ZINC 1
range of ketones (Clemmensen reaction) (eqs 6 8).17 The Clem-
Zinc1
mensen reduction of aromatic ą-hydroxy ketones gives conjugated
alkenes.18 Finally, the Clemmensen reduction can also be per-
Zn
formed by using zinc and Chlorotrimethylsilane in an aprotic
medium, leading to alkenes (eq 9).19 This variation has been ex-
[7440-66-6] Zn (MW 65.39)
ploited for the preparation of alkenes (eq 10)19b and has been
InChI = 1/Zn
used in new cyclization reactions (eqs 11 and 12).20 Trimethyl-
InChIKey = HCHKCACWOHOZIP-UHFFFAOYAS
silyl ethers can be regioselectively prepared by the zinc reduction
of ą-chloro ketones in the presence of TMSCl.21 Mixed pinacol
(reducing agent;2 used for preparation of organozinc reagents,1,3
products have been prepared by using Zn(Cu) as the reducing
Reformatsky reagents,4 and the Simmons Smith reagent
agent (eq 13).22
(cyclopropanation)5)
ć% ć%
Physical Data: mp 419 C; bp 907 C; d 7.14 g cm-3.
1. Zn, KCN
Solubility: insol organic solvents; reacts with aqueous acidic
(2)
2. Bu4NF
solutions.
OH
OTBDMS
Form Supplied in: dust, foil, granular, wire, mossy, rod; widely
available at low cost.
O
O
Handling, Storage, and Precautions: slowly oxidizes in air; no Zn, NiCl2 cat ))))
EtOH, H2O
toxic properties are associated with zinc and zinc organometal-
(3)
30 �C, 2.5 h
lics; in several cases the metal requires an activation procedure
97%
before use.6
O
O CO2H
O
Original Commentary
Zn(Hg), HCl
Ph
Ph (4)
reflux, toluene
79%
Paul Knochel
Philipps-Universit�t Marburg, Marburg, Germany
Reduction of Carbon Carbon Multiple Bonds. Whereas Zn, AcOH
+ O (5)
O
isolated double bonds are rarely reduced by zinc, triple bonds
reflux
OH
are cleanly converted to alkenes using either Zinc/Copper Cou-
O O
OH
48:52
ple or Zinc Amalgam.7 A regio- as well as stereospecific reduc-
tion of a wide range of alkynic derivatives can be performed us-
ing zinc powder (eq 1).8 The reduction of propargylic alcohols
proves to be especially efficient (eq 2).9 Also, the selective cis re-
duction of conjugated dienynes and trienynes proceeds well with
Zn(Hg), HCl
Zn(Cu/Ag).10 The presence of a leaving group at the propargylic
Et2O
position leads to the formation of allenes.11 The conjugation of a
77%
O
double bond with an electron-withdrawing substituent consider- H
ably facilitates the reduction of the double bond.12 The reduction
of ą,�-unsaturated ketones produces the corresponding saturated
ketones.13 Nickel catalysis allows the reduction of unsaturated
aldehydes, ketones, and esters in an aqueous medium under ultra- (6)
sonic irradiation (eq 3).14
Zn, ethanol H
Et Et
(1)
OH reflux, 3 h OH
>95%
O
>95% (Z)
Zn(Hg), HCl
Cl Cl
(7)
EtOH, PhH
Reduction of Carbonyl Groups. Zinc reduces ketones to ei-
56%
Cl Cl
ther alcohols or to a methylene unit, depending on the reaction
conditions and the nature of the substrate. For example, con-
O
OO
jugation is required if reduction to a hydroxy group is desired.
Zn(Hg), HCl
(8)
The reduction of aryl ketones provides benzylic alcohols (eq 4)15
CO2H CO2H
50%
and ą-diketones can be converted selectively to ą-hydroxy ke-
tones (eq 5).16 The reduction of the carbonyl group of noncon-
Zn(Hg), TMSCl
jugated ketones to a methylene unit with zinc and hydrochlo-
O
(9)
ric acid in organic solvents such as ether, acetic anhydride, Et2O
72%
or benzene ethanol proceeds in satisfactory yields with a wide
Avoid Skin Contact with All Reagents
2 ZINC
Reduction of Carbon Halide Bonds. Alkyl and alkenyl
Zn(Hg), THF
O
24 h
halides are readily reduced with zinc under various reaction condi-
(10)
Me Me
tions. The reduction produces, as an intermediate, an organic rad-
Cl Si
Si Cl
ical which can undergo carbon carbon bond formation (Barbier
Me Me
reaction)28 or can be further reduced, usually under acidic con-
ditions. Aliphatic iodides or bromides and benzylic chlorides re-
O
Zn, TMSCl Zn, TMSCl
act readily with Zinc Acetic Acid, providing the corresponding
without 2,6-lutidine hydrocarbon.29 Although aromatic halides are reduced less eas-
t-Bu
2,6-lutidine t-Bu 66%
H ily, the tribromothiophene 1 is reduced selectively to the bro-
71%
mide 2 (eq 19).29e,g Various �-chloro enones are cleanly reduced
to enones with Zinc/Silver Couple in methanol at rt (eq 20).29f
HO ą-Dihalo ketones are reduced smoothly, allowing the preparation
of a variety of ketones (eqs 21 and 22).30 The reductive couplings
(11)
of ą-bromo ketones, tropylium, and 1,3-dithiolylium cations have
t-Bu
H been observed.31 In the case of 1,3-dihalides, cyclopropanes are
obtained in good yields.32 If the reduction of the carbon halide
HO
O
bond is performed in the presence of an electrophile, a radical
Zn, TMSCl
(12) addition often occurs. Thus phenacyl halides can be coupled with
THF
t-Bu
