ZINC IODIDE 1
Activation of C=X Bonds. Catalysis of aldol condensation
Zinc Iodide1
reactions using silyl ketene acetals and ZnI2 has been the subject
of several studies.7 It is observed that ZnI2 favors the activation
ZnI2
of functionalized carbonyl compounds via ²-chelates to impart
useful stereoselectivity (eq 4).7a In analogous fashion, diastereos-
[10139-47-6] I2Zn (MW 319.19)
elective additions to imines and nitrones have been reported which
InChI = 1/2HI.Zn/h2*1H;/q;;+2/p-2/f2I.Zn/h2*1h;/q2*-1;m offer useful access to ²-lactams (eq 5).8 Ä…,²-Unsaturated esters
InChIKey = UAYWVJHJZHQCIE-KOSDEYJJCK are subject to conjugate addition reactions by silyl ketene acetals,
also through the agency of ZnI2 activation (eq 6).9
(used in the preparation of organozinc reagents via
transmetalation;1 a mild Lewis acid useful for promoting addition2 O OH
and substitution reactions3) OTBDMS
ZnI2
MeO
O
+ (4)
O
O
MeO MeCN O
ć% ć%
Physical Data: mp 446 C; bp 625 C (dec); d 4.740 g cm-3. CHO
67%
Solubility: sol H2O (1 g/0.3 mL), glycerol (1 g/2 mL); freely sol
96% anti
EtOH, Et2O.
Form Supplied in: white, odorless, granular solid; principal
NTMS
impurities are H2O and iodine.
OMe
ZnI2
H
+
Analysis of Reagent Purity: mp.
Ph
Et2O, 20 °C
OTBDMS
ć% TMS
Purification: heat to 300 C under vacuum for 1 h, then sublime.
53%
Handling, Storage, and Precautions: very hygroscopic and light
sensitive; store under anhydrous conditions in the absence of
light. TMSHN O
(5)
OMe
TMS Ph
Organozinc Reagents. Organozinc reagents may be prepared
92:8
through transmetalation of organolithium, organomagnesium, and
organocopper species with ZnI2, although Zinc Chloride and Zinc
O
ZnI2
Bromide are used far more frequently.1a It is more usually the
TMS
OTMS
+ (6)
CO2Et
MeO
case that organozinc iodides are prepared by zinc insertion into
CH2Cl2
CO2Et
OMe 74%
alkyl iodides using Zinc/Copper Couple1a These zinc reagents
possess reactivity analogous to the other organozinc halides,
finding particular use in palladium-catalyzed coupling reac-
An important role for ZnI2 has been found in the catalysis of
tions (eq 1).4 An alternative method for the preparation of the
R3SiCN addition to ketones and aldehydes to afford silyl protected
Simmons Smith reagent (Iodomethylzinc Iodide) involving the
cyanohydrins.10 This is a very general reaction that is effective
treatment of Diazomethane with ZnI2 has been reported (eq 2).5
even with very hindered carbonyl compounds (eq 7).11 Diastere-
oselective cyanohydrin formation has been reported when these
reaction conditions are applied to asymmetric carbonyl substrates
I
PdCl2(PPh3)2
(eq 8).2a
+
IZn CO2Et
PhH, DMA, rt
78% O
N
TBDMSO CN
TBDMSCN
(7)
ZnI2, CH2Cl2, rt
92%
N (1)
CO2Et
1. TMSCN
TBDMSO
TBDMSO
ZnI2
CN
(8)
CH2N2 + ZnI2 ICH2ZnI + N2 (2)
Ph
Ph CHO 2. SiO2, CH2Cl2
OH
90%
81:19
Cycloaddition Reactions. The catalytic effect of ZnI2 on the
Diels Alder reaction has been noted (eq 3),6 but its use in such
Activation of C X Bonds. The Lewis acidity of ZnI2 may
cycloaddition reactions is rare compared with ZnCl2 and ZnBr2.
