Organic Letters
Letter
Figure 1. Free-energy profiles (in kcal/mol) for the reaction of 1a with 2a in dimethylacetamide.
electrostatic interaction and the Iσ−···π anion−π interaction.
The complex was predicted to feature an absorption peak at
430 nm, which is in agreement with the UV−vis spectrum of
NaI and 1a. The absorption originates from excitation from the
iodine lone pair to the π* orbital of the pyridine ring.
With the optimized conditions in hand, we then investigated
the generality of this protocol (Scheme 3). A series of
phenylalanine-derived Katritzky salts bearing electron-donating
or electron-withdrawing substituents (4-NO2C6H4, 4-FC6H4,
4-tBuOC6H4, and 4-HOC6H4) reacted smoothly and gave the
corresponding products 3a−e in 43−81% yields. This was also
true for the homophenylalanine- and phenylethylamine-
derived Katritzky salts, giving rise to products 3f and 3g.
Moreover, the method tolerated a variety of functional groups,
such as thioether, esters, ketone, and nitrile (3h−n). The effect
of alkenes was examined as well. Both electron-donating (4-Me
and 4-MeO) and electron-withdrawing (4-F, 4-Cl, and 4-Br)
groups on the phenyl ring of 1,1-diphenylethylenes were
tolerable and afforded the desired products 3o−s in good
yields. Notably, the reaction of the styrene gave the
corresponding β,γ-unsaturated product 3t with excellent
diastereomeric ratios, albeit in somewhat decreased yield. In
addition, substituted styrenes were also suitable reaction
partners, whereas a decrease in E/Z selectivity was observed
(3u−x).
photoinduced NaI-catalyzed reaction of 1a+ and 1,1-diphenyl-
ethylene (2a). According to the computational results, we
propose a plausible mechanism, as illustrated in Figure 1.
Starting with the electron donor−acceptor complex
1
(namely, EDA), the blue light first excites the singlet ground
state 1EDA to the first singlet excited state 1EDA*.
Subsequently, 1EDA* undergoes homolytic C−N bond
cleavage to generate the alkyl radical through two possible
mechanisms. It may take place on the first singlet excited state,
2
directly giving the IM1 radical. Previously, we have shown
that the first singlet excited state of an EDA complex could
undergo homolytic bond cleavage without an apparent
barrier.14 Alternatively, 1EDA* may convert to the triplet
3
3EDA via intersystem crossing; then EDA, breaks the C−N
3
bond via TS1+ to give the 2IM1 radical with a barrier of 18.0
kcal/mol. It is not certain which pathway is preferred, but it is
certain that the 2IM1 radical can be generated. After the radical
2
generation, the resultant radical IM1 attacks the terminal
2
carbon of 2a via TS2 to form the C−C bond with a low
2
barrier of 12.6 kcal/mol, leading to IM2. We considered two
2
mechanisms to convert IM2 to the final product 3a. On the
one hand, the radical Py−Na+I• released from radical
2
3
generation abstracts a hydrogen atom from IM2 via TS3+
with a barrier of 23.1 kcal/mol to afford 3a. The regeneration
of the NaI catalyst is achieved via intramolecular electron
transfer from the PyH fragment and Na+I•, with the byproduct
The reaction scope of this protocol was further demon-
strated by using widely available carboxylic acids as starting
materials. Various substituted cinnamic acids were readily
reacted under the standard reaction conditions, and the
corresponding products (3t and 3y−b′) were obtained with
high E/Z ratios.
−
PyH+ being stabilized by the counteranion (BF4 ). On the
2
other hand, Py−Na+I• and IM2 first undergo intermolecular
single-electron transfer (SET) to regenerate the catalyst NaI,
1
1
1
giving IM3+ and Py. Then, Py deprotonates IM3+ via TS4+
with a barrier of 15.4 kcal/mol, giving 3a and PyH+. Overall,
the reaction has accessible kinetic barriers with gradually
To understand the reaction mechanism, we performed DFT
calculations to construct the free-energy profile for the
1579
Org. Lett. 2021, 23, 1577−1581