Alkynyl tosylates, synthesis

Recent examples of the rearrangement or alkynylation pathway include conversions of arylethynyl- and er -butylethynyl(phenyl)iodonium tosylates 24 and 25 to alkynylphosphonates, -selenides, and -tellurides with the appropriate anion salts in DMF (Scheme 50) [145-147], and a similar synthesis of push-pull selenides and tellurides from alkynyliodonium triflates containing electron-withdrawing groups in the alkynyl moiety [148]. 

The synthesis of the first alkynyliodonium tosylates was achieved by the treatment of terminal alkynes with [hydroxy(tosyloxy)iodo]benzene (HTIB) (equation 8)8,10,11. Such reactions are generally conducted with an excess of alkyne in chloroform at reflux, although they can be carried out at room temperature, and dichloromethane can be employed as solvent. This procedure is, however, restricted to terminal alkynes in which R is either an aryl group or a bulky alkyl group. With linear alkyl groups (i.e. R = n-Pr, n-Bu, fl-C5Hn), phenyl(/ -tosyloxyvinyl)iodonium tosylates are obtained instead (equation 9)8. In some cases (R = /-Pr, /-Bu), mixtures of alkynyl- and (/ -tosyloxyvinyl)iodonium tosylates are produced8. ter -Butylacetylene appears to be the optimum substrate for this approach and has been employed with a series of [hydroxy(tosyloxy)iodo]arenes for the synthesis of various aryl(ter/-butylethynyl)iodonium tosylates (equation 10)9. 

The trans allylic alcohol needed to make this compound was made using one of the methods we introduced in Chapter 3i reduction of an alkynyl alcohol with LiAlEL]. Here is the full synthesis alkylation of an ester enolate with prenyl bromide gives a new ester, which itself is turned into an alkylating agent by reduction and tosylation. The alkyne is introduced as its lithium derivative with the alcohol protected as a THP acetal. Hydrolysis of the acetal with aqueous acid gives the hydroxy-alkyne needed for reduction to the E double bond, which is then epoxidized. 

This catalytic system was successfully applied to the alkynylation of tosyl aziridine with adjacent ether functionality this should provide a promising method for the synthesis of amino alcohols. Treatment of tosyl aziridine 81 with PhC CLi in the presence of catalytic Mc3Al in toluene at 0 °C for 5 h gave rise to the corresponding alkynylation product 82 in 66 % yield (Sch. 53), whereas reaction in the absence of Me3Al proceeded sluggishly under similar reaction conditions (7 % yield). The control experiment with simple aziridine 83, in which addition of catalytic McaAl had almost no influence on the reaction rate, supports the proposed catalytic cycle its efficacy is based on the formation of the pentacoordinate organoaluminum complex. 

Zhang, J.-L., and Chen, Z.-C., Hypervalent iodine in synthesis. Part 25. Alkynylphenyliodonium tosylates as alkynylating reagents. Direct conversion of alkynylphenyhodonium tosylates to dialkyl alkynylphosphonates with sodium dialkylphosphonates, Synth. Commun., 28, 175, 1998. 

Various flve-membered heterocycles can be prepared by inter- or intramolecular addition/cyclizations of appropriate nucleophiles with alkynyliodonium salts via alkylidene carbene intermediates [856, 978, 979]. The intermolecular variant of this cyclization has been employed in the synthesis of 3-substituted-5,6-dihydroimidazo[2,l-( ]thiazoles [997], 2-substituted imidazo[l,2-a]pyrimidines [998] and 2-substituted-imidazo[l,2-fl]pyridines [999]. In a representative example, 2-substituted imidazo[l,2-fl]pyridines 744 were synthesized in good yield by cyclocondensation of 2-aminopyridine (742) with alkynyl(phenyl)iodonium tosylates 743 under mild conditions (Scheme 3.293) [999]. The mechanism of this cyclization involves... 

A-tosylhydrazones (equation 2) [52]. The reaction can also be executed in one pot from arylhalide, aldehyde, and tosyl hydrazine. A novel 2-arylindole synthesis that was discovered by Rashinkar entails the Pd-catalyzed reaction of o-nitrobenzyl cyanides with arylboronic acids (equation 3) [53]. Tobisu and Chatani accomplished the direct Pd-catalyzed alkynylation of anihdes leading to indoles (equation 4) [54], Lee and colleagues induced nitriles into becoming indole-3-carboxylates through the Blaise reaction (equation 5) [55]. 

