A 1,3-lithium shift of propargylic/allenylic lithium and the subsequent transmetalation coupling reaction with aryl halides

Article abstract of DOI:10.1002/anie.200352924

The lithiation reagent and temperature may be the key factors controlling the 1,3-lithium shift of propargylic/allenylic lithium (see scheme). Under the right conditions, 1,1-diarylallenes and 1,3-diarylallenes can be easily and highly selectively synthes

Full text of DOI:10.1002/anie.200352924

Communications
Scheme 1. Protocol for the selective synthesis of 1,1-diarylallenes or
1,3-diarylallenes by monolithiation of 1-aryl-1-alkynes, transmetalation,
and Pd-catalyzed coupling with aryl halides.
coupling with aryl halides leading to 1,1-diarylallenes (1) or
1,3-diarylallenes (2) highly selectively from the same 1-aryl-1-
alkynes has been developed (Scheme 1).
Recently, we developed a monolithiation reaction of 1-
aryl-1-alkynes with or without the mediation of HgCl2.[2,3] The
propargylic/allenylic lithium formed in this reaction under-
goes sequential transmetalation and Pd-catalyzed coupling
with organic halides leading to alkynes or allenes depending
on the structures of the starting materials.[4] Quite recently,
however, we observed that the sequential monolithiation of 1-
aryl-1-alkynes beyond 1-aryl-1-propyne, (1-phenyl-1-butyne),
the transmetalation, Pd-catalyzed coupling reaction with aryl
halides when conducted by different chemists, or even the
same chemist at different times, surprisingly gave two
products. These products were identified as allenes 1a and
2a and formed in very different ratios ranging from 0:100 to
100:0; in other words, in terms of the ratio of 1a to 2a, the
results were difficult to reproduce (entries 1 and 2, Table 1).
Further investigations showed that with different lithia-
tion reagents, the ratios of 1a and 2a are also different, some
of the representative results are summarized in Table 1 with
the following noteworthy points: (1) No lithiation was
observed with nBuLi or tBuLi at À788C (entry 7, Table 1);
Li Reactions in Organic Synthesis
A 1,3-Lithium Shift of Propargylic/Allenylic
Lithium and the Subsequent Transmetalation
Coupling Reaction with Aryl Halides**
Shengming Ma* and Qiwen He
Selective synthesis has been a formidable challenge in organic
synthesis, especially controlled highly selective synthesis
beginning from the same starting materials.[1] Herein, we
report a novel clean 1,3-lithium shift reaction of propargylic/
allenylic lithium (Scheme 1). Based on this observation, the
corresponding sequential transmetalation and Pd-catalyzed
Table 1: The effect of base on the lithiation of 1-aryl-1-butyne, trans-
metalation, and the Pd-catalyzed coupling with phenyl iodide.
[*] Prof. S. Ma, Ms. Q. He
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
354 Fenglin Lu, Shanghai 200032 (P. R. China)
Fax: (+86)21-6416-7510
E-mail: masm@mail.sioc.ac.cn
Entry
T[a]
Yield[b] (1a/2a)
tBuLi
nBuLi
LDA
1
2
3
4
5
6
7
88C
100:0–0:100
100:0–0:100
70% (100:0)
54% (100:0)
–
100:0–0:100
54% (89:11)
28% (93:7)
54% (100:0)
–
84%[c] (0:100)
–
98% (0:100)
96% (19:81)
94% (45:55)
88% (77:23)
50% (91:9)
[**] Financial supports from the Major State Basic Research Develop-
ment Program (Grant No. G2000077500), National Natural Science
Foundation of China, and Shanghai Municipal Committee of
Science and Technology are greatly appreciated. Shengming Ma is
the recipient of 1999 Qiu Shi Award for Young Scientific Workers
issued by Hong Kong Qiu Shi Foundation of Science and
Technology (1999–2003).
À108C
À208C
À408C
À558C
À658C
À788C
–
–
no lithiation
no lithiation
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
[a] Lithiation temperature. [b] NMR yield determined with CH2Br2 as the
internal standard. [c] Yield of the isolated product.
988
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200352924
Angew. Chem. Int. Ed. 2004, 43, 988 –988

