of them involves the oxidative cleavage reaction of the alkenyl... 

A widely applied strategy for the synthesis of various difunctionalized organic molecules, e.g. diols, dialdehydes, etc., relies on the oxidative cleavage of olelinic double bonds. Besides transition metal catalysis for asymmetric synthesis, periodate oxidation and ozonolysis are the standard tools for oxidative bond cleaving reactions. For economic and safety reasons, technically applicable alternatives to osmium-based chemistry and ozonolysis are of great interest. 

In 1998, Langlois et al. completed the third synthesis of manzamine C using a strategy based on Sila-Cope elimination (Scheme 8.9) [80]. In this approach, the key intermediate, piperidine derivative 146, was prepared in six steps from 2-methylpyr-idine 143. Oxidation of 146 afforded a mixture of diastereomeric N-oxides 147 and 148. Sila-Cope elimination of N-oxide 147 led to compound 149, while Cope elimination of N-oxide 148 led to compound 150. Oxidative cleavage of the N-O bond in 149 followed by treatment with N-chlorosucdnimide provided the chlor-oamine 153. Elimination, hydrolysis, ditosylation, and finally basic treatment of the ditosylate intermediate afforded the cyclic sulfonamide 124, which is the direct synthetic precursor of manzamine C [73]. 

The strategy eluded to in Scheme 7.3.7 is elaborated upon in Scheme 8.10.5 and involved the starting material prepared in Scheme 8.10.3. Cyclization of the polyol is effected on removal of the acetonide under acidic conditions followed by the oxidative cleavage of the resulting diol. Spontaneous formation of the hemiacetal is followed by protection as the p-nitrobenzyl ether. Although two diastereomers are formed in this sequence, the minor product is easily converted to the major under mild basic hydrolysis of the p-nitrobenzyl ether followed by reprotection of the isomerized hemiacetal. This compound is then converted to the allene, shown, on treatment with propargyltrimethylsilane in the presence of trimethylsilyl triflate. 

Brooks, P.R. Caron, S. Coe, J.W., et al. Synthesis of 2,3,4,5-tetrahydro-l,5-methano-lh-3-benza-zepine via oxidative cleavage and reductive amination strategies. Synthesis 2004, 11, 1755-1758. 

Furan can give rise to a variety of five membered oxacycles. There are four main strategies oxidation of the furan ring, reduction of the furan ring, addition reactions or cycloaddition followed by cleavage of a carbon-carbon bridge. 

Reconnection is the usual strategy for synthesising 1,6 dlfunctlonallsed compounds since the cyclohexenes required for the oxidative cleavage are easily made. Adipic acid (1) is available from cyclohexene Itself and Is a source of five-membered rings by condensation reactions Chapter 19). 

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