Tosylates formation

Alternatively, an alcohol can be made more reactive toward nucleophilic substitution by treating it with p ra-toluenesulfonyl chloride to form a tosylate. As noted on several previous occasions, tosylates are even more reactive than halides in nucleophilic substitutions. Note that tosylate formation does not change the configuration of the oxygen-bearing carbon because the C-0 bond is not broken. 

Back in Section 6-6 you were shown that two successive SN2 displacements ( double inversion ) at the same carbon atom would result in net retention of the original configuration. Could something of this sort be happening in the example given for this problem Using the hint, let us consider the implications of the fact that chloride ion is produced in the course of tosylate formation. Suppose some of this chloride ion, a nucleophile, were to react with some of the tosylate formed in the first step. This process would be an SN2 displacement, at Cl, with inversion, producing an (S) chloroalkane ... 

Recall that the goal was to arrive at aminoketone 56. The projected Mannich reaction requires that the amino group be on the concave face surface of the m-decalin ring system. Notice that the alcohol stereochemistry in 67 is set such that an 8 2 reaction at the carbinol center would establish the required stereochemistry in 56 [We will see another approach to establishing this stereochemistry shortly]. Tosylate formation followed by acetal hydrolysis provided 68, but treatment of this material with azide failed to give any of the desired 8 2 product. Treatment of 68 with methylamine, however, gave 56 in excellent yield. Given the results with azide, it is probable that this displacement occurs with intramolecular delivery the nucleophile via involvement of an N,W-acetal (69). The final Mannich reaction proceeded as anticipated to provide luciduline (55). 

The mono- and dianions of [ C2]acetylene, readily accessible by deprotonation with n-BuLi (1 equivalent) and MeLi (2.5 equivalents), respectively, can be trapped with monomeric formaldehyde to give [2,3- C2]propargyl alcohol in 40% yield and 2-[2,3- C2]butyne-l,4-diol in 72% yield. Both compounds may serve as valuable intermediates for the preparation of additional low-molecular weight building blocks and intermediates. [2,3- C2]propargyl alcohol, for example, can be reduced with aqueous CrCl2 to [2,3- C2]allyl alcohol, which was shown to be activated through tosylate formation toward nucleophilic displacement of the hydroxy function to produce radio-... 

Tosylate Formation with Inversion of Configuration. Alkyl tosylates can be formed directly from secondary alcohol functionality with retention of carbon stereochemistry by treatment withp-Toluenesulfonyl Chloride and Pyridine. However, conversion of an alcohol to the corresponding tosylate of opposite stereochemistry typically requires a minimum of three steps. For example, inversion of the stereocenter with benzoic acid under Mitsunobu reaction conditions, hydrolysis of the resulting ester, and finally conventional tosylation of the alcohol, provides an attractive route for this transformation. A similar route, the inversion of a secondary alcohol directly with p-TsOH, Diethyl Azodicarboxylate (DEAD), and Triphenylphosphine, does not produce the desired tosylate product. ... 

The desired transformation can be achieved via reduction of the carboxylic acid, followed by substitution. Direct conversion of the resultant alcohol may be accomplished using PBr3, or one can utilize a two-step method involving 1) tosylate formation using TsCl and pyridine followed by, 2) Sn2 displacement using sodium bromide in DMSO ... 

Hirschmann, F. B., and H. Hirschmann Inversions of Both Adjacent Centers in the Formolysis of a 2,2,6-Trialkylcyclohexyl Tosylate. Formation of a 13a-D-Homo Steroid. J. Organ. Chem. (USA) 38, 1270 (1973). 

C7H7CIO1S, p-CHjCjsH SOjCI. Colourless crystals, m.p. 7l°C, formed by the action of chlorosulphonic acid on toluene. Esters of toluenesulphonic acid are frequently called tosylatesand their formation tosylation. Many tosylates are easily obtained crystalline, and the reaction is thus of considerable importance. 

Diels-Alder reaction of 2-bromoacrolein and 5-[(ben2yloxy)meth5i]cyclopentadiene in the presence of 5 mol % of the catalyst (35) afforded the adduct (36) in 83—85% yield, 95 5 exo/endo ratio, and greater than 96 4 enantioselectivity. Treatment of the aldehyde (36) with aqueous hydroxylamine, led to oxime formation and bromide solvolysis. Tosylation and elimination to the cyanohydrin followed by basic hydrolysis gave (24). 

Vapour phase pyrolysis of sulfoximides (529) results in the formation of the nitriles (530) (75JCS(Pl)4l). The tosylate (273), when treated with acetic anhydride, rearranges to (531)... 

Dialkylation of an amine or sulfonamide with a 1,3-dihalide provides a further route to azetidines <79CRV33l, 64HC( 19-2)88 5). Examples of this approach are the formation of N-tosylazetidine from tosylamide and l-bromo-3-chloropropane and the formation of N-alkylazetidinyl esters (36). The latter reaction works well except for R=Me the former provides a useful route to azetidine since the tosyl group can be removed by reductive methods. 

