Tosyl group, cleavage

Reduction of Sulfonamides Cyclization Promoted by Af-Tosyl Group Cleavage... 

The mitomycins (191) have attracted much attention as a result of their interesting structure and potent anticancer properties [43]. One approach to these materials is illustrated in Eq. 36 [44]. A key intermediate in the implementation of this plan is azocinone (193), a substance that proved accessible in high yield via the novel mediated A-tosyl group cleavage-cyclization-fragmentation of 194. Here, ascorbic acid behaves as a proton donor and a reductant in combination with anthracene (Scheme 17). 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The tosyl group has also been removed by reductive cleavage with Na/NH3 (65-73% yield), Na/naphthalene (50-87% yield),and Na(Hg)/MeOH (96.7% yield)."... 

In general, the benzenesulfonyl group is somewhat more reactive than the tosyl group, in both its formation and ease of cleavage. 

Replacement of the tosylate group in 35 with a saturated butyl chain is achieved with an excess of lithium di-n-butylcuprate and, after hydrolytic cleavage of the isopropylidene and ethoxyethyl (EE) protecting groups, lactone 23 is obtained in an overall yield of... 

The last step is simply cleavage of the tosyl group. 

The RRM with [Ru-1] gave compound 68, which has the same configuration at C2 and C8 as (-)-halosaline. Desilylation, hydrogenation and cleavage of the tosyl group gave (-)-halosaline in a 40% yield from acetate 66 (Scheme 21). 

The tosyl group has been used for protection of side-chain amino as well as of a-amino groups (see Section 2.1.1.5). The resulting tosylamides are very stable functionalities, resistant to acid, base, and nucleophiles. They are usually prepared by reacting an amine with tosyl chloride in the presence of base. Traditional removal requires use of sodium in liquid ammonia, which can lead to unwanted side reactions. The photochemical electron transfer reaction discussed above allows for the mild removal of the tosyl protection. No cleavage of peptide bonds or Boc groups has been observed under these conditions. 

Bis(tosyloxy)benzene derivatives may be selectively cleaved a tosyl group ortho or para to an electron-withdrawing group (e.g., an ester group) is cleaved preferentially to one in the meta position, whereas in derivatives of anisol, cleavage of the tosyl group meta to the methoxy group is preferred [252]. 

The reduction of sulfonamides has been extensively studied in connection with the protection of amino groups [154, 246-250, 256-260] the cleavage of Tv -tosyl groups probably follows Eq. (62) ... 

N-Protective group. Tosyl chloride reacts with amino acids in alkaline solution to give N-tosylamino acids. The protective group is removed by reductive cleavage with sodium in liquid ammonia. The tosyl group is particularly useful for protection of the w-amino groups of lysine and ornithin peptides. 

In general, the benzenesulfonyl group is somewhat more reactive than the tosyl group, both in its formation and its ease of cleavage. On the whole, these are extremely robust protective groups and often require very harsh conditions for removal. The exception to this is for aromatic amines vida infra. The benzenesulfonyl group also has the advantage that the sulfonyl chloride is a liquid, which is much easier to handle on scale. 

Mg, MeOH, 8-75% yield. These conditions were used to cleave a tosyl group from an aziridine, a special case over normal amines. The reaction should work better with a benzenesulfonamide. This method is very good for carbamate and amide protected sulfonamides, but does not work with normal aliphatic amines. Since sulfonamides are readily acylated, this constitutes a relatively mild method for the cleavage of sulfonamides. Lactones and esters are compatible with this methodology. 

The lithium aluminum hydride reductive method to cleave tosyl groups is also convenient and will likewise reduce any carbonyl groups present in the macrocycle at the same time. Isolation of the products of this cleavage reaction is relatively easy. 

Arenesulfonyl derivatives are frequently employed in organic synthesis to activate hydroxy groups for nucleophilic substitution reactions or to protect primary and secondary amines. The PET cleavage of tosyl groups is closely related to reductions... 

A relatively concise synthesis of a compactin lactone (99) derivative makes use of 590 as the source of chirality (Scheme 93) [142]. Addition of ethyl acetate enolate to 590 produces a 1 1 mixture of aldols 633 in 58% yield. After silylation of the hydroxyl group, cleavage of the acetonide furnishes lactone 635 as a crystalline solid. Tosylation of the primary alcohol and separation of the isomers furnishes 636 (47% yield) and 637 (44% yield). The desired isomer 636 is a suitably protected and functionalized version of compactin lactone . 

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