DABCO-promoted photocatalytic C-H functionalization of aldehydes

Abstract

Herein we present a direct application of DABCO, an inexpensive and broadly accessible organic base, as a hydrogen atom transfer (HAT) abstractor in a photocatalytic strategy for aldehyde C-H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the HAT step energetics and determined an optimized geometry for the transition state, showing that the hydrogen atom transfer between aldehydes and DABCO is a mildly endergonic, yet sufficiently fast step. The same calculations were performed with quinuclidine, for comparison of both catalysts and the differences are discussed.

Keywords: C–H functionalization; DABCO; HAT; photocatalysis.

Figure 1

Redox potentials of representative nitrogenated HAT catalysts and photocatalysts [––23].

Figure 2

Previous reports of DABCO as hydrogen abstractor in HAT reactions and this work.

Scheme 1

Aryl bromide and aldehyde scope. Isolated yields. ^aYield determined by ¹H NMR analysis with 1,3-benzodioxole as internal standard. ^bAlso performed in the absence of DABCO (see Supporting Information File 1, Scheme S2 for details). ^cAldehyde (10 equiv), performed at 40 °C without cooling fan. ^dAldehyde (10 equiv).

Scheme 2

Mechanistic investigations of the HAT reaction using DABCO.

Scheme 3

Proposed mechanism for aldehyde arylation. PC = photocatalyst Ir[dF(CF₃)ppy]₂(dtbbpy)PF_6. SET = single-electron transfer event.

Figure 3

Free energy profile for the HAT step reactions between isovaleraldehyde with (top) DABCO and (bottom) quinuclidine radical cations. The red lines are for the gas phase results while the blue lines are for the PCM single points from the gas phase optimized geometry. RC – reactants complex; PC – product complexes. On both graphs the structure shown on the left represents the RC, on the right, PC and the top centre structure is for the TS between DABCO and the aldehyde.

Figure 4

TS structure for the HAT reaction between the DABCO radical cation and isovaleraldehyde obtained at the DFT/M06-2X/cc-pVTZ level. Bond lengths and angle are presented.