D
L. Ouyang et al.
Letter
Synlett
On the basis of the above results and on previously re-
ported studies, a tentative mechanism for the Reformatsky
reaction of ketones and aldehydes is proposed in Scheme
6.14 As the strong reducing agent of Mn, Cu0 was reduced to
an active form in situ. Then the active form inserts into the
carbon–halogen bond to produce the organometallic, which
undergoes subsequent nucleophilic addition to the carbon-
yl. The Mn(II) obtained in the redox reaction between
Mn(0) and Cu(I), reacts with the alkoxide to generate man-
ganese alkoxide. Finally, the desired products were ob-
tained with the help of CF3COOH. The CuII complex was re-
duced to Cu0 with the help of Mn powder, and continued in
the next catalytic cycle.
References and Notes
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1735.
2 CuI + Mn
2 Cu0 + MnI2
O
O
Cu0
OCuI
OEt
I
Cu
OEt
I
OEt
(5) (a) Rieke, R. D.; Uhm, S. J. Synthesis 1975, 452. (b) Santaniello, E.;
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Shen, Z.-L. Org. Lett. 2019, 21, 5873. (g) Cao, Q.; Stark, R. T.;
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Mn0
O
R
R'
I
MnI2
I
CuI2
Cu
H2O, H+
Mn
OH
O
O
O
O
O
R
OEt
R
OEt
R
OEt
R'
R'
R'
Scheme 6 Proposed mechanism
In conclusion, we have disclosed an efficient and simple
application of the Reformatsky reaction to synthesize -hy-
droxyl esters via a Cu-catalyzed and Mn-mediated system.15
A variety of ketones and aldehydes with a range of func-
tional groups are highly compatible, especially for the natu-
ral product-derived substrates. More importantly, the con-
venient, practical and efficient transformation is likely to
have larger ramifications. Ongoing studies are focused on
exploring asymmetric catalyzed applications and on exam-
ining details of the mechanism of the reaction.
(9) Cozzi, P. G. Angew. Chem. Int. Ed. 2006, 45, 2951.
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2019, 119, 2524.
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Umani-Ronchi, A.; Cozzi, P. G. J. Organomet. Chem. 2007, 692,
3191. (b) Kakiya, H.; Nishimae, S.; Shinokubo, H.; Oshima, K.
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2015, 44, 1155.
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(b) Yao, H.; Cao, C.-R.; Jiang, M.; Liu, J.-T. J. Fluorine Chem. 2013,
156, 45.
Funding Information
This project was funded by the National Natural Science Foundation
of China (21962004, 21961002, 21562004), Jiangxi provincial depart-
ment of science and technology (20192BAB203004), the emergency
research project for Gannan Medical University (YJ202027), and the
Fundamental Research Funds for Gannan Medical University
(QD201810) for financial support.
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(14) (a) Durandetti, M.; Périchon, J. Synthesis 2009, 1542.
(b) Chattopadhyay, A.; Dubey, A. K. J. Org. Chem. 2007, 72, 9357.
(c) Hojo, M.; Harada, H.; Ito, H.; Hosomi, A. J. Am. Chem. Soc.
1997, 119, 5459. (d) Suh, S.; Rieke, R. D. Tetrahedron Lett. 2004,
45, 1807. (e) Liu, X.-Y.; Li, X.-R.; Zhang, R.; Chu, X.-Q.; Rao, W.;
Loh, T.-P.; Shen, Z.-L. Org. Lett. 2019, 21, 5873.
Supporting Information
Supporting information for this article is available online at
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(15) Preparation of 3 and 5: To a 25 mL dried Schlenk tube was
added the mixture of carbonyl compounds (0.5 mmol), Mn
powder (3 equiv), CuI (10 mol%), ethyl iodoacetate (0.75 mmol),
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E