The alkynylation of propargyl and allenyl electrophiles gives satisfactory results for the synthesis of allenynes, as illustrated by the highly stereoselective conversion of the chiral propargyl tosylate 311 into the allenyne 312, which is the key step of a recent total synthesis of nemotin (Scheme 4.72) [225]. 

The intramolecular capture of the homoallylic 5-norbornen-2-yl cation by an alkynyl substituent, as exemplified by the sequence (443)->(444)->(445)->(446), has been used to advantage in a stereospecific synthesis of rf,/-cyclosativene (448). Treatment of the tosylate ester (443 R = Me, X = OTs), prepared in several steps from l,2-dimethylcyclopenten-3-ol, with pyridine in trifluoroethanol solution gave the vinyl ether (447) which was transformed by several more steps into (448). ... 

The alkynylation of phosphorus nucleophiles has been less investigated (Scheme 7). Ochiai and co-workers first demonstrated in 1987 that the alkynylation of triphenyl-phosphine was possible with alkynyliodonium tetrafluoroborate salts under light irradiation (Scheme 7, A) [69]. The reaction most probably involves radical intermediates. In 1992, Stang and Critell showed that light irradiation was not needed if alkynyliodonium triflates were used [70]. Later, this methodology could be extended to other triaryl- or alkyl phosphines [71, 72]. In 1990, Koser and Lodaya also reported the synthesis of alkynylphosphonates by the Arbusov reaction of alkynyliodonium tosylates with trialkyl phosphites (Scheme 7, B) [73]. Alternatively, the same compotmds can be obtained by the reaction of alkynyliodonium tosylates with sodium phosphonate salts [74]. 

Up to now, no efficient alkynylation of oxygen nucleophiles with EBX reagents has been reported. Also, in the case of nitrogen nucleophiles, alkynyUodonium salts remain the reagents of choice. Nevertheless, Cossy and co-workers reported in 2013 that the alkynylation of sulfonamides was possible with TMS-EBX 36 [157], Interestingly, no alkynylation was observed in the case of carbamates, although these substrates are readily alkynylated with alkynyliodonium salts. Selective alkynylation of the tosyl amide in the presence of a carbamate was possible. This selectivity was exploited for the synthesis of tetrahydropyrazine heterocycles. 

In 2014, Ohno and co-workers reported the synthesis of the more complex ynamides 68 based on the copper-catalyzed alkynylation of tosyl amide 66 using aryl EBX reagent 67 (Scheme 34) [158]. Interestingly, this constituted the first example of a copper-catalyzed reaction with an EBX reagent in which the alkyne group is kept in the product. Although alkynyl bromides have traditionally been used in copper catalysis for the synthesis of ynamides, they were not successful in this case. 

In ccHitrast to aIkynyliod(Miiiim salts, which have been used in organic synthesis for decades, EBX reagents have been used intensively only in the last 5 years. However, they have already made a strong impact in the synthesis of alkynes, as they allowed new transformations which were not accessible before. They were especially successful in transition metal catalysis, where they allowed the development of new C-H functionalization and domino reactions. They also demonstrated important advantages for the functionalization of acidic C-H bonds or carbon centered radicals. EBX reagents allowed new transformations with heteroatoms, such as the alkynylation of thiols, or presented distinct highly useful properties, for example in the alkynylation of tosyl amides, sulhnates, or phosphorus nucleophiles. 

Methanesulfonates. The most common use of methanesulfonyl chloride is for the synthesis of sulfonate esters from alcohols. This can be readily accomplished by treatment of an alcohol with mesyl chloride in the presence of a base (usually Triethy-lamine or Pyridine). The methanesulfonates formed are functional equivalents of halides. As such they are frequently employed as intermediates for reactions such as displacements, eliminations, reductions, and rearrangements. Selective mesylation of a vicinal diol is a common method of preparation of epoxides." Alkynyl mesylates can be used for the synthesis of trimethylsilyl allenes. Oxime mesylates undergo a Beckmann rearrangement upon treatment with a Lewis acid. Aromatic mesylates have been used as substrates for nucleophilic aromatic substitution. Mesylates are more reactive than tosylates toward nucleophilic substitution, but less reactive toward solvolysis. 

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