methylenecyclohexanes (eq 23).33a Performing the reaction in the
t-Bu
74%
H
presence of an unsaturated ketone provides the 1,4-adducts. In-
terestingly, the reduction proceeds well in an aqueous medium
supporting a radical mechanism, since zinc organometallics react
O
O
HO
Zn(Cu), H2O
instantaneously with water but only very sluggishly with enones
OH
+ (13)
)))) (eq 24).33b-h The addition of Chloromethyl Methyl Ether to 1,2-
87%
bis-silyl enol ethers in the presence of zinc leads to ring-enlarged
1,3-cycloalkanediones after acidic treatment.34 An interesting
three-component reaction has been described (eq 25).34b A wide
Reduction of Carbon Oxygen Bonds. Carbon Oxygen
range of allylic halides undergo Barbier-type addition to carbonyl
bonds situated ą to an unsaturation are easily reduced with zinc in
groups (eqs 26 and 27).35,36 The reduction of ą,ą -dihalo ketones
an acidic medium. In the case of ą-hydroxy ketones, ketones are
with a zinc copper couple in the presence of a diene such as Iso-
obtained in good yields (eq 14).23 A wide range of allylic or
prene provides cycloaddition products via a zinc oxyallyl cation.37
benzylic ethers, acetates, and alcohols are reduced with zinc
Br Br
(eq 15).24,25 The reduction of epoxides can lead to either alcohols
Zn, AcOH
(eq 16)26 or alkenes.26b-e In the presence of catalytic amounts of
(19)
H2O, heat
Pd0 and zinc dust, allylic acetates are coupled to give 1,5-dienes
Br Br
S S
89 90%
(eq 17).27 Under similar reaction conditions and in the presence
(1)(2)
of an aldehyde, homoallylic alcohols are obtained in satisfactory
O
O
yields (eq 18).27b-d
Zn(Ag), MeOH
HO (20)
Zn(Hg), HCl
20 �C
( )n ( )n (14)
65%
AcOH
Cl
H
O O
75 78%
Cl
Cl
Zn, AcOH
OH
(21)
59%
Zn(Hg), HCl
O O
(15)
H H
Et2O,  15 �C
68 75%
Bu
Bu
Zn, EtOH
(22)
Cl
AcOH, TMEDA
C5H11O Zn, TMSCl
OH
C5H11
84% O
O
Cl
+ (16)
C5H11
CH2Cl2
H H
OH
97%
O
Zn(Cu), DMSO
2:1
Br
Ph
Zn, Pd0
OAc (17)
THF, 25 �C
70%
O O
OH
Zn, Pd0
Ph + (23)
Ph
+ PhCHO (18)
OAc
Ph
THF, 25 �C
70%
syn:anti = 1:1
43% 5%
A list of General Abbreviations appears on the front Endpapers
ZINC 3
O O
Cl
O
Zn(Cu), )))) Zn(Cu), ether
Cl
+ (24) + (29)
I
EtOH H2O 77 83%
Cl3C Cl
95%
O
H
CH2I
Zn(Cu), ether
(30)
CN
>80%
Zn, heat
CH2I
+ (25)
I
CN
acetone
98% OH
F
Zn, EtOH
F3C
(31)
F3C CF3
CF3
90%
OH OH
F
Zn, THF
Br
+ (26)
H aq NH4Cl, 25 �C
OMe
75%
MeO OMe
MeO
O OH
Zn(Ag)/graphite
I
(32)
CHO
O THF, 10 min
MeO
93%
OMe
O
OHC
Zn, THF OMe
Br
+
aq NH4Cl, 25 �C
92%
The Reformatsky Reaction.4 The insertion of zinc into
ą-halo esters produces zinc ester enolates which react readily
OH
with aldehydes or ketones, leading to aldol products. Histori-
O
cally, this reaction has been important since it allowed the first
(27)
quantitative generation of an ester enolate. However, several mod-
ern synthetic methods for the stereoselective preparation of aldol
products using metal enolates compete favorably with the Refor-
matsky reaction.51 The nature of the zinc activation6 has proved
to be important for fast and quantitative zinc insertion. Remark-
Reduction of Carbon Nitrogen and Carbon Sulfur Bonds.
Aldimines and oximes are converted to amines, and various hete- ably, the Zn(Ag) couple on graphite reacts with ethyl bromoac-
ć%
etate at -78 C within 20 min,52a whereas Rieke zinc requires 1
rocycles bearing carbon nitrogen double bonds are reduced with
ć%
h at 25 C,52b as does zinc generated from the reaction of Zinc
zinc under acidic conditions.38 Cyanamides can be cleanly cleaved
leading to amines,39a and the zinc reduction of acylnitriles pro- Chloride with Lithium under ultrasound irradiation52c (eq 33).52a
Interesting synthetic applications have been reported (eqs 34
vides ą-amino ketone derivatives (eq 28).39b Aromatic amides
can be reduced with zinc dust to aromatic aldehydes.39c Acti- and 35).4,52 4-Bromocrotonate reacts with ketones and Zn(Cu)
with solvent-dependent regioselectivity.52f See also Ethyl Bromo-
vated carbon sulfur bonds ą to a carbonyl group40a,b and sulfur
zincacetate.
ylides40c,d can be reduced with zinc.
1. Zn(Ag)/graphite
O O
HO
Zn, THF
THF,  78 �C, 20 min
Br OEt
NHAc (28)
(33)
MeO2C CN Ac2O MeO2C CO2Et
2. cyclohexenone
O
83%
92%
O
1. Rieke Zn
O O
THF, 25 �C
Reduction at Heteroatoms.2 Nitrogen oxygen bonds of
(34)
O Br 2. HMPA
O
oximes,41 nitro,42 and nitroso43 groups are readily reduced by
64%
zinc in acidic medium. Zinc in acetic acid has often been used for
O
the workup procedure of alkene ozonolysis to afford aldehydes or
Br
ketones.2 Sulfinates and thiols can be obtained selectively by the
reduction of aromatic sulfonyl chlorides or disulfides.44
CO2Et
CO2Et
Dehalogenation and Related Reactions.6c,45 Zinc dust is
OH
Br
a very efficient reducing agent for the dehalogenation of 1,2-
Zn, THF
(35)
O
