SAMARIUM(II) IODIDE 1
meric alkenes and overreduction in these transformations. When
Samarium(II) Iodide1
SmI2 is employed as the reductant, isomeric purities are generally
>97% and overreduction products comprise <3% of the reaction
SmI2
mixture.
Cl
xs. SmI2
[32248-43-4] I2Sm (MW 404.16)
HO
THF, "x
InChI = 1/2HI.Sm/h2*1H;/q;;+2/p-2/f2I.Sm/h2*1h;/q2*-1;m (3)
O
75% Ph
Ph
InChIKey = UAWABSHMGXMCRK-ZFDXCKRNCZ
(one-electron reducing agent possessing excellent chemoselectiv-
Ä…
Ä…-Heterosubstituted Carbonyl Compounds.
ity in reduction of carbonyl, alkyl halide, and Ä…-heterosubstituted Reduction of Ä…
carbonyl substrates;1 promotes Barbier-type coupling reactions, Samarium(II) iodide provides a route for the reduction of
ketyl alkene coupling reactions, and radical cyclizations1) Ä…-heterosubstituted carbonyl substrates. A wide range of Ä…-hetero-
substituted ketones is rapidly reduced to the corresponding unsub-
ć% ć%
Physical Data: mp 527 C; bp 1580 C; d 0.922 g cm-3.
stituted ketone under mild conditions (eq 4).7 The reaction is
Solubility: soluble 0.1M in THF.
highly selective and may be performed in the presence of isolated
Form Supplied in: commercially available as a 0.10 M solution
iodides as well as isolated ketones.7
in THF.
Preparative Methods: typically prepared in situ for synthetic O O
2 equiv SmI2
purposes. SmI2 is conveniently prepared by oxidation of Y
THF, MeOH
(4)
Samarium(0) metal with organic dihalides.2
 78 °C
Handling, Storage, and Precautions: is air sensitive and should
be handled under an inert atmosphere. SmI2 may be stored over
Isolated yield (%)
Y
THF for long periods when it is kept over a small amount of
100
Cl
samarium metal.
76
SPh
64
S(O)Ph
88
SO2Ph
Original Commentary
Samarium(II) iodide-induced reductive cleavage of Ä…-hydroxy
Gary A. Molander & Christina R. Harris
ketones provides a useful entry to unsubstituted ketones (eq 5).8
University of Colorado, Boulder, CO, USA
SmI2
Reduction of Organic Halides and Related Substrates.
THF, t-BuOH
HH
Alkyl halides are readily reduced to the corresponding hydrocar-
rt, 12 h
(5)
bon by SmI2 in the presence of a proton source. The ease with
O
O H
O
87%
which halides are reduced by SmI2 follows the order I > Br > Cl.
H
HH
The reduction is highly solvent dependent. In THF solvent, only
primary alkyl iodides and bromides are effectively reduced;2 how-
ever, addition of HMPA effects the reduction of aryl, alkenyl,
Samarium(II) iodide promotes the reductive cleavage of
primary, secondary, and tertiary halides (eq 1).3,4 Tosylates are Ä…-alkoxy ketones. Pratt and Hopkins have utilized this protocol in
also reduced to hydrocarbons by SmI2. Presumably, under these
synthetic studies en route to betaenone B (eq 6).9
reaction conditions the tosylate is converted to the corresponding
iodide which is subsequently reduced.4,5
H H H H
SmI2
Br O 2.5 equiv SmI2
O
THF
THF, HMPA
(6)
rt, 2 h
O
O
 78 °C
O H OOH
(1)
H
H
99%
O
Samarium(II) iodide provides a means to reduce substrates in
Likewise, this procedure provides a route for the reduction of
which the halide is resistant to reduction by hydride reducing
Ä…,²-epoxy ketones and Ä…,²-epoxy esters to generate the corre-
agents (eq 2).
sponding ²-hydroxy carbonyl compounds (eqs 7 and 8).3,10 The
epoxy ketone substrates may be derived from Sharpless asymmet-
Br
2.5 equiv SmI2
ric epoxidation. Consequently, this procedure provides a means to
THF, MeCN, HMPA, i-PrOH
prepare a variety of chiral, nonracemic ²-hydroxy carbonyl com-
rt, 10 min
(2)
pounds that are difficult to acquire by more traditional procedures.
