Nickel-catalyzed organozinc-induced unexpected 1,3-migration of tert-butyl from sulfur to carbon in N-tert-butanesulfinyl iminoacetates

Article abstract of DOI:10.1016/j.tetlet.2008.07.182

The nickel-catalyzed reaction for an unexpected 1,3-migration of tert-butyl from sulfur to carbon, upon treatment of functionalized N-tert-butanesulfinyl iminoacetate in the presence of organozinc reagent, was developed. The generality has been explored b

Full text of DOI:10.1016/j.tetlet.2008.07.182

Tetrahedron Letters 49 (2008) 6195–6197
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Tetrahedron Letters
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Nickel-catalyzed organozinc-induced unexpected 1,3-migration of tert-butyl
from sulfur to carbon in N-tert-butanesulfinyl iminoacetates
Xun Sun a, , Wei Zheng a,b, Bang-Guo Wei b,
*
*
a Department of Chemistry of Natural Drugs, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China
b Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The nickel-catalyzed reaction for an unexpected 1,3-migration of tert-butyl from sulfur to carbon, upon
treatment of functionalized N-tert-butanesulfinyl iminoacetate in the presence of organozinc reagent,
was developed. The generality has been explored by considering the flexibility in the structure of each
reactive component, organozinc halide and N-tert-butanesulfinyl iminoacetate.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 27 June 2008
Revised 24 July 2008
Accepted 25 July 2008
Available online 7 August 2008
Keywords:
1,3-Migration
Organozinc
Ni(acac)2
N-sulfinylimines
The carbon–carbon bond-forming reaction catalyzed by either a
nickel or palladium catalyst between organometallic reagents and
electrophiles is a powerful tool for constructing complex natural
and unnatural organic molecules in the last decades.1 Among these
organometallic reagents, organozinc halides represent an optimal
compromise in terms of reactivity and wide functional group
tolerance. Most of them have been used for the alkylation of alkyl
was treated with organozinc reagent in the presence of nickel,
instead of the desired product (nucleophilic addition) which was
only detected as a small amount, the predominant product was
the unexpected product which was generated by the 1,3-migration
of tert-butyl group from sulfur to carbon. To our best knowledge,
this is the first example of a 1,3-migration of tert-butyl from sulfur
to carbon that occurred in this system. Herein, we wish to report
this novel 1,3-migration which was achieved by organozinc halides
with N-tert-butanesulfinyl iminoacetate catalyzed by Ni(acac)2
(Scheme 1).
In order to investigate the scope and limitations of this novel
1,3-migration, various functionalized zinc reagents and catalysts
had been executed. When organozinc iodides were used, it was
found that all the reactions achieved good to excellent yields in
the presence of 10 mol % Ni(acac)2 (Table 1, entries 1–13) in a mild
reaction condition. We had also tested the organozinc bromides
instead of iodide and found that bromides were active enough to
obtain the desired products in this condition (entries 3 and 15),
although the yield was relatively low for benzylzinc bromide
(entry 14). Intensive screening revealed that the unexpected
migration was generated in lower yield (25%) when Et2Zn was used
in the same conditions.
electrophiles,2 aldehyde, ketone,3
a,b-unsaturated carbonyl
compounds,4 and imines5 (N-sulfonyl imines6) in mild conditions.
Recently, some new types of reactions (e.g., formation of E-stil-
benes by witting-type reaction via organozinc halides with high
selectivity and excellent yield) have also been developed.7
The N-sulfur imines, one of the most versatile intermediates,
have been extensively used in organic synthesis. Especially, the
commercially available chiral N-tert-butanesulfinamide is widely
used due to its excellent diastereocontrol and the mild conditions
for its cleavage.8,9 The direct additions of Grignard, organolithium,
and aryl boron reagents to N-sulfur imines represent the most reli-
able methods to prepare enantiopure amines,
a- and b-amino
acids, and
a
- and b-amino phosphonates.10,11 Unfortunately, these
reagents usually could not be tolerant to the labile functional
groups of nucleophiles. In order to find a general approach to pre-
pare amino acids bearing some unusual substituents, we are inter-
ested in exploring this challenging reaction by using organozinc
halides with glyoxylate N-tert-butanesulfimine catalyzed by Ni-
(acac)2. Surprisingly, when the N-tert-butanesulfinyl iminoacetate
The effects of the catalysts on this reaction were studied using
n-C3H7CH2ZnI as a substrate. As shown in Table 1, Ni(acac)2 gave
the best result with the 10 mol % loading (entries 1 and 16–19).
Interestingly, in the absence of Ni(acac)2, the reaction could contin-
ued to take place although the yield was relatively lower (entry
20). Consequently, catalysts may play an important role regarding
the reaction efficiency and the reactivity.
* Corresponding authors. Tel./fax: +86 21 54237757 (B.-G.W.).
E-mail address: bgwei1974@fudan.edu.cn (X. Sun).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.182

