TIN(II) CHLORIDE 1
Tin(II) Chloride can be prepared by reduction of cyanosilyl ethers (5) with SnCl2
in AcOH and HCl (eq 3).7
SnCl2
Cl
HCl SnCl2
CN
NH
ether HCl, ether
[7772-99-8] Cl2Sn (MW 189.61)
InChI = 1/2ClH.Sn/h2*1H;/q;;+2/p-2/f2Cl.Sn/h2*1h;/q2*-1;m
(1)(2)
InChIKey = AXZWODMDQAVCJE-VDZLWFDJCG
H
(reducing agent for many functional groups; carbonyl allylation;
CHO
NH" HCl
Lewis acid catalyst in C C bond-forming reactions; catalyst with (2)
AgClO4 for the synthesis of Ä…-glycosides; synthesis of alkenes,
dienes, cis-vinyloxiranes, and allylic selenides; deoxygenation of (4) 73 80%
(3)
1,4-endoperoxides; protection of carboxylic acids as 1,3-dithi-
OTMS SnCl2, AcOH
anes; selective p-methoxybenzyl ether cleavage reagent; additive O
conc. HCl
TMSCN
CN
in hydroformylation and carbonylation reactions1)
68% (2 steps)
Alternate Name: stannous chloride.
(5)
ć% ć%
Physical Data: mp 246.8 C; bp 623 C; d 3.95 g cm-3.
Solubility: insol xylenes; sol water, ethanol, acetone, diethyl
CO2H
ether, methyl acrylate, methyl ethyl ketone, isobutyl alcohol.
(3)
Form Supplied in: white crystalline solid; widely available.
Preparative Methods: analytical reagent grade tin(II) chloride is
Organic azides are reduced by SnCl2 in methanol to the corres-
prepared by adding the dihydrate to a vigorously stirred solution
ponding amines in 85 98% yield.8 For less reactive azides, it is
of acetic anhydride (120 g salt per 100 g anhydride). After ca.
necessary to initiate the reaction by adding catalytic amounts of
one hour, the anhydrous SnCl2 is filtered on a dry sintered glass
Aluminum Chloride.
or Buchner funnel, washed free from acetic acid with dry Et2O,
Ä…-Halo ketones are hydrodehalogenated to the correspon-
and dried in vacuo. It is best stored in a sealed container.2
ding ketones in good yield using SnCl2 in combination with
a variety of additives, e.g. sodium halides (chloride, bromide,
iodide) and pseudohalides (thiocyanate, cyanate, chloride),9 sul-
fur compounds (NaSH, Na2S, NaHSO3, Na2SO3), and aromatic
Original Commentary
compounds (benzene, pyridine, aniline) (eq 4).10 SnCl2 is more
effective than other metal halides, such as SnCl4, FeCl2, AlCl3,
Margaret M. Faul
and CrCl3.
Eli Lilly and Company, Indianapolis, IN, USA
NaY, SnCl2
O
O
Functional Group Reductions. SnCl2 is an effective
THF, H2O
R1
(4)
R1
reducing agent under acidic conditions.3 SnCl2 selectively R2
R2
40 96%
reduces aromatic nitro compounds under nonacidic and nona- X
queous conditions. Nearly quantitative yields of arylamines are
X = Cl, Br; Y = Cl, Br, I, SCN, OCN, ClO2, HS, HSO3, NO2
obtained by using SnCl2·2H2O in ethanol or ethyl acetate, or
ć%
anhydrous SnCl2 in alcohol at 70 C. Under these conditions, other
Treatment of an Ä…-bromo carbonyl compound with SnCl2
reducible or acid sensitive groups such as ketones, esters, nitriles,
and Diethylaluminum Chloride effects dehydrohalogenation with
halogen, oximes, and alkenes are unaffected (eq 1).4
formation of an aluminum enolate, which can react with an alde-
hyde or ketone to give the ²-hydroxy carbonyl compound in
NH2
NO2
61 95% yield, in a modification of the Reformatsky reaction
(eq 5).11 Catalytic quantities of Tetrakis(triphenylphosphine)-
(1)
R
R
palladium(0) promote the reduction and improve the yield of the
desired aldol adducts.
