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Organic & Biomolecular Chemistry
Page 4 of 5
DOI: 10.1039/C5OB02072G
ARTICLE
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in detail to explain the high regioselectivity by chemistry
experiments, hydrogen-deuterium exchange and mass
spectrometry. An interesting Br-/Cl- exchange was discovered
firstly in the process.
Acknowledgements
We are grateful to the financial support of NSFC (No.
21072087).
Scheme 6 The Proposed Reaction Mechanism.
Notes and references
Based on the reaction mechanism and the results shown in
1
2
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Scheme 6, we supposed that i-PrMgCl may promote the one-
pot successive Grignard reactions of the acyclic 1,3-dione and
cyclic 1,3-dione14. Relative experimental results reached the
target as expected (Table 4). The results in Table 4 showed
that the sub-stoichiometric amount of i-PrMgCl can
successfully promoted the one-pot successive Grignard
reactions to obtain two different adducts compared to the
one-substrate-one-product method14. The two products
tertiary hydroxyl ketone and -substituted enone can be
β-
β
readily separated and purified by one column. The i-PrMgCl
loading in the successive two Grignard reactions was actually
decreased by 50% in comparison with the one-substrate-one-
product method and thus its catalytic efficiency was greatly
increased. Such a one-pot successive two-substrate-for-two-
product Grignard reaction has not yet been reported.
3
4
P. Canonne and H. Bilodeau, Can. J. Chem., 1966, 44, 2849.
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5
6
Table 4 The Successive Grignard Reactions.a
7
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9
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entry
R1
R2
yield of 1
yield of 2
(%)b
(%)b
,
1c
2
3
4
5
6
7
Me
Me
Me
Me
Ph
Ph
Ph
56
90
89
85
88
88
76
47
82
85
79
81
86
68
Lett., 2014, 16
Zambrano, A. Sartori, C. Curti, L. Battistini, G. Pelosi, G.
Casiraghi and F. Zanardi, J. Am. Chem. Soc., 2014, 136, 11107.
, 3912; (e) L. Dell’Amico, G. Rassu, V.
2-naphthyl
4-MeOC6H4
Ph
10 (a) Y. Moritani, D. H. Appella, V. Jurkauskas and S. L.
Buchwald, J. Am. Chem. Soc., 2000, 122, 6797; (b) S. Kehrli, D.
Martin, D. Rix, M. Mauduit and A. Alexakis, Chem. Eur. J.,
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Gopakumar, W. Thiel and B. List, J. Am. Chem. Soc., 2013,
135, 6677.
Ph
2-naphthyl
n-heptyl
Ph
aIn THF. The amounts of the two 1,3-diones were both 0.5 mmol, and the total 20
mol% i-PrMgCl was used. bIsolated yield based on the respective theoretical yield.
cWithout i-PrMgCl.
11 C. Grison, Preparation and reactivity of magnesium enolates.
In The Chemistry of Organomagnesium Compounds; Z.
Rapporport, and I. Marek, Eds.; John Wiley
Chichester, 2008, chapter 11, pp 437.
& Sons,
Conclusions
12 S. Yamabe and S. Yamazaki, Theoretical studies of the
addition of RMgX to carbonyl compounds. In The Chemistry
of Organomagnesium Compounds; Z. Rapporport, and I.
Marek, Eds.; John Wiley & Sons, Chichester, 2008; chapter 9,
pp 369.
13 (a) E. A. Standley and T. F. Jamison, J. Am. Chem. Soc., 2013,
135, 1585; (b) F. Proutiere, M. Aufiero and F. Schoenebeck, J.
Am. Chem. Soc., 2012, 134, 606; (c) T. Kinzel, Y. Zhang and S.
L. Buchwald, J. Am. Chem. Soc., 2010, 132, 14073; (d) L. T.
Ball, G. C. Lloyd-Jones and C. A. Russell, J. Am. Chem. Soc.,
This work developed a first effective unilateral one-step
additions of Grignard reagents to acyclic or cyclic
promoted by sub-stoichiometric amount of i-PrMgCl to afford
-tertiary hydroxyl ketones or 3-substituted cyclic-2-enones
respectively. A new method to gain -tertiary hydroxyl ketones
and 3-substituted cyclic enones from -diketones in one-pot
β-diketones
β
β
β
was also put forward. The reaction mechanism was discussed
4 | J. Name., 2012, 00, 1-3
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