dihalides or 1-halo-2-alkoxy derivatives, leading to alkenes. N
25 �C, ))))
N
70%
The reaction allows an access to highly reactive ketenes,46
O
O
alkenes,47 or alkynes48 not readily available by standard methods
(eqs 29 31). The reduction of �-alkoxy halides using Zinc
Graphite proved to be especially interesting when applied to sugar The Simmons Smith Reaction.5,53 Cut Zn foil readily in-
derivatives (eq 32).6c,45e,49 The dehalogenation using zinc is such serts into Diiodomethane providing iodomethylzinc iodide,53
a straightforward and chemoselective reaction that several pro- which cyclopropanates a wide range of alkenes in good yields
tecting groups have been devised which use this reaction as a (see Ethylzinc Iodide, Iodomethylzinc Iodide, Diethylzinc,
deblocking step.50 Ethyliodomethylzinc). The in situ generation of iodomethylzinc
Avoid Skin Contact with All Reagents
4 ZINC
SO2-t-Bu
iodide is often used. The Zn(Ag) couple has proved to be espe-
ZnI
cially active for cyclopropanations (eq 36).53d
N
IZn
IZn
H
O
OTMS OTMS
(9) (10) (11)
Zn(Ag)
(36)
CH2Cl2, py
OTMS OTMS
OAc O CN
40%
ZnBr
ZnCl Cy ZnBr
Preparation of Organozinc Reagents.1,3a The insertion of
OAc
zinc into organic halides provides the most general synthesis
(12) (13) (14)
of organozinc halides. Primary and secondary organic iodides
ć%
react with zinc dust (2 3 equiv) in THF between 20 C and
ć%
50 C, leading to organozinc iodides in high yields.3a,54a-c Ben-
THF
zylic chlorides and bromides react under even milder conditions,
FG-RX + Zn FG-RZnX (37)
5 45 �C
providing the corresponding benzylic zinc halides without the for-
>85%
mation of significant amounts of Wurtz coupling products.54d-f
X = I, Br; R = alkyl, aryl, benzyl, allyl
Two remarkable properties characterize organozinc reagents:
FG = CO2R, enoate, CN, enone, halide, (RCO)2N,
(i) their high functional group compatibility, which allows the
(TMS)2Si, RNH, NH2, RCONH, (RO)3Si, (RO)2P(O), RS,
preparation of polyfunctional organometallic zinc species bearing
RS(O), RSO2, PhCOS
almost all common functional groups with the exception of nitro,
azido, or hydroxy functions (see the reagents 3,54b 4,54g,h 5,54i
6,54j 7,54k-o 8,54p 9,54n,o 10, 11,54q and 12 14,54f and eq 37); and
R2X 1. CuCN � 2LiCl
(ii) their ability to undergo transmetallation with other metallic (38)
FGR1R2 FGR1ZnX FGR1E
Pd0 2. E+
salts, such as copper salts, thus giving polyfunctional copper
reagents which react readily with a wide range of electrophiles
(enones,54b,r aldehydes,54s alkynes,54t-v nitro alkenes,54w-y
H
allylic halides,54b,z alkynyl halides,54g acid chlorides,54b,54aa and O
1. Zn, THF
I 2. CuCN � 2LiCl
alkylidenemalonates54ab). Similarly, efficient transmetalations
(39)
I
3. cyclohexenone, TMSCl
with PdII salts allow the coupling reactions to be performed
4. allyl bromide
(eq 38).55,56 Zinc insertion also proceeds well with various
74%
polyfluorinated alkyl iodides57 and with primary alkyl and benzyl
phosphates and mesylates.58 Alkenyl and aromatic halides un-
dergo the zinc insertion far less readily and require the use of polar
1. Zn(Cu)
DMA PhH
solvents59 or highly activated zinc.60 The use of a sacrificial zinc
(40)
CO2Et
I CO2Et
electrode offers an interesting alternative.61 Allylic zinc halides 2.
O
COCl
are formed under very mild conditions and, contrary to other
Pd0 cat
classes of organozinc reagents, display a high reactivity toward
87 88%
organic electrophiles (comparable to organomagnesium
species).36e-h54a,62 A wide range of synthetic applications of
1. Rieke Zn
NC Br
zinc reagents for the formation of carbon carbon bonds has been
2.
I CO2Et
reported (eqs 39 44).56,60a,63-66 Diorganomercurials also react
with zinc dust, providing diorganozincs.67,68
Pd0 cat
82%
O
(41)
NC CO2Et
1. Zn(Cu), DMA, PhH
ZnBr
ZnI
ZnI
(EtO)2P NHBoc
)))), 20 35 �C, 0.5 h
NHBoc
NC
O
(42)
I
O
2.
CO2Bn
CO2Bn
I NO2
O2N
O
(3) (4) (5)
Pd0 cat
61%
O
O OAc
CO2Et
B 1. Zn, THF
Et
O
O
ZnBr N Ph
(43)
Br
N
Et
2.
Ph N CO2Me
IZn
BrZn CN
CO2Et
O Ph CO2Me
Ph
(6) (7) (8)
80%
A list of General Abbreviations appears on the front Endpapers
ZINC 5
1. Zn, THF
O O
MgBr
2.
Br
(44)
Zn, ))))
3. CO2Et AcO
N NH4Cl, MeOH
CO2Et H
O
20 �C, 30 min
( )6
AcO
94%
O
88%
O O
(47)
N
H
O
Zn, AlCl3
First Update
CH3CN
70 �C, 20 h
Paul Knochel & Nathalie Grenouillat
Ludwig-Maximilians-Universit�t, M�nchen, Germany
O
During these last 10 years, the reductive behavior of zinc dust
+ (48)
has been widely used. The insertion of zinc dust into organic
halides is still a common method for the formation of organozinc
reagents. Organozincs have been used for cross-coupling reactions
95%
under milder reaction conditions. 5%
Reduction of Carbon Oxygen Bonds. Activated C O bonds
on functionalized compounds can be selectively reduced by zinc.
