Phosphine-Catalyzed Intermolecular Acylfluorination of Alkynes via a P(V) Intermediate

Abstract

We report on the phosphine-catalyzed intermolecular carbofluorination of alkynes using acyl fluorides as fluorinating reagents. This reaction promises to be a useful method for the synthesis of highly substituted monofluoroalkene derivatives, since acyl fluorides can be easily prepared from the corresponding carboxylic acid derivatives and the reaction proceeds under ambient conditions without the need for a transition-metal catalyst. Experimental and computational studies indicate that a five-coordinated fluorophosphorane is involved as the key intermediate in the fluorination step. File list (2) download file view on ChemRxiv SI_full_Fujimoto_acylfluorination0612.pdf (3.65 MiB) download file view on ChemRxiv Main_text_Fujimoto_carbofluorination_0612.pdf (391.19 KiB)

Recent Advances in C–F Bond Activation of Acyl Fluorides Directed toward Catalytic Transformation by Transition Metals, N-Heterocyclic Carbenes, or Phosphines

“…In 2020, they achieved an unprecedented phosphinecatalyzed carbofluorination of alkynes, in which acyl fluorides served as acylating and fluorinating reagents to construct a series of alkenyl fluorides in the excellent yields with great functional-group tolerance (Scheme 50(a)). 96 A series of subsequent mechanistic studies and DFT calculations revealed that an unprecedented ligand coupling on phosphine constructs the C-F bond according to the mechanism shown in Scheme 50 (b) Recently, the same research group developed a novel PCy3catalyzed three-component coupling reaction of acyl fluorides, silyl enol ethers, and alkynes based on previous research. This strategy provides for the synthesis of a variety of 1,3-dienes with good substrate scope and high yields (Scheme 50(c)).…”

C-F bond activation under transition-metal-free conditions

“…In analogy to previous protocols which utilized i Bu 2 AlH or LiGaH 4 (vide supra), Weaver and co-workers [62] reported the HDF of perfluoroarenes with NaBH 4 (Scheme 20). The advantage of this reaction is that it is compatible with both EDG and EWG substituted substrates (103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114). Specifically, the use of NaBH 4 rather than more potent reductant LiAlH 4 allowed for the incorporation of ester ( 103) and amide (104).…”

“…Interestingly, Tobisu's group [110] reported a phosphinecatalyzed intermolecular acylfluorination of alkynes using acyl fluorides as the fluorinating reagents (Scheme 40). Halogen groups (207) were compatible in the reactions.…”

Highly Stereoselective Intramolecular Carbofluorination of Internal α,β-Ynones Promoted by Selectfluor

“…In addition, BF 3 ·Et 2 O and Ph 3 CBF 4 could be used as Lewis acids and fluoride sources to react with enynols to afford tetrasubstituted monofluoroalkenes via formation of allylic carbocation intermediates. Recently, Tobisu and co-workers reported the organophosphine-catalyzed intermolecular carbofluorination of alkynes to produce tetrasubstituted monofluoroalkene derivatives with a low E/Z ratio (Scheme b) . However, this reaction sequence typically involves the consumption of expensive transition-metal catalysts and corrosive/toxic reagents and often results in low regioselectivities.…”

“…Recently, Tobisu and co-workers reported the organophosphinecatalyzed intermolecular carbofluorination of alkynes to produce tetrasubstituted monofluoroalkene derivatives with a low E/Z ratio (Scheme 1b). 14 However, this reaction sequence typically involves the consumption of expensive transitionmetal catalysts and corrosive/toxic reagents and often results in low regioselectivities. Thus, the development of a simple protocol for the direct access to monofluoroalkenes with suitable regioselectivity control has attracted significant attention in the scientific community.…”