Peer review of: Stereospecific Si-C coupling and remote control of axial chirality by enantioselective (2020)

Reviewers' comments: 

Reviewer #1 (Remarks to the Author): 

The manuscript by Xu and collaborators is an interesting example of a Pd catalyzed hydrosilylation 
of activated maleimides. The synthesis of novel organosilicon compounds is realized in an 
enantioselective fashion. The optimization is well performed and allows to find the best conditions 
to obtain a very high enantiocontrol. A limitation is given by the yields which are not always very 
high and do not reflect the same efficiency exerted by the catalyst on the enantioselectivity. In 
general, the scope of the hydrosilylation is quite good and a large number of alkyl and aryl 
maleimides is employed. The scope is furthermore implemented by the use of arylmaleimides with 
ortho substituents which drives the reaction to an enantio- atropo- and diastereoselective 
hydrosilylation process. The manuscript surely reports a novel reaction which is however limited 
only to maleimides as activated alkenes. However, the lack of generality is compensated with a 
rare example of axially chiral organosilicon compounds. Despite the concept of the 
desymmetrization of prochiral maleimides is not new, the novelty can be found in the way the 
desymmetrization is realized that is by means the Pd catalyzed hydrosilylation. The manuscript is 
of good quality but in my personal opinion sufficient for publication on Nature communication after 
the following revisions: 
1) Novel axially chiral compounds have been prepared. However, no full characterization has been 
provided. It is necessary for some representative examples to have the experimental value of the 
rotational barrier in order to know the stability of this new kind of products. 
2) The absolute configuration has been determined via X-ray analysis on compound 3. On 
compounds 5 the absolute configuration has been obtained through experimental ECD compared 
with the DFT simulated CD of a certain enantiomer. Which criteria has been followed by the author 
to use for the simulation the reported diastereoisomer? Are there any experimental evidences for 
this. In fact, It appears strange that the silicon group is syn to the largest ortho substituent of the 
N-Aryl moiety. The B-value for the Ph group is 7.5 and for the OMe group is 5.6 see: Chem. Eur. J. 
2009, 2645. Indeed, as reported in other examples of atroposelective desymmetrization, the 
addition to the maleimide double bond is anti to the large substituent of the aryl group: 
Tetrahedron 2016, 72, 5191, Org. Lett. 2015, 17, 1728, Synthesis, 2017, 49, 1519, Tetrahedron 
2007, 8529. The correlation between the configuration of the chiral center in compounds 3 and 5 
is too risky and it is necessary to determine the relative configuration of the 5 series and then their 
absolute configuration and eventually re-discuss the mechanism of the reaction. 
4) In the case of compounds 3, yields are not always at high level. Is there a plausible explanation 
for this poor result. In the case of compounds 3d, 3e, 3g as representative examples, do you have 
traces of the corresponding succinimides 4? 
3) Together with the previous references, the following should be added: Chem. Rev. 2015, 115, 
11239 

Reviewer #2 (Remarks to the Author): 

Xu and co-workers reported a highly enantioselective hydrosilylation of maleimides using 
palladium catalysis, in which the stereospecific preparation of a series of silyl succinimides was 
achieved in up to 99% yield, and >99:1 er. And the remote control of axial chirality for efficient 
synthesis of functionalized succinimides bearing axial C-N is also very interesting. This is very good 
and thorough work, and the novel aspects in the stereoselctive synthesis of these point and axially 
chiral silylated maleimides are well recognized. The reaction could be easily scaled up and the 
products could be also derivatized. This reviewer would recommend this manuscript for publication 
on Nature Communications after minor revision. 
(1) Figure 1 looks a bit messy, it is recommended to repaint it more beautifully. In fig.1b, this 
challenge is not that strong. Because in the computational studies, the hydride was added first 
which is same as classic Michael addition. It should be noted that the hydrosilylation of 

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should be “Insertion”. 
(2) For the Line 145, the “a Si-H activation-driven palladium complex shuttle” could be replaced by 
“palladium catalysis”. Because the palladium complexes have not been well studied. 
(3) A recent review on hydrofunctionalization of alkenes including hydrosilylation should be cited, 
such as Chin. J. Chem. 2018, 36, 1075–1109. A recent paper on asymmetric hydrosilylation of 
vinylsilanes should be cited, such as Chin. J. Chem. 2019, 37, 457–461. 
(4) It will be better to attach the F NMR spectra for the fluorine-containing compounds. 
(5) The English grammar should be corrected for some expressions, for example, there are a little 
cumbersome in Introduction part, please carefully modify them.