MAGNESIUM 1
Br Br
Magnesium1 BrMg MgBr
Mg
(3)
Mg
Br
MgBr
[7439-95-4] Mg (MW 24.31)
The form of the magnesium metal employed is often criti-
InChI = 1/Mg
cal to the successful formation of the organomagnesium reagent.
InChIKey = FYYHWMGAXLPEAU-UHFFFAOYAI
For simple primary or secondary alkyl bromides or iodides, and
simple aryl or vinyl bromides or iodides, commercially available
(formation of organomagnesium compounds; reduction of metal
magnesium turnings or powders of modest purity (>98%) are
halides; reduction of organic functional groups)
often suitable. If necessary, activating the surface of the mag-
ć% ć%
nesium with iodine,1,24 dibromoethane,1,25 or ultrasound26 treat-
Physical Data: mp 651 C; bp 1107 C; d 1.74 g cm-3.
ment, or employing ultrapure magnesium metal,27 is usually suffi-
Preparative Methods: widely commercially available in forms
cient to facilitate Grignard reagent formation with such substrates.
(most commonly turnings and powders) and in purity (98
In the case of many organochlorine or organofluorine compounds,
99.95%) suitable for many applications in organic synthesis.
as well as unreactive bromides and iodides, a more reactive form
For some applications magnesium powder or activated mag-
of magnesium must be employed. Three practical methods have
nesium is freshly prepared via the reduction of a magne-
been developed for the preparation of highly reactive magnesium
sium(II) salt or the evaporative deposition of magnesium metal.
(active magnesium) for use in organic synthesis. A highly re-
The commercially available magnesium anthracene adduct
active magnesium slurry is prepared via the evaporative depo-
[86901-19-1] also provides a highly reactive form of magne-
sition of magnesium in THF using a relatively simple prepara-
sium metal.
tive apparatus.28 30 Magnesium halides are reduced by Potas-
Handling, Storage, and Precautions: most freshly prepared
sium metal,31,32 or better Lithium Naphthalenide,33,34 to afford
magnesium powders and organomagnesium compounds are
an active magnesium powder often referred to as  Rieke mag-
pyrophoric.
nesium . Magnesium metal can be activated by treatment with
anthracene,35 or the magnesium anthracene adduct,36 which is
in equilibrium with the finely divided metal powder, can be used
Original Commentary
directly.
The formation of allyl or benzylic Grignard species is often
James M. Takacs
accompanied by dimerization of the allylic or benzylic halide. In-
University of Nebraska-Lincoln, Lincoln, NE, USA
deed, this reductive dimerization can be preparatively useful using
the classical Grignard-forming reaction conditions,37 but to avoid
Formation and Reactions of Organomagnesium Com-
it, an active magnesium is typically employed.38,39 Oppolzer40
pounds. The carbon carbon bond forming reactions of organo-
reported a comparison of the three methods discussed above in a
magnesium (Grignard) reagents via their reaction with carbon
1984 study of the metallo ene reaction. The magnesium variant of
electrophiles constitute one of the cornerstones of organic synthe-
the metallo ene reaction41 features the formation and subsequent
sis (eq 1). Much is known about this most famous of organometal-
cycloisomerization of an allylmagnesium chloride from an al-
lic reactions. The mechanisms of Grignard formation2 13 and
lylic chloride. As shown in eq 4, magnesium-mediated cyclization
reaction14,15 have been studied extensively. Structural16,17 and
and trapping with the electrophilic oxygen source Oxodiperoxy-
thermochemical18 data of the organomagnesium compounds have
molybdenum(pyridine)(hexamethylphosphoric triamide) (i.e.
been reported.
MoOPH) proceeds in 55% yield with magnesium slurry prepared
by evaporative deposition, in 55% yield with Rieke magnesium,
E+
and in 56% yield with magnesium anthracene.
RX + Mg [RMgX] RE (1)
Many novel organomagnesium compounds have been prepared.
1. Mg*,  65 °C
These include dimetallic species19,20 such as methylenedimag-
(4)
2. MoOPH
nesium dibromide (see also Magnesium Amalgam)21 and 1,n-
OH
55 56%
Cl
(dimagnesio)alkanes such as 1,4-bis(bromomagnesio)pentane, an
intermediate which has been used for the stereoselective conver-
sion of esters to trans-1,2-disubstituted cyclopentanols (eq 2).22 The extent to which these activated forms of magnesium have
expanded the range of substrates suitable for formation of organo-
Remarkably, even a soluble trimagnesium compound was recently
prepared under relatively routine reaction conditions (eq 3).23 magnesium species cannot be overemphasized. For example,
alkyl fluorides are very poor substrates for the classical Grignard
conditions. In contrast, treatment of octyl fluoride with Rieke
MgBr
magnesium32,34 affords the corresponding organomagnesium
reagent which reacts with Carbon Dioxide in 89% yield (eq 5).
+ MeCO2Et (2)
MgBr
77% OH
The chloride shown in eq 6 is benzylic, thus prone to dimeriza-
tion with classical magnesium sources, and requires formation
96% trans
of a dianionic intermediate. Magnesium powder is reported to
Avoid Skin Contact with All Reagents
2 MAGNESIUM
OH
afford the diorganomagnesium species in only 43% yield. In con-
O I
Mg
trast, the dichloride reacts with magnesium anthracene in 92%
(9)
54%
yield.36,42 Cyclopropylmethyl compounds are prone to rearrange
H
via ring opening to the n-butenyl isomers. Formation of the Grig-
cis:trans = 8:1
nard reagent from cyclopropylmethyl bromide under classical
conditions followed by trapping with carbon dioxide affords 4-
The complementary magnesium-mediated cyclizations of
pentenoic acid (eq 7). In contrast, treatment of cyclopropylmethyl
cyanoiodoalkanes can be an efficient reaction. For example,
ć%
bromide at -78 C with the magnesium slurry prepared via evap-
the iodonitrile shown (eq 10) undergoes magnesium-mediated
orative deposition affords mostly cyclopropylacetic acid (92% of
cyclization to form the relatively sterically congested 2,2-
the product mixture, 78% yield) after trapping with carbon
disubstituted cyclohexanone in 71% yield.52
dioxide.28
O
Mg
I NC i-Pr
Mg* CO2
(10)
C8H17F [C8H17MgF] C8H17CO2H (5)
Et2O i-Pr
71%
89%
Magnesium is an alternative to zinc metal for effecting the Re-
Cl Cl ClMg MgCl
formatsky reaction and has been used in the synthesis of ²-keto
Mg*
esters.53 For example (eq 11), t-butyl bromoacetate is condensed
(6)
with cyclohexanone in 80% yield.54
92%
O
O
Mg
+ (11)
Br
O-t-Bu
O-t-Bu Et2O
O
80%
Br MgBr
OH
Mg*
 78 °C MgBr
Organomagnesium species can effect the carbometalation of
alkenes and alkynes.55,56 The more common variants, however,
(7)
are the copper-catalyzed reactions, a subject which has been com-
CO2H prehensively reviewed by Lipshutz and Sengupta.57 For exam-
ple (eq 12), the Ethylmagnesium Bromide/Copper(I) Bromide
+
combination effects net syn addition across 1-octyne. The result-
CO2H
92:8
ing alkenyl metal species can be stereospecifically trapped by a
variety of electrophiles, including Allyl Bromide (85%) and 1-
The chemistry of organomagnesium compounds is extraordi- heptene oxide (94%).58 This reaction constitutes a useful stereos-
narily rich and diverse. It is impossible to detail comprehen- elective alkene synthesis. Dichlorobis(cyclopentadienyl)titanium
sively their many reactions with classical organic electrophiles
also catalyzes the net syn addition of organomagnesium reagent
(e.g. aldehydes, ketones, carboxylic acid derivatives, carbon diox- across alkynes.59 (See also the corresponding organolithium and
ide, C N multiple bonds, epoxides, alkyl halides, etc.) within the
organocopper compounds for alternative reagents.57)
space limitations here. Fortunately, several standard texts give a
Et Cu(SMe2)MgBr2 E+
1. CuBr(SMe2)
good account of these procedures.43,44 The following paragraphs
EtMgBr
highlight several of the many less routine uses of these reagents. 2. C6H13Ca"CH
C6H13 H
For example, in addition to the reaction with traditional carbonyl
Et E
electrophiles, organomagnesium reagents add efficiently to cer-
(12)
tain mixed orthoformates to afford acetals. For example (eq 8),
C6H13 H
E = CH2CH=CH2 (85%)
n-butylmagnesium bromide adds to phenyl diethyl orthoformate
CH2CH(OH)C5H11 (94%)
in 90% yield.45
Organomagnesium reagents undergo efficient copper-catalyzed
BuMgBr + PhOCH(OEt)2 BuCH(OEt)2 (8)
90%
conjugate addition reactions.57 For example (eq 13), n-
butylmagnesium bromide undergoes CuBr Me2S-catalyzed
The one-pot combination of alkyl halide, magnesium metal, addition to acrolein in the presence of Chlorotrimethylsilane and
and carbon electrophile is often referred to as the Barbier Hexamethylphosphoric Triamide (HMPA) to afford the (E)-silyl
reaction.46 This strategy is particularly appropriate for the cy- enol ether in 89% yield (96% E).60
clization of substrates containing both reacting partners within
O 5 mol % CuBr(Me2S) OTMS
their structure. The intramolecular reaction of halo ketones can
2 equiv TMSCl
BuMgBr + (13)
afford cyclized products, but often in only modest-to-good yield H H
2 equiv HMPA
with magnesium.47 For example (eq 9), the cycloheptanone
THF,  78 °C, 3 h
Bu
derivative cyclizes to the hydroazulene ring skeleton in 54% 89%
96% E
yield. Lithium/ultrasound,48,49 Lithium, Tin(II) Chloride,50 and
Samarium(II) Iodide51 may offer suitable alternative reagents for
Organomagnesium reagents undergo copper-catalyzed reaction
such cyclizations.
