Synthesis of Methyl 2-((4R)-3-Acryloyl-4-phenyloxazolidin-2-yl)acetates

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

 

In this revised version the authors have correctly responded to my suggestions. The work can now be published

Reviewer 2 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

The manuscript was well-revised according to the previous reviewer’s comments. Especially structure of final compound was unambiguously elucidated by NOESY study on both diastereomers. Thus, I recommend this article to be published in Molbank.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Actually, adduct 7a is already known in the literature; however it has not been isolated and characterized. 

Asymmetric synthesis of nitrogen heterocycles by reaction of chiral β-enaminocarbonyl substrates with acrylate derivatives

Agami, Claude; Dechoux, Luc; Hebbe, Séverine [Tetrahedron Letters, 2002, vol. 43, # 14, p. 2521 - 2523]

The main flaw of the proposed procedure is that the diastereoselectivity is not very high. Didn't the authors try a chiral catalyst as an alternative to DABCO? Better diastereoselectivity would be an added value

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript describes a novel synthetic approach to chiral oxazolidnes through N-acylation and DABCO catalyzed double Michael addition. However, structural assignments of final compounds are not enough to avoid other structural possibility. Due to uncertainty in structural elucidation of final cmpounds as a main reason and other minor reasons, as a reviewer, I could not recommend this article for publication in Molbank. Detailed comments related with this decision is provided below.

 

1.     Uncertainty in structural determination of 7b.

Authors insist that absolute configuration of chiral centers in 7b as (2S) and (4R) based on NOESY NMR study. NOESY data of 7b in supplementary information shows two kinds of correlations.

A)    correlations between protons at C4 and C5 of oxazolidine ring

B)    correlations between protons at C2 of oxazolidine ring and alpha protons of methyl ester

These two correlations elucidate connectivity, which is already induced by COSY data. However, They could not confirm any relative configuration of C2 position.

In reference 13 (C. Agami et al. / Tetrahedron Letters 43 (2002) 2521–2523), simple description of NOE study of 7a compound (compound number 4 in reference 13) without detailed spectral data. This might be negative proof for structure of 7b. But, I think, more solid and positive proofs for structural elucidation is crucial for further research by authors themselves and other’s related research.

 

2.     Questions on mechanistic proposal

Authors describes possible catalytic role of DABCO in Scheme 3. Addition of DABCO to unsaturated amide to provide zwitter ionic intermediate. However, in reference 15 (J. Org. Chem. 2013, 78, 5832−5842) DABCO is added into methyl propynoate, which is same zwitter ionic compound, which deprotonates amide proton to facilitate Michael addition. I think the latter is more likely to occur in this reaction. At least author would be better describes other possible mechanism. Or if authors have other proof for mechanism in Scheme 3, detailed discussion should be added in test.

 

3.     Minor corrections

Line 25: [5,6] à [5,6] plain character

Line 58: (10 m01%) à (10 mol%)

Line 219: please, check reference!