98%
OO
Samarium(II) iodide has been utilized as the reductant in the
2 equiv SmI2, THF
 90 °C, <5 min
Boord alkene-type synthesis involving ring scission of 3-halotetra-
(7)
hydrofurans (eq 3).6 SmI2 provides an alternative to the sodium-
76%
OO
O OH
induced reduction which typically affords mixtures of stereoiso-
Avoid Skin Contact with All Reagents
2 SAMARIUM(II) IODIDE
2 equiv SmI2 2 equiv SmI2
OH
O THF, HMPA, DMA THF, HMPA
CO2Me CO2Me O
rt, <1 min rt, 1 min
(8) S S (12)
Bu Bu Bu Bu
68% 99%
>98% ee
2 equiv SmI2
Vinyloxiranes undergo reductive epoxide ring opening with
THF, HMPA
samarium(II) iodide to provide (E)-allylic alcohols (eq 9).3,10b,11 O O
rt, 10 min
S S (13)
These reaction conditions are tolerant of ketone, ester, and
Ph Ph Ph Ph
99%
nitrile functional groups. Again, Sharpless asymmetric epoxida-
tion chemistry may be utilized to gain entry to the desired non-
racemic substrates, thereby providing a useful entry to highly func-
Barbier-type Reactions. Samarium(II) iodide is quite use-
tionalized, enantiomerically enriched allylic alcohols.
ful in promoting Barbier-type reactions between aldehydes or ke-
2 equiv SmI2
tones and a variety of organic halides. The efficiency of SmI2
O
THF, MeOH
promoted Barbier-type coupling processes is governed by the
Y
 90 °C substrate under consideration in addition to the reaction condi-
2
tions employed. In general, alkyl iodides are most reactive while
OH
Y alkyl chlorides are virtually inert. Typically, catalytic Iron(III)
(9)
2
Chloride or Hexamethylphosphoric Triamide can be added to
SmI2 to reduce reaction times or temperatures and enhance yields.
Isolated yield (%)
Y
Kagan and co-workers have recently applied an intermolecular
SmI2-promoted Barbier reaction towards the synthesis of hin-
80
COSEt
82 dered steroidal alcohols. An intermolecular Barbier-type reaction
SO2Ph
P(O)(OEt)2 84
between the hindered ketone and Iodomethane produced a 97:3
69
H
mixture of diastereomers in excellent yield (eq 14).15
42
Me
54
SPh
HO
O
SmI2
A useful method for preparation of ²-hydroxy esters is accom-
MeI
H
H
rt, 24 h
plished by SmI2-promoted deoxygenation of an Ä…-hydroxy ester
(14)
followed by condensation with a ketone (eq 10).12 In some in- H H
H H
96%
stances, excellent diastereoselectivities are achieved, although this RO
RO
appears to be somewhat substrate dependent.
R = TBDMS 97:3
SmI2, THF, HMPA Samarium(II) iodide-promoted intramolecular Barbier-type
OBz
23 °C
reactions have also been employed to produce a multitude of cyclic
OEt
i-Pr
(10)
Bu
HO
O
and bicyclic systems.1 Molander and McKie have employed an in-
OEt
O i-Pr
Bu
tramolecular Barbier-type reductive coupling reaction to promote
O
the formation of bicyclo[m.n.1]alkan-1-ols from the correspond-
ing iodo ketone substrates in good yield (eq 15).16
A useful reaction sequence for transforming carbonyl com-
O
pounds to one-carbon homologated nitriles has evolved from the
2 equiv SmI2
ability of SmI2 to deoxygenate cyanohydrin O,O -diethyl phos-
cat. Fe(dbm)3, THF
 78 °C to rt, <2 h
phates (eq 11).13 The procedure is tolerant of a number of func- OH
I (15)
n
tional groups including alcohols, esters, amides, sulfonamides,
75 85%
n
acetals, alkenes, alkynes, and amines. Furthermore, it provides a
distinct advantage over other previously developed procedures for
Annulation of five- and six-membered rings proceeds with
similar one-carbon homologations.
excellent diastereoselectivity via an intramolecular Barbier-type
process (eq 16).17 The Barbier-type coupling scheme provides
3 equiv SmI2
a reliable and convenient alternative to other such methods for
(EtO)2P(O)CN
THF, t-BuOH
LiCN, THF
rt
preparing fused bicyclic systems.