be exploited to activate various carbon heteroatom bonds to
nucleophilic substitution. Treatment of epoxides and oxetanes
O
O
with Cyanotrimethylsilane/ZnI2 results in selective C N bond
ZnI2
CO2Me
+ (3)
CO2Me formation with ring opening (eq 9).12 Similarly, C S and C Se
40 °C
H
55% bonds may be formed by treating cyclic ethers with ZnI2 and
endo:exo = 67:33
RSSiMe3 and RSeSiMe3, respectively (eq 10).13
Avoid Skin Contact with All Reagents
2 ZINC IODIDE
OH OH OH
Deprotection. Methyl and benzyl ethers may be cleaved by
OTMS OH
the combination of (Phenylthio)trimethylsilane/ZnI2 (eq 15).18
TMSCN 1. KF
(9)
O
Similar cleavage of alkyl and benzyl ethers takes place us-
2. HCl
ZnI2
NC NH2 · HCl
MeOH
ing Acetic Anhydride/ZnI2 to afford the corresponding acetate
61% overall
(eq 16).19
PhSTMS
PhSeTMS
OTMS
(15)
PhSe (10)
ZnI2
ZnI2, CH2Cl2
O
OMe OH
98%
80%
OO
Treatment of 4-acetoxy- and 4-sulfoxyazetidin-2-ones with
H H
ZnI2 results in the formation of the corresponding imine or
Ac2O
H H
(16)
iminium species which subsequently suffers silyl-mediated addi-
ZnI2
H H H H
tion. These reactions result in the formation of trans substitution
81%
MeO AcO
(eqs 11 and 12).14,15
TBDMSO
H
ZnI2
S(O)Ph
N NTMS
+
MeCN
NH
99%
O 1. (a) Knochel, P., Comprehensive Organic Synthesis 1991, 1, Chapter 1.7.
(b) Rathke, M. W.; Weipert, P., Comprehensive Organic Synthesis 1991,
N
2, Chapter 1.8.
TBDMSO
H H
2. For examples: (a) Effenberger, T.; Hopf, M.; Ziegler, T.; Hudelmayer, J.,
N
(11)
Chem. Ber. 1991, 124, 1651. (b) Klimba, P. G.; Singleton, D. A., J. Org.
Chem. 1992, 57, 1733. (c) Colvin, E. W.; McGarry, D. G., J. Chem. Soc.,
NH
O Chem. Commun. 1985, 539.
3. For examples: (a) Paquette, L. A.; Lagerwall, D. R.; King, J. L.;
O
TMSO Niwayama, S.; Skerlj, R., Tetrahedron Lett. 1991, 32, 5259. (b) Howk,
TBDMSO
H
OAc ZnI2 B. W.; Sauer, J. C., Org. Synth., Coll. Vol. 1963, 4, 801. (c) Kubota, T.;
N O
+
Iijima, M.; Tanaka, T., Tetrahedron Lett. 1992, 33, 1351.
CH2Cl2
NH
4. (a) Sakamoto, T.; Nishimura, S.; Kondo, Y.; Yamanaka, H., Synthesis
93%
O
1988, 485. (b) See also: Yamanaka, H.; An-naka, M.; Kondo, Y.;
Sakamoto, T., Chem. Pharm. Bull. 1985, 38, 4309.
O
5. (a) Wittig, G.; Schwarzenback, K., Justus Liebigs Ann. Chem. 1961, 650,
1
TBDMSO
O
1. (b) Wittig, G.; Wingher, F., Justus Liebigs Ann. Chem. 1962, 656, 18.
H HR R2
N
(12)
6. Brion, F., Tetrahedron Lett. 1982, 23, 5239.
7. (a) Kita, Y.; Yasuda, H.; Tamura, O.; Itoh, F.; Yuan Ke, Y.; Tamura,
NH O
O
Y., Tetrahedron Lett. 1985, 26, 5777. (b) Kita, Y.; Tamura, O.; Itoh, F.;
Yasuda, H.; Kishino, H.; Yuan Ke, Y.; Tamura, Y., J. Org. Chem. 1988,
(R1 = Me, R2 = H):(R1 = H, R2 = Me) = 3:1
53, 554. (c) Annunziata, R.; Cinquini, M.; Cozzi, P. G.; Consolandi, E.,
J. Org. Chem. 1992, 57, 456.
Substitution reactions of orthoesters3b and acetals,3c including
8. (a) Colvin, E. W.; McGarry, D.; Nugent, M. J., Tetrahedron 1988, 44,
anomeric bond formation in carbohydrates (eq 13),16 have been
4157, and reference 2c. See also: (b) Kita, Y.; Itoh, F.; Tamura, O.; Yuan
catalyzed by ZnI2.
