Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis

Abstract

Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp3-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp2-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps.

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

“…[57] Although only activated alkyltrifluoroborates were described in the initial study, the dual Ir/Ni catalysis system was subsequently successfully applied to the functionalization of unactivated secondary alkyltrifluoroborates. [58][59][60] The alkyl radical intermediates were formed through an oxidative activation process by SET between the alkyltrifluoroborate substrates and the excited-state Ir III * catalyst. The alkyl radical was then captured by the Ni II (or alternatively the Ni 0 ) catalyst, and a second SET between the Ni I complex, formed after reductive elimination of the cross-coupled product, and the reduced photocatalyst regenerated both catalysts (see Schemes 7D and 23B).…”

“…To highlight the powerful and orthogonal nature of the radical photocatalytic reaction manifold, the intermediate alkylated products were subjected to further functionalization. [59] The majority of substrates investigated were activated alkyltrifluoroborates; however, a few examples of unactivated, cyclic secondary alkyltrifluoroborates were also reported (Scheme 22). In these reactions, initial radical cross-coupling in the presence of (4-bromophenyl)boronate pinacol ester (40) delivered the alkylated intermediates 41, and subsequent peroxide-mediated oxidation gave the final phenol derivatives 42.…”

Photoredox Catalysis in Nickel-Catalyzed Cross-Coupling

“…The former are more easily oxidized not only because the radical generated upon oxidation is more stable, but also because the boronate esters are isoelectronic with electron deficient carbocations, and thus highly resistant toward single electron oxidation. In the event, reaction of benzylic trifluoroborates with aryl bromides containing tricoordinate, sp2-hybridized boron species was achieved under photoredox/Ni dual catalytic conditions (Scheme 10) [22]. The products obtained Scheme 6 Photoredox/Ni dual catalytic cross-coupling of secondary alkyltrifluoroborate Scheme 7 Photoredox/Ni dual catalytic cross-coupling of cyclopropyltrifluoroborate were further reacted in known transformations to build molecular complexity in an efficient, modular manner, taking advantage of the highly selective cross-coupling of the benzyltrifluoroborate with aryl bromides (Scheme 11).…”

Recent advances in dual transition metal–visible light photoredox catalysis

“…Due to their high stability and storability wide application was achieved. 27 In a Ni transition metal merged Ir photocatalyzed coupled system, a wide variety of (hetero)aryl bromides were coupled with subtituated benzyl BF 3 K salts, 26,28 secondary alkyl trifluoroboates, 29 α-alkoxymethyltrifluoroborates, 30 Bocprotected N-trifluoroboratomethyl amino acids 31 and aryl or aralkyl acyl chlorides with α-alkoxymethyltrifluoroborates. 32 In 2016, the synthesis of 1,1-diaryl-2,2,2-trifluoroethanes (16) were investigated by Molander and his co-workers (Figure 6).…”