6196
X. Sun et al. / Tetrahedron Letters 49 (2008) 6195–6197
O
S
O
S
10%Ni(acac)2
O
THF/-20 oC-rt
O
+
FGCH2ZnX
N
CH2FG
N
H
O
O
Scheme 1.
Table 1
Organozinc-induced 1,3-migration of tert-butyl from N-tert-butanesulfinyl iminoacetates12
O
O
10%Ni(acac)2
THF/-20 oC-rt
O
S
O
S
+
FGCH2ZnX
N
CH2FG
N
H
O
O
3 a~n
1 a~n
Entrya
FGCH2À
X
Catalyst
T (°C)
Product
Yb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
CH3CH2
C2H5CH2
I
I
I
I
I
I
I
I
I
I
I
I
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
10% Ni(acac)2
20% Ni(acac)2
5% Ni(acac)2
10% In(OTf)3
10% Cu(OTf)2
None
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
À20 to rt
3a
3b
3c
3d
3e
3f
3g
3h
3i
92
88
89
81
85
76
79
83
74
71
68
72
78
47
87
87
74
18
23
61
n-C3H7CH2
n-C4H9CH2
n-C5H11CH2
n-C9H19CH2
(CH3)2CH
(CH3)2CHCH2
Cyclopentyl–
Cyclohexyl–
BnOOC(CH2)2CH2
CH3OOC(CH2)2CH2
BnOCH2(CH2)2CH2
PhCH2
n-C3H7CH2
n-C3H7CH2
3j
3k
3l
I
3m
3n
3c
3c
3c
3c
3c
3c
Br
Br
I
I
I
n-C3H7CH2
n-C3H7CH2
n-C3H7CH2
n-C3H7CH2
I
I
a
2.5 mmol alkyl zinc halides, 1 mmol N-tert-butanesulfinyl iminoacetate.
Isolated yield.
b
Table 2
Influence of the N-sulfinyl imines on the reactivity
O
S
1. HCl/MeOH
2. LiOH/H+
HO
EtO
O
R2
O
S
NH2
N
C4H9
C3H7CH2ZnI
H
S
O
O
R1
N
R2
R1
N
H
C4H9
10%Ni(acac)2
Scheme 2.
Entry
R1
R2
Ya ( %)
1
2
3
4
5
6
Ph
Ph
EtOOC
EtOOC
MeOOC
PhOOC
tert-Butyl
p-CH3C6H4
p-CH3C6H4
tert-Butyl
tert-Butyl
tert-Butyl
0
0
0
89
84
71
With optimal reaction condition in hand, a survey of various N-
sulfinyl imines was carried out (Table 2). If the ethyl, methyl, and
benzyl esters (entries 4–6) were applied, the 1,3-migration prod-
ucts were produced in high yields, while no desirable products
could be detected if benzylimines and N-substituted sulfimines
(entries 1–3) were used. By the removal of the N-sulfinyl and ethyl
a
Isolated yield.
XZnCH2FG
Ni(acac)2
O
O
O
S
R
O
O
S
+
N
CH2FG
fast
N
radical attacked sulfur
O
O
S
O
S
O
O
N
CH2FG
+
N
CH2FG
H
O
O
Scheme 3. Plausible mechanism of 1,3-migration of tert-butyl catalyzed by Ni(acac)2.