Thus, by using TiCl4, zinc dust leads to the deoxygenation of oxy-
Reduction of Carbon Nitrogen Bonds. Zinc-mediated
genated derivatives of type (15), affording dibromonaphthalenes
reduction of imines proceeds under mild conditions. A reductive
(eq 45).69 Reduction of functionalized ą,�-unsaturated ł,�-dioxy-
dimerization leading to useful diamines can be realized (eq 49).75
carboxylates with zinc dust in refluxing ethanol provides an
Symmetrical and unsymmetrical aromatic diimines undergo a
efficient route to substituted allylic alcohols (eq 46).70 Under
reductive intramolecular coupling, leading to substituted ethylene-
ultrasonic irradiation, ł-enone-lactones are selectively cleaved
diamines (eqs 50 and 51).76 Interestingly, reductive coupling of
by zinc under acidic conditions.71 A modification of this method
aromatic aldoximes and azines to 1,2-diamines is achieved in
using zinc dust in the presence of ammonium chloride allows a
one-step using zinc in the presence of MsOH or TiCl4 (eq 52).77a
reductive deacetoxylation of 2-acyloxy-3-keto amides (eq 47).72 N-Hydroxy-ą-imino esters are reduced to ą-amino esters with
Reduction of alkyl phenyl ketones by zinc and aluminium chloride
Zn-MsOH in high yields (eq 53).77bActivation with TMSCl
in acetonitrile results in a pinacol condensation followed by an in
allows the zinc reductive homocoupling of 2-aryl-2-oxazolinium
situ rearrangement, with exclusive migration of the phenyl group
salts (eq 54).78 N-Bn, S-Bn, and O-Bn derivatives can be
(eq 48).73 These results contradict a previous report in which aryl
hydrogenolyzed using zinc dust with ammonium for-
alkyl ketones are condensed to the corresponding alkenes.74
mate under microwave irradiation (eq 55).79 Zinc dust in
refluxing methanol allows a selective monodeprotection of
di-Boc-protected amides, affording the corresponding mono-
Hex Hex
Boc-protected amines (eq 56).80
Zn, TiCl4
Br Br
THF
O (45)
reflux, 12 h
Br Br
70%
Me
Hex Hex Zn, TMSCl
CH3CN
15
35 �C, 1 h
N Me
H
O O
Zn, EtOH
O
Me Me Me
CO2Et reflux, 12 h
91%
O
+
(49)
NH
O
O (46) Me NH HN Me
Me
CO2Et
94% 5%
HO dl:meso = 1:1
Avoid Skin Contact with All Reagents
6 ZINC
MeO
N
Zn, MsOH Zn, TMSCl O O
O N N
N
O
DMF/THF DMF
I
(54)
-20 �C
20 �C, 16 h
86%
O 76%
N
MeO
Cl Cl
Cl
MeO
Zn, HCO2NH4
CH3 MeOH, )))) CH3
H3C H3C
7 7
NH O (55)
20 �C, 3 h
NHBn NH2
(50)
90%
NH O
N(Boc)2
Zn, MeOH
MeO TBDMSO OMe
reflux, 24 h
trans:cis = 90:10 87%
O
NHBoc
TBDMSO OMe
(56)
SO2
N
N O
Zn, TMSCl
DMF
Reduction of Carbon Sulfur Bonds. 2-Thioxo-4-thiazolidi-
20 �C, 12 h
nones can be converted to 4-thiazolidinones by utilizing excess
85%
Me
zinc dust in acetic acid (eq 57).81 Residual lead present in the
SO2 commercial source of zinc dust is essential for the success of the
reaction.82
HN NH
O
Zn, � Pb
(51)
AcOH
NH
reflux
S
90%
HO
Me
S
trans:cis = 1:2
O
NH
(57)
S
HO
Zn, MsOH
H CH3CN
20 �C
N
67%
OH Reduction of Nitrogen Nitrogen and Nitrogen Oxygen
Bonds. In the presence of ammonium chloride and ammonium
formate, the reduction of N O functions and N N functions with
(52)
zinc dust proceeds with good yields under very mild conditions.
H2N NH2
Many functional groups, which are known to be reducible moieties
(OH, OCH3, CH3, CO2H, COCH3, SO3Na, halogens, etc.) are
Zn, TiCl4
tolerated during this cleavage step. Thus, alkyl or aryl azides and
THF
acyl azides are reduced to the corresponding amines and amides
N
20 �C
N
73% (eqs 58 60).83,84 Azobenzenes are cleaved to their corresponding
anilines in a few minutes (eqs 61 and 62).85 Heteroaromatic
N-oxides are reduced to the corresponding pyridines through an
efficient deoxygenation (eq 63).86 Reduction of ł-nitro carbonyl
compounds produces nitrones without isolation of the intermedi-
HO Ph
ate hydroxylamines (eq 64).87
N
1. Zn, MsOH, THF, 25 �C
Zn, NH4Cl
2. (Boc)2O, aq NaHCO3
Me CONH CO2Me O
EtOH/H2O
N3
2
85%
reflux, 10 min
96%
Ph
NHBoc
O
(53)
NH2 (58)
Me CONH CO2Me
2
A list of General Abbreviations appears on the front Endpapers
ZINC 7
O O
Zn, NH4Cl
OBn
OBn
Zn, TFA
N3 EtOH/H2O NH2 (59)
25 �C, 1 h
(65)
20 �C, 2 h
94%
MeO2CCO2Me MeO2C
CO2Me
N
N N
H
N3 CH(SEt)2 Zn, HCO2NH4
MeOH
OBn
20 �C, 25 min
N
90%
O
MeO2CCO2Me
NH2CH(SEt)2
N NH
(60)
N
O
Zn, aq HCl
aq EtOH
N CN
N NH(66)
Zn, HCO2NH4
78 �C
MeOH
65%
H3C N N
20 �C, 12 min
90%
O2N
H2NH3C
(61) A zinc-mediated chemoselective reduction of nitroarenes to
H3C NH2 + H2N
amines and azobenzenes to hydrazobenzenes can be performed
H2N H3C in ionic liquids (eqs 67 and 68).90 A selective reduction of
nitroarenes is also reported by using zinc in near-critical water
ć% 91
(250 C). Interestingly, under microwave irradiation, nitro and
Zn, NH4Cl
azido arenes are reduced to N-arylformamides by using ammo-
MeOH
nium formate (eq 69).84 Zinc hydrazinium monoformate is an
N N N
20 �C, 20 min
efficient system to reduce aliphatic and aromatic nitro compounds
80%
to the corresponding amines (eq 70).92 Zinc dust combined with
HO2C
nickel chloride hexahydrate allows the selective reduction of
alkyl, aryl, aroyl and arylsulfonyl azides to amines (eq 71).93
Interestingly, nitro substituted aromatic azides are selectively
N NH2 + H2N
(62)
reduced to their corresponding anilines without any further
reduction of the nitro group (eq 72).
