(S,S)-2-(((Hydroxynaphth-1-yl)(4′-nitrophenyl)methyl)amino)-3-methylbutanoic Acid Methyl Ester

Round 1

Reviewer 1 Report

The compound (S,S)-2-(((hydroxynaphth-1-yl)(4'-nitrophenyl)methyl)amino)-3- methylbutanoic acid methyl ester was synthesized and characterized by NMR spectra, mass spectra. The synthesis and characterization are doing well down.

  The synthesis process is similar with other known compounds. We are looking forward the “ee” value if it is possible or the applications of this compound are created.

Author Response

Two lines (99-100) were added to describe the future application of the molecule.

As far as the ee values are concerned, we added in the Supporting Information the graphical representation of the HPLC of the (S,S)-stereoisomer and of an almost 3:1 mixture of (S,S) and (R,R)-stereoisomer.

Reviewer 2 Report

This article “(S,S)-2-(((hydroxynaphth-1-yl)(4'-nitrophenyl)methyl)amino)-3-methylbutanoic acid methyl ester” reported a enantioselective synthesis of titled compound via Betti reaction with the assistant of (S)-valine. The authors worked on the Betti reaction extensively. Herein, this report unveiled an approach to obtain the chiral product as their well-continuing research in this area. The chiral product has been well-characterized with 1H NMR, 13C NMR, HRMS, as well as chiral HPLC. Meanwhile, the manuscript is well-written and well-organized. Therefore, the reviewer recommends it be published on Molbank. 

However, there are a few concerns that should be addressed.

1)    Figure 1, Figure 2, Figure 3 should be Scheme 1, Scheme 2, Scheme 3.

2)    Figure 3, as described in the context, the (S)-valine was used. Please draw the structure as chiral. It would be better that the reaction conditions are provided thereby. 

3)    Page 3, line 85: If possible, please provide the spectra that determine the ratio of (S,S) and (R,S) in the supplementary materials.

4)    The authors described the results from chiral HPLC. Please included the spectra in the supplementary materials.

5)    If possible, please include the peak labels from both 1H NMR and 13C NMR in the supplementary materials

Author Response

(1) Figures 1, 2 and 3 were changed to Schemes 1, 2 and 3.

(2) The stereochemistry and the reaction conditions were added in Scheme 3.

(3) In the Supplementary Materials, we added the H(1)-NMR spectrum of the crude reaction mixture, with a particular focus on the benzyl hydrogen atom zone.

(4) We added in the Supporting Materials the graphical representation of the HPLC of the (S,S)-stereoisomer and of an almost 3:1 mixture of (S,S) and (R,R)-stereoisomer.

(5) The peak labels were added in the H(1)- and C(13)-NMR spectra in the Supplementary Materials.