2-nitrobenzyl diastereomers

A soln of a (—)-4-nitrobenzyl [cyclohexyl(Fmoc-amino)methyl]phosphonic add (57 40.0 mg, 0.073 mmol) in CH2C12 (2mL) was cooled to 0°C, and dry DMF (6pL, 0.01 mmol) and oxalyl chloride (13 pL, 0.147 mmol) were added. The mixture was stirred for 0.5 h at 0°C, diluted with benzene (5mL), and concentrated. The phosphonochloridate was redissolved in benzene (2mL), and treated with TEA (20 pL, 0.147 mmol) followed by AgCN (29 mg, 0.217 mmol). After 5 min at rt, D-2-hydroxy-3-(l//-indol-3-yl)propanamide (22.4mg, 0.011 mmol) was introduced, and the mixture was heated at reflux for 2h, cooled to rt, filtered, and concentrated. The phosphonate diester was purified via flash chromatography (2% MeOH/CH2Cl2) to give a mixture of diastereomers (19.8mg, 37%), which were separated by RP-HPLC. For the minor diastereomer (4.5 mg, amorphous solid) [a]D +15 (c 0.47, EtOH). 

Bis(o-nitrophenyl)ethanediol (50) has been proposed as a practical photolabile protecting group for ketones and aldehydes which is superior to the monosub-stituted o-nitrophenylethanediol. The presence of a single stereocentre in the latter leads to the formation of two diastereomers when it is used with another chiral molecule, thus complicating NMR signal patterns, and often making purification difficult. In addition, the obvious alternative of ketal formation from two molecules of o-nitrobenzyl alcohol instead of a diol is usually impractical. On the other hand (50) is easily accessible as a pure enantiomer, and the ketals which it forms with aldehydes and ketones are smoothly deprotected in neutral conditions by irradiation at 350 nm. 

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. 

Piatnitski and Deshayes developed photosensitive hemicarcerands 32, which has a photocleavable ortho-nitrobenzyl ether linkage (Figure 1 la). The DMA hemicarceplex of 32 is stable toward dissociation in the dark, but releases its guest upon UV irradiation, whereby the ortho-nitrobenzyl ether bond is broken in a one-photon process. Incorporation of three additional 3-nitro-ortfto-xylyl linkers, as in 33 DMA, which was prepared as a mixture of inseparable diastereomers, increased the rate of light-induced guest release 3.2-fold compared to 32 DMA due to the higher probability of photon absorption. 

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