1. INTRODUCTION
Arenes are one of the most extensively used substrates to access
important products in the pharmaceutical and agrochemical industry. Much
efforts have been devoted to their
functionalization in the few
decades.[1-11] Among of them, alkynes are often
employed as the powerful C2 coupling
partners.[12-14] Rhodium-catalyzed C−H
functionalization of arenes has been established as an effective
strategy to synthesize desired functional
structures.[15-32] However, the multitudinous C−H
bonds in arenes would lead to diverse regioselectivity. In the previous
reports, many multifunctional directing groups have been introduced to
improve the desired regioselectivity. Despite great progress has been
achieved, the nucleophilic directing group was limited to amide,
carboxylic acid, phenol, and enolate. Thus, such coupling assisted by a
NH directing group still remains rare.
Recently, Li group[33] reported
the
Cp*Rh(OAc)2-catalyzed
coupling of N-methoxybenzamide R1 and alkyl-terminated enyneR2 (Scheme 1). As shown in Scheme 1, by
employing Cu(OAc)2as additive and ethanol as solvent, the major product is
lactam P1 (reaction A).
While the major product becomes iminolactone P2 in the presence
of Cu(OAc)2 and
NaOAc, with 1,4-dioxane as the
solvent (reaction B).
SCHEME 1Cp*Rh(OAc)2-catalyzed
coupling of N-methoxybenzamide with alkyl-terminated enyne reported by
Li group
To account for the distinct regioselectivity, Li group postulated
possible reaction mechanisms that are summarized in Scheme 2. Theortho arene C−H bond activation firstly occurs to afford
rhodacycle complex I catalyzed by Cp*Rh(OAc)2(1cat ). Then the enyneR2’ migratory inserts
into the alkyne unit selectively to afford Rh(III) alkenyl II .
Subsequent 1,4-Rh migration gives
a Rh(III) π-allyl species III . In reaction A, III then
rearranges to form allyl complex IV , which is followed by the
nucleophilic attack of the softer amide nitrogen at theη 3 position to produce P1 together
with a Rh(I) complex 2cat . The Rh(I) complex could then be
re-oxidized by Cu(II) salt to regenerate the active catalyst1cat for the next cycle. For comparison, in the presence of an
excess of NaOAc (reaction B), acetate coordination triggers allyl
rearrangement to theη 1 intermediate V , which is followed
by the C−O reductive elimination to deliver product P2 .
SCHEME 2 Plausible reaction pathways for the
Cp*Rh(OAc)2-catalyzed coupling of N-methoxybenzamide
with alkyl-terminated enyne proposed by Li et al
Although the plausible mechanistic pathway has been proposed by the Li
group, some key issues still need to
be further discussed. (1) Which
steps are rate- and regioselectivity-determining in both of the two
reactions? (2) By using Cu(OAc)2 as additive and ethanol
as solvent, the product is P1 , while the product becomesP2 in the presence of
Cu(OAc)2 and NaOAc, with 1,4-dioxane as the solvent.
Why? (3) What is the role of NaOAc in reaction B. To address these
questions, a theoretical investigation for detailed reaction mechanisms
is needed. Herein, we report our detailed density functional theory
(DFT) calculations on the reaction mechanisms, in order to gain insight
into the interesting experimental observations and distinct selectivity.
We expect this work would help understand the detailed mechanisms and
design new related reactions.