HO2C
Zn, NH4Cl
O
[bmim][PF6]/H2O
Zn, HCO2NH4
N N HO NO2
20 �C, 8 h
MeOH
(63)
77%
reflux, 4 h
CO2Me CO2Me
78%
HO NH2 (67)
Zn, aq NH4Cl
EtO2C THF
[bmim][PF6] = 1-butyl-3-methylimidazolium
0 �C, 5 h
EtO2C
NO2 O
hexafluorophosphate
77%
EtO2C
EtO2C
Zn, HCO2NH4
(64)
EtO2C
[bmim][BF4]/H2O
O EtO2C
NH N
Me N N Me
20 �C, 35 min
HO
O
94%
Under acidic conditions, pyridazines are converted to pyrroles
Me N N Me (68)
H H
through a ring contraction proceeding via a 1,4-dihydro-1,2-
diazine (eq 65).88 Reduction with zinc of a nitroarene possessing a
cyano group leads to an interesting cyclization reaction (eq 66).89 [bmim][BF4] = 1-butyl-3-methylimidazolium tetrafluoroborate
Avoid Skin Contact with All Reagents
8 ZINC
Zn, HCO2NH4
good yield by the reaction of �-((trimethylsilyl)oxy)alkyl iodides
)))), 300W
with zinc dust in THF (eq 77).97 Likewise, zinc-induced elimina-
Cl NO2
20 �C, 3 min
tion of a bromomesylate thymidine derivative affords the desired
80%
elimination product (eq 78).98 p-Toluenesulfonates of chiral 2,
(69) 3-epoxy alcohols are converted into allylic alcohols by a two-step
Cl NHCHO
reaction (iodination and reduction) (eq 79).99 A rearrangement
Zn, HCO2NH4
of the iodomesylate derivative (16) produces an interesting inter-
)))), 300W
mediate of (+)-8-deoxyvernolepin (eq 80).100 The reductive ring
Cl N3 20 �C, 2.5 min
opening of bromopyranose sugars, first developed by Vasella,101
90%
allows a zinc dust reduction of iodoglycosides under sonication102
NO2 Zn, H2N-NH2 � HCO2H
and furnishes highly functionalized unsaturated carbohydrates
MeOH
(eq 81).102d,e,f A chemoselective deprotection of prenyl carba-
20 �C, 2 min
mates was performed in a one-pot procedure (iodoetherification
94%
and reduction) (eq 82).103 A mild cleavage of allyl protection is af-
forded using perfluoroalkylation and subsequent elimination with
NH2
zinc dust (eq 83).104
(70)
NiBr2-bpy (10 mol %)
I
Zn-NiCl2 � 6H2O
O O
Zn, DMF
THF
Me S S Me
+
S N3 S NH2 (71)
110 �C, 48 h
20 �C, 2 h
81%
O O
85%
Zn-NiCl2�"6H2O
Me
THF
O2N N3
(75)
S
20 �C, 2.5 h
80%
Zn, Me2SiCl2
O2N NH2 (72)
SO2Cl SH
1,2-DCE, DMA
75 �C, 1.5 h
H3CS H3CS
97 %
(76)
Reduction of Sulfur Sulfur and Sulfur Oxygen Bonds. A
Zn/AlCl3 system in aqueous media is a convenient method for
the reduction of alkyl and aryl disulfides to zinc thiolates, which PhO
Zn, THF
PhO
react with alkyl or aryl halides and alkyl tosylates providing the (77)
reflux, 1 h
Me3SiO I
corresponding thioethers (eqs 73 and 74).94 Unsymmetrical aryl
93%
sulfides are also prepared by cleavage of the S S bond by zinc and
nickel bromide/bipyridine (bpy) followed by trapping with an aryl
O
iodide (eq 75).95 Zinc with dichlorodimethylsilane in dimethyl-
HN
acetamide allows a nonaqueous reduction of aromatic sulfonyl
O
Zn, AcOH cat.
chlorides affording various thiols (eq 76).96
BzO N
EtOAc, MeOH
O
Zn, AlCl3
20 �C, 3.5 h
DMF/H2O
97%
+ Bu Br
S S MsO Br
65 �C, 17 h
O
95%
HN
O
(78)
BzO N
O
S Bu
(73)
Zn, AlCl3
CH3CN/H2O
OTs
H
Bu S S Bu +
H O
65 �C, 6 h
1. KI, DMF, 55 �C, 1.5 h
90% OTs
O
2. Zn. NH4Cl, 0 �C, 20 min
O
H
86%
S Bu
OH
(74)
H
O (79)
H
O
Dehalogenation and Related Reactions. Zinc is well known
96% de
to promote dehalogenation reactions. Thus, olefins are obtained in
A list of General Abbreviations appears on the front Endpapers
ZINC 9
MsO
homologation of aldehydes (eq 84). Oxyallyl cations are easily
I
generated by zinc reduction of ą,ą -diiodoketones under sono-
Zn, NaI, aq DME
O
chemical conditions. Their reaction with dienes leads to the
O
reflux
cycloadducts in high yields (eq 85).107 A synthesis of octaflu-
78%
O
H
oro[2.2]paracyclophane (AF4) based on the generation of a
H O
O ć%
p-xylylene intermediate with zinc in DMA at 100 C has been
O
O
16
reported (eq 86).108
Reductive defluorination of pentafluorobenzoic acid proceeds
(80)
with high regioselectivity para to the carboxy group using zinc in
MsO
ammonia (eq 87).109
O
CBr4, PPh3
O
O
CH2Cl2
O
Cl
O
O
H
H
O
O Br
Zn, H2O
O
O (84)
275 �C, 4 h
Br
Cl Cl
I
1. Zn dust (excess), ))))
78%
O OMe
THF, BnNH2
O
O
2.
O
Br
BnO OBn
Zn, )))), CH3CN
+
73%
OBn
O
-44 �C, 15 min
(85)
I I
90%
cis:trans = 100:0
BnO
endo:exo = 91:1
Zn
O
(81)
reduction
BnO
NH [4+3]
Bn
ZnII
BnO
I
O
85:15
, I
O
oxyallyl cation
1. I2, MeOH, rt, 7 h
HN
2. Zn, 30 min
Zn, DMA
83%
ClF2CCF2Cl
MeS CO2Me
100 �C, 3 h
NH2
F
F F F
(82)
F F F
+ (86)
MeS CO2Me
F F F
FF F
F
I(CF2)6F, Na2SO4
SPh
NaHCO3
6%
AF4 : 60%
CH3CN/H2O
O
AllO
CO2H CO2H
20 �C, 30 min
O
98%
O
F F F F
Zn, NH3
(87)
-45 �C, 3.5 h
F F F F
90%
SPh
Zn, NH4Cl
I
F H
O EtOH
F(F2C)6 O
reflux, 15 min
O
O 90%
Zinc-mediated Cross-coupling Reactions. Zinc dust pro-
motes, under mild conditions, the acylation of alcohols,110
SPh
amines,111 thiols,112 ylides,113 the synthesis of carbamates,114 and
Friedel-Crafts acylation of electron rich arenes (eqs 88 92).115
O
HO
(83)
Under microwave irradiation, the Friedel-Crafts acylation can be
O
O
performed in solvent-free conditions and not only on activated
arenes but also on benzene, toluene, or chlorobenzene.116 It is
presumed that the electrophilic character of the acyl chloride is
1,1-Dibromo-1-alkenes are reduced to the corresponding enhanced by the zinc which undergoes nucleophilic displacement.
