A Broadly Applicable Alkyl-Alkyl Suzuki-Miyaura Cross-Coupling Reaction Catalyzed by an Iron-Based Complex

Abstract

An iron-based catalyst for the Suzuki-Miyaura reaction between two sp3-hybridized substrates has been developed for a broad range of unactivated alkyl halides and alkyl boranes. Key to success was using a Cs-symmetric beta-diketiminate ligand that contained a tert-butyl and trifluoromethyl functionalized backbone. The breadth of the cross-coupling reaction was demonstrated with high yields of cross-coupled products observed from reactions using primary and secondary alkyl bromides as well as primary alkyl boranes and even some secondary alkyl boranes. Complementary methylation reactions using methyl iodide or methyl-9-BBN was also possible. The facile diversification of a steroid derivative using these reactions demonstrated the synthetic utility of such complementary cross coupling reactions.

A Rationally Designed Iron(II) Catalyst for C(sp3)−C(sp2) and C(sp3)−C(sp3) Suzuki–Miyaura Cross‐Coupling

“…However, no coupling was noticed for 3 i and cyclopentene. It is worth noting that, in contrast to the scarce contributions on C(sp 3 )À C(sp 3 ) SMC using iron catalysis, [39,40] the wide scope of our Fe-catalyzed alkyl-alkyl SMC methodology was reached without any electronic or steric alteration of the structure of catalyst 2 b, efficiently applied to alkyl-aryl couplings. This features the high versatility of this AA-based iron catalyst in SMC involving sp 3 -hybridized partners and represents a step forward to a universal iron catalyst for C(sp 3 )À C(sp 2 ) and C(sp 3 )À C(sp 3 ) SMC.…”

“…[77][78][79][80] Despite prominent advances using nickel catalysis, [22][23][24][25] C(sp 3 )À C(sp 3 ) SMC remains highly challenging and is exceedingly rare in iron catalysis. [39,40] Seeking to expand the scope of our catalytic SMC method involving C(sp 3 )partners, we next examined the challenging coupling of alkyl halide electrophiles and alkyl boron nucleophiles. Although disappointing results were initially obtained for the reaction of (1-octyl)-Bpin and (3-bromobutyl)benzene under the conditions developed for C(sp 3 )À C(sp 2 ) coupling (Table S2), the use of more Lewis-acidic 9-octyl-9-BBN (9-BBN = 9borabicyclo[3.3.1]nonane) and less bulky and commercially available LiNMe 2 base afforded the coupled product 7 a in 63 % yield after 24 h at 25 °C (Scheme 4).…”

“…[22][23][24][25][26] In contrast, iron catalysts are still in their infancy for sp 3 -hybridized partners and thus many challenges remain. [27][28][29][30][31][32][33][34][35][36][37][38][39][40] Iron is a more terrestrial abundant, less toxic and cheaper metal which would hold great promise for greener and more sustainable SMC methods amenable to industrial-scale applications. Initial works on iron-catalyzed SMC with C(sp 3 )-derived partners required the use of lithium or magnesium-activated boron nucleophiles (in conjunction with MgBr 2 co-catalyst) to promote the key transmetalation step as neutral boron nucleophiles were not effective (Scheme 1, A.1).…”

C(sp3)–C(sp3) Reductive Elimination from (Phenoxyimine)Cobalt(III)(CH3)2(PMe3)2 Complexes

“…Reductive elimination of C–C bonds from transition-metal complexes is a key bond-forming step in many catalytic reactions, most prominently metal-catalyzed cross-coupling. , For C­(sp 2 )–C­(sp 2 ) coupling, palladium catalysts are state-of-the-art, and fundamental studies into the reductive elimination step are well precedented. − In the past decade, there has been increased emphasis on use of catalysts with Earth-abundant rather than precious metals for C–C bond-forming reactions. , In addition to potential cost and environmental advantages, the availability of one-electron chemistry opens the possibility for new reactivity modes and subsequent reaction development . With respect to catalytic cross-coupling, first-row transition metals have demonstrated unique compatibility with C­(sp 3 )-based coupling partners, and examples with nickel, iron, − and cobalt − have been reported. Given the increasing emphasis on molecular targets with increased C­(sp 3 ) content, understanding fundamental organometallic transformations such as C­(sp 3 )–C­(sp 3 ) reductive elimination with first-row transition metals is of interest.…”

Copper-Catalyzed Coupling of Alkyl Vicinal Bis(boronic Esters) to an Array of Electrophiles

“…A significant limitation of this strategy has been that the Pd-catalyzed coupling of alkyl boronic esters only applies to C­(sp 2 ) electrophiles and this severely limits the reaction scope. To engage alkyl electrophiles in Suzuki–Miyaura reactions, palladium, copper, nickel, and iron catalysts have been employed; however, these processes generally require trialkylborane derivatives for productive reaction. While copper catalysis can extend to alkylboronic esters, , until recently, this process was similarly limited to C­(sp 2 ) electrophiles .…”