CHO
(11)
CN
rt 91%
O 2 equiv SmI2
HO
I cat. FeCl3, THF
 78 °C to rt
4
(16)
65%
Deoxygenation Reactions. Sulfoxides are reduced to sulfides
only diastereomer
by SmI2 (eq 12).2,3,14 This process is rapid enough that reduc-
tion of isolated ketones is not a competitive process. Likewise,
aryl sulfones are reduced to the corresponding sulfides by SmI2 The SmI2-promoted Barbier-type reaction has also been uti-
(eq 13).3,12 lized in the synthesis of polyquinanes. Cook and Lannoye have
A list of General Abbreviations appears on the front Endpapers
m
m
SAMARIUM(II) IODIDE 3
OH
HO
employed this method to effect a bis-annulation of an appropri-
H
H
SmI2, MeOH, THF
ately substituted diketone (eq 17).18
 78 °C
(22)
75 85%
Y
O
Br
OH
H
Br H
3 H 3
2 equiv SmI2
Y
X
H X
THF, HMPA
X = CO2Me, Y = H X = CH2CO2Me, Y = H
O
O (17)
68% OH X = H, Y = CO2Me X = H, Y = CH2CO2Me
HO
H
H
A similar strategy utilizing ²-keto esters provided very high
Substituted ²-keto esters also provide excellent substrates for diastereoselectivities in the ketyl alkene coupling process. In
the intramolecular Barbier cyclization (eq 18).19 Diastereoselec- these examples, chelation control about the developing hydroxyl
tivities are typically quite good but are highly dependent on sub- and carboxylate stereocenters was the source of the high diastere-
stituent and solvent effects. oselectivity achieved (eq 23).22
2 equiv SmI2 OH
O
2 equiv SmI2 O O
OH
O
THF, t-BuOH
O O
THF
 78 °C
 78 °C to rt
(23)
O O
(18)
O O
I 2 87%
2 100%
92% de
Alkynic aldehydes likewise undergo intramolecular coupling to
generate five- and six-membered ring carbocycles. This protocol
has been utilized as a key step in the synthesis of isocarbacyclin
Nucleophilic Acyl Substitutions. Samarium(II) iodide facil-
(eq 24).23 SmI2 was found to be superior to several other reagents
itates the highly selective intramolecular nucleophilic acyl substi-
in this conversion.
tution of halo esters (eqs 19 and 20).20
HO
CHO
2 equiv SmI2
O
I O
2 equiv SmI2
OH
THF, t-BuOH
cat. FeIII, THF
 70 °C, 0.5 h
(19)
O
3
3
(24)
R' R'
91%
RO RO
71%
OH OH
80% de
R = TBDMS, R' = C5H11
OH
O
O 2 equiv SmI2
Samarium(II) iodide in the presence of HMPA effectively
O
cat. FeIII, THF
promotes the intramolecular coupling of unactivated alkenic ke-
(20)
91% tones by a reductive ketyl alkene radical cyclization process (eq
I
25). This protocol provides a means to generate rather elaborate
carbocycles through a sequencing process in which the resulting
organosamarium species is trapped with various electrophiles to
Unlike organolithium or organomagnesium reagents, SmI2-
afford the cyclized product in high yield.24
promoted nucleophilic substitution does not proceed with double
addition to the carbonyl, nor are any products resulting from re-
1. 2.2 equiv SmI2
duction of the final product observed. With suitably functionalized
HO
THF, HMPA
O
substrates, this procedure provides a strategy for the formation of 2. El
(25)
eight-membered rings (eq 21). El
75 85%
3
El = RCHO, RCOR, CO2, Ac2O, O2
O
2 equiv SmI2
OH
O
cat. FeIII, THF
O Cl
(21)
82% Pinacolic Coupling Reactions. In the absence of a proton
( )2
source, both aldehydes and ketones are cleanly coupled in the
presence of SmI2 to the corresponding pinacol.25 Considerable
diastereoselectivity has been achieved in the coupling of aliphatic
Ketone Alkene Coupling Reactions. Ketyl radicals derived
1,5- and 1,6-dialdehydes, providing near exclusive formation of
from reduction of ketones or aldehydes with SmI2 may be coupled
the cis-diols (eq 26).26
both inter- and intramolecularly to a variety of alkenic species.