monobromoalkenes with zinc in the presence of NH4Cl,105 but The recovery of zinc and its reuse make these general meth-
are efficiently converted to methyl ketones by using zinc metal ods more economic. Zinc metal allows also acylation and sul-
in near-critical water.106 This reductive process was applied to fonation of pyrrole and its derivatives in high regioselectivity
Avoid Skin Contact with All Reagents
10 ZINC
(no N-acylated products were obtained under these conditions) Zn, toluene
+ Cl SO2Cl
(eq 93).117 Symmetrical thiosulfonic S-esters are obtained in good
20 �C, 1 h
N
85%
yield by the reduction of sulfonyl chlorides in the presence of
H
acetyl chloride (eq 94).118
Cl
(93)
S
O N
O2
H
Zn, benzene
Cl
+ Zn, TMSCl
OH
O
20 �C, 15 min
N
1,2-diobromoethane
O 94%
S Cl
CH3COCl, EtOAc, 20 �C
O
O 90%
O
O
(88)
N
S S (94)
O
O
O O
-
Wittig Reaction and Simmons Smith Reactions. Resid-
FmocHN Cl+H3N
Zn, THF
Cl OMe
ual lead found in commercial zinc dust has a dramatic ef-
+
20 �C, 10 min
fect on the Simmons Smith reaction (addition of TMSCl is
Ph
90%
necessary to suppress this negative effect), whereas it has a
positive catalytic effect on Wittig-type olefination with the
CH2I2, Zn, TiCl4 system.119 The reaction of aldoses with di-
bromomethyltriphenylphosphonium bromide, in the presence
O
(89) of zinc, gives the corresponding unsaturated olefination prod-
FmocHN OMe
N
ucts with good yields (eq 95).120 A variety of organoz-
H
O
inc carbenoids can be generated by the reaction of acetals,
Ph
ketals,121a ortho formates,121b carbonyl compounds,121c,d or
N-diethoxymethyl amides121e with metallic zinc in the pres-
ence of a triorganosilyl chloride. Organozinc carbenoids undergo
O
several useful reactions including direct deoxygenation to alkenes,
Zn, toluene
Ph SH
+
Cl
cyclopropanation, and dicarbonyl coupling (eqs 96 and 97).121
20 �C, 15 min
91%
Ph3PCHBr2, Br
O
O
OH Zn, dioxane
Ph (90) TrO
reflux, 40 min
S
90%
HO
Br
OH
(95)
TrO
O
N Br
Zn, benzene
+ H2N HO
BnO Cl 20 �C, 8 min
S
93%
Zn(Hg), Me3SiCl
O
ZnCl2, Et2O
(96)
13
O reflux
O 13
N 86%
BnO N (91)
MeO
H
S
OAc Si Si
Cl Cl
+
Zn, Et2O, reflux
OMe
69%
Cl CHO
Zn, toluene
Me
+
Cl 70 �C, 8 h MeO
COCl OAc
89%
(97)
H
OMe
Cl
cis:trans = 6.4:1
Me
(92)
Cl
Preparation of Organozinc Reagents. A broad range of
O
functionalized zinc organometallics have been prepared by us-
A list of General Abbreviations appears on the front Endpapers
ZINC 11
ZnI
ing the direct insertion of zinc into organic halides.122 In most
cases, activation of zinc dust is necessary, and the most com-
N
N
mon method remains the activation with 1,2-dibromoethane and
O
N
AcO
TMSCl in THF.54b In some cases, only trimethylsilyl chloride N
Bn
N
has been used to prepare activated zinc. For solubility reasons,
O
it is sometimes necessary to use a dipolar aprotic solvent such
O N ZnI
as DMF, DMSO, or DMAC instead of THF. Thus, chiral
OAc OAc
Bn
�-carbamate- and amido-alkylzincs bearing an acidic N H group
34 35
are prepared under mild conditions (17,123a 18,123b and 19,123c).
This activation allows the preparation of serine-derived organo-
zinc reagents as developed by Jackson (20,124a,b 21,124c 22,124d
An efficient procedure using a catalytic amount of I2 in a
23,124d 24,124e,f 25,124g,h,i 26,124g,h,i 27,124j 28,124k 29,124k).
polar aprotic solvent for activation of zinc allows the preparation
Various nitrogen-containing iodo- or bromo-substituted hetero- of alkylzinc compounds starting from unactivated alkyl bromides
cycles were converted to their corresponding zincated hetero- and chlorides (eq 98).128 The use of a sacrificial zinc anode
cycles derivatives (30 33).125,126 This reaction was extended to
offers an interesting alternative. Hence, in the presence of cat-
the preparation of zinc organometallics derived from nucleosides
alytic amounts of NiBr2bpy catalyst, 2,5-dibromo-3-substituted
and nucleic bases (34 and 35).126,127 The reaction of these new
thiophenes are electrochemically converted to their correspond-
zinc reagents with various electrophiles under palladium(0) or
ing thienylzinc species with good regioselectivity (eq 99).129 Aryl-
copper(I) catalysis allows the preparation of a broad range of poly- zinc compounds are also efficiently prepared by electroreduction
functional nitrogen-containing heterocycles.
of aryl chlorides and bromides with a zinc anode in the pres-
ence of cobalt bromide or a cobalt chloride pyridine complex
in DMF or acetonitrile (eqs 100 and 101).130 Arylzincs undergo
O
cross-couplings with aromatic halides or activated olefins.131 An
alternative to this electrochemical process uses allyl chloride and
X NH
NHBoc
zinc dust activated by traces of an acid as a reducing agent.132
ZnI
Various aromatic ketones are obtained by trapping these organo-
ZnI
Me
18, X = O
zinc derivatives with carboxylic acid anhydrides (eq 102).132c
19, X = C
17
O
Zn, I2
DMA
Br
EtO
3 80 �C, 3 h
NHBoc
IZn n
CN
Z
CO2R
IZn N
CN
O O
Cl
20, n = 1, R = Bn
(98)
O
Cl2Ni(PPh3)2
ZnBr
21, n = 1, R = Me
EtO EtO
O
22, n = 2, R = Bn 3 3
