Journal of the American Chemical Society
Communication
2010, 1574. (c) Kohmura, Y.; Mase, T. J. Org. Chem. 2004, 69, 6329.
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A. R.; Hong, Q.; Yang, Z. J. Org. Chem. 1995, 60, 3405.
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37, 560. (b) Clayden, J.; Yasin, S. A. New J. Chem. 2002, 26, 191.
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manganese carbene complex E, followed by a 1,2-aryl shift
affording intermediate G (path b). To distinguish these two
possibilities, we performed the corresponding DFT calculations.
Due to the open-shell character of Mn(II) system, all three
electronic states were explored.9 It turned out that only high (S =
5/2) and medium (S = 3/2) spin states are energetically relevant
in the reaction and promote different THF ring-opening modes.
In the ground high-spin state, transition state TSD‑F is located
that directly links D and F via a rearrangement of four chemical
bonds in a concerted but nonsynchronized manner with a
reaction barrier of 23.1 kcal/mol. In contrast, in the medium spin
state, C−O breakage takes place first through TSD‑E to generate
E, followed by 1,2-aryl migration through TSE‑G to form G.
Because the medium-spin-state reaction profile is always higher
in energy than the high-spin one,9 we conclude that the reactivity
in the high-spin state (path a) dominates the reaction. The
ensuing insertion of imine 1b into the C−Mn bond of F provides
H. Final transmetalation regenerates A and produces 1,5-amino
alcohol 3ba after quenching with water. In addition, LiCl might
contribute to tuning the reactivity and stability of organo-Mn
species in the catalytic cycle.16
In summary, a first Mn-catalyzed three-component reaction of
Grignard reagents, imines/nitriles, and THF has been developed,
by which a wide range of 1,5-amino/keto alcohols is expediently
synthesized in a convergent manner. Strikingly, THF is formally
transformed by the Mn/Mg bimetallic system into a 1-butoxide
4-carbenoid equivalent, which reacts amphiphilically with both
electrophilic and nucleophilic reagents. The reaction also
features Mn catalysis, low-cost and readily accessible starting
materials, reliable scalability, and mild reaction conditions.
Simple derivatizations of the 1,5-amino/keto alcohols provide a
facile access to piperidines and dihydropyrans. Experimental and
computational mechanistic studies disclose the pivotal role of
Mn in the radical initiation, C−O bond cleavage, and formation
of two geminal C−C bonds. Considering that hundreds of
thousands of tonnes of THF is produced annually, exploration of
THF as a versatile building block holds great promise in organic
synthesis.
(5) Selected examples for C−C bond formation of THF: (a) Liu, D.;
Liu, C.; Li, H.; Lei, A. Angew. Chem., Int. Ed. 2013, 52, 4453. (b) Xie, Z.;
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Wan, X.-L.; Che, C.-M. Chem. Commun. 2012, 48, 4299. (e) Zhang, S.-
Y.; Zhang, F.-M.; Tu, Y.-Q. Chem. Soc. Rev. 2011, 40, 1937. (f) Singh, P.
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Pan, S.; Liu, J.; Li, Z. J. Org. Chem. 2009, 74, 8848. (i) Inoue, A.;
Shinokubo, H.; Oshima, K. Synlett 1999, 10, 1582. (j) Ishida, A.; Sugita,
D.; Itoh, Y.; Takamuku, S. J. Am. Chem. Soc. 1995, 117, 11687.
(k) Mudryk, B.; Cohen, T. J. Am. Chem. Soc. 1991, 113, 1866. C−B
bond formation of THF: (l) Liskey, C. W.; Hartwig, J. F. J. Am. Chem.
Soc. 2012, 134, 12422. C−O bond formation: (m) Tortoreto, C.;
́ ́
Achard, T.; Zeghida, W.; Austeri, M.; Guenee, L.; Lacour, J. Angew.
Chem., Int. Ed. 2012, 51, 5847. C−N bond formation: (n) Ochiai, M.;
Yamane, S.; Hoque, Md. M.; Saito, M.; Miyamoto, K. Chem. Commun.
