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.
Directed catalytic asymmetric hydroborations of 1,1-disubstituted alkenes afford γ-dioxaborato amides and esters in high enantiomeric purity (90–95% ee).
A two-point binding mechanism for
the cationic rhodium(I)-catalyzed
carbonyl-directed catalytic asymmetric hydroboration of a cyclic γ,δ-unsaturated
amide is investigated using density functional theory. Geometry optimizations
and harmonic frequency calculations for the model reaction are carried
out using the basis set 6-31+G** for C, O, P, B, N, and H and LANL2DZ
for Rh atoms. The Gibbs free energy of each species in THF solvent
is obtained based on the single-point energy computed using the PCM
model at the ECP28MWB/6-311+G(d,p) level plus the thermal correction
to Gibbs free energy by deducting translational entropy contribution.
The Rh-catalyzed reaction cycle involves the following sequence of
events: (1) chelation of the cyclic γ,δ-unsaturated amide
via alkene and carbonyl complexation in a model active catalytic species,
[Rh(L2)2S2]+, (2) oxidative
addition of pinacol borane (pinBH), (3) migratory insertion of the
alkene double bond into Rh–H (preferred pathway) or Rh–B
bond, (4) isomerization of the resulting intermediate, and finally,
(5) reductive elimination to form the B–C or H–C bond
with regeneration of the catalyst. Free energy profiles for potential
pathways leading to the major γ-borylated product are computed
and discussed in detail. The potential pathways considered include
(1) pathways proceeding via migratory insertion into the Rh–H
bond (pathways I, I-1, and I-2), (2) a potential pathway proceeding via migratory insertion into
the Rh–B bond (pathway II), and two potential
competing routes to a β-borylated byproduct (pathway III). The results find that the Rh–H migratory insertion pathway I-2, followed in sequence by an unanticipated isomerization
via amide rotation and reductive elimination, is the most favorable
reaction pathway. A secondary consequence of amide rotation is access
to a competing β-hydride elimination pathway. The pathways computed
in this study are supported by and help explain related experimental
results.
A wide range of azolo[1,3,5]triazines were obtained by Rh(III)-catalyzed annulation of N-azolo imines and dioxazolones. The reaction proceeds by the first catalytic C-H amidation of an imidoyl C-H bond followed by cyclodehydration. Good yields were obtained for N-azolo imines derived from aminoazoles and aromatic and heteroaromatic aldehydes. A range of dioxazolone amidating reagents were employed to introduce aryl, heteroaryl, and alkyl substituents. The reaction was also performed with a benchtop setup at 1 mmol scale using microwave heating.
An efficient, three-component strategy for Rh(III)-catalyzed annulation of readily available 3-aminopyrazoles, aldehydes, and sulfoxonium ylides to give diverse pyrazolo[1,5-a]pyrimidines is disclosed. The reactions were performed under straightforward benchtop conditions using microwave heating with short reaction times. Good yields were obtained for a number of substituted aminopyrazoles and a very large variety of aromatic and heteroaromatic aldehydes, including those incorporating electron-withdrawing, electron-donating, basic nitrogen, halide and acidic functionality. Ester and methoxy functionalities could also be directly installed on the pyrimidine ring by employing ethyl glyoxylate and trimethyl orthoformate in place of the aldehyde, respectively. Additionally, a range of sulfoxonium ylides provided products in good yields to establish that aryl, heteroaryl, and branched and unbranched alkyl substituents can be introduced with this reagent. Finally, the first use of a formyl sulfoxonium ylide in a chemical transformation enabled the preparation of products with only a single substituent on the pyrimidine ring as introduced by the aldehyde coupling partner. For the formyl ylide, a one-pot, stepwise reaction sequence was used to prevent competitive condensation of the formyl group with the aminopyrazole.
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