20 �C, 1 h
23, n = 3, R = Bn
24 97% overall
Zn anode
Hex
e, NiBr2bpy
NHR2
ZnBr2
IZn
Br DMF, -10 �C
Br
S
n
CO2R1
Hex Hex
25, n = 1, R1 = Me, R2 = Boc
I2
26, n = 2, R1 = Me, R2 = Boc (99)
ZnI
76%
BrZn I
Br Br
S S
27, n = 1, R1 = Me, R2 = TFA
28, n = 1, R1 = Bn, R2 = TFA N 100% 5-substitued
29, n = 1, R1 = Bn, R2 = Boc
30
Zn anode
e, CoCl2
Cl
ZnBr2
NC
DMF/pyridine
ZnI
N H3CO2S
20 �C
N
NC
ZnBr
N
I
ZnBr ZnCl
Cl
Me S N
I2
(100)
31 32 33 90%
H3CO2S
H3CO2S
Avoid Skin Contact with All Reagents
12 ZINC
Zn anode
Br
e, CoBr2
F3C Br
ZnBr2
O
Acetonitrile, 20 �C
Zn, aq NH4Cl
CO2Et
20 �C, 5 h
F3C ZnCl
F3C I
I2
(101)
90%
O
O
DBU
THF, 20 �C
(105)
1. Allyl chloride
60%
acetonitrile, TFA, 20 �C
overall
Zn
CoBr2 +
CO2Et
2. MeO CO2Et
Br
I
O
Zn
O
CO2Me
tert-amyl alcohol/H2O
MeO Me O MeO
20 �C, 3 h
2
(102) 87%
Me
ZnBr
O
O
CO2Me
83%
71%
(106)
Reformatsky Reaction and Barbier-type Reactions. The
Reformatsky reaction can be carried out in aqueous media by addi-
tion of salts (NH4Cl, CaCl2, Mg(ClO4)2, BF3�OEt2) (eq 103).133
Zn, aq NH4Cl
+
Barbier-type zinc-mediated reactions have been widely devel-
20 �C, 8 h
O O
Br
75%
oped, particularly the allylation and propargylation of carbonyl
compounds.134 Such reactions proceed well in saturated aque-
CHO
ous ammonium chloride solution with or without addition of or-
ganic solvent and also in liquid ammonia.135 Thus, intramolecular
carbonyl allylations of cyclic �-keto ester derivatives in aqueous
(107)
media allows a ring expansion of one or two carbons (eqs 104
O O
and 105).136 The same ring expansion of various ą-halomethyl
cyclic �-keto esters was performed in a mixture of tert-amyl
OH
alcohol and water with good yield (eq 106).137 With chiral alde-
hydes or with the enantiopure 2-sulfinylallyl chloride the addition syn:anti = 3:97
is highly stereoselective (eqs 107 109).138,139 Similar alkylation
on sulfonamines provides the corresponding homoallylic sulfon-
O
amides (eq 110)140 and difluoroacetyltrialkylsilane reacts with
Zn, THF/NH4Cl
H Br
+
various allyl bromides affording homoallylic alcohols (eq 111).141
0 �C, 30 min
NBn2
Aldimines and ketimines are efficiently allylated by commercial
95%
zinc dust without any activation (eq 112).142
OH
(108)
Zn, BF3�OEt2
O
Br
H2O /THF
NBn2
+
CO2Et
20 �C, 2 h
H
dr = 7:1
92%
Zn, NaI
OH p-Tol O
aq NH4I/THF
S
(103)
CO2Et +
CHO
0 �C
Cl
80%
Br
p-Tol O
O S OH
O
1. Zn, aq HCl/THF
(109)
20 �C, 20 h
CO2Et
(104)
CO2Et
2. DBU, THF, 2 h, rt
50%
dr = 6:1
A list of General Abbreviations appears on the front Endpapers
ZINC 13
H
momethane; Diiodomethane Zinc Titanium(IV) Chloride;
Zn, aq NH4Cl
SO2Ph Ph Br
+ Molybdenum(V) Chloride Zinc; Niobium(V) Chloride Zinc;
Ph N 20 �C, 2 h
Phosphorus(III) Bromide Copper(I) Bromide Zinc; Potassium
87%
Hexachloroosmate(IV) Zinc; Titanium(IV) Chloride Zinc;
NHSO2Ph Zinc Acetic Acid; Zinc Amalgam; Zinc Copper(II) Acetate
Silver Nitrate; Zinc Copper(I) Chloride; Zinc/Copper Couple;
(110)
Ph
Zinc 1,2-Dibromoethane; Zinc Dimethylformamide; Zinc
Ph
Graphite; Zinc/Nickel Couple; Zinc/Silver Couple; Zinc
Zinc Chloride.
Zn, aq NH4Cl
O
THF
Br
+
HF2C SiEt3 20 �C, 30 min
88%
1. (a) N�tzel, K., Methoden Org. Chem. (Honben-Weyl) 1973, 13/2, 552.
(b) Sheverdina, N. I.; Kocheshkov, K. A. In Methods of Elemento-
OH
Organic Chemistry; Nesmeyanov, A. N.; Kocheshkov, K. A., Ed.;
North-Holland: Amsterdam, 1967; Vol. 3. (c) Crompton, T. R. Analysis
Et3Si (111)
of Organoaluminium and Organozinc Compounds; Pergamon: Oxford,
CF2H
1968.
1. Zn, THF
2. (a) Martin, E. L., Org. React. 1942, 1, 155. (b) Staschewski, D., Angew.
Ph
20 �C, 2 h
Chem. 1959, 71, 726. (c) Buchanan, J. G. S. C.; Woodgate, P. D., Q.
Br
N
+
2. aq NaHCO3
Rev., Chem. Soc. 1969, 23, 522. (d) Vedejs, E., Org. React. 1975, 22,
Me Bn
98%
401. (e) Muth, M.; Sauerbier, M., Methoden Org. Chem. (Honben-Weyl)
1981, 4/1c, 709.
Ph 3. (a) Knochel, P., Chem. Rev. 1993, 93, 217. (b) Elschenbroich, C.;
Salzer, A. Organometallics: A Concise Introduction; VCH: Weinheim,
(112)
BnHN
1989. Carruthers, W. In Comprehensive Organometallic Chemistry;
Me
Wilkinson, G., Ed.; Pergamon: Oxford, 1982; Vol. 7, p 661.
4. (a) Gaudemar, M., Organomet. Chem. Rev. (A) 1972, 8, 183. (b) Rathke,
Allylic zinc halides add easily to acid chlorides providing �,ł-
M. W., Org. React. 1975, 22, 423. (c) F�rstner, A., Synthesis 1989, 571.
unsaturated alcohols, or in the presence of TMSCl promoting
5. (a) Simmons, H. E.; Cairns, T. L.; Vladuchick, A.; Hoiness, C. M., Org.
a gem-bisallylation (eq 113).143 Likewise, allylic or benzylic
React. 1972, 20, 1. (b) Furukawa, J.; Kawabata, N., Adv. Organomet.
bromides add to alkyl and aryl sulfonyl chlorides providing
Chem. 1974, 12, 83. (c) Zeller, K.-P.; Gugel, H., Methoden Org. Chem.
�,ł-unsaturated sulfones in ether or aqueous media (eq 114).144
(Houben-Weyl) 1989, EXIXb, 195.
An efficient addition to ą-amidoalkylphenyl sulfones is also
6. (a) Erdik, E., Tetrahedron 1987, 43, 2203. (b) Rieke, R. D., Science
1989, 246, 1260. (c) F�rstner, A., Angew. Chem., Int. Ed. Engl. 1993,
reported (eq 115).145
32, 164.