CO2Me
CO2Me
Excellent diastereoselectivities are achieved with intramolecular
2 equiv SmI2, THF
COMe
coupling of the ketyl radical with Ä…,²-unsaturated esters.21 In
 78 °C to rt, 2 h
(26)
the following example, ketone alkene cyclization took place in
OH
81%
RO CHO
RO
a stereocontrolled manner established by chelation of the result-
OH
R = TBDMS
ing Sm(III) species with the hydroxyl group incorporated in the
92% de
substrate (eq 22).21b
Avoid Skin Contact with All Reagents
4 SAMARIUM(II) IODIDE
Intramolecular cross coupling of aldehydes and ketones pro- Highly functionalized bicyclic and spirocyclic products are
ceeds with excellent diastereoselectivity and high yield in suitably obtained in good yield and high diastereoselectivity by a tandem
functionalized systems wherein chelation control by the resulting reductive cleavage cyclization strategy (eq 32).31 Radical ring
Sm III species directs formation of the newly formed stereocenters opening of cyclopropyl ketones mediated by samarium(II) iodide-
(eq 27).22a,27 A similar strategy has been utilized with a ²-keto induced electron transfer permits the elaboration of a tandem ring
amide substrate to provide a chiral, nonracemic oxazolidinone opening cyclization strategy wherein the resultant samarium eno-
species. This strategy permits entry to highly functionalized, enan- late may be trapped by either oxygen or carbon electrophiles.
tiomerically pure dihydroxycyclopentanecarboxylate derivatives
SmI2 OAc
O
(eq 28).
THF DMPU
AcCl
2 equiv SmI2
(32)
O
O
OH
THF, MeOH
57%
 78 °C
HO
OHC
O O (27)
2 44%
O
O
O O
HO
2 equiv SmI2
THF, t-BuOH
Xc H OH
First Update
O N
(28)
52%
O
2 CHO
André Charette
i-Pr
Université de Montréal, Montréal, Québec, Canada
Radical Addition to Alkenes and Alkynes. Samarium(II)
Reductive Cross-coupling of Imines and Aldehydes.
iodide has proven effective for initiation of various radical addition
Samarium iodide-mediated intramolecular reductive cross-
reactions to alkenes and alkynes. Typically, tin reagents are used in
coupling of aldehydes or ketones with oximes (eq 33),32 hydra-
the initiation of these radical cyclization reactions; however, the
zones (eq 34),33 and imines (eq 35)34 is well-documented.
SmI2 protocol often provides significant advantages over these
more traditional routes.
BnO OBn
Samarium(II) iodide-mediated cyclization of aryl radicals onto
SmI2, t-BuOH, THF, -78 °C
alkene and alkyne acceptors provides an excellent route to
BnO O
80%
nitrogen- and oxygen-based heterocycles (eq 29).28
BnO
NOBn
Br
SmI2
BnO
THF, HMPA
BnO
rt, 6 h
N (29)
OH
BnO (33)
55%
N
NHOBn
BnO
The SmI2 reagent is unique in that it provides the ability to con- Ph2N
N O
SmI2, THF, HMPA
struct more highly functionalized frameworks through a sequential
63%
radical cyclization/intermolecular carbonyl addition reaction.29
HMe
Thus the intermediate radical formed after initial cyclization may
NHNPh2
be further reduced by SmI2, forming an organosamarium inter-
Me
mediate which may be trapped by various electrophiles, affording
(34)
highly functionalized products (eq 30).
OH
OH
NPh
Et2N
I SmI2
3
THF, HMPA H
O
O
rt
+ (30)
NEt2
1. SmI2, THF, 0 °C
76% O
3
2. h½, O2, Et2O
Me
(OC)3Cr
75%
Samarium(II) iodide further mediates the cyclization reactions
O
of alkynyl halides (eq 31).30 When treated with SmI2, the alkynyl
halides are converted to the cyclized product in good yield.
Addition of DMPU as cosolvent provides slightly higher yields in
some instances.
