Regioselective tosylation

Preparation of cyclodextrin derivatives substitution at a secondary hydroxyl group of the cyclodextrin annulus. Murakami and cowor-kers described a new and convenient method for the regioselective tosylation of the 2-hydroxyl groups of alpha, beta, and gamma cyclodextrin by means of a cyclic tin intermediate. The method is based on the reaction of dibutyltin oxide with 1,2-diols to form five-membered dibutyl-stannylidene derivatives. Useful yields of the 2-6>-tosyl derivatives of the cyclodextrins were obtained. 

DMF in the dark at room temperature for many hours [40-43] (for this compound, a two-step procedure based on regioselective tosylation of OH-6 followed by SN2 displacement with sodium benzoxide proved more practical [44, 45]). Barium carbonate [46] or sodium hydroxide [43] as a base have also been used. Without protection ofOH-3, the order of reactivity seems to be OH-6 > OH-3 > OH-4 40% of 3,6-di-O-benzyl and 20% of 3,4,6-tri-O-benzyl derivative have been isolated after 4 days stirring with 2 molar equiv. of benzyl bromide [41], Ultrasonication increases the rate of this benzylation substantially [47]. 

Further processing of 57 towards the ketone 60 is readily effected by highly regioselective tosylation of the primary hydroxyl group (66), hydride reduction 58 -> 59, and oxidation with pyridinium chlorochromate (PCC) on aluminum oxide to afford 60 in a yield of 70 % over the three steps (63). Due to the now practical accessibility of these furanoid building blocks supplementary modifications, that have already been performed, become preparatively relevant, e. g. the conversion of tosylate 58 into the 5,6-epoxide (66), C-extensions (63, 66), shortening of the carbon chain via periodation of 57 (63), and transformation of the respective products into acyclic derivatives by acid hydrolysis of the 1,2-0-isopropylidene group (63, 66). 

Fortunately, we were able to regioselectively tosylate the primary hydroxyl in 42 with p-toluenesulfonyl chloride, triethylamine, and DMAP in dichloromethane at room temperature over 14 h tosylate 63 was isolated in 85% yield. The subsequent nucleophilic displacement with iodide also proceeded satisfactorily delivering the 6-deoxy-6-iodopyranoside 41 in 92% yield. With the desired 6-iodo sugar successfully prepared, we examined its Vasella reductive ring cleavage with Zn dust (size <10 pm) in a 4 1 THF / water mixture at reflux (Scheme 13). A single product was formed according to TLC analysis. However, our H-NMR examination of this product revealed that it was in fact a 1 1 mixture of the two anomeric hemiacetals 40a and 40P formed in 80% yield. 

Regioselective tosylation of the primary free alcoholic function of 113, followed by reductive removal of the tosylate, Swem oxidation of secondary free alcoholic function and reductive cleavage of the ether bond of the tetrahydrofiirane ring, gave the required norbomanone 110. 

The regioselective tosylation of various cyclodextrins has been reported. The two major products resulting from the tosylation of /3-cyclodextrin are heptakis(6-0-(p-tosyl))- 8-cyclodextrin... 

Sodium hydride in DMF followed by tosyl chloride has been used for the regioselective tosylation of myo-inositol orthoesters.Very selective mono- and ditosylation could be achieved depending on the reaction conditions. The tosyl groups were used as protecting groups and later removed using Mg(0) in methanol. 

Regioselective lithiation of the formamidine 365 followed by tosylation afforded the corresponding 7-sulfone 367 which upon reaction with... 

Recent progress of basic and application studies in chitin chemistry was reviewed by Kurita (2001) with emphasis on the controlled modification reactions for the preparation of chitin derivatives. The reactions discussed include hydrolysis of main chain, deacetylation, acylation, M-phthaloylation, tosylation, alkylation, Schiff base formation, reductive alkylation, 0-carboxymethylation, N-carboxyalkylation, silylation, and graft copolymerization. For conducting modification reactions in a facile and controlled manner, some soluble chitin derivatives are convenient. Among soluble precursors, N-phthaloyl chitosan is particularly useful and made possible a series of regioselective and quantitative substitutions that was otherwise difficult. One of the important achievements based on this organosoluble precursor is the synthesis of nonnatural branched polysaccharides that have sugar branches at a specific site of the linear chitin or chitosan backbone [89]. 

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

Alkynes react with electrophilic selenium reagents such as phenylselenenyl tosylate.155 The reaction occurs with anti stereoselectivity. Aryl-substituted alkynes are regioselective, but alkyl-substituted alkynes are not. 

Ethenylcyclopropyl tosylates 131 and 2-cyclopropylideneethyl acetates 133, readily available from the cyclopropanone hemiacetals 130, undergo the re-gioselective Pd(0)-catalyzed nucleophilic substitution via the unsymmetrical 1,1-dimethylene-jr-allyl complexes. For example, reduction with sodium formate affords a useful route from 131 to the strained methylenecyclopropane derivatives 132. The regioselective attack of the hydride is caused by the sterically... 

Scheme 8.13 and Eqs. 8.6-8.10 reveal that lithiated methoxyallene 42 is sufficiently reactive towards a variety of electrophiles such as alkyl halides [44, 45], ethylene oxide [12c], tosylated aziridine 45 [46], dimethyl disulfide [12b], trialkylstannyl and trialkylsilyl chlorides [47, 48] and iodine [49]. These substitution reactions proceed with excellent regioselectivity and the corresponding a-functionalized products are obtained in good to high yields. An exceptional case was found by treatment of 42 with a guanidinium salt, which led to a 60 40 mixture of a- and y-adducts 50 and 51 (Eq. 8.11) [50],... 

Sulfonamides are suitable pronucleophiles, as was first established with N-tosyl-amines [59]. Particularly good results were achieved with L2 as ligand and activa-hon of the catalyst with TBD (Scheme 9.26) for example, the regioselectivity of b/l = 98 2 and an ee-value of98% were obtained in the reaction of LiN(CH2Ph)p-Ts with cinnamyl carbonate. With a substrate containing a sphsubstituent, however,... 

Additionally, Wu and co-workers have shown regioselective ring-opening of aziridines with acid anhydrides mediated by imidiazolinylidene 3 [157]. This pathway requires the use of an electron withdrawing tosylated aziridine 310 in order for the reaction to proceed. The mild reaction conditions allow for a variety of products to be formed in high yields (Table 25). 

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