The synthesis and unique reactivity of a series of arylsulfonate-based nucleophile assisting leaving groups (NALG) containing oligomeric ether units (including crown ethers) attached to the arylsulfonyl ring in the ortho orientation are described. The reactions of a variety of these ethercontaining alkyl sulfonates with metal halides proceeded at substantially greater rates than electronically similar sulfonates. These ether-containing leaving groups also displayed marked selectivity for lithium halides relative to the corresponding sodium and potassium salts in nucleophilic displacement reactions.

A series of arylsulfonate nucleophile assisting leaving groups (NALGs) were prepared in which the metal chelating unit is attached to the aryl ring via an ether linker. These NALGs exhibited significant rate enhancements in halogenation reactions using metal halides. Studies with a NALG containing a macrocyclic ether unit suggest that rate enhancements of these nucleophilic halogenation reactions are facilitated by stabilization of charge in the transition state rather than through strong precomplexation with metal cation. In several cases, a primary substrate containing one of the new leaving groups rivaled or surpassed the reactivity of triflates when exposed to nucleophile but was otherwise highly stable and isolable. These and previously disclosed chelating leaving groups were used in 18 F-fluorination reactions using no-carrier-added [ 18 F]fluoride ion (t 1/2 = 109.7 min, β + = 97%) in CH 3 CN. Under microwave irradiation and without the assistance of a cryptand, such as K2.2.2, primary substrates with select NALGs led to a substantial improvement (2 to 3 fold) in radiofluorination yields over traditional leaving groups.

Arylsulfonates of hindered secondary alcohols are converted to the corresponding alkyl chlorides very rapidly and in good yields in the presence of titanium tetrachloride at low temperatures. These reactions proceed with exclusive retention of configuration.We are interested in the development of highly efficient leaving groups containing chelating units capable of attracting incoming nucleophiles. We envision that electrophiles containing sulfonate leaving groups could be rendered more reactive by modifying them to contain a metal chelating moiety. 1 In this chelated form, the nucleophilic portion of a salt or Lewis acid is localized near the electrophilic center thus decreasing the entropic barrier relative to intermolecular reactions. The chelated metal would also be expected to stabilize the developing negative charge on the oxygens of the sulfonate leaving group in the transition state. 2 We have recently demonstrated that metal halides react at greatly accelerated rates with arylsulfonatebased nucleophile assisting leaving groups (NALGs) that contain a polyether unit (including macrocyclic) attached to the aryl ring ortho to the sulphonate. 3 In an attempt to further explore the generality of the NALG technology, we discovered a highly efficient method to convert NALG sulfonates of hindered alcohols to the corresponding chlorides using TiCl 4 at low temperatures.While a related chlorination procedure with alkyl tosylates has been reported, 4 in this note, we demonstrate, for the first time, the stereospecificity and utility of the sulfonate/TiCl 4 technique in the synthesis of a variety of alkyl chlorides. 5 A series of alcohols were reacted with aryl sulfonyl chlorides containing a diethylene glycol moiety to give sulfonate esters 1 (Table 1). In general, the treatment of sulfonate esters 1 with TiCl 4 in methylene chloride at −78 °C led to high yields of the corresponding alkyl chlorides. In each case, the reaction was complete in less than 2 minutes. With 1,3-diphenyl-2-propanol, we have observed that its NALG and tosyl esters primarily give the elimination product in the With sulfonates of chiral secondary alcohols (Table 1, entries 2-4), the chloride products were obtained as single diastereomers with complete retention of configuration. 8 Thus, the NALG sulfonates of highly hindered menthol and isomenthol were both converted to the corresponding chlorides of the same configuration in excellent yields by exposure to TiCl 4 for two minutes. Similarly, the NALG sulfonate of cholesterol (entry 4) was converted to the corresponding chloride almost instantaneously at −78 °C. Proton NMR confirms the formation of one stereoisomer with retention of configurationIn the 2-adamantyl system, we observed a 90% conversion to the chloride with no side product arising from rearrangement of the adamantine nucleus (entry 5). 9 Backside nucleophilic displacement of 2-adamantyl sulfonate is essentially precluded due to steric crowding, 10 thus the chlorination reaction likely proceeds via a front-side S N i-type ...

[reaction: see text] A study of the role of base in the isomerization of manganese-coordinated conjugated alkynyl carbonyls to the corresponding allenyl carbonyls is described. The use of phosphine additives indicates that manganese requires a ligand prior to isomerization with amine bases. A series of amine bases were also examined for their efficacy in this isomerization reaction revealing a strong dependence on pK(a). By contrast, potassium tert-butoxide led to rapid isomerization in the absence of added manganese ligand.

Supporting Information Table of ContentsCopies of NMR spectra for: Sulfonate intermediates (NALGs) of alcohol substrates given in Table 1Chloride products shown in Table 1 (entries 1 -6):(S8 -S13)Chloride products shown in Scheme 1: (S14 -S15)