Divergent reactivities of 2-pyridyl sulfonate esters. Exceptionally mild access to alkyl bromides and 2-substituted pyridines

Abstract

A series of 2- and 3-pyridyl sulfonate and tosylate esters of primary and secondary alcohols were synthesized and evaluated in the bromination reaction with MgBr2·Et2O. The greater coordinating ability of the 2-pyridyl sulfonate esters accounted for its observed superior reactivity and selectivity. Reaction of neopentyl and phenyl 2-pyridyl sulfonates with a variety of aryl and heteroaryl Li reagents led to 2-substituted pyridines at temperatures as low as −78 °C via an SNAr process. Mechanistic considerations are discussed.

Halogenation Reactions of Alkyl Alcohols Employing Methyl Grignard Reagents

“…We set out to distinguish whether the Grignard reagent itself, or MgI 2 , formed in situ via competitive Wurtz coupling during Grignard formation and the Schlenk equilibrium, serves as the iodide source for this reaction. ,, To investigate the source of iodide, we subjected mesylate 1 to reactions with MgI 2 . We observed a decrease in yield compared to the standard reaction conditions employing the Grignard reagent (c.f.…”

“…Alkyl halides are versatile reagents in synthetic chemistry, most commonly employed in the alkylation of enolates and as starting materials for XC and XEC reactions, as well as the synthesis of Wittig and alkylmetal reagents. − Therefore, we sought to develop new halogenation reactions that start from alkyl alcohols. Numerous methods have been established to transform alcohols into alkyl halides, in general, by coupling alcohol activation with a nucleophilic halide source. , For example, the Appel reaction, which converts alcohols to iodides with PPh 3 and I 2 , is a robust method employed by synthetic organic chemists . In this manuscript, we report a halogenation reaction with methylmagnesium iodide and bromide for the rapid synthesis of alkyl iodides and bromides (Scheme d).…”

“…Numerous methods have been established to transform alcohols into alkyl halides, in general, by coupling alcohol activation with a nucleophilic halide source. 14 , 15 For example, the Appel reaction, which converts alcohols to iodides with PPh 3 and I 2 , is a robust method employed by synthetic organic chemists. 16 In this manuscript, we report a halogenation reaction with methylmagnesium iodide and bromide for the rapid synthesis of alkyl iodides and bromides ( Scheme 1 d).…”