1. Practical olefin hydroamination with nitroarenes
by Jinghan Gui, Chung-Mao Pan, Ying Jin, Tian Qin, Julian C. Lo, Bryan J. Lee, Steven H. Spergel, Michael E. Mertzman, William J. Pitts, Thomas E. La Cruz, Michael A. Schmidt, Nitin Darvatkar, Swaminathan R. Natarajan, and Phil S. Baran
Science
Volume 348(6237):
May 22, 2015
Published by AAAS

2. Fig. 1 Amine synthesis via coupling of nitroarenes and olefins.
Amine synthesis via coupling of nitroarenes and olefins. (A) Amine retrosynthesis: a case study from drug discovery. (B) Invention and optimization of a nitroarene-based olefin hydroamination. Cbz, benzyloxycarbonyl; PG, protecting group; Me, methyl; Ph, phenyl; Et, ethyl; acac, acetylacetonate; dpm, 2,2,6,6-tetramethylheptane-3,5-dionate; dibm, 2,6-dimethylheptane-3,5-dionate; OTMS, trimethylsilyloxy; ND, not determined.
Jinghan Gui et al. Science 2015;348:
Published by AAAS

3. Fig. 2 Olefins explored in the hydroamination process.
Olefins explored in the hydroamination process. Bn, benzyl; D, deuterium.
Jinghan Gui et al. Science 2015;348:
Published by AAAS

4. Fig. 3 Scope of the olefin hydroamination.
Scope of the olefin hydroamination. Isolated yields are shown in parentheses along with the donor olefin used. Standard conditions: nitro(hetero)arene (1 equiv), olefin (3 equiv), Fe(acac)3 (30 mol %), PhSiH3 (2 equiv), EtOH, 60°C, 1 hour; Zn (20 equiv), HCl(aq), 60°C, 1 hour. Bu, butyl; Pr, propyl.
Jinghan Gui et al. Science 2015;348:
Published by AAAS

5. Fig. 7 Limitations of the hydroamination.
Limitations of the hydroamination. (A) Nitroalkanes give low yields. (B) Limitations of functional group tolerance.
Jinghan Gui et al. Science 2015;348:
Published by AAAS

6. Fig. 5 Olefin hydroamination applied to shorter syntheses of known pharmaceutical targets.
Olefin hydroamination applied to shorter syntheses of known pharmaceutical targets. (A) Glucocorticoid receptor modulator intermediate 108. (B) HIV-1 reverse transcriptase inhibitor intermediate 111. Boc, tert-butyloxycarbonyl. (C) ORL1 receptor inhibitor intermediate 113.
Jinghan Gui et al. Science 2015;348:
Published by AAAS

7. Fig. 6 Creative uses of the olefin hydroamination technique.
Creative uses of the olefin hydroamination technique. (A) Cascade reductive aminations for amine annulation. (B) An efficient method to access hindered Michael adducts. (C) Application to deuterium labeling using isobutylene-d8 (AA). (D) Temperature profile of the formation of a current intermediate in process chemistry over 6 hours shows the absence of an induction period.
Jinghan Gui et al. Science 2015;348:
Published by AAAS

8. Fig. 4 Scope of the olefin hydroamination, continued.
Scope of the olefin hydroamination, continued. Isolated yields are shown in parentheses along with the donor olefin used. Standard conditions: nitro(hetero)arene (1 equiv), olefin (3 equiv), Fe(acac)3 (30 mol %), PhSiH3 (2 equiv), EtOH, 60°C, 1 hour; Zn (20 equiv), HCl(aq), 60°C, 1 hour.
Jinghan Gui et al. Science 2015;348:
Published by AAAS