with alkyl, allyl, vinyl, and aryl halides or sulfonates, and with
A list of General Abbreviations appears on the front Endpapers
MAGNESIUM 3
OOH
CdCl2, Mg
epoxides.57 For example (eq 14), n-butylmagnesium bromide un-
aq. THF
dergoes copper-catalyzed substitution of the propargyl methyl
(19)
25 °C, 15 min
ether to afford an allene.61 The substitution proceeds in high chem-
95%
ical yield and with good stereochemical control.
CdCl2, Mg
H
OAc
OAc
OMe
aq. THF
5 mol % CuBr 2Bu3P
(20)
BuMgBr + (14)
Bu " Bu
25 °C, 15 min
Bu
THF,  78 to 5 °C
O
82%
100%
H
OH
90% ee
The combination of magnesium Chlorotrimethylsilane has
A number of other transition metals catalyze interesting reac-
been used for the reductive silylation of 1,1-dibromides,84
tions of organomagnesium reagents.59,62 Of particular novelty is
conjugated trienes,85 heterocycles,86 and, as shown in eq 21,
the titanium-catalyzed hydromagnesiation of alkenes. For exam-
certain chloro-substituted enynes.87 Magnesium has been also
ple (eq 15), vinylcyclohexanol transmetalates with ethylmagne-
used as a reactive metal electrode in an electroreductive silyla-
sium bromide in the presence of catalytic Cp2TiCl2 to afford, after
tion of alkenes.88
capture by carbon dioxide, the Å‚-lactone shown in 58% yield.63 65
H H
O
Mg, TMSCl
Cl H
1. EtMgBr
(21)
HO
Cp2TiCl2 O
HMPA, 25 °C
(15) H H " H
80%
2. CO2
H
TMS
1,3-Dienes form reactive complexes with magnesium.89 In this
Reductions with Magnesium. Magnesium is a common
capacity, active magnesium has been used for the reductive silyla-
agent for reducing a variety of transition metal salts,66 68 for ex- tion and dialkylation of certain conjugated 1,3-dienes. For exam-
ample the reduced titanium reagent (Titanium(IV) Chloride Mg)
ple (eq 22), treatment of 1,4-diphenyl-1,3-butadiene with Rieke
used widely in carbonyl coupling reactions.69 Magnesium itself
magnesium affords the magnesium diene complex. Addition of
effects the reductive dimerization (pinacol coupling) of ketones70 Dichlorodimethylsilane affords the cis-diphenylsilacyclopentene
and enones71 (see also Magnesium Amalgam and TiCl4 Mg).
in 66% yield.90
Magnesium effects the reductive dimerization of organotin
Ph
Ph
oxides72 (eq 16) and dialkylantimony bromides (eq 17).73
1. Mg*
Mg, THF SiMe2 (22)
2. Me2SiCl2
(i-Bu)3SnOSn(i-Bu)3 (i-Bu)3SnSn(i-Bu)3
(16)
82%
66%
Ph
Ph
Mg, THF
2 Bu2SbBr Bu2SbSbBu2
(17)
Magnesium has been used for the reduction of 1,1-dibromo-
alkanes,74 although reductive dimerization has been found to com- First Update
pete in some cases,75,76 and in the formation of Ph3P=CCl2 from
Jens Högermeier & Martin G. Banwell
triphenylphosphine and carbon tetrachloride.77 Magnesium has
The Australian National University, Canberra, Australian Capital
been used as an alternative to n-Butyllithium or lithium amalgam
for the conversion of 1,1-dibromoalkenes to alkynes (eq 18).78 Territory, Australia
Ph3P Mg, THF
Introduction. Since the original entry, many new applica-
RCHO RCH=CBr2 65 °C RCa"CH (18)
tions and/or modified synthetic protocols involving magnesium
CBr4
75 95%
have emerged. This update is concerned with the use of mag-
nesium metal91 for the preparation of organomagnesium com-
Magnesium reacts with amines to form magnesium amides,79
pounds and the application of these in synthesis. It includes dis-
and with alcohols to form magnesium alkoxides. In the latter
cussions of activated forms of the metal such as RiekeTM-Mg92,93
context, magnesium has been used as a drying agent for alcohols,80 Mg anthracene. The use of Mg metal as a reducing agent,
and
but the combination of magnesium methanol has also found
particularly in pinacolic coupling reactions, is also covered. In
significant utility as a selective reducing agent for certain or-
contrast, this article does not deal with those reactions involving a
ganic functional groups (e.g. conjugated ketones, esters, nitriles,
magnesium source other than Mg metal. So, for example,
amides).81 The combination of Cadmium Chloride magnesium
i-PrMgBr, which is now used extensively in metal halogen
in aqueous THF also shows interesting selective functional group
exchange reactions for the synthesis of organomagnesium com-
reductions, e.g. the selective 1,2-reduction of enones (eq 19) and
pounds (see iso-propylmagnesium bromide in this series and
the selective reduction of an epoxide in the presence of an allylic
selected reviews),94,95 is not dealt with here. Other related
acetate (eq 20).82,83
Mg-based reagents and organomagnesium compounds that are
Avoid Skin Contact with All Reagents
4 MAGNESIUM
not included but that have been reviewed recently include highly substituted cyclopentadiene derivatives in a concise
Mg/MeOH (see Mg/MeOH in this series and a review article96), manner (eq 23).105
Mg/amalgam (see Mg/amalgam in this series), magnesium bis-
R2 R2
amides,97 and heterocyclic organomagnesium compounds more
R R
generally.98 Mg, Br(CH2)2Br
Br MgBr
Br MgBr
60 °C, 8 h
Formation and Reactions of Organomagnesium Com- R R
pounds. The reaction of Mg metal with organic halides has been R2 R2
used routinely for about a century to form Grignard reagents. How-
R2 2 COR2 2 2 31 61%
ever, the mechanism of this transformation remains the subject of
R = Me, Pr,  (CH2)4
study. By using a cell suitable for photomicrographic observations,
R2 = Me, Pr
an assessment of the behavior of magnesium surfaces during the
R2 2 = Ph, Pr,  (CH2)5 , H
R
formation of Grignard reagents was undertaken and it has thus
R
R2 2 2 = R2 2 , Ar, het-Ar
R2 2 2
been confirmed that the addition of iodine or ferric chloride in-
(23)
creases the reactivity of Mg surfaces as much as scratching them R2 2
R
does.99
R2
The identification of efficient methods for the formation of
organomagnesium reagents continues. A comparison of several Similarly, reaction of 1,4-dibromobutane with Mg in THF
ć%
means for metallating electron-rich aryl bromides has established at 30 C gives the corresponding bis-Grignard reagent that is
that heating Mg metal under reflux in THF for 24 48 h is ef- readily transformed into the analogous bis-heterocuprate, a
fective while protocols involving i-PrMgCl are not. However, species that can react with axially-chiral bromoallenes to give
the use of (s-Bu)2Mg·LiCl and (n-Bu)2Mg·LiCl proved supe- 1,9-decadiynes.106
rior, delivering the relevant organomagnesium species derived Organomagnesium reagents are sometimes used as bases. For
from 4-bromoanisole in 8 h or under 5 min, respectively.100 In- example, a highly effective synthesis of 3-butyn-1-ol employs
vestigations into the formation of Grignard reagents containing EtMgBr, prepared from Mg and ethyl bromide, to deprotonate
electron-withdrawing substituents such as those derived from 3- acetylene. The resulting ethynyl Grignard then reacts with ethy-
or 4-iodobenzoates show that these can be formed smoothly at lene oxide to give 3-butyn-1-ol.107 This procedure is superior to
low temperature. However, the decomposition of such species is the equivalent employing lithium acetylide, which is less reactive
observed if they are allowed to stand at room temperature for toward ethylene oxide.
