Iron‐Catalyzed Coupling of Propargyl Bromides and Alkyl Grignard Reagents

Abstract

An iron‐catalyzed Kumada‐type cross‐coupling reaction of propargyl halides with alkylmagnesium reagents is described. The reaction is fast, takes place in smooth conditions, tolerates several functional groups that would be able to react with the Grignard reagent, and may afford either allene or propargyl coupling derivatives. Factors involved in the observed regioselectivity have been studied.

Divergent Mechanisms of the Banert Cascade with Propargyl Azides

“…Purification by column chromatography (0–40% EtOAc/hexanes) afforded alcohol 2a (850 mg, 74%) as a yellow oil. Characterization data for this compound has been reported . An image of the 1 H NMR spectrum is supplied in the Supporting Information.…”

“…The product (573 mg, 67%) was isolated as a pale yellow solid. Characterization data for this compound has been reported . An image of the 1 H NMR spectrum is supplied in the Supporting Information.…”

“…Characterization data for this compound has been reported. 63 An image of the 1 H NMR spectrum is supplied in the Supporting Information.…”

Propargyl Radicals in Organic Synthesis

“…Conversely, the Cárdenas group has demonstrated the low‐temperature coupling of alkylmagnesium halides ( 156 ) mediated by Fe(OAc) 2 and IMes ⋅ HCl, affording propargylation ( 157 ) and allenylation ( 158 ) in moderate yields (Scheme 42). [66a] Their initial mechanistic proposal also included propargyl radicals, based on the observation of homocoupling side products and on earlier alkyl‐alkyl couplings involving radical clock experiments, [66b] Subsequent work with arylmagnesium halide nucleophiles and enantiomerically enriched substrates [66c] have led the Cárdenas group to conclude that propargyl radicals are most likely not involved in the process. It is clear that a close competition between radical and non‐radical pathways is possible for iron catalyzed propargylations.…”

Metal-Free Hydroamination of Alkynes: A Mild and Concise Synthesis of Thiazolo[3,2-a]indoles and their Cytotoxic Activity

“…reported procedure, propargylation of thiones 6 was attempted and achieved in aqueous K 2 CO 3 medium using commercially available propargyl halides 10 in near quantitative yields, without compromising any reaction efficacy, under the new and simplified conditions. Additional propargyl halides 1-(3-bromoprop-1-yn-1-yl)-4-methoxybenzene and 1-(3-bromoprop-1-yn-1-yl)-4-nitrobenzene, derivatives with an electron-donating (OCH 3 ) and electronwithdrawing (NO 2 ) group, respectively, were synthesized following a literature procedure 28 to produce the corresponding sulfides. The p-methoxy-substituted product 11q was obtained in high yield while the p-nitro-substituted propargyl halide failed to undergo the substitution reaction under these conditions.…”