Mesyl with phenols

Alkanesulfonyl chlorides can also react by an initial elimination in water, mesyl chloride hydrolyses below pH 6.7 by an S 2 reaction of water at sulfur, between pH 6.7 an 11.8 by capture of the sulfene by water and above pH 11.8 by capture of the sulfene with hydroxide ion. An extended study of mesylations of phenols catalysed by various pyridines revealed a competition between the sulfene pathway and a general base-catalysed attack of the phenol, which was dependent on the pAa of both phenol and pyridine, with no mention of an A-mesylpyridinium ion. However, formation of an A-triflylpyr-idinium ion occurs immediately pyridine and triffic anhydride are mixed and this is probably the triflating species. Reaction via an A-sulfonyl quaternary ammonium ion therefore becomes important with more basic amines and more electrophilic sulfonylating reagents. 

Utilizing similar conditions as Ackermann. Ackermann [153] also showed the C-H arylation of azine N-oxides with aryl tosylates and mesylates with their own protocol (but changed the base from K2CO3 to CsF). Very recently, Itami [154] discovered the first nickel-catalyzed C-H/C-O coupling between 1,3-azoles and various phenol derivatives such as aryl pivalates, carbamates, sulfamates, mesylates, and tosylates. Surprisingly, these reactions only proceeded when 1,2-bis(dicydohexylphosphino)ethane (108 dcype) was used as Hgand (Scheme 17.30). 

More recently, Itami and coworkers described a new catalyst system for the coupling of phenol derivatives 26 (pivalates, carbamates, carbonates, sulfamates, triflates, tosylates, and mesylates) with azoles 25 in the presence of a Ni(cod)2. dcype catalyst in generally excellent yields (80%-99%). Solvents used were dioxan, toluene, and DMF, compatible bases were caesium carbonate, potassium phosphate, and lithium t-butoxide, and reactions were generally run at 120°C (Scheme 5.8, Table 5.6)." Monocylic azoles behaved in a similar fashion to afford 28, 29, and 30 in good yield. 

Itami et al. observed that an aryl ester could replace an aryl halide in their azole arylation protocol such a finding led to the first method for Ar-H/Ar-0 couplings and dramatically increased its synthetic utility simply due to the availability of phenols. The Ni(cod)2/dcype catalyst system was active for the coupling of azoles 152 with phenol derivatives such as carbamates, carbonates, mesylates, triflates, and tosylates to afford 2-arylazole products 153A-D in high yields (Scheme 10.53). ... 

Alkylation of the monobenzyl ether of hydroquinone 34 with mesylate 35, gives ether 36. Hydrogenolytic removal of the benzyl group gives phenol 37. This affords cicloprolol (38) when subjected to the standard alkylation scheme 17]. In much the same vein, alkylation of g-hydroxy-phenylethanol 39, obtainable from the corresponding phenylacetic acid, with epichlorohydrin... 

A departure from the catechol pattern of the natural neurotransmitters was achieved following application of the fact that arylsulfonamido hydrogens are nearly as acidic as phenolic OH groups. Nitration of p-benzyloxyacetophenone gave 18 which was reduced to 19 with Raney nickel and hydrazine, and in turn reacted with mesyl chloride to give sulfonamide 20. Methanesulfonate 20 was then transformed to soterenol (21), a clinically useful bronchodilator, in the... 

In this route a dihydroisoquinoline (58) is N alkylated with a highly functionalized o -bromoacetophenone (59) to give a quaternary salt (60), which is treated with base and cyclizes to a pyrroloisoquinoline (60). The pyrrole nucleus is then formylated under Vilsmeier-Haack conditions at position 5 and a proximate mesylated phenolic group is deprotected with base to yield a pen-tasubstituted pyrrole (61). Subsequent oxidative cyclization of this formylpyr-role produces the 5-lactone portion of lamellarin G trimethyl ether (36). This sequence allows for rapid and efficient analog synthesis as well as the synthesis of the natural product. 

The synthesis of organozinc compounds by electrochemical processes from either low reactive halogenated substrates (alkyl chlorides) or pseudo-halogenated substrates (phenol derivatives, mesylates, triflates etc.) remains an important challenge. Indeed, as mentioned above, the use of electrolytic zinc prepared from the reduction of a metal halide or from zinc(II) ions does not appear to be a convenient method. However, recent work reported by Tokuda and coworkers would suggest that the electroreduction of a zinc(II) species in the presence of naphthalene leads to the formation of a very active zinc capable of reacting even with low reactive substrates (equation 23)11. 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

The phenolic OH group can be removed by Pd-catalysed hydrogenolysis of its triflate 522 with triethylammonium formate [261]. Naphthol can be converted to naphthalene by the hydrogenolysis of its triflate. The Ni-catalysed reduction of aryl mesylates 523 is possible using MeOH and Zn as the hydrogen donor [262]. Smooth removal of phenol groups as triflates and mesylates is not possible by any other means. 

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