several hours.101 An electrochemical alternative to the classical One of the most common applications of organomagnesium
method of using Mg turnings for the preparation of Grignard reagents involves their reaction with electrophiles. An interest-
reagents containing electron-withdrawing substituents has been ing group of electrophiles is the aryl bis-chalcogenides, parti-
identified and involves using a Mg anode and a Pt cathode in a cularly ArSe SeAr and ArTe TeAr. In the presence of Mg, these
solution of KClO4/DMSO. During electrolysis, the strong base undergo copper-catalyzed cleavage reactions of the chalcogene
dimsyl2Mg is produced while potassium accumulates at the cath- chalcogene single bond to give unsymmetrical diarylselenides
ode. The dimsyl2Mg derived from the sacrificial Mg anode can or tellurides (eq 24).108 Another copper-catalyzed process in-
deprotonate even weakly acidic substrates such as substituted fluo- volves the reaction of alkyl Grignards with allyl chlorides, which
renes, thereby generating Grignard reagents that contain electron- proceeds with high Å‚-selectivity.109
withdrawing substituents.102 Another somewhat unusual way of
Mg, cat Cu2O-bpy
Ar XAr2 (24)
preparing Grignard reagents from Mg metal involves the use of mi- Ar I + 1/2 Ar2 X XAr2
DMF, 110 °C
crowave irradiation. While the irradiation of metals in a microwave
53 95%
oven can be problematic, and even dangerous on occasion, heating
Ar = o- and p-Ar
bromo- and chloro-aryls with Mg turnings under such conditions
Ar2 = p-Ar, naph, 2- and 3-pyr, 2-thiophene
has been shown to give the corresponding Grignard reagents that X = Se or Te
can then be reacted with CO2 to afford, after acidic workup, var-
A useful procedure for the carboethoxylation of organomag-
ious aryl carboxylic acids in good yields. The Grignard reagents
nesium compounds involves the reaction of such species with
prepared by this same method participate in transmetallation re-
diethyl dicarbonate and a Lewis acid under sonication conditions.
actions with ZnCl2 TMEDA to give the corresponding aryl zinc
The best results are obtained using BF3·OEt2 as the Lewis acid.
species that then engage in microwave-promoted Negishi cross-
The method allows for the efficient mono- and di-carboxylation
coupling reactions.103
of dibromoarenes of various types (eq 25).110
Traditionally, the preparation of propargylic Grignard reagents
involved using HgII salts as catalysts, but these can now be re-
Mg, Br(CH2)2Br
(EtO2C)2O, THF
placed by ZnBr2. The method requires only 2% of ZnBr2 for the
S S
Br Br
sonication, BF3·OEt2 EtO2CCO2Et
smooth preparation of a range of different propargylic Grignard
63%
(25)
reagents.104
(+29% 2-bromo-5-ester)
The preparation of bis-metallic derivatives of Mg has often
been challenging but now 1,4-bis(bromomagnesio)butadienes
also other ArBr where Ar = m-, p-Ar, Ph, pyr, indole
can be readily generated, using Mg and dibromoethane, from
the corresponding 1,4-dibromobutadienes. The reaction of such The replacement of both halogens in ring-fused gem-
species with various ketones, aldehydes, and PhNO provides dichlorocyclopropanes can be accomplished using TMSCl in the
A list of General Abbreviations appears on the front Endpapers
MAGNESIUM 5
Mg, THF, heat
presence of either lithium (containing 1% sodium) or with a mix-
I (CH2)8 I or
ture of Mg, Zn, and CuCl. Generally, the former protocol is
Br (CH2)12 Br
(28)
superior (eq 26).111
O O (CH2)n Br O O (CH2)m O O
Li (1% Na), TMSCl, THF
Cl SiMe3
n = 6, 12, 14 m = 20, 32, 40
(26)
or
Cl SiMe3
Mg, Zn (0.3 equiv), TMSCl
Among the many transition metal-catalyzed methods available
CuCl (0.03 equiv), THF
for C C bond formation, the Pd0-catalyzed coupling reactions
with Li 95%
with Mg/Zn/Cu(I) 47% are probably the most versatile, particularly the Kumada vari-
ant involving organomagnesium compounds and various elec-
trophiles. A few examples of Kumada cross-coupling reactions
A nucleophilic addition elimination reaction of a Grignard
are known where the requisite Grignard is synthesized directly
compound to a suitably substituted naphthalene has been used
to synthesize axially chiral biaryl ligands required in the assem- from Mg metal and not via exchange from a commercial Grig-
nard source (e.g., i-PrMgBr). For example, a diaryl bromide can
bly of metathesis catalysts. The requisite Grignard reagent, formed
ć%
be converted into the corresponding bis-magnesio reagent by re-
by treating the precursor aryl bromide with Mg at 60 CinTHF, is
fluxing it in THF with Mg metal and the bis-Grignard reagent
added to a 2-menthyl 1-menthyloxy-2-naphthoate thus giving the
desired product in 84% yield and with excellent diastereoselecti- so-formed can, in turn, be coupled, under Pd0 catalysis, with var-
ious dibromoarenes to generate a range of conjugated polymers
vity (19:1) (eq 27). Recrystallization of the crude reaction mixture
in good yields (eq 29).120
gives a single diastereoisomer.112
OC8H17
i-Pr
PdCl2(ddpf)
MgBr
O THF, reflux
conjugated
Br Ar Br
Br + (29)
polymers
O
O Me MeO BrMg
+
OC8H17
Me
i-Pr CF3
Br Ar Br:
Mg, THF
Br Br Br
C6H6, 60 °C
Br
51% 58%
i-Pr
S
O
Br
Br
Br Br
(27)
O
MeO
40% 73%
Me
CF3
A related and very useful process involves the FeIII-catalyzed
84% (19:1 ds)
homo- or cross-coupling Grignard reagents. For example, such
reagents, when generated from the corresponding bromide using
Barbier-type processes, involving the reaction of Grignard
metal Mg in THF at room temperature, homocouple very effi-
reagents with aldehydes or ketones, provide a remarkably
ciently in the presence of Fe(acac)3 or Fe(DBM)3 (eq 30).121
reliable means for C C bond formation. Furthermore, while
2% Fe(acac)3 or Fe(DBM)3
Grignard reagents are generally considered moisture sensitive,
Mg, THF
Barbier reactions have been carried out in aqueous media. Thus,
R Br R R (30)
41 92%
by using a combination of Mg and BiCl3 in THF/water, allyl Grig-
nard reagents can be formed and then reacted in situ with various
DBM = dibenzoyl methane
aldehydes to give the expected secondary alcohols in up to 90%
R = o-, m- or p-aryl, alkyl, cycloalkyl
yield. In contrast, with THF alone the same reagent combination
gave only 78% of the desired product.113 Related studies have
Highly activated forms of magnesium have been studied
shown that aqueous NH4Cl alone can serve as a medium for such
extensively in recent years. For example, RiekeTM-Mg has been
reactions, although under these conditions the products were ob-
successfully employed in the generation of organomagnesium
tained in low to moderate yields (viz. 21 40%).114,115 Barbier-
compounds that can react with electrophiles as varied as Weinreb
type reactions involving imines can also be effective processes,
amides,122 aldehydes,123 furanoses,124 and CO2.125 In a study
thus providing a range of linear and branched amines.116 118
of the addition of organometallics to an acylpyridinium salt,
Efficient C C bond formation can be achieved through re-
RiekeTM-Mg proved to be a good choice as metal source for
ductive coupling of a Grignard reagent with an alkyl halide.
