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
. 2020 Jun 23;11(27):7204-7209.
doi: 10.1039/d0sc01998d.

Ti-catalyzed ring-opening oxidative amination of methylenecyclopropanes with diazenes

Evan P Beaumier  1 , Amy A Ott  1 , Xuelan Wen  1 , Zachary W Davis-Gilbert  1 , T Alexander Wheeler  1 , Joseph J Topczewski  1 , Jason D Goodpaster  1 , Ian A Tonks  1
Affiliations

Ti-catalyzed ring-opening oxidative amination of methylenecyclopropanes with diazenes

Evan P Beaumier et al. Chem Sci. .

Abstract

The ring-opening oxidative amination of methylenecyclopropanes (MCPs) with diazenes catalyzed by py3TiCl2(NR) complexes is reported. This reaction selectively generates branched α-methylene imines as opposed to linear α,β-unsaturated imines, which are difficult to access via other methods. Products can be isolated as the imine or hydrolyzed to the corresponding ketone in good yields. Mechanistic investigation via density functional theory suggests that the regioselectivity of these products results from a Curtin-Hammett kinetic scenario, where reversible β-carbon elimination of a spirocyclic [2 + 2] azatitanacyclobutene intermediate is followed by selectivity-determining β-hydrogen elimination of the resulting metallacycle. Further functionalizations of these branched α-methylene imine products are explored, demonstrating their utility as building blocks.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Top: Eisen's report of Ti-catalyzed ring-opening hydroamination of MCPs. Bottom: TI-catalyzed oxidative amination of MCPs (this work).
Fig. 2
Fig. 2. Computational analysis (M06/6-311G(d,p), SMD PhCF3, 388.15 K) of Ti-catalyzed oxidative amination of 1a. Free energies reported in kcal mol−1. Both a monometallic pathway (blue) and bimetallic pathway (red) are energetically feasible. Similarly, catalyst species with a ligated pyridine (black) or without ligated pyridine (grey) also possible, although the ligated pyridine pathway is lower in energy.
Fig. 3
Fig. 3. Simplified catalytic cycle for α-methylene imine formation via ring-opening oxidative amination of MCPs.
Fig. 4
Fig. 4. β-Carbon elimination from 1a thermodynamically favors formation of IM4 over IM4′, and kinetic formation of IM4′ is reversible (M06/6-311G(d,p), SMD PhCF3, 388.15 K). Ln = pyCl2.
Fig. 5
Fig. 5. β-Carbon elimination from 1b both kinetically and thermodynamically favors formation of IM4′ over IM4 (M06/6-311G(d,p), SMD PhCF3, 388.15 K). Ln = pyCl2.
Fig. 6
Fig. 6. Regioselectivity of hydroamination and oxidative amination of 1a and 1b follow the same substrate control mechanisms. Conditions: 115 °C, 62 h (ox. amination) 20 h (hydroamination). *Yield determined via No-D 1H NMR spectroscopy.
Fig. 7
Fig. 7. Further functionalizations of products 2a (A) and 2e (B). *Denotes yields that were determined via1H NMR spectroscopy.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Park Y. Kim Y. Chang S. Chem. Rev. 2017;117:9247–9301. doi: 10.1021/acs.chemrev.6b00644. - DOI - PubMed
    2. Louillat M.-L. Patureau F. W. Chem. Soc. Rev. 2014;43:901–910. doi: 10.1039/C3CS60318K. - DOI - PubMed
    3. Zhou Y. Yuan J. Yang Q. Xiao Q. Peng Y. ChemCatChem. 2016;8:2178–2192. doi: 10.1002/cctc.201600079. - DOI
    4. Stokes B. J. Driver T. G. Eur. J. Org. Chem. 2011:4071–4088. doi: 10.1002/ejoc.201100150. - DOI
    5. Shin K. Kim H. Chang S. Acc. Chem. Res. 2015;48:1040–1052. doi: 10.1021/acs.accounts.5b00020. - DOI - PubMed
    6. Díaz-Requejo M. M. Pérez P. J. Chem. Rev. 2008;108:3379–3394. doi: 10.1021/cr078364y. - DOI - PubMed
    7. Davies H. M. L. Manning J. R. Nature. 2008;451:417–424. doi: 10.1038/nature06485. - DOI - PMC - PubMed
    8. Müller P. Fruit C. Chem. Rev. 2003;103:2905–2919. doi: 10.1021/cr020043t. - DOI - PubMed
    9. Lu H. Zhang X. P. Chem. Soc. Rev. 2011;40:1899–1909. doi: 10.1039/C0CS00070A. - DOI - PubMed
    10. Collet F. Lescot C. Dauban P. Chem. Soc. Rev. 2011;40:1926–1936. doi: 10.1039/C0CS00095G. - DOI - PubMed
    11. Halfen J. A. Curr. Org. Chem. 2005;9:657–669. doi: 10.2174/1385272053765024. - DOI
    12. Alderson J. M. Corbin J. R. Schomaker J. M. Acc. Chem. Res. 2017;50:2147–2158. doi: 10.1021/acs.accounts.7b00178. - DOI - PubMed
    1. Müller T. E. Hultzsch K. C. Yus M. Foubelo F. Tada M. Chem. Rev. 2008;108:3795–3892. doi: 10.1021/cr0306788. - DOI - PubMed
    2. Odom A. L. McDaniel T. J. Acc. Chem. Res. 2015;48:2822–2833. doi: 10.1021/acs.accounts.5b00280. - DOI - PubMed
    1. Gilbert Z. W. Hue R. J. Tonks I. A. Nat. Chem. 2016;8:63–68. doi: 10.1038/nchem.2386. - DOI - PubMed
    2. Davis-Gilbert Z. W. Yao L. J. Tonks I. A. J. Am. Chem. Soc. 2016;138:14570–14573. doi: 10.1021/jacs.6b09939. - DOI - PMC - PubMed
    3. Chiu H.-C. Tonks I. A. Angew. Chem., Int. Ed. 2018;57:6090–6094. doi: 10.1002/anie.201800595. - DOI - PMC - PubMed
    4. Davis-Gilbert Z. W. Wen X. Goodpaster J. D. Tonks I. A. J. Am. Chem. Soc. 2018;140:7267–7281. doi: 10.1021/jacs.8b03546. - DOI - PMC - PubMed
    5. Davis-Gilbert Z. W. Kawakita K. Blechschmidt D. R. Tsurugi H. Mashima K. Tonks I. A. Organometallics. 2018;37:4439–4445. doi: 10.1021/acs.organomet.8b00474. - DOI - PMC - PubMed
    6. Chiu H.-C. See X. Y. Tonks I. A. ACS Catal. 2019;9:216–223. doi: 10.1021/acscatal.8b04669. - DOI - PMC - PubMed
    7. Beaumier E. P. McGreal M. E. Pancoast A. R. Wilson R. H. Moore J. T. Graziano B. J. Goodpaster J. D. Tonks I. A. ACS Catal. 2019;9:11753–11762. doi: 10.1021/acscatal.9b04107. - DOI - PMC - PubMed
    8. Pearce A. J. Harkins R. P. Reiner B. R. Wotal A. C. Dunscomb R. J. Tonks I. A. J. Am. Chem. Soc. 2020;142:4390–4399. doi: 10.1021/jacs.9b13173. - DOI - PMC - PubMed
    9. Beaumier E. P. Pearce A. J. See X. Y. Tonks I. A. Nat. Rev. Chem. 2019;3:15–34. doi: 10.1038/s41570-018-0059-x. - DOI - PMC - PubMed
    10. Davis-Gilbert Z. W. Tonks I. A. Dalton Trans. 2017;46:11522–11528. doi: 10.1039/C7DT02319G. - DOI - PMC - PubMed
    1. Smolensky E. Kapon M. Eisen M. S. Organometallics. 2005;24:5495–5498. doi: 10.1021/om050518h. - DOI
    2. Smolensky E. Kapon M. Eisen M. S. Organometallics. 2007;26:4510–4527. doi: 10.1021/om700455e. - DOI