(35)
NHPh
TMS 3 equiv SmI2
TMS
THF
Me OH
"x, 24 h
Br
(31)
The intermolecular coupling of imine derivatives and alde-
74%
hydes can be achieved using samarium iodide. For example,
A list of General Abbreviations appears on the front Endpapers
SAMARIUM(II) IODIDE 5
OH O
N-tosylimines and aldehydes gave syn-²-amino alcohol deriva-
SmI2, THF
tives in good yields and diastereoselectivities (eq 36).35 Access
C7H15 OEt
75%
to enantiopure syn-²-amino alcohols can be achieved if chiral
Cl Me
chromium complex of the aldehyde is used (eq 37).
O
(39)
C7H15 OEt
Ts
O
N
Me
1. SmI2
H
E:Z >98:2
H
+
2. Ac2O, pyr
73%
O
OH O
SmI2, THF
NEt2 (40)
Ts Ts
Ph NEt2 90% Ph
HN HN
Cl E:Z >98:2
+
(36)
OH O
OAc OAc
SmI2, THF
97:3
C6H13 OEt
79%
Cl Me
Ts
O
O
N
1. SmI2
H
C6H13 OEt (41)
H
+
2. Ac2O, pyr, 67%
Me
Me
3. h½, air, Et2O, 90%
(OC)3Cr
E:Z >98:2
Ts
HN
The stereoselective reduction of Ä…,Ä…-dichloro-²-hydroxy
esters using samarium iodide yields (Z)-Ä…-chloro-Ä…,²-unsaturated
(37)
esters (eq 42).39
OAc Me
OH O
SmI2, THF
It is also possible to couple planar chiral ferrocenecarbox- OMe
62%
Cl Cl
aldehydes with imines with excellent diastereocontrol.36 Oximes
can be coupled with aldehydes in good to excellent yields.
O
However, the level of diastereocontrol is usually quite modest
OMe
(eq 38).
(42)
Cl
Z:E >98:2
O Bn
N O
SmI2
Similarly, Å‚-acetoxy-Ä…,²-enoates are reduced by samarium
+
Ph H H
diodide to generate dienolates which are kinetically trapped at
the Ä…-position by electrophiles (proton, aldehydes, or ketones).40
HO Bn
N (Z)-Alkenylsilanes are obtained in high diastereoselectivities
if O-acetyl-1-chloro-1-trimethylsilylalkan-2-ols are treated with
(38)
Ph
samarium iodide (eq 43). The stereochemical outcome is indepen-
OH
dent from the relative stereochemistry of the starting material.41
75%, 1:1
Cl
SmI2, THF
Bu
SiMe3
(43)
SiMe3 reflux, 96%
It is possible to use samarium iodide catalytically in several
Bu
OAc
reactions if a cheap alloy of the light lanthanides (La, Ce, Nd, Pr,
Sm) called Mischmetall is used.37
Samarium iodide can also be used as an alternative to sodium/
Synthesis of Alkenes by Reductive Elimination. The treat- mercury amalgam for the reductive elimination of 1,2-acetoxy-
ment of 2-halo-3-hydroxy esters and amides with samarium sulfones in the Julia-Lythgoe olefination.42 The alkene is gener-
iodide leads to the corresponding di- or trisubstituted (E)-Ä…,²- ated in a two-step process that first involves DBU or LDA treat-
unsaturated derivatives in high yields and diastereoselectivities ment to generate a vinyl sulfone that is then reductively cleaved
(eqs 39 and 40).38 The precursors are readily accessible by con- with samarium iodide (eq 44). The diastereoselectivity of both
densation of the lithium enolate of Ä…-haloesters or amides. If the transformations is usually quite good and the method is com-
substrate contains Å‚,´-unsaturation, the ²,Å‚-unsaturated ester is patible with the synthesis of monoalkenes as well as dienes and
generated in the process (eq 41). trienes.
Avoid Skin Contact with All Reagents
6 SAMARIUM(II) IODIDE
OAc
In a related fashion, benzyloxymethyl 2-pyridylsulfone can be
DBU
Ph
used as a hydroxymethylation equivalent to provide a convenient
Ph
94%
approach for the one-carbon homologation of carbonyl com-
SO2Ph
pounds (eq 47).48 The pyridylsulfone derivative is a superior pre-
cursor than the corresponding chloride.