Angewandte
Chemie
(2) Lithiation with LDA at À788C followed by transmetala-
tion and coupling afforded 1a and 2a in 50% yield with a
ratio of 91:9 (entry 7, Table 1). Lithiation with LDA at a
higher temperature favors the formation of 2a; (3) lithiation
with nBuLi or tBuLi at À208C or À408C led to the highly
selective or exclusive formation of the nonisomerized product
1a (entries 3 and 4, Table 1). These facts indicate that the
temperature and amine may be the factors that control the
isomerization of 1-aryl-1-alkyn-3-yl or 1-aryl-1,2-alkadien-1-
yl lithium to 1-aryl-2-alkyn-1-yl or 1-aryl-1,2-alkadien-3-yl
lithium, respectively (Scheme 1).
In fact, it was observed that when the lithiation of 1-
phenyl-1-butyne was conducted at À208C for 1 h then at
room temperature for 2 h, instead of 1,1-diphenyl-1,2-buta-
diene (1a), the sequential reaction afforded 1,3-diphenyl-1,2-
butadiene (2a) in 74% yield (Scheme 2). With a longer
Scheme 3. The effect of TMEDA on the 1,3-lithium shift.
In conclusion, we have observed a clean and complete 1,3-
lithium shift reaction of 1-aryl-1-alkyn-3-yl or 1-aryl-1,2-
alkadien-1-yl lithium leading to 1-aryl-1,2-alkadien-3-yl or 1-
aryl-2-alkyn-1-yl lithium, respectively. Although this kind of
1,3-metal shift has been observed,[5–7] the present protocol
provides a clear-cut control of the lithiation as well as the
isomerization. Under conditions A and B, 1,1-diarylallenes
and 1,3-diarylallenes, respectively, can be prepared starting
from the same alkynes. Although the mechanism of 1,3-
lithium shift is not clear, this work may open up a new area for
the study and control of 1,3-metal shifts in propargyl/allenylic
species. Further investigations in this area are continuing in
our laboratory.
Experimental Section
Typical procedure (conditions A): nBuLi (0.45 mL, 1.6m in hexanes,
0.72 mmol) was added to a solution of 1-phenyl-1-butyne (78 mg,
0.6 mmol) in THF (3 mL) in a dry Schlenk tube at À208C under N2.
The reaction mixture was stirred at À208C for 1 h, then a solution of
dry ZnBr2 (275 mg, 1.2 mmol) in THF (4 mL) was added. After a
further 10 min at this temperature the reaction mixture was warmed
up to room temperature and kept there for 20 min. [Pd(PPh3)4]
(35 mg, 5 mol%) and iodobenzene (83 mL, 0.72 mmol) were sub-
sequently added, and the resulting mixture was stirred at room
Scheme 2. Different lithiation conditions gave different ratios of 1a/
2a.
reaction time for the lithiation at room temperature, the
yields of 1a and 2a decreased dramatically. When the
lithiation was performed at À208C for 1 h followed by the
addition of N,N,N’,N’-tetramethyl ethylene diamine
(TMEDA) at À208C, the same sequential
reaction also afforded the isomerized prod-
uct 1,3-diphenyl-1,2-butadiene (2a) in 94%
yield, thus indicating an interesting effect of
amine on the 1,3-lithium shift (Scheme 3).
Through trial and error, we were happy
to identify two suitable sets of reaction
conditions: A) lithiation at À208C with
nBuLi for 1 h followed by transmetalation
(ZnBr2 was added at À208C followed by
stirring at room temperature) and coupling
at room temperature for the selective for-
mation of 1,1-diarylallenes; B) lithiation at
room temperature with LDA for 1 h fol-
lowed by transmetalation and coupling at
room temperature for the selective forma-
tion of 1,3-diarylallenes. Under condi-
tions A and B, the results can be easily
reproduced. Some typical results are pre-
sented in Table 2, which indicates that:
1) the reaction is general for differently
substituted 1-aryl-1-alkynes/aryl halides;
2) the regioselectivity for the formation of
1,1-diarylallenes and 1,3-diarylallenes is
excellent.
Table 2: Reaction under conditions A (nBuLi) and B (LDA)
Entry
Ar1
CH2R
Ar2I
Base
T [8C]
Yield [%][a]
(1/2)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-PhC6H4
p-PhC6H4
C2H5
C2H5
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
C3H7
C3H7
C3H7
C3H7
C6H5I
C6H5I
C6H5I
C6H5I
p-MeC6H4I
p-MeC6H4I
a-C10H8I
a-C10H8I
p-MeOC6H4I
p-MeOC6H4I
p-MeO2CC6H4I
p-MeO2CC6H4I
C6H5I
nBuLi
LDA
nBuLi
LDA
nBuLi
LDA
nBuLi
LDA
nBuLi
LDA
nBuLi
LDA
nBuLi
LDA
nBuLi
LDA
À20
8
55 (1a:2a=100:0)
84 (1a:2a=0:100)
71 (1b:2b=99:1)
89 (1b:2b=0:100)
79 (1c:2c=99:1)
99 (1c:2c=0:100)
63 (1d:2d=100:0)
56 (1d:2d=0:100)
74 (1e:2e=98:2)
83 (1e:2e=0:100)
93 (1 f:2 f=100:0)
71 (1 f:2 f=0:100)
76 (1g:2g=100:0)
96[b] (1g:2g=0:100)
77 (1h:2h=100:0)
72 (1h:2h=0:100)
À20
10
À20
20
À20
20
9
À20
30
10
11
12
13
14
15
16
À20
19
À20
11
C6H5I
C6H5I
C6H5I
À20
18
1
[a] Yield of isolated products with the ratios determined by 300MHz H NMR analysis. [b] NMR yield
determined with CH2Br2 as the internal standard.
Angew. Chem. Int. Ed. 2004, 43, 988 –988
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ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
989