generation of the required organomagnesium compound since
Thus, various É-tetrahydropyranyloxyalkyl bromides have been
higher yields of product were obtained with this species than
transformed under conventional conditions into the corresponding
when the corresponding lithiates or cuprates were employed.126
Grignard reagents and these were then reacted with various long-
Thienylmagnesium compounds derived from the direct reaction of
chain 1,É-dihaloalkanes to produce bis-THP acetals (eq 28).119 RiekeTM-Mg with thienyl iodides can be successfully employed
Avoid Skin Contact with All Reagents
6 MAGNESIUM
in Pd0- or NiII-catalyzed cross-coupling reactions with a range of An interesting and sometimes efficient two-fold C-acylation
electrophiles (eq 31).127,128 reaction of anthracene or benzyl acrylates with acid chlorides was
discovered when these compounds were treated with acyl chlo-
S S S
Mg* electrophile
I MgI E
rides and Mg metal in DMF. The acylation of anthracene is readily
(31)
THF, rt
Pd0 or NiII achieved to give the product 9,10-diacyl-9,10-dihydroanthracene
THF in good yield. The two-fold C-acylation of benzyl acrylates with
33 87%
E = PhCO , RCH(OH) , C6H13S
various acid chlorides can be effected in a similar fashion and
1,4-diketones are thus obtained.139
Applications of activated Mg in total syntheses continue to be
Magnesation of allyl sulfides can be achieved by treating such
disclosed. Thus, RiekeTM-Mg has been employed for the forma-
substrates with Mg, anthracene and dibromoethane and then
tion of an aryl bromide-derived Grignard reagent that reacts in the
subjecting the resulting mixture to sonication.140 In suitably
expected manner with oxirane so as to install the ²-hydroxyethyl
constituted substrates, the resulting allylmagnesium compounds
side chain of the cytotoxic and antibacterial sesquiterpenes
undergo an ene-type cyclization with a pendant alkene and the
pterosines B and C.129 During studies directed toward the
product of this process can then be trapped with various elec-
total synthesis of the phomoidride CP-255,917, the C9 side chain
trophiles, including PhSe SePh. Such a reaction cascade has been
of the molecule was introduced by reacting the relevant alkyl
employed in the total synthesis of the monoterpene metatabiether
ć%
bromide with RiekeTM-Mg at -78 C in the presence of TMEDA.
(eq 33).
Subsequent addition of the resulting long-chain alkyl Grignard to
1. MeMgBr, THF,  20 °C
two different aldehydes then gave the desired products in 94 and
2. Mg, Br(CH2)2Br
92% yield, respectively.130
OH
OH
anthracene, sonication
The synthesis of Mg metallacycles using RiekeTM-Mg has been
23 °C, 8 10 h, THF
SePh
reported.131 Thus, the treatment of 1,3-dienes with RiekeTM-Mg
3. THF, reflux, 5 h
leads to a diene Mg complex that reacted with epoxides to deliver
4. PhSe SePh
another Grignard reagent that can itself undergo a second reaction PhS
with other electrophiles such as CO2. By such means, the rapid 78%
(33)
and efficient assembly of ´-lactones is achieved (eq 32). In an anal-
OH
ogous fashion, and by using imines as primary electrophiles and
CO2 as the secondary one, a range of Å‚-lactams can be formed.132
MgSPh
R
O
R
R
Mg*
Mg
THF,  78 °C
THF, rt
R
R
R O
Mg
Reductions with Magnesium. Because of its ability to act as
a one-electron donor, Mg metal (reduction potential  2.37 eV) is
often employed as a reducing agent. For example, the metal can
R
R
effect the reductive desulfonylation of difluoromethyl sulfonates
CO2
1. H+
(32)
( CF2SO2Ph) to difluoromethyl groups ( CF2H). Such conver-
0 °C to rt 2. 40 °C R
R
O
sions can be carried out using Mg/HOAc/AcONa in DMF/H2O
OMg
CO2
(5:1 v/v) at room temperature.141 Efficient defluorinative alkyla-
O
tions and silylations of trifluoromethylated aromatics,142,143 ke-
39 84%
tones, and imines144,145 have been reported using Mg and such
conversions have been reviewed.146 By using Mg metal in a flash
Mg anthracene complexes represent another synthetically
vacuum pyrolysis (FVP) apparatus, various o-disubstituted bis-
useful source of activated Mg. The preparation and properties of
halomethyl arenes can be converted, by dehalogenation, into the
such complexes have been explored extensively,133,134 and it has
corresponding benzocyclobutenes (eq 34).147
been shown that Mg anthracene is especially effective in the gen-
eration of Grignard reagents.135 Solid-supported Mg anthracene
X
R
RR
FVP, Mg
complexes have been reported and are available on silica136 as well
+ (34)
as on organic polymers.137 Both such supported reagents display
X
good reactivity in the formation and reaction of benzylic Grig-
nards and the support itself can be reloaded with Mg by treating 73 80% 8 15%
X = Cl, Br
R = H, CH3, F, Cl, Br, I
it with fresh Mg anthracene.
