Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Aug 3;83(15):8214-8224.
doi: 10.1021/acs.joc.8b00961. Epub 2018 Jun 14.

Evidence for a Sigmatropic and an Ionic Pathway in the Winstein Rearrangement

Amy A Ott  1 , Mary H Packard  1 , Manuel A Ortuño  1 , Alayna Johnson  1 , Victoria P Suding  1 , Christopher J Cramer  1 , Joseph J Topczewski  1
Affiliations

Evidence for a Sigmatropic and an Ionic Pathway in the Winstein Rearrangement

Amy A Ott et al. J Org Chem. .

Abstract

The spontaneous rearrangement of allylic azides is thought to be a sigmatropic reaction. Presented herein is a detailed investigation into the rearrangement of several allylic azides. A combination of experiments including equilibrium studies, kinetic analysis, density functional theory calculations, and selective 15N-isotopic labeling are included. We conclude that the Winstein rearrangement occurs by the assumed sigmatropic pathway under most conditions. However, racemization was observed for some cyclic allylic azides. A kinetic analysis of this process is provided, which supports a previously undescribed ionic pathway.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Plot of log(k/k0) vs σ+ for substituent effects on the racemization of azides 30a–f in MeOH. Rates were measured in duplicate, replicates shown.
Figure 2
Figure 2
Plot of log(k/k0) vs σ+ for substituent effects on the solvolysis of azides 30a–f in MeOH. Rates were measured in duplicate, replicates shown.
Scheme 1
Scheme 1
Winstein Rearrangement
Scheme 2
Scheme 2
Effects of Conjugation on Keq
Scheme 3
Scheme 3
Rearrangement of 15N-Labeled Allylic Azide
Scheme 4
Scheme 4
Equilibration of Azides 23 and 24a a(a) Values determined by 1H NMR. (b) Free energies (kcal/mol, 1 M standard state, 75 °C) computed at the SMD(CHCl3)/M06-2X/6-311+G(2df,p)//SMD(CHCl3)/M06-2X/6-31G(d) level of theory. The vertical scale has been compressed by 15.0 kcal/mol between the ground states and transition states.
Scheme 5
Scheme 5
Equilibration of Chiral Allylic Azidea a(a) Values determined by 1H NMR. (b,c) Free energies (kcal/mol, 1 M standard state, 75 °C) computed at the SMD(CHCl3)/M06-2X/6-311+G(2df,p)//SMD(CHCl3)/M06-2X/6-31G(d) level of theory. The vertical scale has been compressed by 15.0 kcal/mol between the ground states and transition states.
Scheme 6
Scheme 6
Relative Ionization Energies of Azide 26a aFree energies (kcal/mol, 1 M standard state, 75 °C) computed at the M06-2X/6-311+G(2df,p)//M06-2X/6-31G(d) level of theory for gas-phase and SMD-solvated reaction coordinates. The vertical scale has been compressed by 60.0 kcal/mol between chloroform and gas phase.
Scheme 7
Scheme 7
Racemization and Solvolysis of Cyclic Azides
See this image and copyright information in PMC

References

    1. Lutz RP. Catalysis of the Cope and Claisen Rearrangements. Chem. Rev. 1984;84:206–243.
    1. Nakai T, Mikami K. [2,3]-Wittig Sigmatropic Rearrangements in Organic Synthesis. Chem. Rev. 1986;86:885–902.
    1. Wilson SR, Price MF. The Ester Enolate Carroll Rearrangment. J. Org. Chem. 1984;49:722–725.
    1. Kantor SW, Hauser CR. Rearrangements of Benzyltrimethylammonium Ion and Related Quaternary Ammonium Ions by Sodium Amide Involving Migration into the Ring. J. Am. Chem. Soc. 1951;73:4122–4131.
    1. Evans DA, Andrews GC. Allylic Sulfoxides: Useful Intermediates in Organic Synthesis. Acc. Chem. Res. 1974;7:147–155.

Publication types