PhO2S
Ph SmI2, THF
O
O O
DMPU, MeOH
BnO S N
SmI2, THF
94%
+
91%
Ph
Ph
(44)
Ph
OH
BnO
(47)
Ä…
Synthesis of Ä…
Ä…-Heteroalkyl Samarium. Samarium iodide is
the reagent of choice to generate Ä…-alkoxyalkylsamarium species
Another hydroxymethyl equivalent is the silylmethyl group.
from suitable precursors. For example, the anomeric position of
Tamao oxidation of the product obtained from the samarium
glycosides can be functionalized by treating a pyridylsulfone
iodide-promoted intramolecular reductive cyclization of bromosi-
precursor with samarium iodide (eq 45). A subsequent quench
lyloxy derivatives leads to the hydroxymethyl group (eq 48).49
with an aldehyde generates the corresponding C-glycoside via the
Barbier reaction with outstanding diastereoselectivity.43 It
Me Me
is also possible to generate similar reactive intermediates
Si Br
from the corresponding glycosyl phenylsulfones44 or glycosyl
O O
SmI2 (2 equiv), HMPA (4 equiv)
phosphates.45
THF, -78 °C
Ph Et
61%
Me Me
N
Si
OBn OBz
O
O
(48)
O S O OMe
SmI2 (3 equiv)
O Ph Et
+
OH
THF, 20 °C
H
BnO OTBS BzO
73%
OBn OBn O
The diiodomethylation of carbonyl compounds is also possible
if samarium iodide is used in conjunction with iodoform.50 The
products are synthetically useful since they are easily converted
BzO
into Ä…-hydroxyacids or Ä…-iodoaldehydes upon basic treatment
BzO
(eq 49).
O
BnO BnO OMe O
SmI2, THF, 0 °C
(45)
H H
+ CHI3
O
75%
OH Ph H
BnO OTBS
OH
(49)
OBn
I
Ph
I
An alternative but related approach involves the coupling of
epoxides and carbonyl compounds (eq 46).46 In this reaction,
It is possible to generate an Ä…-heteroalkyl radical by a 1,5-
the addition of a catalytic amount of nickel(II) iodide47 produced
hydrogen atom transfer from the radical obtained from an
slightly higher yields of the C-glycoside.
o-iodobenzyl protected amine (eq 50). It can then be subjected
to several reactions such as condensation with a ketone.51
OBn
SmI2, NiI2 (cat)
O
O
OH
THF, -78 °C
O +
SmI2
63%
Me Me
N I
N
BnO
(50)
OBn
O
OBn OH
Me
O
85%
Me
(46)
BnO OH
Alternatively, an Ä…-amino radical can be generated from an
OBn
Ä…-benzotriazolylamine precursor (eq 51).
A list of General Abbreviations appears on the front Endpapers
SAMARIUM(II) IODIDE 7
O O
Cl
Ph SmI2, CH3CN
N
SmI2
n-C7H15CHO
COOEt
N 75%
72%
N
N
O OH O OH
O
(55)
Ph n-C7H15 Ph n-C7H15
N +
(51)
COOEt
96:4
O
SmI2, THF
O
N
+
Ä… ²-Epoxy Esters and Amides. Treatment of
Opening of Ä… ²
Ä…,²
75%
aromatic Ä…,²-epoxyamides with samarium iodide leads to the
O
highly stereoselective synthesis of Ä…,²-unsaturated amides with
O
high diastereocontrol (eq 52).52 If the reaction is run on a substrate
H
OH
N
that contains Å‚-protons, then a base-promoted reaction produces (56)
the (E)-Ä…-hydroxy-²,Å‚-unsaturated amide (eq 53).53
O
O SmI2 (2.5 equiv), MeOH
It is also possible to couple imides with alkyl halides both
CONEt2
Ph
75%
interintramolecularly57 and intramolecularly.58 Alternative pre-
cursors to generate acylsamarium species also include acyl
CONEt2 (52)
chlorides59 and amides.60
Ph
Synthesis of 1,2-Dicarbonyl by Coupling Reactions. It is
Me
SmI2 (0.5 equiv) possible to generate 1,2-diketones easily by treating an appropri-
O
ate precursor with samarium iodide. For example, the transforma-
Me CONEt2 82%
tion of N-acylbenzotriazoles into 1,2-diketones can be achieved
Me
in good to excellent yields (eq 57).61
Me
O
(53)
Me CONEt2
SmI2 (2.2 equiv), THF
OH N
Me
N
N
Br
Analogous reactions with the Ä…,²-unsaturated ester generates Br
O
the saturated ester derivative (eq 54).54
(57)
O
O
SmI2 (2.5 equiv), MeOH
Br
COOi-Pr
Bu
71%
95%
Ph
COOi-Pr
Synthesis of Homoenolate Equivalent. The samarium
Bu
(54)
iodide-induced coupling of carbonyl derivatives with methoxyal-
Ph
lene provides 4-hydroxy 1-enol ethers in high yields (eq 58).62
An almost equimolar mixture of the two enol ethers are usually
observed but acid hydrolysis leads to the aldehyde.