Ke, Y.; Tamura, Y., Tetrahedron Lett. 1987, 28, 1431. (c) Reider, P. J.;
Grabowski, E. J. J., Tetrahedron Lett. 1982, 23, 2293. (d) Chiba, T.;
Nakai, T., Chem. Lett. 1987, 2187. (e) Chiba, T.; Nagatsuma, M.; Nakai,
OH
OTMS
1. TMSCl, py
O
T., Chem. Lett. 1985, 1343.
HO
O
TMSO
(13)
HO
TMSO
2. PhSTMS
9. Quendo, A.; Rousseau, G., Tetrahedron Lett. 1988, 29, 6443.
HO
SPh
TMSO
ZnI2, Bu4NI
10. (a) Rassmussen, J. K.; Heihmann, S. M., Synthesis 1978, 219.
OMe
60%
(b) Gassman, P.; Talley, J. J., Tetrahedron Lett. 1978, 3773. (c) Foley, L.
H., Synth. Commun. 1984, 14, 1291. (d) Higuchi, K.; Onaka, M.; Izumi,
Y., J. Chem. Soc., Chem. Commun. 1991, 1035. (e) Quast, H.; Carlson, J.;
Klaubert, C. A.; Peters, E.-M.; Peters, K.; von Schnering, H. G., Liebigs
Reduction. Allyl and aryl ketones, aldehydes, and alco-
Ann. Chem. 1992, 759. (f) Batra, M. S.; Brunet, E., Tetrahedron Lett.
hols are reduced to the corresponding hydrocarbon by Sodium
1993, 34, 711.
Cyanoborohydride/ZnI2 (eq 14).17 This is a reasonably reactive
11. Golinski, M.; Brock, C. P.; Watt, D. S., J. Org. Chem. 1993, 58, 159.
reducing mixture which will also attack nitro and ester groups.
12. (a) Gassman, P. G.; Gremban, R. S., Tetrahedron Lett. 1984, 25, 3259.
(b) See also: Gassman, P. G.; Haberman, L. M., Tetrahedron Lett. 1985,
Br
Br O
26, 4971.
NaCNBH3
13. (a) Miyoshi, N.; Hatayama, Y.; Ryu, I.; Kambe, N.; Murai, T.; Murai,
(14)
ZnI2, CH2Cl2
S.; Sonoda, Synthesis 1988, 175. (b) See also: Guidon, Y.; Young, R. N.;
70%
MeS
MeS
Frenette, R., Synth. Commun. 1981, 11, 391.
A list of General Abbreviations appears on the front Endpapers
ZINC IODIDE 3
14. (a) Kita, Y.; Shibata, N.; Yoshida, N.; Tohjo, T., Tetrahedron Lett. 1991, 18. Hanessian, S.; Guidon, Y., Tetrahedron Lett. 1980, 21, 2305.
32, 2375. (b) See also: Kita, Y.; Shibata, N.; Miki, T.; Takemura, Y.;
19. Benedetti, M. O. V.; Monteagudo, E. S.; Burton, G., J. Chem. Soc. (S)
Tamura, O., J. Chem. Soc., Chem. Commun. 1990, 727.
1990, 248.
15. Fuentes, L. M.; Shinkai, I.; Salzmann, T. N., J. Am. Chem. Soc. 1986,
108, 4675.
Glenn J. McGarvey
16. (a) Hanessian, S.; Guidon, Y., Carbohydr. Res. 1980, 86, C3. (b) Chu,
University of Virginia, Charlottesville, VA, USA
S.-H. L.; Anderson, L., Carbohydr. Res. 1976, 50, 227.
17. Lau, C. K.; Dufresne, C.; Bélanger, P. C.; Piétré, S.; Scheigetz, J., J. Org.
Chem. 1986, 51, 3038.
Avoid Skin Contact with All Reagents