Organic Letters
Letter
intermediate C via a low barrier of 9.5 kcal/mol. Subsequently,
a concerted phospha-Brook rearrangement through TSCD and
protonation gives product 4 with a barrier of 20.4 kcal/mol.
Obviously, the lower activation energy of phospha-Brook
rearrangement pathway is confirmed to be more favorable.
In summary, we have developed a mild and practical route to
prepare phosphoric ester compounds. Aldehydes and ketones
were both coupled with secondary phosphine oxides, forming
P−O bond in the presence of base. Enantioenriched
phosphoric esters could be facilely prepared from chiral
phosphine oxide precursors. Three different reaction mecha-
nisms including phospha-Brook rearrangement, direct anti-
regioselective addition, and [3 + 2] cycloaddition/elimination
were proposed according to the experimental results. The
former was proved to take effect by DFT calculations. Further
investigations on the reaction system are ongoing in our lab.
Scheme 4. Proposed Reaction Mechanism
reversible according to the experimental results (Scheme 3).
1,2-Brook rearrangement would deliver the phosphinates as
final products (path a).6d,11 Alternatively, the involvement of
another aryl aldehyde molecule through [3 + 2] cycloaddition
may result in a five-membered species II, which eliminates the
aldehyde to afford the final product 4 upon protonation (path
b). In the presence of ethyl acetate, intermediate I might be
captured leading to byproduct 5 (path c). Direct nucleophilic
attack of cesium phosphite on the O atom of the carbonyl
group to create intermediate III cannot be excluded (path d).
To gain further insight into the reaction mechanism and
distinguish the three possibilities mentioned above, density
functional theory (DFT) calculations were carried out using
the Gaussian 09 software package (for details, see the SI).18,19
The free energy profiles are shown in Figure 1. First, Cs-
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
Computational details, experimental procedures, and
characterization data (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
Zhiming Li − Department of Chemistry, Fudan University,
Yu Liu − College of Chemistry and Life Science, Jilin Provincial
Key Laboratory of Carbon Fiber Development and Application,
Changchun University of Technology, Changchun 130012, P.R.
Junliang Zhang − Department of Chemistry, Fudan University,
Shanghai 200438, P.R. China; Zhuhai Fudan Innovation
Authors
Yanyan Qian − College of Chemistry and Life Science, Jilin
Provincial Key Laboratory of Carbon Fiber Development and
Application, Changchun University of Technology, Changchun
130012, P.R. China
Qiang Dai − Shanghai Key Laboratory of Green Chemistry and
Chemical Processes, School of Chemistry and Molecular
Engineering, East China Normal University, Shanghai 200062,
P.R. China
Figure 1. Computed free energy profiles for the reaction process.
mediated [3 + 2] cycloaddition leading to the five-membered
species E (TSBE) was found to require a barrier of 24.3 kcal/
mol. A stepwise cycloaddition path was also located, which is
less favored due to a slightly higher barrier (Figure S1). The
following elimination process is stepwise according to our
computation results, since no concerted elimination transition
states can be located despite many attempts. From E,
elimination occurs to form intermediate F. Further elimination
of benzaldehyde delivers the final intermeidate D with a barrier
of 13.0 kcal/mol. Direct nucleophilic attack of cesium
phosphite on the O atom of the carbonyl group required a
barrier of 29.5 kcal/mol through TSAD. Alternatively, cesium
phosphite attacks benzaldehyde nucleophilically leading to
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (Nos. 21971066, 21772042) and the Science and
Technology Commission of Shanghai Municipality
(18JC1412300) for financial support.
D
Org. Lett. XXXX, XXX, XXX−XXX