Unprotected hydroxyl

Generally, the successful conversion of 20-ketopregnanes to 17-hydroxy-androstanes with peracids requires the protection of other ketones, with the exception of those at C-11, and possibly C-12 e.g., as ketals or cyanohydrins ) and isolated double bonds e.g., as dibromides). Unprotected hydroxyl groups do not interfere, except, as expected, a 17a-hydroxy-20-keto steroid is oxidized to the 17-ketone. The use of nitrate esters to protect... 

No or little side reactions either with the unprotected hydroxy group present in the phenylamines, or with the unprotected hydroxyl group present in the carboxylic acids are observed. The catalytic amidation of unprotected a-hydroxycarboxylic acids also proceeds well under similar conditions. 

In order to explore the generality of this new domino reaction the conversion of various primary amines with 2-341 and the cyclohexane analogue was investigated (Scheme 2.81). For example, the reaction proceeds with high yields when benzyl- or (2-phenylethyl)amine are used (entries 1 and 2). In comparison, sterically more hindered amines such as 2-butylamine produced much lower yield (entry 4) Furthermore, the reaction tolerates other functional groups, such as an unprotected hydroxyl group (entry 5), and variation of the enone ring size is possible (entries 6 and 7). More recent results have revealed that the addition of Sn(OTf)2 or In(OTf)2 makes the transformation more reliable. 

A synthesis of (-)-4a,5-dihydrostreptazolin was accomplished in a similar manner only a reductive palladium-catalyzed cyclization was utilized.104 The hydride source was polymethylhydroxysilane (PMHS), and the unprotected hydroxyl group of 174 (Equation (89)) had an accelerating effect, since the reaction was completed in minutes instead of hours, as in the example above. 

Subsequent deprotection of the desired z-isomer (39a) afforded desoxye-pothilone B (epothilone D), which had previously been epoxidized to epothilone B (5) [14b]. Alcohol 37 did not undergo RCM using 1 or 3 [14b]. The failure of initiator (1) to effect this transformation may be due to its incompatibility with unprotected hydroxyl groups [19]. 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

Amides and carbaminates are a further class of substrates [255, 274-278], Compound 114 shows a substrate with an unprotected hydroxyl group and an aryl iodide [279] (Scheme 1.50), 116 an aryl iodide and the competition of an amide with an amine, yielding a 2.5 1 mixture of amide isomers favoring the (Z)-amide configuration depicted in 117 [280] (Scheme 1.51). 

For the mono-C-glycosylphenol, the commercially available 2,4,6-trihydroxyacetophe-none was chosen and selectively methylated at C-2 and C-4. The partially protected phenol was glycosylated with the C-benzyl-protected glucosyl trichloroacetimidate in the presence of trimethylsilyl triflate as promoter to give directly a C-(benzyl protected)glycosylphenol. The unprotected hydroxyl group of this compound was converted with benzoyl chloride into a fully protected C-glycoside phenol. Treatment of the benzoate derivative with sodium hydroxide in... 

If amino acids with unprotected hydroxyl groups are incorporated, it is better to use carbodiimide activation (such as DIC/HOBt-activation) instead of more reactive procedures to avoid acylation of the hydroxyl-groups. 

In the event, Mitsunobu-type displacement of the unprotected hydroxyl of 24 delivered the iodinated sugar 25, which was then elaborated into acyclic iodohexenitol 26 via ring opening using activated zinc in refluxing ethanol, followed by reduction, tosylation and iodination. The pivotal radical cyclization/oxygenation of 26 was finally carried out in the presence of a catalytic amount of cobalt(salen) complex in air. This... 

Dimethyldiacetoxysilane can also be used as a reagent for the preparation of siliconides, as it reacts simultaneously with other unprotected hydroxyl groups and blocks them. 

The isothiocyanate 10, having an unprotected hydroxyl group at C-6, was prepared from the anhydro sugar 8. Benzylation of 8 produced 9, which was treated with (Bu4N)NCS and BF3-OEt2 to give 10 in 50% yield (Scheme 3).49... 

Acylated carbohydrate derivatives. Treatment of glycosides with polymer-supported boronic acid (1) with azeotropic removal of water aSords the more stable five- or six-membered boronate. The unprotected hydroxyl groups of the protected glycosides can be acylated, often in yields higher than those realized by classical methods. 

The protection of sterically demanding secondary alcohols as TBS-ethers requires the use of the more reactive TBSOTf instead of TBSCl. The procedure used here is widely applied. As hydroxy diol 42 contains three unprotected hydroxyl groups, one primary and two secondary, the formation of three TBS-ether moieties is performed in a one-pot reaction. 

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