Selective monotosylation

In similar vein, Richardson, Hough, and Monroe devised conditions that permitted the selective monotosylation of 4,6,4, 6 -di-0-benzylidene-a,a-trehalose at the... 

Bouzide, A. Sauve, G. Silver(I) oxide mediated highly selective monotosylation of symmetrical diols. Application to the synthesis of poly-substituted cyclic ethers. Org. Lett. 2002, 4, 2329-2332. 

Bu2SnO, toluene reflux TsCl, CHCI3, 36-99% yield. The primary alcohol of a 1,2-diol is selectively tosylated, but when hexamethylene stannylene acetals are used, selectivity is reversed and the secondary diol is preferentially tosylated. This methodhas been made catalytic in Bu2SnO to rapidly sulfonate the primary alcohol of 1,2-diols and to selectively monotosylate internal 1,2-diols. " A fluorous version of this process has been developed which allows for the simple recycling of the tin species. ... 

When the reactivity difference between the two hydroxyl functions is not sufficient to attach selectively the tosyl group on one of the alcohol substituents, recourse to triisopropylphenyl sulfonylchloride generally provides a useful solution [ 136]. This strategy has been employed in numerous cases. For example, selective monotosylation of diol 218 followed by base-catalyzed cycHzation gave the useful glyceraldehyde building block 219 [137] (Scheme 56). 

Selective monotosylations of symmetrical diols have been accomplished in good yields (75-93%) with a stoichiometric amount of tosyl chloride in the presence of Ag(I) oxide and a catalytic amount of potassium iodide. When excess Ag(I) oxide is used, polysubstituted cyclic ethers are formed in 61-88% yield. This method was also used for the synthesis of substituted crown ethers. 

We prepared the cis-isomer of 1-phenyl-l-hydroxy-2-tosyloxycyclohexane (7) of mp 109-110 °C starting from 1-phenylcyclohexene, which was converted into the corresponding cu-diol with the acid of a mixture of hydrogen peroxide and formic acid, followed by selective monotosylation. The cis configuration was sdected here in order to minimize a stereoelectronic effect of CH group leading to die enhanced elimination of the p-tosyloxy residue. 

Selective monotosylation of symmetric diols was also reported. i This technique was further applied to the s)mthesis of cyclic ethers (eq 22). This process, performed in the presence of at least 3 equiv of Ag20, was particularly favorable when steri-cally undemanding five- or six-membered rings could be formed. However, the technique was also used for the formation of the three-membered oxirane ring and of a substituted 5-0-crown ether. 

The reaction of arenesulfonyl chlorides with alcohols to yield sulfonates is relatively slow (if compared, e.g., with the formation of mesylates or sulfonamides), and treatment of diols with tosyl chloride can readily yield the statistically expected amount of monotosylated product [35, 36]. The selectivity of such reactions can sometimes be enhanced by additives such as AgO [37] or Bu2SnO [38]. Deprotonation of the diol can be used to increase its nucleophilicity and thereby reduce the reaction time (Scheme 10.9). This strategy can, however, lead to problems, because the products are sensitive toward strong bases, and may cyclize, oligomerize, or undergo elimination. 

A plethora of ligands has been reported in the literature but the most effective ones are 1,2-amino alcohols, monotosylated diamines and selected phosphine-oxazoline ligands. The active structures of the complexes reported are half-sand-... 

This amorphous alkaloid from B. microphylla (209) is cyclomicro-phylline-A 16-benzoate (CCCXXXII). In accord with this structure it yields cyclomicrophylline-A and benzoic acid on alkaline hydrolysis cyclomicrophyllidine-A monotosylate (CCCXXXIV) is identical with the compound obtained from cyclomicrophylline-A by selective tosyla-tion followed by benzoylation. The 16-position of the benzoxy group was demonstrated by oxidation of the free hydroxyl group in the monotosylate CCCXXXIII to a five-membered ketone which, in typical manner, readily eliminated dimethylamine on alumina to yield an a,jS-unsaturated ketone. On benzoylation the dihydro derivative CCCXXXV yielded the base CCCXXXVII identical with dihydrocyclomicrophyllidine-A tosylate. Dihydrocyclomicrophyllidine-A (CCCXXXVI) is a natural alkaloid isolated from B. microphylla (209). 

The diol (7.152) was produced as a mixture of diastereomers and these were separated at this stage. The two diastereomers required for further elaboration were (7.153) and (7.154) as shown in Figure 7.31. Having been isolated in pure form these were converted to their monotosylates (7.155) and (7.156), respectively. This selectivity was easy to achieve because of the greater reactivity of the secondary alcohol functions relative to the tertiary. The stage is now set for the key step of the synthesis. We will look at this for each of the isomers individually, starting with (7.155). 

Starting from 6-monotosyl CyD, many derivatives can be obtained, including aldehyde [19], iodide, chloride, azide, amino-, and alkyldiamino-CyDs. Dimeric yS-CyD receptors were synthesized from mono-6-iodo-CyD with a dithiol core, and they have potential as selective receptors of a-helical peptides [20]. Fullerene derivatives bearing a-, and y-CyD units were synthesized by the reaction of C o and peracetylated CyD 6-azides [21]. From 6-monoazide-yS-peracetylated CyD or... 

In a catalytic version, the regioselective sulfonylation of a-chelatable alcohols can be accomplished with tosyl chloride and 1 equiv of an amine in the presence of 2 mol % of Bu2Sn0.4 The reactions are generally high yielding, regioselective, and exclusive monotosylation is observed in many cases. For unsym-metrical diols, the less hindered alcohol is tosylated. The reaction rate is dependent on the solvent and the pXa of the amine. This reaction was also used for the selective tosylation of various carbohydrates and for the selective monosulfonylation of internal l,2-diols.4 ... 

Monotosylation of 1,6-anhydro /3-L-idofuranose (26) using 1.1 mol. equiv. of reagent gave 77% 5-, 6% 2-, 5% 2,5-di, and 5% 3,5-di-O-tosylates. Selective tosylation of 1,2-O-isopropylidene-Of-D-glucofuranose gave 80% 6-ester and 11% 3,6-diester whereas the selectivity is much lower with the corresponding allo-furanose, the products being around 45% 6-ester, 25% 3,6-diester, and 5% 3-ester. 

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