Rhodium(III)-Catalyzed Imidoyl C-H Activation for Annulations to Azolopyrimidines

Abstract

Azolopyrimidines are efficiently prepared by direct imidoyl C-H bond activation. Annulations of N-azolo imines with sulfoxonium ylides and diazoketones under redox-neutral conditions and alkynes under oxidizing conditions provide products with various arrangements of nitrogen atoms and carbon substituents. We have also probed the mechanism of this first example of Rh(III)-catalyzed direct imidoyl C-H activation by structural characterization of a catalytically competent rhodacycle obtained after C-H activation and by kinetic isotope effects.

Scheme 1

Catalytic C(sp²)–H functionalization for the preparation of bridgehead N-fused [5,6]-bicyclic heterocycles.

Scheme 2. Rh(III)-Catalyzed C–H Functionalization of Azoloaldimines 1 with Sulfoxonium Ylide 2a^a

^aReactions performed on 0.3 mmol scale. ^bReaction performed with tetrahydrofuran as solvent. ^cReaction performed with 4.0 equiv of PivOH at 120 °C. ^dReaction performed on 1 mmol scale on the benchtop under an inert atmosphere.

Scheme 3. Rh(III)-Catalyzed C–H Functionalization of Azolobenzaldimines 1 with Sulfoxonium Ylides 2^a

^aReactions performed on 0.3 mmol scale. ^bReaction performed with tetrahydrofuran as solvent.

Scheme 4. Rh(III)-Catalyzed C–H Functionalization of Azoloaldimines 1 with Diazoketone 4^a

^aReactions performed on 0.3 mmol scale. ^bReaction performed with 4.0 equiv of PivOH at 120 °C.

Scheme 5. Rhodium(III)-Catalyzed C–H Functionalization of Azoloaldimines 1 with Alkynes 6^a

^aReactions performed on 0.3 mmol scale. ^bReaction conditions: [Cp*RhCl₂]₂ (5 mol %), AgOAc (2.2 equiv), PivOH (4.0 equiv), THF, 100 °C, 18 h.

Scheme 6

Formation and Reaction of Rhodacycle 8

Scheme 7

Deuterium Isotope Studies with 1a-D

Scheme 8

Proposed Mechanism of Rhodium(III)-Catalyzed C–H Functionalizations of Iminyl Azoles