O
7. (a) Morris, S. G.; Herb, S. F.; Magidman, P.; Luddy, F. E., J. Am. Oil
Zn, TMSCl
Chem. Soc. 1972, 49, 92. (b) Sondengam, B. L.; Charles, G.; Akam, T.
THF
Cl
Cl
M., Tetrahedron Lett. 1980, 21, 1069.
+
50 �C, 3 h
8. (a) Aerssens, M. H. P. J.; van der Heiden, R.; Heus, M.; Brandsma, L.,
92%
Synth. Commun. 1990, 20, 3421. (b) Solladi�, G.; Stone, G. B.; Andr�s,
J.-M.; Urbano, A., Tetrahedron Lett. 1993, 34, 2835.
Ph
9. (a) N�f, F.; Decorzant, R.; Thommen, W.; Willhalm, B.; Ohloff, G.,
(113)
HO
Helv. Chim. Acta 1975, 58, 1016. (b) Oppolzer, W.; Fehr, C.; Warneke,
J., Helv. Chim. Acta 1977, 60, 48. (c) Winter, M.; N�f, F.; Furrer, A.;
Pickenhagen, W.; Giersch, W.; Meister, A.; Willhalm, B.; Thommen,
O
Zn, Et2O
W.; Ohloff, G., Helv. Chim. Acta 1979, 62, 135.
Br
+ S Cl
10. (a) Boland, W.; Schroer, N.; Sieler, C.; Feigel, M., Helv. Chim. Acta
20 �C, 3 h
O
81% 1987, 70, 1025. (b) Avignon-Tropis, M.; Pougny, J. R., Tetrahedron
Lett. 1989, 30, 4951. (c) Chou, W.-N.; Clark, D. L.; White, J. B.,
Tetrahedron Lett. 1991, 32, 299.
O
11. (a) Biollaz, M.; Haefliger, W.; Verlade, E.; Crabb�, P.; Fried,
(114)
S
J. H., J. Chem. Soc., Chem. Commun. 1971, 1322. (b) Maurer, H.; Hopf,
O
H., Angew. Chem., Int. Ed. Engl. 1976, 15, 628. (c) Kloster-Jensen, E.;
Wirz, J., Helv. Chim. Acta 1975, 58, 162.
O SO2Ph
Zn, THF
12. (a) Davis, B. R.; Woodgate, P. D., J. Chem. Soc. (C) 1966, 2006.
Br
Bn
+
(b) Davis, B. R.; Woodgate, P. D., J. Chem. Soc. 1965, 5943. (c) Toda,
O N Ph 20 �C, 1.5 h
F.; Iida, K., Chem. Lett. 1976, 695.
H 99%
13. (a) Chaykovsky, M.; Lin, M. H.; Rosowsky, A., J. Org. Chem. 1972, 37,
2018. (b) Marker, R. E.; Crooks, H. M., Jr.; Wagner, R. B.; Wittbecker,
O
E. L., J. Am. Chem. Soc. 1942, 64, 2089.
(115)
Bn
14. Petrier, C.; Luche, J.-L., Tetrahedron Lett. 1987, 28, 2347, 2351.
O N Ph
H
15. (a) Weeks, D. P.; Cella, J., J. Org. Chem. 1969, 34, 3713. (b) Dickinson,
J. D.; Eaborn, C., J. Chem. Soc. 1959, 2337. (c) Wiselogle, F. Y.;
Related Reagents. Dibromomethane Zinc Titanium(IV)
Sonneborn, H., Org. Synth., Coll. Vol. 1941, 1, 90. (d) Gardner, J. H.;
Chloride; Dichlorobis(cyclopentadienyl)zirconium Zinc Dibro- Naylor, C. A., Org. Synth., Coll. Vol. 1943, 2, 526.
Avoid Skin Contact with All Reagents
14 ZINC
16. (a) Coulombeau, C.; Rassat, A., Bull. Soc. Chem. Fr. 1970, 1199. 35. (a) Petrier, C.; Luche, J.-L., J. Org. Chem. 1985, 50, 910. (b) Petrier, C.;
(b) Rosnati, V., Tetrahedron Lett. 1992, 33, 4791. Einhorn, J.; Luche, J.-L., Tetrahedron Lett. 1985, 26, 1449. (c) Einhorn,
C.; Luche, J.-L., J. Organomet. Chem. 1987, 322, 177. (d) Knochel,
17. (a) Yamamura, S.; Toda, M.; Hirata, Y., Org. Synth., Coll. Vol. 1988,
P.; Normant, J. F., Tetrahedron Lett. 1984, 25, 1475. (e) Knochel, P.;
6, 289. (b) Marchand, A. P.; Weimar, W. R., Jr., J. Org. Chem. 1969,
Normant, J. F., J. Organomet. Chem. 1986, 309, 1.
34, 1109. (c) Winternitz, F.; Mousseron, M., Bull. Soc. Chem. Fr. 1949,
16, 713. (d) Nesty, G. A.; Marvel, C. S., J. Am. Chem. Soc. 1937, 36. (a) �hler, E.; Reininger, K.; Schmidt, U., Angew. Chem., Int. Ed. Engl.
59, 2662. (e) Minabe, M.; Yoshida, M.; Fujimoto, M.; Suzuki, K., 1970, 9, 457. (b) L�ffler, A.; Pratt, R. D.; Pucknat, J.; Gelbard, G.;
J. Org. Chem. 1976, 41, 1935. (f) Mayer, R.; B�rger, H.; Matauschek, Dreiding, A. S., Chimia 1969, 23, 413. (c) Auvray, P.; Knochel, P.;
J. Prakt. Chem. 1961, 285, 261. (g) Borden, W. T.; Ravindranathan, T., Normant, J. F., Tetrahedron 1988, 44, 4495. (d) Auvray, P.; Knochel,
J. Org. Chem. 1971, 36, 4125. (h) Martin, E. L., Org. Synth., Coll. Vol. P.; Normant, J. F., Tetrahedron 1988, 44, 4509. (e) El Alami, N.; Belaud,
1943, 2, 499. (i) Read, R. R.; Wood, J., Org. Synth., Coll. Vol. 1955, 3, C.; Villi�ras, J., J. Organomet. Chem. 1987, 319, 303. (f) El Alami, N.;
444. (j) Schwarz, R.; Hering, H., Org. Synth., Coll. Vol. 1963, 4, 203. Belaud, C.; Villi�ras, J., J. Organomet. Chem. 1988, 348, 1. (g) Belaud,
(k) Burdon, J.; Price, R. C., J. Chem. Soc., Chem. Commun. 1986, 893. C.; Roussakis, C.; Letourneux, Y.; El Alami, N.; Villi�ras, J., Synth.
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