Addition of Vinylsamarium to Aldehydes. Treatment of
O
(Z)-Ä…-chloro-Ä…,²-unsaturated ketones with samarium iodide leads
to the vinylsamarium reagent that can be trapped with aldehydes
SmI2, t-BuOH
+
or ketones to produce Baylis-Hillman type adducts with inversion
85%
OMe
of stereochemistry at the alkene (eq 55).55
OMe
Coupling of N-Acyl Lactams with Aldehydes or Ketones.
HO
Treatment of N-acyl lactams with samarium iodide leads to an
(58)
acylsamarium species that is trapped by ketones or aldehydes
(eq 56).56
Avoid Skin Contact with All Reagents
8 SAMARIUM(II) IODIDE
Related examples include the coupling of ketones with indole in good yield upon treatment with excess samarium iodide in
(eq 59)63 and alkynyl moieties (eq 60).64 In the latter case, THF.67,68
tetrakis(triphenylphosphine)palladium must also be added to gen-
erate the electrophilic component. Reductive Cleavage of N O Bonds. An efficient process for
the reductive cleavage of N O bonds using samarium iodide that
is compatible when base sensitive substrate is available (eqs 63
SmI2, THF, HMPA
69
and 64). This reagent is sometimes superior to aluminum amal-
Me
70%
N
gam or sodium amalgam. Furthermore, the direct quenching of
O
the reduction mixture with acylating agents provides high yields
H
OH
of the corresponding protected amine.
(59)
Me
N
OMOM
MOMO
O
SmI2, THF, rt
O
O
69%
NHOBn
Ph OCOPh SmI2, Pd(PPh3)4 O
OMOM
MOMO
O
Me O
(63)
O
O
(60)
OH
NH2
O
Ph
Me
O
Synthesis of Amidines from Amines and Nitriles. An effi- O
N CF3 SmI2, THF, rt
cient one-step preparation of N,N -disubstituted amidines is pos-
93%
OBn
O
sible by direct nucleophilic addition of an amine to a nitrile using
catalytic amounts of samarium iodide (eq 61).65 Alternatively, an
O
azide can be used instead of an amine.66
O
N CF3 (64)
CN
SmI2, THF
+ H
NH2
O
59%
Cleavage of Haloethyl Derived Protecting Groups. Samar-
NH
ium diiode is a mild and effective reagent for the deprotection of
(61)
N
2-bromoethyl and 2-iodoethyl esters70 and (2,2,2-trichloroethoxy)
methoxy ethers.71
Cleavage of N-Tosyl Protecting Groups. The deprotec-
Chemoselective Reduction of Carboxylic Acids. The facile tion of N-benzenesulfonamides or N-p-toluenesulfonamides of
chemoselective reduction of carboxylic acids in the presence of an the parent primary or secondary amines occurs in good yield
aldehyde proceeds smoothly with samarium iodide in combination upon heating with excess samarium iodide in a mixture of THF
with lanthanide triflate and methanol (eq 62). and DMPU (eq 65).72 The method has also been used in the
epimerization-free deprotection of protected Ä…-chiral amines.73
Me
COOH CHO
SmI2, Sm(OTf)3, MeOH, KOH Me CPh3
Me CPh3
SmI2, THF, DMPU
+
(65)
N
N
97%
SO2Tol
H
Me
It is also possible to deprotect N-sulfonylated amides under
OH OH
similar conditions.74
(62)
+
Tishchenko Reduction of Carbonyl Derivatives. The samar-
82% 8%
ium iodide-catalyzed Tishchenko reaction has been used quite
extensively in synthesis. Interesting examples include the
Reduction of Azides. Reduction of alkyl, aryl, and aroyl- diastereoselective synthesis of anti-1,3-diols (eq 66)75 and
