Axial hydroxyls

A similar intramolecular oxidation, but for the methyl groups C-18 and C-19 was introduced by D.H.R. Barton (1979). Axial hydroxyl groups are converted to esters of nitrous or hypochlorous acid and irradiated. Oxyl radicals are liberated and selectively attack the neighboring axial methyl groups. Reactions of the methylene radicals formed with nitrosyl or chlorine radicals yield oximes or chlorides. 

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

The stereoselective reactions in Scheme 2.10 include one example that is completely stereoselective (entry 3), one that is highly stereoselective (entry 6), and others in which the stereoselectivity is modest to low (entries 1,2,4, 5, and 7). The addition of formic acid to norbomene (entry 3) produces only the exo ester. Reduction of 4-r-butylcyclohexanone (entry 6) is typical of the reduction of unhindered cyclohexanones in that the major diastereomer produced has an equatorial hydroxyl group. Certain other reducing agents, particularly sterically bulky ones, exhibit the opposite stereoselectivity and favor the formation of the diastereomer having an axial hydroxyl groi. The alkylation of 4-t-butylpiperidine with benzyl chloride (entry 7) provides only a slight excess of one diastereomer over the other. 

This indirect method of selective benzoylation at C-4 is of special interest in the galacto series (47). Reaction of methyl 4,6-O-benzylidene-a-D-galactopyranoside 97 with NBS afforded the corresponding 6-bromo-4-benzoate (98) in over 90% yield. The axial hydroxyl group at C-4... 

Fig. 18.—Antiparallel packing arrangement of 2-fold poly(ManA) (15) helices, (a) Stereo view of two unit cells roughly normal to the hoplane. The helix at the center (filled bonds) is antiparallel to the two in the back (open bonds). Intrachain hydrogen bonds stabilize each helix. Association of helices through direct hydrogen bonds involve the carboxylate groups for parallel chains, but involve the axial hydroxyl groups for antiparallel chains, (b) A view of the unit-cell contents down the t-axis highlights the interactions between the helices.

A number of effects of conformation have been reported Crowding of the hydroxyl group results in faster oxidation and alcohols with axial hydroxyl groups are oxidised more readily than the equatorial isomers, e.g. cis-4-tert-butylcyclohexanol is oxidised about three times faster than the trans isomer at 25 °C. 

Figure 9.9 Conformation of D-glucose. The pyranoses adopt a non-planar ring conformation and the chair form with the highest number of equatorial rather than axial hydroxyl groups is favoured. It should be noted that a-D-glucopyranose, in contrast to /3-D-glucopyranose, has an axial hydroxyl group.

Optically pure P-ethanolamines react with dichlorocarbene under phase-transfer catalytic conditions to produce epoxides of high configurational retention [30]. Initial reaction occurs at the tertiary nitrogen centre (Scheme 7.29) with subsequent cleavage of the C-N bond. The reaction is configurationally controlled, as shown by the reaction of the conformationally rigid cyclic systems epoxide formation occurs with the equatorial hydroxyl system (50%), but not with the axial hydroxyl compound. 

The isolation of vincadioline (31) from C. roseus has been reported (96) only in the patent literature. The C-NMR data of 31 (76) (Table X) support the 3 -hydroxyvinblastine structure. Both C-2 and C-4 absorptions shifted downfield compared to the corresponding values of vinblastine (1). In addition, upfield shifts of C-1 and C-19 were observed as a result of the y-effect of the new oxygen atom at C-3. The resonance of C-19 shifted 4.8 ppm, a magnitude consistent with an axial hydroxyl at C-3. Such circumstances should lead to a nearly equal shielding effect at C-5, as is indeed observed. These data allow the assignment of the a relative steric position of the C-3 hydroxyl group. 

An acidic medium favors alcohols with an axial hydroxyl an alkaline medium favors alcohols with an equatorial hydroxyl [848],... 

For example, reduction of 2-alkylcycloalkanones with lithium aluminum hydride in tetrahydrofuran gave the following percentage proportions of the less stable cu-2-alkylalkanol (with axial hydroxyl) 2-methylcyclobutanol 25%, 2-methylcyclopentanol 21%, 2-methylcyclohexanol 25%, 2-methylcy-cloheptanol 73%, and 2-methylcyclooctanol 73% (the balance to 100% being the other, trans, isomer) [837. ... 

Different stereoselectivities caused by solvent effects are demonstrated in the reduction of dihydroisophorone (3,3,5-trimethylcyclohexanone) with sodium borohydride which gave less stable tranj-3,3,5-trimethylcyclohexanol (with axial hydroxyl) by reduction in anhydrous isopropyl alcohol (55-56%), in anhydrous tert-butyl alcohol (55%), in 65% aqeuous isopropyl alcohol (59.5%), in anhydrous ethanol (67%), and in 71% aqueous methanol (73%) (the balance to 100% being the more stable cis isomer with equatorial hydroxyl) [849]. 

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