H-Azepine, 2-methyl-1-methoxycarbonyl-rearrangement, 7, 504 1 //-Azepine, 3-methyl-1 -methoxycarbonyl-cycloaddition reactions, 7, 520 IH-Azepine, 1-phenyl-synthesis, 7, 542 1 H-Azepine, N-phthalimido-formation, 7, 508 IH-Azepine, N-sulfonyl-UV spectra, 7, 501 1 H-Azepine, tetrahydromethylene-synthesis, 7, 540 IH-Azepine, N-p-tosyl-protonation, 7, 509 synthesis, 7, 537 3H-Azepine, 3-acyl-2-alkoxy-synthesis, 7, 542-543 3H-Azepine, 3-acyl-2-methoxy-rearrangements, 7, 505 3H-Azepine, 2-alkoxy-hydrolysis, 7, 510... 

This group is prepared by the reaction of the anion of 9-hydroxyanthracene and the tosylate of an alcohol. Since the formation of this group requires an S 2 displacement on the alcohol to be protected, it is best suited for primaiy alcohols. It is cleaved by a novel singlet oxygen reaction followed by reduction of the endo-peroxide with hydrogen and Raney nickel. 

The ion-pair return phenomenon can also be demonstrated by comparing the rate of loss of enantiomeric purity of reactant with the rate of product formation. For a number of systems, including 1-aiylethyl tosylates, ftie rate of decrease of optical rotation is greater than the rate of product formation. This indicates the existence of an intermediate that can re-form racemic reactant. The solvent-separated ion pair is the most likely intermediate in the Winstein scheme to pl this role. 

An interesting feature of the synthesis is the use of allyl as a two-carbon extension unit. This has been used in the stereospecific synthesis of dicyclohexano-18-crown-6 (see Eq. 3.13) and by Cram for formation of an aldehyde unit (see Eq. 3.55). In the present case, mannitol bis-acetonide was converted into its allyl ether which was ozonized (reductive workup) to afford the bis-ethyleneoxy derivative. The latter two groups were tosylated and the derivative was allowed to react with its precursor to afford the chiral crown. The entire process is shown below in Eq. (3.59). 

The product composition from these reactions is influenced by the location of the functional group in the substrate. Olefin formation is the most common side reaction and in certain cases, especially with reductions of tosyl-hydrazones (section IV-B), it may become dominant so that the reaction can be used for the preparation of mono-labeled olefins. 

A mechanism which is consistent with the various experimental results for olefin formation involves the initial abstraction of the hydrazone proton (103->106) In this case, however, expulsion of the tosylate anion is associated with the abstraction of a second hydrogen from C-16 instead of hydride attack on the C=N bond (compare 97 98 and 106 107). Ex-... 

The displacement of homoallylic tosylates follows an entirely different course with a strong tendency for the formation of cyclo steroids. Thus, when the 3/ -tosylate of a A -steroid (187) is treated with lithium aluminum deuteride, the product consists mainly of a 3l3-di-A -steroid (188) and a 6c-dj-3,5a-cyclo steroid (189). The incorporation of deuterium at the 3 -position in (188) indicates that this reaction proceeds via a 3,5-cyclo cholesteryl cation instead of the usual S, 2 type displacement sequence. This is further substantiated by the formation of the cyclo steroid (189) in which the deuterium at C-6 is probably in the p configuration. ... 

Dimethyl sulfoxide (DMSO) has been used to effect the elimination of sulfonates at elevated temperatures (see, for example, ref. 237). Benzene-sulfonates are recommended. The elimination of a variety of sulfonates proceeds readily in this medium in the presence of potassium /-butoxide. A -Compounds have been formed at 100°, but heating is not necessary. The effects of temperature change, orientation of the hydroxy group and changes in the sulfonate employed have been examined. The principal side reaction appears to be formation of the original alcohol (uninverted), particularly with equatorial mesylates at low temperatures it is minimized with axial tosylates. 

In contrast to phosphorus esters, sulfur esters are usually cleaved at the carbon-oxygen bond with carbon-fluorine bond formation Cleavage of esteri nf methanesulfonic acid, p-toluenesidfonic acid, and especially trifluoromethane-sulfonic acid (tnflic acid) by fluoride ion is the most widely used method for the conversion of hydroxy compounds to fluoro derivatives Potassium fluoride, triethylamine trihydrofluoride, and tetrabutylammonium fluoride are common sources of the fluoride ion For the cleavage of a variety of alkyl mesylates and tosylates with potassium fluoride, polyethylene glycol 400 is a solvent of choice, the yields are limited by solvolysis of the leaving group by the solvent, but this phenomenon is controlled by bulky substituents, either in the sulfonic acid part or in the alcohol part of the ester [42] (equation 29)... 

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