Communications
temperature. After the reaction was complete, as monitored by TLC
(eluent: petroleum ether, 60–908C), it was quenched with saturated
NH4Cl and extracted with ether. The product solution was dried over
MgSO4, the solvent was removed by rotary evaporation, and the
crude product was purified by flash chromatography on silica gel
1
(petroleum ether) to afford 1a[8] (68 mg, 55%) as a liquid. H NMR
(CDCl3, 300 MHz): d = 7.43–7.25 (m, 10H), 5.72 (q, J = 7.1 Hz, 1H),
1.89 ppm (d, J = 7.1 Hz, 3H); 13C NMR (CDCl3, 75.4 MHz): d =
206.32, 137.24, 128.42, 128.28, 126.98, 109.18, 88.85, 14.33 ppm; MS
(70 eV): m/z (%): 206 (84.30) [M+], 191 (100) [M+ÀCH3]; IR (neat):
n˜ = 1943 cmÀ1; HRMS calcd for C16H14 [M+]: 206.10955, found:
206.10914.
Typical procedure (conditions B): LDA (0.4 mL, 2.0m in THF/
ethylbenzene/pentane, 0.8 mmol) was added to a solution of 1-
phenyl-1-butyne (58 mg, 0.45 mmol) in THF (3 mL) in a dry Schlenk
tube at room temperature under N2. After the solution had been
stirred for 1 h at room temperature, a solution of dry ZnBr2 (499 mg,
2.22 mmol) in THF (4 mL) was added. After a further 25 min at this
temperature, [Pd(PPh3)4] (22 mg, 5 mol%) and iodobenzene (42 mL,
0.38 mmol) were added. After the reaction was complete as
monitored by TLC (eluent: petroleum ether, 60–908C), it was
quenched with saturated NH4Cl and extracted with ether. The
resulting solution was dried over MgSO4, the solvent was removed by
rotary evaporation, and the crude product was purified by flash
chromatography on silica gel (petroleum ether) to afford 1b[9] (65 mg,
84%) as a liquid. 1H NMR (CDCl3, 300 MHz): d = 7.53–7.47 (m, 2H),
7.40–7.20 (m, 8H), 6.50 (q, J = 2.7 Hz, 1H), 2.25 ppm (d, J = 2.7 Hz,
3H); 13C NMR (CDCl3, 75.4 MHz): d = 206.77, 136.23, 134.44, 128.67,
128.43, 127.01, 126.99, 126.85, 125.78, 104.48, 96.56, 16.75 ppm; MS
(70 eV): m/z (%): 206 (79.98) [M+], 191 (100) [M+ÀCH3]; IR (neat):
n˜ = 1936 cmÀ1
.
Received: September 22, 2003 [Z52924]
Keywords: allenes · cross-coupling · isomerization · lithiation ·
.
palladium
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990
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Angew. Chem. Int. Ed. 2004, 43, 988 –990