Expedient Iron‐Catalyzed Coupling of Alkyl, Benzyl and Allyl Halides with Arylboronic Esters

Abstract

While attractive, the iron-catalyzed coupling of arylboron reagents with alkyl halides typically requires expensive or synthetically challenging diphosphine ligands. Herein, we show that primary and secondary alkyl bromides and chlorides, as well as benzyl and allyl halides, can be coupled with arylboronic esters, activated with alkyllithium reagents, by using very simple iron-based catalysts. The catalysts used were either adducts of inexpensive and widely available diphosphines or, in a large number of cases, simply [Fe(acac)3] with no added co-ligands. In the former case, preliminary mechanistic studies highlight the likely involvement of iron(I)-phosphine intermediates.

The Role of Low Valent Transition Metal Complexes in Homogeneous Catalysis: An EPR Investigation

“…The [Fe(Bpin)(dpbz) 2 ] complex showed poor activity as a catalyst in the coupling of alkyl halides with Li[(B 2 pin 2 ( t Bu)], suggesting that it is not an active catalyst, but rather converts in solution to an active species upon reaction with the borate ion. In a similar fashion to the inverse first-order dependence on the diphosphine concentration reported above for reactions catalyzed by [FeBr(dppe) 2 ], additional equivalents of ligand had a highly deleterious effect on the [8,9,40]. Copyright (2015) American Chemical Society reaction rate using the Li[(B 2 pin 2 ( t Bu)] ion, thereby indicating that the active species is diphosphine-free.…”

“…Indeed, dpbz and dppe complexes of iron readily form low-spin (S = ) 5-coordinate complexes of the form P 4 FeX in the presence of a range of nucleophilic substrates. With the desire to exploit more substrate and media-tolerant nucleophiles beyond aryl Grignard reagents, Bedford et al, initially explored Fe(I) complexes formed in situ during reactions catalyzed by organoboron-based nucleophiles, derived in situ from arylboron pinacol esters [40]. Using the simple Fe-based dppe or dppp (bis(diphenylphosphino)propane) catalysts, and in a number of cases even phosphine-free [Fe(acac) 3 ] systems, excellent yields (94-99 %) of organoboron-based nucleophiles coupling with primary and secondary alkyl halides were reported [40].…”

“…With the desire to exploit more substrate and media-tolerant nucleophiles beyond aryl Grignard reagents, Bedford et al, initially explored Fe(I) complexes formed in situ during reactions catalyzed by organoboron-based nucleophiles, derived in situ from arylboron pinacol esters [40]. Using the simple Fe-based dppe or dppp (bis(diphenylphosphino)propane) catalysts, and in a number of cases even phosphine-free [Fe(acac) 3 ] systems, excellent yields (94-99 %) of organoboron-based nucleophiles coupling with primary and secondary alkyl halides were reported [40]. To elucidate the mechanistic details of the reaction, EPR spectroscopic measurements were performed on solutions of the [FeBr 2 (dppe)] catalyzed reaction between an alkyl halide and a preformed Li[BpinPh( t Bu)] borate, which revealed the presence of the Fe(I) complex [FeBr(dppe) 2 ] characterized previously.…”

Iron Catalysis: Historic Overview and Current Trends

“…The role of cosolvents or additives is still not really well understood. Also, the employment of nucleophiles beyond Grignard reagents (e.g., based on zinc or boron) needs to be further pursued, and efforts in this direction appeared recently in the literature [48,49]. Finally, further mechanistic investigations are necessary, as little is currently known concerning the nature (and especially the oxidation state) of the catalytically active iron species.…”

Cobalt‐Catalyzed Suzuki Biaryl Coupling of Aryl Halides

“…The results shown in Table 1 summarize selected12 optimization studies using 4‐chorotoluene and the activated phenylboronic ester 1 a ,6b,6c,6e, 8 catalyzed by species formed in situ from cobalt(II) chloride with a range of different ligands and ligand precursors. …”