Facile Ruthenium(II)-Catalyzed α‑Alkylation
of Arylmethyl Nitriles Using Alcohols Enabled by Metal–Ligand
Cooperation
Posted on 2017-07-21 - 18:21
A facile ruthenium(II)-catalyzed
α-alkylation of arylmethyl
nitriles using alcohols is reported. The ruthenium pincer catalyst
serves as an efficient catalyst for this atom-economical transformation
that undergoes alkylation via borrowing hydrogen pathways, producing
water as the only byproduct. Arylmethyl nitriles containing different
substituents can be effectively alkylated using diverse primary alcohols.
Notably, using ethanol and methanol as alkylating reagents, challenging
ethylation and methylation of arylmethyl nitriles were performed.
Secondary alcohols do not undergo alkylation reactions. Thus, phenylacetonitrile
was chemoselectively alkylated using primary alcohols in the presence
of secondary alcohols. Diols provided a mixture of products. When
deuterium-labeled alcohol was used, the expected deuterium transposition
occurred, providing both α-alkylation and α-deuteration
of arylmethyl nitriles. Consumption of nitrile was monitored by GC,
which indicated the involvement of first-order kinetics. Plausible
mechanistic pathways are suggested on the basis of experimental evidence.
The ruthenium catalyst reacts with base and generates an unsaturated
intermediate, which further reacts with both nitriles and alcohols.
While nitrile is transformed to enamine via [2 + 2] cycloaddition,
alcohol is oxidized to aldehyde. The metal bound enamine adduct reacts
with aldehyde via Michael addition, resulting in an ene-imine adduct,
which perhaps undergoes direct hydrogenation by a Ru dihydride intermediate,
produced from alcohol oxidation. However, in situ monitoring of the
reaction mixture confirmed the presence of unsaturated vinyl nitrile
in the reaction mixture in minor amounts (10%), indicating the possible
dissociation of ene-imine adduct during the catalysis, which may further
be hydrogenated to provide the α-alkylated nitriles. Overall,
the efficient α-alkylation of nitriles using alcohols can be
attributed to the amine-amide metal–ligand cooperation that
is operative in the ruthenium pincer catalyst, which enables all of
the catalytic intermediates to remain in the +2 oxidation state throughout
the catalytic cycle.
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Thiyagarajan, Subramanian; Gunanathan, Chidambaram (2017). Facile Ruthenium(II)-Catalyzed α‑Alkylation
of Arylmethyl Nitriles Using Alcohols Enabled by Metal–Ligand
Cooperation. ACS Publications. Collection. https://doi.org/10.1021/acscatal.7b01427
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AUTHORS (2)
ST
Subramanian Thiyagarajan
CG
Chidambaram Gunanathan