2012, 48, 5280.
(6) Reviews: (a) Albrecht, M. Chem. Rev. 2010, 110, 576. (b) Flood, T.
C. In Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, F.
G. A., Wilkinson, G., Eds.; Pergamon: Oxford, U.K., 1995, Vol. 6, 21−82.
(c) Wang, C. Synlett 2013, 24, 1606.
(7) (a) Kuninobu, Y.; Nishina, Y.; Takeuchi, T.; Takai, K. Angew.
Chem., Int. Ed. 2007, 46, 6518. (b) Zhou, B.; Chen, H.; Wang, C. J. Am.
Soc. Chem. 2013, 135, 1264.
(8) Yoshikai, N.; Mieczkowski, A.; Matsumoto, A.; Ilies, L.; Nakamura,
E. J. Am. Chem. Soc. 2010, 132, 5568.
(9) For more details, see Supporting Information.
(10) Cahiez, G.; Lepifre, F.; Ramiandrasoa, P. Synthesis 1999, 2138.
(11) (a) Sapountzis, I.; Knochel, P. Angew. Chem., Int. Ed. 2002, 41,
1610. (b) Shirakawa, E.; Hayashi, Y.; Itoh, K.; Watabe, R.; Uchiyama, N.;
Konagaya, W.; Masui, S.; Hayashi, T. Angew. Chem., Int. Ed. 2012, 51,
218.
(12) Piperidine: (a) Itoh, A.; Ikuta, Y.; Tanahashi, T.; Nagakura, N. J.
Nat. Prod. 2000, 63, 723. (b) Watson, P. S.; Jiang, B.; Scott, B. Org. Lett.
2000, 2, 3679. (c) Kam, O.-S.; Anuradha, S. Phytochemistry 1995, 40,
313. (d) Ferris, J. P.; Briner, R. C.; Boyce, C. B. J. Am. Chem. Soc. 1971,
93, 2958. Dihydropyran: (e) Lin, C.-N.; Lu, Y.-H.; Ko, H.-H.; Yang, S.-
Z.; Tsao, L.-T.; Wang, J.-P. Helv. Chim. Acta 2003, 86, 2566. (f) Kakeya,
H.; Onose, R.; Koshino, H.; Yoshida, A.; Kobayashi, K.; Kageyama, S.-I.;
Osada, H. J. Am. Chem. Soc. 2002, 124, 3496. (g) Albers-Schonberg, G.;
Schmid, H. Helv. Chim. Acta 1961, 44, 1447.
ASSOCIATED CONTENT
* Supporting Information
Experimental and computational details, and characterization
data. This material is available free of charge via the Internet at
■
S
AUTHOR INFORMATION
Corresponding Author
■
Notes
(13) Yamada, K.; Fujihara, H.; Yamamoto, Y.; Miwa, Y.; Taga, T.;
Tomioka, K. Org. Lett. 2002, 4, 3509.
The authors declare no competing financial interest.
(14) (a) Cahiez, G.; Duplais, C.; Buendia, J. Chem. Rev. 2009, 109,
1434. (b) Nakao, J.; Inoue, R.; Shinokubo, H.; Oshima, K. J. Org. Chem.
1997, 62, 1910.
ACKNOWLEDGMENTS
■
Generous financial support from the National Basic Research
Program of China (973 Program, No. 2012CB821600) and the
National Natural Science Foundation of China (21322203,
21272238, 21290194, 21221002) is gratefully acknowledged.
(15) A related review: Fernan
Rev. 2009, 109, 6687.
́
dez, I.; Cossío, F. P.; Sierra, M. A. Chem.
(16) (a) Hevia, E.; Mulvey, R. E. Angew. Chem., Int. Ed. 2011, 50, 6448.
(b) Cahiez, G.; Razafintsalama, L.; Laboue, B.; Chau, F. Tetrahedron
Lett. 1998, 39, 849.
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