Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle 'Stitching' by N-H Insertion and Cyclization
DOI: 10.14469/hpc/4818 Metadata
Created: 2018-11-28 17:53
Last modified: 2019-02-05 16:48
License: Creative Commons: Public Domain Dedication 1.0
Funding: (none given)
Co-author: Alan Spivey Co-author: James A. Bull Co-author: Christopher Cordier
Description
Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2-disubstituted azetidines, pyrrolidines, piperidines and azepanes bearing ester and diverse aryl substituents. A one-pot rhodium catalyzed NâH insertion and cyclization sequence uses diazo compounds to stitch together linear 1,m-haloamines (m = 2 to 5) to rapidly assemble 4-, 5-, 6- and 7-membered saturated nitrogen heterocycles in excellent yields. Over fifty examples are demonstrated, including with diazo compounds derived from biologically active compounds. The products can be functionalized to afford alpha,alpha-disubstituted amino acids and applied to fragment synthesis.
Files
| Filename | Size | Type | Description |
|---|---|---|---|
| 1. Protected amine starting materials.zip | 33MB | application/zip | Data for Protected Amine Starting Materials 1â3, 9, 10, 16â18, S1âS8 (raw NMR data, mnova file for processed data, IR and HRMS) |
| 1. Protected amine starting materials.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 1. Protected amine starting materials.zip |
| 2. Ester and Diazo Compounds .zip | 32MB | application/zip | Data for Ester and Diazo Compounds 11b,dâi,k,l,o, S9âS17 (raw NMR data, mnova file for processed data, IR and HRMS) |
| 2. Ester and Diazo Compounds .mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 2. Ester and Diazo Compounds .zip |
| 3. Diester Saturated Nitrogen Heterocycles.zip | 3MB | application/zip | Data for Diester Saturated Nitrogen Heterocycles 6â8 (raw NMR data, mnova file for processed data, IR and HRMS) |
| 3. Diester Saturated Nitrogen Heterocycles.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 3. Diester Saturated Nitrogen Heterocycles.zip |
| 4. Azetidines.zip | 37MB | application/zip | Data for Azetidines 12aâm and 13a (raw NMR data, mnova file for processed data, IR and HRMS) |
| 4. Azetidines.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 4. Azetidines.zip |
| 5. Pyrrolidines.zip | 100MB | application/zip | Data for Pyrrolidines 14aâf, iâm and 15a,k (raw NMR data, mnova file for processed data, IR and HRMS) |
| 5. Pyrrolidines.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 5. Pyrrolidines.zip |
| 6. Piperidines.zip | 68MB | application/zip | Data for Piperidines 19aâf, jâm and 20 d,e and S18 (raw NMR data, mnova file for processed data, IR and HRMS) |
| 6. Piperidines.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 6. Piperidines.zip |
| 7. Azepanes.zip | 87MB | application/zip | Data for Azepanes 21a,b,e,h (raw NMR data, mnova file for processed data, IR and HRMS) |
| 7. Azepanes.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 7. Azepanes.zip |
| 8. Products of Derivatization.zip | 84MB | application/zip | Data for Products of Derivatization 22â36 and S19â21 (raw NMR data, mnova file for processed data, IR and HRMS) |
| 8. Products of Derivatization.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 8. Products of Derivatization.zip |
| 9. Late Stage Functionalization.zip | 102MB | application/zip | Data for Late Stage Functionalization 37â45 and S22â25 (raw NMR data, mnova file for processed data, IR and HRMS) |
| 9. Late Stage Functionalization.mnpub | 0 | chemical/x-mnpub | Mestrenova signature file for 9. Late Stage Functionalization.zip |
Associated DOIs
| Current dataset ... | DOI | Description |
|---|---|---|
| References | 10.1002/ange.201812925 | doi for paper published in Angew. Chem. |
| References | 10.1002/anie.201812925 | doi for paper published in Angew. Chem. Int. Ed. |