    3. ; For other examples of metal-catalyzed hydroamination of MCPs see

    4. Nakamura I. Itagaki H. Yamamoto Y. J. Org. Chem. 1998;63:6458–6459. doi: 10.1021/jo981468b. - DOI
    5. Nakamura I. Itagaki H. Yamamoto Y. Chem. Heterocycl. Compd. 2001;37:1532–1540. doi: 10.1023/A:1014513411239. - DOI
    6. Ryu J.-S. Li G. Y. Marks T. J. J. Am. Chem. Soc. 2003;125:12584–12605. doi: 10.1021/ja035867m. - DOI - PubMed
    7. Shi M. Liu L.-P. Tang J. Org. Lett. 2006;8:4043–4046. doi: 10.1021/ol0614830. - DOI - PubMed
    8. Nishikawa D. Sakae R. Miki Y. Hirano K. Miura M. J. Org. Chem. 2016;81:12128–12134. doi: 10.1021/acs.joc.6b02483. - DOI - PubMed
    9. Liu Y. Ogunlana A. A. Bao X. Dalton Trans. 2018;47:5660–5669. doi: 10.1039/C8DT00131F. - DOI - PubMed
    10. Timmerman J. C. Robertson B. D. Widenhoefer R. A. Angew. Chem., Int. Ed. 2015;54:2251–2254. doi: 10.1002/anie.201410871. - DOI - PubMed
    11. Timmerman J. C. Widenhoefer R. A. Adv. Synth. Catal. 2015;357:3703–3706. doi: 10.1002/adsc.201500866. - DOI
    12. Shi M. Chen Y. Xu B. Org. Lett. 2003;5:1225–1228. doi: 10.1021/ol034146p. - DOI - PubMed
    1. O'Reilly M. E. Dutta S. Veige A. S. Chem. Rev. 2016;116:8105–8145. doi: 10.1021/acs.chemrev.6b00054. - DOI - PubMed