Mg anthracene has been used for the conversion of certain
perfluoroalkanes and perfluoroarenes into the corresponding Freshly prepared Grignard reagents have been shown to readily
arylfluoro-Grignard reagents. Thus, reaction of either perfluo- and efficiently reduce 9,10-diformylanthracene to the corres-
robenzene (C6F6) or perfluorocyclohexane (C6F12) with the rele- ponding 9,10-dialkyldienyl- or 9,10-diaryldienyl-9,10-dihydro-
vant quantities of Mg anthracene affords C6F5MgF, which when anthracenes. Activated Mg that was obtained by the reaction of
treated with CO2 gives perfluorobenzoic acid in 6 34% yield. It Li naphthalene with MgCl2 gives similar results.148 Some very
should also be noted that fluoro-Grignards (R MgF) can sponta- efficient reducing agents are obtained by combining Mg metal
neously decompose.138 with different metal halides. Thus, Mg ZnCl2 in an aqueous
A list of General Abbreviations appears on the front Endpapers
MAGNESIUM 7
medium is an effective reagent for the selective reduction of Ä…,²- ethers and bis-conjugated enones can be achieved by using Mg
unsaturated carbonyl compounds to the corresponding ketones.149 metal in the presence of TMSCl (eq 37).162
Mg SnCl2 can be used for the reduction of aldehydes to primary
alcohols while ketones are unaffected by this reagent. However, it
does transform ketones into ethylene ketals when used in the pres-
R
ence of glycol. The reagent also dehalogenates benzyl halides.150 R2 2
R2
R
Similarly, a combination of SnCl2·2H2O and Mg metal in aque-
Mg, TMSCl, DMF
(37)
R2 R2 2 OTMS
ous media allows for the conversion of nitroalkenes into carbonyl
48 72%
OTMS
compounds.151
O
Various active metals can be formed when the corresponding
R2
R2 2
metal salt is reduced with Mg. Thus, activated Mn0 can be gen-
R = H, Me,  (CH2)n R2
R
erated (for use in radical cyclization reactions) from Li2MnCl4
R2 = H, Me,  (CH2)n R, or  (CH2)n R2 2
and Mg.152 Another good reagent combination for reductions
R2 2 = H,  (CH2)n R2
is Mg/hydrazine hydrate. This has been used to convert azoxy-
=  (CH2)n, n = 2,3,4
arenes into hydrazoarenes.153 The same system effects the reduc-
tive removal of common peptide protecting groups such as the N-
benzyloxycarbonyl, N-2-chlorobenzyloxycarbonyl, benzyl ester,
The Mg metal-mediated reduction of 1,3-cyclohexanedione has
and o-benzyl ether moieties.154 Similarly, the Mg/AcOH system
been reported to give the desired pinacolic coupling product ex-
has been explored in peptide synthesis for the selective deprotec-
clusively while the analogous SmI2-mediated reaction furnished
tion of phenacyl esters in the presence of Boc, Fmoc, and/or Cbz
the hydrodimerization product.163
groups.155
A wide variety of mixtures of Mg metal and metal salts can be
The reduction of carbonyl compounds to alcohols with Mg in
used to effect various pinacolic coupling reactions. Thus, activated
the presence of trimethylsilyl chloride or bis(chlorodimethylsilyl)
Ni0, obtained by treating NiCl2 with stoichiometric amounts of
compounds gives rise to Ä…-trimethylsilylalkyl trimethylsilyl ethers
Mg and TMSCl, is a useful reagent for this purpose.164 Other suc-
and cyclic siloxanes. Since such reactions are carried out in the
cessfully applied systems include a mixture of Mg/TMSCl with
absence of a proton source, a pair of TMS residues is incorpo-
catalytic amounts of InCl3,165 catalytic amounts of zirconocene
rated into the product, allowing for further useful transformations
dichloride with Mg,166 and low-valent samarium obtained by
(eq 35).156
reduction of SmCl3 with Mg.167
Mg, TMSCl
O A popular reagent is obtained by treating titanium halides with
TMSO TMS
DMF, 20 h, rt
Mg to generate a low-valent titanium species and this is capa-
(35)
R R2 14 82%
R R2
ble of effecting various reductions. The reagents so-formed have
been employed in the synthesis of imidazolines,168 the synthesis
R = alkyl, alkenyl, aryl
of Ä…,Ä…-disubstituted acids,169 as well as for effecting McMurry-
R2 = H, alkyl
type reactions,170 and in pinacolic couplings that are promoted by
ultrasound.171
The powerful reducing properties of Mg metal also allow it to
be used in ketyl olefin couplings, offering an interesting means
Miscellaneous Reactions. Mg metal turnings, when used in
for forming new C C bonds under radical conditions. For exam-
combination with TMSCl in DMF, provide a mild and efficient
ple, the cyclizations of phenylthiovinyl-tethered ketones were con-
method for the conversion of aliphatic tertiary alcohols into the
ducted using Mg/THF EtOH in the presence of catalytic amounts
corresponding silyl ethers.172 Similarly formed triflates can be
of HgCl2 to obtain various highly substituted cyclopentanes in
excellent yields and with good diastereoselectivity (eq 36).157 converted into ethers. Thus, the alcoholate is formed by reac-
tion, under reflux, of the corresponding alcohol with Mg and I2.
Presumably, the role of the HgII in this process is simply to
After the addition of 0.5 molar equiv of Tf2O, the resulting ethers
provide amalgamated magnesium.
can be isolated in moderate to excellent yields.173 Unsymmetri-
Mg
O EtO2C EtO2C cal ethers can be formed by reacting the Mg alcoholate with the
EtO2C OH OH
cat HgCl2
trifluoromethanesulfonyl ester of a different alcohol (eq 38).
(36)
+
SPh SPh
SPh
Tf2O
Mg, I2
25 90%
R O R
93% (17:1 ds)
reflux
(RO)2Mg (38)
ROH
Related intermolecular variants of such processes involving the
R O R2 40 94%
R, R2 = alkyl, phenyl, benzyl R2 OTf
coupling of stilbene derivatives with carbonyl compounds have
been achieved using Mg/TMSCl in DMF.158
Frequently, pinacolic couplings of ketones or aldehydes are
Novel magnesium enolates can be prepared from Ä…-
best effected using Mg metal and, nowadays, such reactions are
chloroglycidic esters by treating them with MgI2 and then Mg
often promoted by ultrasonication.159,160 Thus, the cross-coupling
metal. The product enolates are versatile building blocks that can
of aromatic ketones with aliphatic carbonyl compounds can be
be used in a variety of ways, particularly for the purpose of prepar-
carried out using Mg/TMSCl.161 The reductive couplings of Ä…,²-
ing Ä…-alkoxy-Ä…,²-unsaturated esters (eq 39).174
unsaturated ketones and 1,3-diketones to produce bis-silyl enol
Avoid Skin Contact with All Reagents
8 MAGNESIUM
Related Reagents. Tetrachloro(·5-cyclopentadienyl)nio-
O
Cl bium Magnesium.
MgI2 Mg
R Oi-Pr
CO2i-Pr
R
O
I O
1. Lai, Y. H., Synthesis 1981, 8, 585; Fürstner, A., Angew. Chem., Int. Ed.
Engl. 1993, 32, 164.
R2
OMgI O 2. Davis, S. R., J. Am. Chem. Soc. 1991, 113, 4145.
R2 X
3. Liu, L.; Davis, S. R., J. Phys. Chem. 1991, 95, 8619.
R Oi-Pr R Oi-Pr (39)
20%-quant.
4. Garst, J. F.; Ungvary, F.; Batlaw, R.; Lawrence, K. E., J. Am. Chem.
O O
Soc. 1991, 113, 5392.
5. Garst, J. F.; Swift, B. L., J. Am. Chem. Soc. 1989, 111, 241.
6. Garst, J. F.; Swift, B. L.; Smith, D. W., J. Am. Chem. Soc., 1989, 111,
Protocols involving either a cobalt reagent or Mg in 234.
THF have been used to obtain ²-ketophosphonates from Ä…- 7. Nuzzo, R. G.; Dubois, L. H., J. Am. Chem. Soc. 1986, 108, 2881.
halophosphonates and a variety of carboxylic acid esters.175 The
8. Sergeev, G. B.; Zagorskii, V. V.; Badaev, F. Z., J. Organomet. Chem.
preferred choice of metal is determined by the structure of the 1983, 243, 123.
ester used and the cobalt-based method is generally the superior 9. Walborsky, H. M.; Topolski, M., J. Am. Chem. Soc. 1992, 114, 3455.
one.
10. Walborsky, H. M.; Topolski, M.; Hamdouchi, C.; Pankowski, J., J. Org.
Chem. 1992, 57, 6188.