azides to the corresponding primary amine or amide occurs ´-lactones (eq 67).76
A list of General Abbreviations appears on the front Endpapers
SAMARIUM(II) IODIDE 9
SmI2 (15 mol %)
OMe
OH O
CH3CHO
Ph
Me
N
SmI2 (10 mol %)
96%
+
61%
Me
Ph
OTMS
O
Ph
Me O OH
N
(70)
(66)
Me
Ph O
Me
O
Me
>99:1
OSiMe3
CHO
+
+ Me
Ph
O O
OMe
SmI2, i-PrSH
H O
OTMS
H
91%
SmI2 (10 mol %) Ph
(71)
t-Bu
72%
H H
COOMe
O O
Me
Me
(67)
t-Bu
H
Ä…
Three-componentÄ… Phosphonate Synthesis. A sim-
Ä…-Amino
trans:cis 81:19
ple and efficient synthesis of Ä…-amino phosphonates is possible
under relatively mild conditions by the reaction of aldehydes,
A mechanistically different stereoselective reduction of
amines, and a dialkylphosphite using samarium iodide in catalytic
²-hydroxy ketones leading to anti-1,3-diol using stoichiometric
amounts (eq 72).82
amounts of samarium iodide has been reported.77
O
SmI2 (10 mol %)
Preparation of Silyl Enol Ethers. Ketones and Ä…-substituted
+ Ph NH2 + HOP(OEt)2
60%
Ph H
aldehydes are converted into their corresponding silyl enol ethers
by the reaction with trimethylsilyl ketene acetal derived from
methyl isobutyrate in the presence of a catalytic amount of samar-
P(O)(OEt)2
ium iodide (eqs 68 and 69).78 Mixtures are usually obtained with
(72)
unsymmetrical ketones.
Ph NHPh
Me
Me
SmI2 (5 mol %)
H
OSiMe3
Related Reagents. Samarium(II) Iodide 1,3-Dioxolane.
Ph +
Me 72%
O
OMe
1. (a) Molander, G. A., Chem. Rev. 1992, 92, 29. (b) Molander, G. A. In
Ph Me
OSiMe3 OSiMe3 (68)
The Chemistry of the Metal Carbon Bond; Hartley, F. R., Ed.; Wiley:
+
Chichester, 1989; Vol. 5, Chapter, 8. (c) Kagan, H. B., Nouv. J. Chim.
Me Ph
90:10 1990, 14, 453. (d) Soderquist, J. A., Aldrichim. Acta 1991, 24, 15.
(e) Molander, G. A., Comprehensive Organic Synthesis 1991, 1, Chapter
O
1.9.
Me
2. (a) Girard, P.; Namy, J. L.; Kagan, H. B., J. Am. Chem. Soc. 1980, 102,
SmI2 (5 mol %)
OSiMe3
2693. (b) Namy, J. L.; Girard, P.; Kagan, H. B., Nouv. J. Chim. 1977, 1,
+
Me
88%
5. (c) Namy, J. L.; Girard, P.; Kagan, H. B., Nouv. J. Chim. 1981, 5, 479.
OMe
3. Inanaga, J., Heteroatom Chem. 1990, 3, 75.
4. Inanaga, J.; Ishikawa, M.; Yamaguchi, M., Chem. Lett. 1987, 1485.
OSiMe3
5. Kagan, H. B.; Namy, J. L.; Girard, P., Tetrahedron 1981, 37, 175, Suppl.
1.
(69)
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29, 439. (c) Castro, J.; Sörensen, H.; Riera, A.; Morin, C.; Moyano, A.;
Lewis Acid Catalyzed Reactions. Samarium iodide catalyzes
PericÄ…s, M. A.; Greene, A. E., J. Am. Chem. Soc. 1990, 112, 9388.
several transformations by presumably acting as a Lewis acid. For
8. (a) White, J. D.; Somers, T. C., J. Am. Chem. Soc. 1987, 109, 4424.
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(b) Holton, R. A.; Williams, A. D., J. Org. Chem. 1988, 53, 5981.
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reported.81 K.; Inanaga, J.; Yamaguchi, M., Tetrahedron Lett. 1987, 28, 4437.
Avoid Skin Contact with All Reagents
10 SAMARIUM(II) IODIDE
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A list of General Abbreviations appears on the front Endpapers