Copper‐Catalyzed Regioselective Hydroalkylation of 1,3‐Dienes with Alkyl Fluorides and Grignard Reagents

Abstract

Copper complexes generated in situ from CuCl2, alkyl Grignard reagents, and 1,3-dienes play important roles as catalytic active species for the 1,2-hydroalkylation of 1,3-dienes by alkyl fluorides through C-F bond cleavage. The alkyl group is introduced to an internal carbon atom of the 1,3-diene regioselectively, thus giving rise to the branched terminal alkene product.

Regiodivergent Copper Catalyzed Borocyanation of 1,3‐Dienes

“…Crucially, if regioselectivity during borocupration could be controlled by a simple change in ligand, then different products would be accessible from the same simple starting materials . However, previous element‐cupration of 2‐substituted 1,3‐dienes predictably occurred at the vinyl portion of the diene (in a 4,1‐fashion), where in the case of borocupration, 4‐boryl substituted products are observed ,–,. Notably, only Brown has reported a switch in 4,1‐ and 1,2‐selectivity in a boroarylation of 2‐alkyl substituted 1,3‐dienes in a Cu/Pd cooperatively catalyzed process upon the addition of 2 equivalents of DMAP .…”

Nickel‐Catalyzed Dimerization and Alkylarylation of 1,3‐Dienes with Alkyl Fluorides and Aryl Grignard Reagents

“…This reaction is promoted by Grignard reagents,which enable the formation of an anionic nickel complex B as the catalytically active species.However, the use of asimple alkyl electrophile,such as an alkyl halide, in this transformation has not yet been achieved, mainly because of the rapid direct cross-coupling between alkyl halides and organometallic reagents. [7][8][9] We herein report that the use of ac ombination of alkyl fluorides [9][10][11][12] and appropriate aryl Grignard reagents solves this problem, thus enabling the four-component coupling of alkyl fluorides, aryl Grignard reagents,and two 1,3-butadiene molecules that leads to the formation of 1,6-octadienes with alkyl and aryl groups at the 3-and 8-positions (Scheme 1d). [13] Thereaction of nOctF (1a)and oTolMgBr (2a)with 1,3butadiene was examined using 10 mol %o fG roup 10 metal salts in THF (Table 1).…”

Catalytic Hydroalkylation of Allenes

“…[10] In 2015, Kambe et al reported copper-catalyzed hydroalkylation of 1,3-dienes. [11] Thes ame year,o ur group reported E-selective hydroalkylation of terminal alkynes, [12] while the Z-selective hydroalkylation of aryl alkynes was reported by Hu et al [13] In 2016, Fu et al reported Markovnikov hydroalkylation of terminal alkynes using an ickel catalyst. [14] Despite these developments in the hydroalkylation of alkynes and certain alkenes,h ydroalkylations of allenes are still relatively rare.…”

“…Hydroalkylation can be accomplished with ar ange of allenes and alkyl triflates.Inall cases,only one regioisomer of the product is obtained. Thereaction can be performed in the presence of avariety of functional groups,including esters (7), silyl ethers (9), aryl iodides (4), aryl bromides (13), aryl boronic esters (6), alkyl bromides (8), tosylates (11), and sulfonamides (10, 12). 1,1-Disubstituted allenes provide compounds containing aq uaternary carbon center (16).…”

“…Overall, the exploration of the substrate scope demonstrates that the new hydroalkylation reaction provides access to aw ide range of substituted terminal alkenes and vinyl silanes,and is compatible with avariety of functional groups. Theh ydroalkylation is complementary to S N 2' allylic substitution reactions, [18] which require alkyl organometallic reagents as coupling partners.T he reversed polarity of the hydroalkylation reaction allows alkylation with substrates that carry highly electrophilic functional groups,such as alkyl bromides (8)a nd sulfonate esters (11). To provide ab etter understanding of the underlying chemistry and enable further development of the hydroalkylation reaction, we explored the mechanism of the reaction.…”