Visible-Light-Induced Chemoselective Deboronative Alkynylation under Biomolecule-Compatible Conditions

Abstract

Here, we report a visible-light-induced deboronative alkynylation reaction, which is redox-neutral and works with primary, secondary and tertiary alkyl trifluoroborates or boronic acids to generate aryl, alkyl and silyl substituted alkynes. This reaction is highly chemoselective and performs well on substrates containing alkenes, alkynes, aldehydes, ketones, esters, nitriles, azides, aryl halides, alkyl halides, alcohols, and indoles, with no detectable occurrence of side reactions. The mechanism of this novel C(sp(3))-C(sp) bond coupling reaction was investigated by luminescence quenching, radical trapping, on-off light, and (13)C-isotopic-labeling experiments. This reaction can be performed in neutral aqueous conditions, and it is compatible with amino acids, nucleosides, oligosaccharides, nucleic acids, proteins, and cell lysates.

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…process, the solvent acted as hydrogen donor, as was elegantly shown by use of deuterated methanol, and the reactions were performed without the presence of an external oxidant. Hypervalent iodine reagents have also been utilized as oxidants in coupling of alkyltrifluoroborates with alkynes (Scheme 27) [64] and with vinylcarboxylic acids 45 (Scheme 28), [65] as well as in Minisci-type C-H alkylation with alkylboronic acids 46 (Scheme 29). [66] In the coupling of alkyltrifluoroborates with alkynylbenziodoxoles, mechanistic investigations were performed, and 1-hydroxy-1,2-benziodoxol-3-(1H)-one (BI-OH, 47) or the benziodoxole radical were proposed to oxidize the photoexcited Ru II * to Ru III (Scheme 27).…”

“…[66] In the coupling of alkyltrifluoroborates with alkynylbenziodoxoles, mechanistic investigations were performed, and 1-hydroxy-1,2-benziodoxol-3-(1H)-one (BI-OH, 47) or the benziodoxole radical were proposed to oxidize the photoexcited Ru II * to Ru III (Scheme 27). [64] Subsequent oxidation of the alkyltrifluoroborate formed the alkyl radical and regenerated the photocatalyst. The substituted alkyne products were formed after addition of the alkyl radical to the alkyne, followed by elimination of the benziodoxole radical.…”

Alkynylation with Hypervalent Iodine Reagents

“…Addition of the radical on the EBX reagent with reversed regioselectivity followed by an  elimination-1,2-shift sequence could also be considered. In 2014, Chen and co-workers reported an alternative method based on the oxidative alkynylation of trifluoroboronate salts using a photoredox catalyst, substoichiometric amounts of hydroxybenziodoxolone 28 and EBX reagents (Scheme 2.27 [146]). The reaction worked well for the transfer of aryl, silyl and alkyl alkynes.…”

Enantiospecific Alkynylation of Alkylboronic Esters

“…[10] TheSuzuki-Miyaura reaction could potentially be used to transform boronic esters into alkynes in conjunction with an alkynyl halide.However,the use of chiral boronic acids/esters in such cross-coupling reactions is not known;t he only reported examples are those that utilize primary sp 3 -, sp 2 -, and sp-type boron species,w hich are compounds that undergo facile transmetalation. [11,12] Another attractive method involves electrophile-induced 1,2-migration of an alkynyl boronate followed by deboronation (Scheme 1A). However, this approach is only applicable to symmetric trialkylboranes (BR 3 ) [13,14] and borinic esters (BR 2 OR), [15] which suffer from an umber of drawbacks,i ncluding difficulty in preparing an enantioenriched form, poor stability,a nd the poor atom economy of subsequent transformations (two Rg roups are wasted in borane transformations).…”