Organic Letters
Letter
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pound 6, a building block for the synthesis of Lycopodium
alkaloids,17 was converted into alkene 8 via enol triflate
formation followed by reduction.18 Because of the steric
hindrance of 8, the reaction required more time, but
fortunately, competitive reduction of the alkene was minimal.
Regioselective coupling with pyridine 1h gave 9 along with its
epimer (2:1 dr). The achievement of compound 9 constitutes
a formal synthesis of serratezomine E, as we have previously
demonstrated that intermediate 9 can be converted to this
Lycopodium alkaloid in a few steps.19
In summary, we have developed an efficient iron-catalyzed
hydrogen atom transfer (MHAT) reductive cross-coupling
reaction between alkenes and tosylhydrazones. Overall, this
work provides an effective new strategy for the formation of
sp3−sp3 carbon bonds and offers new retrosynthetic design
options for the synthesis of complex molecules. Considering its
use of ubiquitous functional groups, readily available reagents,
high functional group tolerance, nontoxicity, and operational
simplicity, we believe that this methodology should find wide
application as a general C−C bond-forming reaction in target-
oriented synthesis.
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Functionalized olefin cross-coupling to construct carbon−carbon
bonds. Nature 2014, 516, 343−348. (c) Lo, J. C.; Kim, D.; Pan, C.−
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Construction from Olefins via Radicals. J. Am. Chem. Soc. 2017, 139,
2484−2503.
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge at
Detailed experimental procedures, characterization, and
(7) (a) Taniguchi, T.; Goto, N.; Nishibata, A.; Ishibashi, H. Iron-
Catalyzed Redox Radical Cyclizations of 1,6-Dienes and Enynes. Org.
Lett. 2010, 12, 112−115. (b) Crossley, S. W. M.; Barabe, F.; Shenvi,
R. A. Simple, Chemoselective, Catalytic Olefin Isomerization. J. Am.
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Michaudel, Q.; Maxwell, B. D.; Baran, P. S. Hydromethylation of
Unactivated Olefins. J. Am. Chem. Soc. 2015, 137, 8046−8049.
(d) Shen, Y.; Qi, J.; Mao, Z.; Cui, S. Fe-Catalyzed Hydroalkylation of
Olefins with para-Quinone Methides. Org. Lett. 2016, 18, 2722−
2725. (e) Ma, X.; Herzon, S. B. Intermolecular Hydropyridylation of
Unactivated Alkenes. J. Am. Chem. Soc. 2016, 138, 8718−8721.
(f) Bordi, S.; Starr, J. T. Hydropyridylation of Olefins by
Intramolecular Minisci Reaction. Org. Lett. 2017, 19, 2290−2293.
(g) Shen, Y.; Huang, B.; Zheng, J.; Lin, C.; Liu, Y.; Cui, S. Csp−Csp3
Bond Formation via Iron(III)-Promoted Hydroalkynylation of
Unactivated Alkenes. Org. Lett. 2017, 19, 1744−1747. (h) Turner,
O. J.; Murphy, J. A.; Hirst, D. J.; Talbot, E. P. A. Chem. - Eur. J. 2018,
24, 18658−18662. (i) Wang, Y.; Bode, J. Olefin Amine (OLA)
Reagents for the Synthesis of Bridged Bicyclic and Spirocyclic
Saturated N-Heterocycles by Catalytic Hydrogen Atom Transfer
(HAT) Reactions. J. Am. Chem. Soc. 2019, 141, 9739−9745.
(8) (a) George, D. T.; Kuenstner, E. J.; Pronin, S. V. A Concise
Approach to Paxilline Indole Diterpenes. J. Am. Chem. Soc. 2015, 137,
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Asymmetric Total Synthesis of Hispidanin A. Angew. Chem., Int. Ed.
2017, 56, 5849−5852. (c) Liu, J.; Ma, D. A Unified Approach for the
Assembly of Atisine- and Hetidine-type Diterpenoid Alkaloids: Total
Syntheses of Azitine and the Proposed Structure of Navirine C.
Angew. Chem., Int. Ed. 2018, 57, 6676−6680. (d) Lu, Z.; Zhang, X.;
Guo, Z.; Chen, Y.; Mu, T.; Li, A. Total Synthesis of Aplysiasecosterol
A. J. Am. Chem. Soc. 2018, 140, 9211−9218. (e) Godfrey, N. A.;
Schatz, D. J.; Pronin, S. V. Twelve-step Asymmetric Synthesis of
(−)-Nodulisporic Acid C. J. Am. Chem. Soc. 2018, 140, 12770−
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AUTHOR INFORMATION
Corresponding Authors
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ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Financial support for this research was provided by Project
CTQ2016-75350-P from the Ministry of Economy and
Competitiveness (MINECO) of Spain/FEDER funds. B.B.
acknowledges the Serra Hunter Program (Generalitat de
Catalunya).
REFERENCES
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(3) For pioneering work on relevant hydrofunctionalizations, see:
(a) Mukaiyama, T.; Isayama, S.; Inoki, S.; Kato, K.; Yamada, T.;
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