The utility of the Mg/TiCl4/THF reagent combination in gener-
ating useful carbenoids from a range of chloromethanes has been 11. Walborsky, H. M.; Zimmermann, C., J. Am. Chem. Soc. 1992, 114,
4996.
highlighted recently. If reacted with dichloromethane, this com-
12. Root, K. S.; Hill, C. L.; Lawrence, L. M.; Whitesides, G. M., J. Am.
bination forms a carbene complex similar to that associated with
Chem. Soc. 1989, 111, 5405.
the Tebbe reaction, and one which is useful for the methylenation
13. Walling, C., Acc. Chem. Res. 1991, 24, 255.
of sterically hindered ketones and aldehydes. For example, it can
14. Dagonneau, M., Bull. Soc. Claim. Fr., Part 2 1982, 269.
be applied to the methylenation of camphor and fenchone as well
15. Holm, T., Acta Chem. Scand. 1983, B37, 567.
as related substrates (eq 40).176 The methylenation of esters is
also possible177 and enamines can be cyclopropanated using this 16. Markies, P. R.; Akkerman, O. S.; Bickelhaupt, F.; Smeets, W. J. J.; Spek,
A. L., J. Am. Chem. Soc. 1988, 110, 4284.
reagent.178
17. Tinga, M. A. G. M.; Schat, G.; Akkerman, O. S.; Bickelhaupt, F.; Horn,
E.; Kooijman, H.; Smeets, W. J. J.; Spek, A. L., J. Am. Chem. Soc. 1993,
R
115, 2808.
O
TiCl4, Mg R
Cl
R2
18. Holm, T., J. Chem. Soc., Perkin Trans. 1 1981, 464.
CH2Cl2 Ti Mg
(40)
THF
THF Cl R2
19. Bickelhaupt, F., Pure Appl. Chem. 1990, 62, 699.
20. Bickelhaupt, F., Angew. Chem., Int. Ed. Engl. 1987, 26, 990.
61 95%
R = alkyl
21. Bruin, J. W.; Schat, G.; Akkerman, O. S.; Bickelhaupt, F., J. Organomet.
R2 = alkyl, Chem. 1985, 288, 13.
OR, (CH)nCO2R, (CH)nNHAc, (CH)nAryl
22. Canonne, P.; Bernatchez, M., J. Org. Chem. 1987, 52, 4025.
23. Boudjouk, P.; Sooriyakumaran, R.; Kapfer, C. A., J. Organomet. Chem.
Replacing dichloromethane with chloroform in the above-
1985, 281, C21.
mentioned processes leads to the efficient chloromethylenation of
24. Gilman, H.; Kirby, R. H., Recl. Trav. Chim. Pays-Bas 1935, 54, 577.
ketones.179 When carbon tetrachloride is used, then the resulting
25. Pearson, D. E.; Cowan, D.; Beckler, J. D., J. Org. Chem. 1959, 34, 504.
Ti Mg complexes allow for the gem-dichlorocyclopropanation
26. Sprich, J. D.; Lewandos, G. S., Inorg. Chim. Acta 1983, 76, L241.
of cis- and trans-alkenes as well as for carbonyl olefination
27. Ashby, E. C.; Neumann, H. M.; Walker, F. W.; Laemmle, J.; Chao,
(eq 41).180
L.-C., J. Am. Chem. Soc. 1973, 95, 3330.
28. Kuendig, E. P.; Perret, C., Helv. Chim. Acta 1981, 64, 2606.
TiCl4/Mg/THF
29. Oppolzer, W.; Kuendig, E. P.; Bishop, P. M.; Perret, C., Tetrahedron
CCl4
Lett. 1982, 23, 3901.
30. Klabunde, K. J.; Efner, H. F.; Satek, L.; Donley, W., J. Organomet.
Chem. 1974, 71, 309.
(41)
31. Rieke, R. D., Acc. Chem. Res. 1977, 10, 301.
Cl2 R
R2 2 O
32. Rieke, R. D.; Hudnall, S. E. B. M.; Burns, T. P.; Poindexter, G. S., Org.
C
R2 2 R2 2 2 R
Cl R2
Synth. 1988, 6, 845.
CCl2
Ti Mg CCl2
84 94% 62 92%
THF Cl R2
33. Burns, T. P.; Rieke, R. D., J. Org. Chem. 1987, 52, 3674.
R2 2 2
34. Rieke, R. D., Crit. Rev. Surf. Chem. 1991, 1, 131.
35. Boennemann, H.; Bogdanovic, B.; Brinkmann, R.; Spliethoff, B.; He,
A further variation of this interesting new methodology is its D. W., J. Organomet. Chem. 1993, 451, 23.
application to the synthesis of polysubstituted chlorocyclo- 36. Bogdanovic, B., Acc. Chem. Res. 1988, 21, 261.
propanes, which can be achieved using variously substituted
37. Kuroda, S.; Oda, M.; Kitahara, Y., Angew. Chem., Int. Ed. Engl. 1973,
chloroform derivatives, for example, PhCCl3 or Cl3CCO2Me, 12, 76.
as the carbene source.181 38. Jones, K.; Newton, R. F.; Yarnold, C., Synth. Commun. 1992, 22, 3089.
A list of General Abbreviations appears on the front Endpapers
MAGNESIUM 9
39. Yanagisawa, A.; Habaue, S.; Yamamoto, H., J. Am. Chem. Soc. 1991, 83. Bordoloi, M., J. Chem. Soc., Chem. Commun. 1993, 11, 922.
113, 5893.
84. Seyferth, D.; Duncan, D. P., J. Organomet. Chem. 1980, 187, 1.
40. Oppolzer, W.; Schneider, P., Tetrahedron Lett. 1984, 25, 3305.
85. Birkofer, L.; Bockhorst, M.; Steigel, A.; Eichstaedt, D., J. Organomet.
41. Oppolzer, W., Angew. Chem., Int. Ed. Engl. 1989, 28, 38. Chem. 1982, 233, 291.
86. Saito, K.; Kojima, H.; Okudaira, T.; Takahashi, K., Bull. Chem. Soc.
42. Raston, C. L.; Salem, G., J. Chem. Soc., Chem. Commun. 1984, 1702.
Jpn. 1983, 56, 175.
43. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and
87. Dulcere, J. P.; Grimaldi, J.; Santelli, M., Tetrahedron Lett. 1981, 22,
Structure, 4th ed.; Wiley: New York, 1992.
3179.
44. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, Part B:
88. Ohno, T.; Nakahiro, H.; Sanemitsu, K.; Hirashima, T.; Nishiguchi, I.,
Reactions and Synthesis, 3rd ed.; Plenum: New York, 1990.
Tetrahedron Lett. 1992, 33, 5515.
45. Barbot, F.; Poncini, L.; Randrianoelina, B.; Miginiac, P., J. Chem. Res.
89. Dzhemilev, U. M.; Ibragimov, A. G.; Tolstikov, G. A., J. Organomet.
(S) 1981, 11, 343.
Chem. 1991, 406, 1.
46. Blomberg, C.; Hartog, F. A., Synthesis 1977, 18.
90. Xiong, H.; Rieke, R. D., J. Org. Chem. 1989, 54, 3247.
47. Crandall, J. K.; Magaha, H. S., J. Org. Chem. 1982, 47, 5368.
91. For recent reviews on the use of Mg metal in synthesis, see Zhang, J.-H.;
48. Luche, J.-L.; Damiano, J.-C., J. Am. Chem. Soc. 1980, 102, 7926.
Keh, C. C. K.; Li, C.-J. In Science of Synthesis; Yamamoto, H., Noyori,
49. Zhang, W.; Dowd, P., Tetrahedron Lett. 1993, 34, 2095.
R., Eds.; Georg Thieme Verlag: Stuttgart, 2004; Vol. 7, pp 503 512,
50. Imai, T.; Nishida, S., Synthesis 1993, 395.
and references cited therein.
51. Curran, D. P.; Fevig, T. L.; Jasperse, C. P.; Totleben, M. J., Synlett 1992,
92. Rieke, R. D.; Hanson, M. V., Tetrahedron 1997, 53, 1925.
943.
93. Rieke, R. D., Aldrichim Acta 2000, 33, 52.
52. Larcheveque, M.; Debal, A.; Cuvigny, T., J. Organomet. Chem. 1975,
94. Knochel, P.; Dohle, W.; Gommermann, N.; Kneisel, F. F.; Kopp, F.;
87, 25.
