Tosyl chloride, alkylations with

Secondary amines, such as pyrrolidine, must be alkylated with care too polar a solvent leads to participation of a second nearby polymer-bound alkylant in the formation of a quaternary ammonium salt, along with the desired immobilized trialkyl amine. The exception, as seen above, is diisopropylamine, which refuses to displace tosylate even in the refluxing pure amine, or in hot dimethyl-formamide or other polar solvent, while metal diisopropylamide is notorious as a powerful non-nucleophilic base. However, carboxamide is not difficult to form from (carboxymethyl)polystyrene, again using toluenesulfonyl chloride as condensing agent this can then be reduced to (diisopropyl-ethylaminoethyl)polystyrene, which is of interest as a polymer-bound non-nucleophilic base. ... 

Sulphonic esters have been obtained from the sulphonyl chlorides in high yields under mild conditions for a range of alcohols and phenols [e.g. 18, 19]. Of particular value is the protection of glycosides possessing a free hydroxyl group and hydroxy-steroids, which are tosylated readily under phase-transfer conditions [20-22]. Alkyl sulphinites have been obtained in a similar manner [23]. Alternatively, preformed tetra-rt-butylammonium sulphonates or their alkali metal salts have also been alkylated with haloalkanes or alkyl fluorosulphonates [24,25]. In contrast with more classical procedures, tosylation of alcohols, which are susceptible to E/Z-isomerism, e.g. Z-alk-2-en-l-ols, occurs with retention of their stereochemistry under phase-transfer catalysis [26]. 

A rapid one-pot method for converting 1,3-diols into oxetanes by the intramolecular Williamson reaction has recently been described. The monolithium salt is generated by treatment of the diol with one equivalent of butyllithium in cold THF, followed by addition of one equivalent of tosyl chloride to give a monotosylate, which is cyclized by addition of a second equivalent of butyllithium (equation 83). Yields of 70-90% are reported for a variety of alkyl- and aryl-substituted oxetanes (81S550). Another simple method for converting 1,3-diols into oxetanes consists of converting them to cyclic carbonate esters by ester... 

Symmetrical ethers are obtained from the dehydration of two molecules of alcohol with H2SO4 (see Section 5.5.3). Alcohols react with p-toluenesul-phonyl chloride (tosyl chloride, TsCl), also commonly known as sulphonyl chloride, in pyridine or EtsN to yield alkyl tosylates (see Section 5.5.3). Carboxylic acids, aldehydes and ketones are prepared by the oxidation of 1° and 2° alcohols (see Sections 5.7.9 and 5.7.10). Tertiary alcohols cannot undergo oxidation, because they have no hydrogen atoms attached to the oxygen bearing carbon atom. 

Alcohols react with sulphonyl chlorides to yield sulphonate esters via Sn2 reaetions. Tosylate esters (alkyl tosylates) are formed from alcohols from the reaetion with p-toluenesulphonyl ehloride (TsCl). The reaction is most commonly carried out in the presenee of a base, e.g. pyridine or triethyla-mine (Et3N). 

Alkyl sulfonate formation. Alcohols may be converted to alkyl sulfonates, which are sulfonic acid esters. These esters are formed by reacting an alcohol with an appropriate sulfonic acid. For example, methyl tosylate, a typical sulfonate, is formed by reacting methyl alcohol with tosyl chloride. 

In an opposite manner to bases such as 1 and 2 in terms of reactivity, polymer-supported tosyl chloride equivalent 14 is able to capture alcohols as polymer-bound sulfonates 15, which are released as secondary amines, sulfides and alkylated imidazoles with primary amines, thiols and imidazoles as nucleophiles in a substitution process (Scheme 6) [24]. This technique has further been extended for the preparation of tertiary amines [25] and esters [26]. Excess of amine was scavenged by polymer-supported isocyanate 16 [27, 28] while excess of carboxylic acid was removed by treatment with aminomethylated polystyrene 17. 

Tosyl chloride 361 can be applied similarly (entry 23) [404], Here the best cobalt complex was dependent on the structure of the starting olefin. For terminal alkenes 2 mol% of the (salen)Co complex 357a was preferred. Secondary alkyl chlorides were obtained with complete regioselectivity in 73-94% yield, while the catalyst derived from Co(BF4)2 and /V-salicylidene diphenylglycinate 353 proved to be better for the hydrochlorination of 1,1-disubstituted olefins (entry 22). Tertiary alkyl chlorides 362 were obtained in 67-96% yield. The reaction conditions are mild so that acid- and base-sensitive protecting groups are compatible. 

The tosyl compound reacts with aldehydes in the presence of potassium carbonate to yield 5-alkyl- or 5-aryl-oxazoles, the intermediate dihydrooxazoles (which can be isolated) eliminating toluene-p-sulfinic acid (Scheme 30). Use of acyl chlorides in place of aldehydes leads to 4-tosyloxazoles (288). Furthermore, alkylation of tosylmethyl isocyanide with an alkyl halide RfX, followed by treatment with an aldehyde R2CHO, yields a 4,5-disubstituted oxazole (289). A related reaction is that of A-tosylmethyl-iV -tritylcarbodiimide with aromatic aldehydes under phase-transfer catalysis to yield 2-tritylaminooxazoles which are readily converted into 2-amino-5-aryloxazoles (equation 117) (81JOC2069). 

Alcohols react with p-toluenesulfonyl chloride (tosyl chloride, jo-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.2). Only the 0-H bond of the alcohol is broken in this reaction the C-O bond remains intact, and no change of configuration occurs if the oxygen is attached to a chirality center. The resultant alkyl tosylates behave much like alkyl halides, undergoing both S>jl and 8 2 substitution reactions. 

Tosylate esters may be prepared in the absence of pyridine as solvent by converting the hydroxyl group to a lithium salt by addition of methyl or butyllithium. The resultant lithium alkoxide is then treated with tosyl chloride. This approach is recommended for the preparation of tosylates from very sensitive alcohols, provided that they do not contain other functional groups that react with the alkyl lithium reagents. 

A general method fen the synthesis of alkyl iodides is the reaction of tosylates or methanesulfonates with sodium iodide in acetone or magnesium iodide in diethyl ether (equation 30). The reaction is not always a clean Sn2 process. Stereoselectively deuterated neopentyl tosylate, for example, gives with Nal in HMPA only low yields (34%) of the racemic iodide (equation 31). This is in contrast to analogous reactions with bromide and chloride (see Sections 1.7.3.2 and 1.7.2.2), where better yields with complete inversion are observed. 

In the laboratory of T.-L. Ho, the total synthesis of the novel marine sesquiterpene (+)-isocyanoallopupukeanane was completed." In the endgame of the synthesis, it was necessary to install the isocyano group onto the tricyclic trisubstituted alkene substrate so that it will occupy the more substituted carbon atom (according to Markovnikov s rule). The Ritter reaction was chosen to form the required carbon-nitrogen bond. The alkene substrate was dissolved in glacial acetic acid and first excess sodium cyanide followed by concentrated sulfuric acid was added at 0 °C. The reaction mixture was stirred at ambient temperature for one day and then was subjected to aqueous work-up. The product A/-alkyl formamide was subsequently dehydrated with tosyl chloride in pyridine to give rise to the desired tertiary isocyanide which indeed was identical with the natural product. 

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