Air-Stable Iron-Based Precatalysts for Suzuki–Miyaura Cross-Coupling Reactions between Alkyl Halides and Aryl Boronic Esters

Abstract

The development of an air-stable iron(III)-based precatalyst for the Suzuki−Miyaura cross-coupling reaction of alkyl halides and unactivated aryl boronic esters is reported. Despite benefits to cost and toxicity, the proclivity of iron(II)-based complexes to undergo deactivation via oxidation or hydrolysis is a limiting factor for their widespread use in cross-coupling reactions compared to palladium-based or nickel-based complexes. The new octahedral iron(III) complex demonstrates long-term stability on the benchtop as assessed by a combination of 1 H NMR spectroscopy, Mossbauer spectroscopy, and its sustained catalytic activity after exposure to air. The improved stability of the iron-based catalyst facilitates an improved protocol in which Suzuki−Miyaura cross-coupling reactions of valuable substrates can be assembled without the use of a glovebox and access a diverse scope of products similar to reactions assembled in the glovebox with iron(II)-based catalysts.

Iron-Catalyzed C(sp2)–C(sp3) Suzuki–Miyaura Cross-Coupling Using an Alkoxide Base

“…To highlight the advantage of using an alkoxide base, aryl nucleophiles with base-sensitive functionality were examined. Base-sensitive functionality is often not tolerated for the nucleophilic partner in methods that rely on Grignard reagents or methods involving boron-based nucleophiles activated with alkyl lithium or amide bases. ,, The ester-containing nucleophile 4v and the aryl nitrile 4w were compatible with the iron-catalyzed method and the desired product obtained in 93% and 99% yields, respectively (Scheme B). The base-sensitive functionality was also tolerated on the electrophile, allowing cross-coupling of nitrile ( 4x ) and enolizable ester ( 4y ) containing substrates in 90% and 98% yield, respectively.…”

“…A possible pathway of transmetalation is shown in Scheme b, whereby an iron halide intermediate reacts with an aryl boronate to form an iron aryl complex. In contrast, Byers and co-workers have reported that lithium amide boronate nucleophiles were not competent in catalysis, suggesting a potential difference in the mechanism of the transmetalation step …”

“…Initial reports of iron-catalyzed Suzuki cross coupling required preactivation of the aryl boron nucleophile with t BuLi to form lithium aryl boronates, along with catalytic MgBr 2 as an additive, reducing the handling and compatibility advantages of the boron reagents and suggesting that classification as a Kumada-type reaction is more appropriate. More recently, Byers and co-workers have reported the iron-catalyzed cross coupling between aryl BPin (Pin = pinacolato) nucleophiles with alkyl halides using the lithium amide base, LiNMeEt (Scheme A) . Notably, tertiary alkyl halides and heteroaryl boronic esters were tolerated.…”

Collaboration as a Key to Advance Capabilities for Earth-Abundant Metal Catalysis

“…The current state of the art in iron-catalyzed C­(sp 2 )–C­(sp 3 ) SMC is arguably the catalyst system recently developed by Byers and co-workers, which is the first to allow the direct use of neutral, unactivated arylboronic esters. The Byers catalysts are based on L,X-type N,N ligands and utilize LiNMeEt as the base in benzene solvent (Scheme a) . Unfortunately, the use of a strong lithium amide base that is not currently commercially available and a highly toxic solvent pose significant barriers for utilization of this technology in large-scale applications.…”

Incorporation of a cyclobutyl substituent in molecules by transition metal-catalyzed cross-coupling reactions

“…The Suzuki–Miyaura cross-coupling reaction of bromocyclobutane ( 96 ) with phenylboronic ester 103 was catalyzed by an air stable iron( iii )-based complex (Fe cat.) to produce 104 in modest yield (31%) 67 (Scheme 48).…”