Korn, T.; Sapountzis, I.; Vu, V. A., Angew. Chem., Int. Ed. 2003, 42,
53. Viscontini, M.; Merckling, N., Helv. Chim. Acta 1952, 35, 2280.
4302.
54. Moriwake, T., J. Org. Chem. 1966, 31, 983.
95. Ila, H.; Baron, O.; Wagner, A. J.; Knochel, P., Chem. Commun. 2006,
583.
55. Utimoto, K.; Imi, K.; Shiragami, H.; Fujikura, S.; Nozaki, H.,
Tetrahedron Lett. 1985, 26, 2101.
96. Lee, G. H.; Youn, I. K.; Choi, E. B.; Lee, H. K.; Yon, G. H.; Yang, H.
C.; Pak, C. S., Curr. Org. Chem. 2004, 8, 1263.
56. Prasad, J. V. N. V.; Pillai, C. N., J. Organomet. Chem. 1983, 259, 1.
97. Henderson, K. W.; Kerr, W. J., Chem. Eur. J. 2001, 7, 3430.
57. Lipshutz, B. H.; Sengupta, S., Org. React. 1992, 41, 135.
98. For a review on preparation of metallated heterocycles and their
58. Iyer, R. S.; Helquist, P., Org. Synth. 1985, 64, 1.
applications in synthesis, see Chinchilla, R.; Najera, C.; Yus, M., Chem.
59. Sato, F., J. Organomet. Chem. 1985, 285, 53.
Rev. 2004, 104, 2667.
60. Horiguchi, Y.; Matsuzawa, S.; Nakamura, E.; Kuwajima, I.,
99. Teerlinck, C. E.; Bowyer, W. J., J. Org. Chem. 1996, 61, 1059.
Tetrahedron Lett. 1986, 27, 4025.
100. Lau, S. Y. W.; Hughes, G.; O Shea, P. D.; Davies, I. W., Org. Lett. 2007,
61. Marek, I.; Mangeney, P.; Alexakis, A.; Normant, J. F., Tetrahedron Lett.
9, 2239.
1986, 27, 5499.
101. Sugimoto, O.; Aoki, K.; Tanji, K.-i., Tetrahedron Lett. 2004, 45, 1915.
62. Felkin, H.; Swierczewski, G., Tetrahedron 1975, 31, 2735.
102. Lund, H.; Svith, H.; Pedersen, S. U.; Dassbjerg, K., Electrochim. Acta
63. Eisch, J. J.; Galle, J. E., J. Organomet. Chem. 1978, 160, C8.
2005, 51, 655.
64. Qian, Y.; Li, G.; Zheng, X.; Huang, Y., J. Mol. Catal. 1993, 78, L31.
103. Mutule, I.; Suna, E., Tetrahedron 2005, 61, 11168.
65. Scott, F.; Raubenheimer, H. G.; Pretorius, G.; Hamese, A. M., J.
104. Acharya, H. P.; Miyoshi, K.; Kobayashi, Y., Org. Lett. 2007, 9, 3535.
Organomet. Chem. 1990, 384, C17.
105. Fang, H.; Li, G.; Mao, G.; Xi, Z., Chem. Eur. J. 2004, 10, 3444.
66. Samuel, E., Inorg. Chem. 1983, 22, 2967.
106. Caporusso, A. M.; Aronica, L. A.; Geri, R.; Gori, M., J. Organomet.
67. Nugent, W. A.; Thorn, D. L.; Harlow, R. L., J. Am. Chem. Soc. 1987,
Chem. 2002, 648, 109.
109, 2788.
107. Yu, X.-C.; Gu, H.; Xu, W.-M., Org. Prep. Proced. Int. 2006, 38, 467.
68. Kong, K. C.; Cheng, C. H., Organometallics 1992, 11, 1972.
108. Taniguchi, N.; Onami, T., J. Org. Chem. 2004, 69, 915.
69. McMurry, J., Chem. Rev. 1989, 89, 1513.
109. Erdik, E.; Koço
lu, M., Tetrahedron Lett. 2007, 48, 4211.
70. Csuk, R.; Fuerstner, A.; Weidmann, H., J. Chem. Soc., Chem. Commun.
110. Lee, A. S.-Y.; Wu, C.-C.; Lin, L.-S.; Hsu, H.-F., Synthesis 2004, 568.
1986, 24, 1802.
111. Grelier-Marly, M.-C.; Grignon-Dubois, M., Organometallics 1995, 14,
71. Pons, J. M.; Santelli, M., Tetrahedron Lett. 1988, 29, 3679.
4109.
72. Jousseaume, B.; Chanson, E.; Pereyre, M., Organometallics 1986, 5,
112. Van Veldhuizen, J. J.; Gillingham, D. G.; Garber, S. B.; Kataoka, O.;
1271.
Hoveyda, A. H., J. Am. Chem. Soc. 2003, 125, 12502.
73. Breunig, H. J.; Severengiz, T., Z. Naturforsch., Tell B 1982, 4, 395.
113. Wada, M.; Fukuma, T.; Morioka, M.; Takahashi, T.; Miyoshi, N.,
74. Kapur, J. C.; Fasel, H. P., Tetrahedron Lett. 1985, 26, 3875.
Tetrahedron Lett. 1997, 38, 8045.
75. Bartlett, P. D.; Ho, M. S., J. Am. Chem. Soc. 1974, 96, 627.
114. Li, C.-J.; Zhang, W.-C., J. Am. Chem. Soc. 1998, 120, 9102.
76. Bogdanovic, B.; Schlichte, K.; Westeppe, U., Chem. Ber. 1988, 121,
115. Zhang, W.-C.; Li, C.-J., J. Org. Chem. 1999, 64, 3230.
27.
116. Wang, D.-K.; Dai, L.-X.; Hou, X.-L.; Zhang, Y., Tetrahedron Lett. 1996,
77. Vinczer, P.; Struhar, S.; Novak, L.; Szantay, C., Tetrahedron Lett. 1992,
37, 4187.
33, 683.
117. Badorrey, R.; Cativiela, C.; Díaz-de-Villegas, M. D.; Díez, R.; Gálvez,
78. Hijfte, L. V.; Kolb, M.; Witz, P., Tetrahedron Lett. 1989, 30, 3655.
J. A., Eur. J. Org. Chem. 2002, 3763.
79. Dozzi, G.; Del Piero, G.; Cesari, M.; Cucinella, S., J. Organomet. Chem.
118. Legros, J.; Meyer, F.; Colibeouf, M.; Crousse, B.; Bonnet-Delpon, D.;
1980, 190, 229.
Bégué, J.-P., J. Org. Chem. 2003, 68, 6444.
80. Burfield, D. R.; Smithers, R. H., J. Org. Chem. 1983, 48, 2420.
119. Klinger, C.; Vostrowsky, O.; Hirsch, A., Eur. J. Org. Chem. 2006, 1508.
81. Pak, C. S.; Lee, E.; Lee, G. H., J. Org. Chem. 1993, 58, 1523.
120. Babudri, F.; Colangiuli, D.; Farinola, G. M.; Naso, F., Eur. J. Org. Chem.
82. Bordoloi, M., Tetrahedron Lett. 1993, 34, 1681. 2002, 2785.
Avoid Skin Contact with All Reagents
10 MAGNESIUM
121. Xu, X.; Cheng, D.; Pei, W., J. Org. Chem. 2006, 71, 6637. 152. Tang, J.; Shinokubo, H.; Oshima, K., Tetrahedron 1999, 55, 1893.
122. Wessig, P.; Glombitza, C.; Müller, G.; Teubner, J., J. Org. Chem. 2004, 153. Nanjundaswamy, H. M.; Pasha, M. A., J. Chem. Res. 2005, 772.
69, 7582.
154. Gowda, D. C., Tetrahedron Lett. 2002, 43, 311.
123. Kví%0Å„ala, J.; `
tambaskż, J.; Skalickż, M.; Paleta, O., J. Fluorine Chem.