X. Sun et al. / Tetrahedron Letters 49 (2008) 6195–6197
6197
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groups of compound 3c under acidic condition (HCl/MeOH)
followed by ester hydrolysis (LiOH), an important product tert-
leucine would be afforded in 72% yield (Scheme 2). The
spectroscopic and physical data of the synthetic tert-leucine were
in excellent agreement with those reported.13 Thus, this manipula-
tion further unambiguously confirmed the structures of unex-
pected 1,3-migration products. A plausible reaction pathway is
shown in Scheme 3. We proposed that the plausible reaction
mechanism may be involved in a radical addition pathway, since
the CH2FG radical could be easily formed.14 It was reasoned
that the stabilized CH2FG radical by Ni(acac)2 attacks the sulfur
and the single electron on the oxygen atom comes back to re-form
the double bond of the sulfoxide. Meanwhile, the tert-Butyl radical
generated attacks the imine to form a new C–C bond. Further study
of the mechanism is underway.
In summary, nickel-catalyzed organozinc-promoted unex-
pected 1,3-migration of tert-butyl from sulfur to carbon in N-tert-
butanesulfinyl iminoacetates had been described. The structures
of these 1,3-migration products had been confirmed by converting
to the corresponding tert-leucine. The further utilization of these
1,3-migration products will be reported in due course.
11. Zhou, P.; Chen, B.-C.; Davis, F. A. Tetrahedron 2004, 60, 8003.
12. General procedure: To a solution of ethyl N-(tert-butanesulfinyl)iminoacetate
(205 mg, 1 mmol) and Ni(acac)2 (10 mol %) in anhydrous THF (10 mL) was
added a freshly prepared organozinc reagent (2.5 mL, 1 M in THF) at À20 °C
under argon atmosphere. Then the mixtures were allowed to warm to room
temperature. After being further stirred for another 6 h, the reaction mixture
was quenched with saturated aqueous NH4Cl (4 mL) and diluted with EtOAc
(30 mL) and brine (10 mL). The organic layer was separated and the aqueous
phase was extracted with EtOAc (20 mL Â 3). The combined organic layers
were washed with brine (10 mL Â 3), dried over anhydrous Na2SO4, filtered,
and concentrated. The residue was purified by chromatography on silica gel
(EtOAc/petroleum ether) to give mixtures of compounds. Compound 3c (the
ratio is 1:1 based on the GC value) as a colorless oil; IR (KBr) 3244, 2960, 2932,
Acknowledgments
This work was financially supported by the Natural Science
Foundation of China (NSFC 20702007, 20772017) and Fudan
University (EYH1615012). The authors also thank Dr. Hang-Qing
Dong for helpful suggestions.
2866, 1732, 1463, 1364, 1315, 1216, 1151 cmÀ1 1H NMR (CDCl3, 300 MHz) d
;
4.69 (d, J = 7.5 Hz, 1H), 4.45 (d, J = 7.8 Hz, 1H), 4.26–4.17 (m, 4H), 3.64 (d,
J = 10.8 Hz, 1H), 3.54 (d, J = 9.6 Hz, 1H), 2.84–2.69 (m, 4H), 1.72–1.61 (m, 4H),
1.51–1.41 (m, 4H), 1.29 (m, 6H), 1.05–0.94 (m, 24H); 13C NMR (CDCl3,
100 MHz) d 173.0, 172.6, 66.5, 61.3, 61.2, 60.9, 56.2, 54.3, 34.9, 34.0, 26.7, 26.3,
25.2, 25.1, 21.9, 21.8, 14.2, 14.1, 13.8, 13.7; MS (ESI): 286 (M+Na+); HRESIMS
calcd for (C12H25NNaO3S + Na+): 286.1455, found 286.1448.
References and notes
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