Table 2 Halogen–zinc exchange of iodobenzenes
Substrate
R2
R4
R
Electrophile
Product
E
Yield (%)
5a
5b
5c
5c
5c
5c
5d
5d
H
H
H
H
H
H
OMe
OMe
H
But
But
But
But
But
But
Me
But
PhCHO
PhCHO
PhCHO
MeI
CH2᎐᎐CHCH2I
PhCOCl
PhCHO
PhCHO
7a
7b
7c
7d
7e
7f
CH(OH)Ph
CH(OH)Ph
CH(OH)Ph
Me
70
67
53
41
54
56
29
83
OMe
CO2Me
CO2Me
CO2Me
CO2Me
H
CH2CH᎐CH2
᎐
COPh
7g
7g
CH(OH)Ph
CH(OH)Ph
H
Table 3 Halogen–zinc exchange of alkyl halides
Acknowledgements
We are grateful to the Takeda Science Foundation for financial
support.
Yield
(%)
Substrate
R
Conditions
Product
8a
8b
8c
8d
Bu
THF, room temp., 3 h
THF, room temp., 3 h
Et2O, Ϫ78 ЊC, 3 h
10a
10b
10c
10d
86
48
50
77
Pri
References
CH2CO2Et
CH2CN
1 (a) L. Zhu, R. M. Wehmeyer and R. D. Rieke, J. Org. Chem., 1991,
56, 1445; (b) L. Zhu and R. D. Rieke, Tetrahedron Lett., 1991,
32, 2865; (c) P. Knochel and S. A. Rao, J. Am. Chem. Soc., 1990,
112, 6146; (d) P. Knochel, J. Am. Chem. Soc., 1990, 112, 7431;
(e) S. A. Rao and P. Knochel, J. Am. Chem. Soc., 1991, 113, 5735;
( f ) P. Wipf, Synthesis, 1993, 537; (g) P. Knochel and R. D. Singer,
Chem. Rev., 1993, 93, 2117.
THF, Ϫ78 ЊC, 3 h
I
Zn(But)2Li
(But)3ZnLi
–78 °C, 2 h
2 (a) M. Isobe, S. Kondo, N. Nagasawa and T. Goto, Chem. Lett., 1977,
679; (b) W. Tuckmantel, K. Oshima and H. Nozaki, Chem. Ber., 1986,
119, 1581; (c) J. F. G. A. Jansen and B. L. Feringa, Tetrahedron Lett.,
1988, 29, 3593; (d) R. A. Kjonaas and R. K. Hoffer, J. Org. Chem.,
1988, 53, 4133; (e) R. A. Kjonaas and E. J. Vawter, J. Org. Chem.,
1986, 51, 3993; ( f ) T. Harada, K. Katsuhira and A. Oku, J. Org.
Chem., 1992, 57, 5805; (g) T. Harada, K. Katsuhira, K. Hattori and
A. Oku, J. Org. Chem., 1993, 58, 2958; (h) T. Harada, K. Katsuhira,
D. Hara, Y. Kotani, K. Maejima, R. Kaji and A. Oku, J. Org. Chem.,
1993, 58, 4897.
5a
6
O
2-ThCu(CN)Li, THF
–78 °C then room temp.
54%
2-Th = 2-thienyl
O
3 (a) Y. Kondo, N. Takazawa, C. Yamazaki and T. Sakamoto, J. Org.
Chem., 1994, 59, 4717; (b) Y. Kondo, N. Takazawa, A. Yoshida and
T. Sakamoto, J. Chem. Soc., Perkin Trans. 1, 1995, 1207.
4 (a) Y. Kondo, T. Matsudaira, J. Sato, N. Murata and T. Sakamoto,
Angew. Chem., Int. Ed. Engl., 1996, 35, 736; (b) M. Uchiyama,
M. Koike, M. Kameda, Y. Kondo and T. Sakamoto, J. Am. Chem.
Soc., 1996, 118, 8733; (c) Y. Knodo, A. Yoshida and T. Sakamoto,
J. Chem. Soc., Perkin Trans. 1, 1996, 2331.
5 For a recent example of the use of the tert-butyl group as a non-
transfer group, see E. Laloe and M. Srebnik, Tetrahedron Lett., 1994,
35, 5587.
11
Scheme 4
Experimental
6 LTBZ has been used for halogen–zinc exchanges; however no
advantage as a selective metallating reagent has been demonstrated.
See ref. 2( f ), (g), (h).
Reaction of methyl 4-iodobenzoate 5c with LTBZ followed by
reaction with benzoyl chloride
7 For recent examples of halogen–zinc exchanges, see: (a) M. J.
Rozema, S. A. Rao and P. Knochel, J. Org. Chem., 1992, 57, 1956;
(b) R. Ostwald, P.-Y. Chavant, H. Stadtmuller and H. Knochel,
J. Org. Chem., 1994, 59, 4143; (c) I. Klement, P. Knochel, K. Chau
and G. Cahiez, Tetrahedron Lett., 1994, 35, 1177; (d) E. Riguet,
I. Klement, C. K. Reddy, G. Cahiez and P. Knochel, Tetrahedron
Lett., 1996, 37, 5865; (e) H. Shinokubo, H. Miki, T. Yokoo,
K. Oshima and K. Utimoto, Tetrahedron, 1995, 51, 11 681.
8 Reformatsky type organozinc derivatives have been prepared via
an oxidative addition reaction of functionalized alkyl halides to zinc.
See M. W. Rathke, Org. React., 1975, 22, 423.
ButLi (1.37 pentane solution, 3.3 ml, 4.5 mmol) was added to
a mixture of dry THF (6 ml) and a solution of ZnCl2 in dry
THF (1 solution, 1.5 ml, 1.5 mmol) at 0 ЊC, and the mixture
was stirred at 0 ЊC for 30 min. The mixture was cooled to
Ϫ78 ЊC, methyl 4-iodobenzoate (393 mg, 1.5 mmol) was added
and the mixture was stirred at Ϫ78 ЊC for 4 h. Benzoyl chloride
(633 mg, 4.5 mmol) was added at Ϫ78 ЊC. The mixture was
allowed to warm to room temperature gradually during 12 h.
The reaction was quenched with aq. NH4Cl (2 ml) and then the
THF was evaporated in vacuo. The residue was diluted with
H2O (30 ml), and the mixture was extracted with CHCl3 (30
ml × 3). The organic layer was dried over anhydrous MgSO4.
After purification on silica gel column chromatography
(AcOEt–hexane 1:14), the crude material was recrystallized
from AcOEt–hexane to give colourless scales of 7f (202 mg,
56%); mp 106 ЊC; δH (300 MHz, CDCl3) 8.16 (d, 2 H, J 8.0 Hz),
7.79–7.86 (m, 4 H), 7.63 (m, 1 H), 7.51 (m, 2 H), 3.97 (s, 3 H).
9 Some examples of similar types of transmetallation have been
reported. See: B. H. Lipshutz and M. R. Wood, J. Am. Chem. Soc.,
1994, 116, 11 689 and references cited therein.
Paper 6/08294G
Received 10th December 1996
Accepted 20th January 1997
800
J. Chem. Soc., Perkin Trans. 1, 1997