155. Kokinaki, S.; Leonidiadis, L.; Ferderigos, N., Org. Lett. 2005, 7,
2005, 126, 1390.
1723.
124. Lehmann, T. E.; Berkessel, A., J. Org. Chem. 1997, 62, 302.
156. Uchida, T.; Kita, Y.; Maekawa, H.; Nishiguchi, I., Tetrahedron 2006,
125. Bunce, R. A.; Smith, C. L.; Lewis, J. R., J. Heterocycl. Chem. 2004, 62, 3103.
41, 963.
157. Lee, G. H.; Ha, S. J.; Yoon, I. K.; Pak, C. S., Tetrahedron Lett. 1999,
126. Comins, D. L.; Foti, C. J.; Libby, A. H., Heterocycles 1998, 48, 1313. 40, 2581.
127. Wu, X.; Rieke, R. D., J. Org. Chem. 1995, 60, 6658, 158. Yamamoto, Y.; Kawano, S.; Maekawa, H.; Nishiguchi, I., Synlett 2004,
30.
128. Rieke, R. D.; Kim, S.-H.; Wu, X., J. Org. Chem. 1997, 62, 6921.
159. Wang, J.-S.; Li, J.-T.; Lin, Z.-P.; Li, T.-S., Synth. Commun. 2005, 35,
129. Wessig, P.; Teubner, J., Synlett 2006, 1543.
1419.
130. Clive, D. L. J.; Cheng, H.; Gangopadhyay, P.; Huang, X.; Prabhudas,
160. Li, J.-T.; Chen, Y.-X.; Li, T.-S., Synth. Commun. 2005, 35, 2831.
B., Tetrahedron 2004, 60, 4205.
161. Maekawa, H.; Yamamoto, Y.; Shimada, H.; Yonemura, K.; Nishiguchi,
131. Rieke, R. D.; Sell, M. S.; Xiong, H., J. Org. Chem. 1995, 60, 5143.
I., Tetrahedron Lett. 2004, 45, 3869.
132. Sell, M. S.; Klein, W. R.; Rieke, R. D., J. Org. Chem. 1995, 60, 1077.
162. Maekawa, H.; Sakai, M.; Uchida, T.; Kita, Y.; Nishiguchi, I.,
133. Bogdanovic, B.; Janke, N.; Kinzelmann, H.-G.; Seevogel, K.; Treber,
Tetrahedron Lett. 2004, 45, 607.
J., Chem. Ber. 1990, 123, 1529.
163. Handy, S. T.; Omune, D., Org. Lett. 2005, 7, 1553.
134. Bartmann, E.; Bogdanovic, B.; Janke, N.; Schlichte, K.; Spliethoff, B.;
164. Shi, L.; Fan, C.-A.; Tu, Y.-Q.; Wang, M.; Zhang, F.-M., Tetrahedron
Treber, J.; Westeppe, U.; Wilczok, U.; Liao, S., Chem. Ber. 1990, 123,
2004, 60, 2851.
1517.
165. Mori, K.; Ohtaka, S.; Uemura, S., Bull. Chem. Soc. Jpn. 2001, 74,
135. Bogdanovic, B.; Janke, N.; Kinzelmann, H.-G., Chem. Ber. 1990, 123,
1497.
1507.
166. Kantam, M. L.; Aziz, K.; Likhar, P. R., Synth. Commun. 2006, 36, 1437.
136. van den Ancker, T. R.; Raston, C. L., Organometallics 1995, 14, 584.
167. Matsukawa, S.; Hinakubo, Y., Org. Lett. 2003, 5, 1221.
137. van den Ancker, T. R.; Harvey, S.; Raston, C. L., J. Organomet. Chem.
1995, 502, 35. 168. Periasamy, M.; Reddy, M. R.; Bhaskar Kanth, J. V., Tetrahedron Lett.
1996, 37, 4767.
138. Beck, C. M.; Park, Y.-J.; Crabtree, R. H., Chem. Commun. 1998, 693.
169. Garcia, M.; del Campo, C.; Llama, E. F.; Sinisterra, J. V., J. Chem. Soc.,
139. Matsunami, M.; Sakai, N.; Morimoto, T.; Maekawa, H.; Nishiguchi, I.,
Perkin Trans. 1 1995, 1771.
Synlett 2007, 769.
170. Balu, N.; Nayak, S. K.; Banerji, A., J. Am. Chem. Soc. 1996, 118, 5932.
140. Cheng, D.; Zhu, S.; Yu, Z.; Cohen, T., J. Am. Chem. Soc. 2001, 123,
30. 171. Li, J.-T.; Chen, Y.-X.; Li, T.-S., J. Chem. Res. 2005, 361.
141. Ni, C.; Hu, J., Tetrahedron Lett. 2005, 46, 8273. 172. Nishiguchi, I.; Kita, Y.; Watanabe, M.; Ishino, Y.; Ohno, T.; Maekawa,
H., Synlett 2000, 1025.
142. Saboureau, C.; Troupel, M.; Sibille, S.; Périchon, J., J. Chem. Soc.,
Chem. Commun., 1989, 1138. 173. Nishiyama, T.; Kameyama, H.; Maekawa, H.; Watanuki, K., Can. J.
Chem. 1999, 77, 258.
143. Clavel, P.; Léger-Lambert, M.-P.; Biran, C.; Serein-Spirau, F.; Bordeau,
M.; Roques, N.; Marzouk, R., Synthesis 1999, 829. 174. Grison, C.; Petek, S.; Coutrot, P., Synlett 2005, 331.
144. Amii, H.; Kobayashi, T.; Hatamoto, Y.; Uneyama, K., Chem. Commun. 175. Orsini, F.; Di Teodoro, E.; Ferrari, M., Synthesis 2002, 1683.
1999, 1323.
176. Yan, T.-H.; Tsai, C.-C.; Chien, C.-T.; Cho, C.-C.; Huang, P.-C., Org.
145. Mae, M.; Amii, H.; Uneyama, K., Tetrahedron Lett. 2000, 41, 7893. Lett. 2004, 6, 4961.
146. Uneyama, K.; Amii, H., J. Fluorine Chem. 2002, 114, 127. 177. Yan, T.-H.; Chien, C.-T.; Tsai, C.-C.; Lin, K.-W.; Wu, Y.-H., Org. Lett.
2004, 6, 4965.
147. Aitken, R. A.; Hodgson, P. K. G.; Oyewale, A. O.; Morrison, J. J.,
Chem. Commun. 1997, 1163. 178. Tsai, C.-C.; Hsieh, I.-L.; Cheng, T.-T.; Tsai, P.-K.; Lin, K.-W.; Yan,
T.-H., Org. Lett. 2006, 8, 2261.
148. Shah, S. M. I.; Kuroda, S.; Oda, M.; Tanaka, T.; Miyatake, R.; Izawa,
M., Tetrahedron Lett. 2002, 43, 2623. 179. Tsai, C.-C.; Chien, C.-C.; Chang, Y.-C.; Lin, H.-C.; Yan, T.-H., J. Org.
Chem. 2005, 70, 5745.
149. Saikia, A.; Barthakur, M. G.; Boruah, R. C., Synlett 2005, 523.
180. Chien, C.-T.; Tsai, C.-C.; Tsai, C.-H.; Chang, T.-Y.; Tsai, P.-K.; Wang,
150. Bordoloi, M.; Shamra, R. P.; Chakraborty, V., Synth. Commun. 1999,
Y.-C.; Yan, T.-H., J. Org. Chem. 2006, 71, 4324.
29, 2501.
181. Oudeyer, S.; Léonel, E.; Paugam, J. P.; Sulpice-Gaillet, C.; Nédélec,
151. Das, N. B.; Sarangi, C.; Nanda, B.; Nayak, A.; Sharma, R. P., J. Chem.
J.-Y., Tetrahedron 2006, 62, 1583.
Res. (S) 1996, 28.
A list of General Abbreviations appears on the front Endpapers