R = H, Cl, OH, CO2H, CHO, OMe, CO2R, OAc
Al
OAlEt2 PhCHO O OH
SnCl2 is used in the reduction of nitriles to aldehydes.5 For
O Sn
(5)
example, treatment of the nitrile (1) with hydrochloric acid gen-
Br
Ph Ph
Ph
Pd(PPh3)4
erates the intermediate (2). This is reduced with anhydrous SnCl2 Ph
91%
to (3), which precipitates as a complex with SnCl4 and is then
hydrolyzed to the aldehyde (4) (eq 2).2 This protocol, known as The reagent prepared from Sodium Cyanoborohydride and
the Stephen reaction, is most successful with aromatic nitriles, SnCl2 in a 2:1 ratio will reduce tertiary, allyl, and benzyl halides
but it has been reported for aliphatic nitriles with up to six car- in good yields and is thus comparable to NaBH3CN ZnCl2. How-
bons. An alternative procedure in which (2) is obtained from the ever, other functional groups such as aldehydes, ketones, and
N-phenylamide, ArCONHPh, by treatment with Phosphorus(V) acid chlorides are reduced to alcohols. Esters and amides are
Chloride is known as the Sonn Müller method.6 Carboxylic acids unaffected.12
Avoid Skin Contact with All Reagents
2 TIN(II) CHLORIDE
SnCl2, Al
Carbonyl Reduction. Asymmetric reduction of prochiral
Ph Cl
+ C6H13CHO
ketones,13 Ä…-, ²-, and Å‚-keto esters,14 and prochiral hydroxy
THF H2O
75%
ketones15 can be achieved with a reagent prepared from SnCl2
and Diisobutylaluminum Hydride, in the presence of a chiral
OH
OH
diamine derived from (S)-proline (eq 6).
+
C6H13
C6H13 (10)
OOH
Ph
Ph
SnCl2, DIBAL
(6) anti 98:2 syn
R1 R2 R1 R2
*
N
N
Me
SnCl2 acts as a reducing agent in the allylation of carbonyl
R1 R2 Yield (%) ee (%)
compounds using allylic alcohols and Pd0; this reaction proceeds
through a Ä„-allylpalladium complex (eq 11). The order of reac-
Bn Me 71 78
Ph Me 80 76 tivity of allylating agents is allylic carbonate > allylic alcohol >
Ph Et 74 74
allylic acetate, and that of carbonyl compounds is aldehyde > ke-
Ph CH2OMEM 81 91
tone. High regioselectivity is obtained in polar solvents such as
Ph CO2MEM 82 89
Me CO2MOM 60 48
DMF, DMI (1,3-dimethyl-2-imidazolidone), and DMSO, where
the carbonyl compound attacks the more substituted allylic posi-
tion of the Ä„-allylpalladium complex.
²
² Ester Synthesis. Aldehydes are efficiently con-
²-Diketo
verted to ²-diketo esters in 50 90% yield by addition of Ethyl
Pd0 Sn2+ RCHO
OX SnX2
n
Diazoacetate in the presence of SnCl2 (eq 7). Although the reac-
Pd+
tion can be effected by a variety of Lewis acids, SnCl2, BF3, and
GeCl2 are the most effective.16 X = H, Ac, CO2Me
OH
(11)
O O
O R
SnCl2
(7)
Bn OEt
Bn H N2=CHCO2Et
71%
Diastereocontrol in the Pd-catalyzed carbonyl allylation of
allylic alcohols with SnCl2 is dependent on the nature of the sol-
ć%
vent. Use of DMSO at 25 C affords the syn-adduct, while anti
Treatment of a number of trisubstituted alkenes with Ozone
selection is found in THF, DMF, and DMI. The addition of water in
followed by the addition of SnCl2 and ethyl diazoacetate affords
any solvent accelerates the rate of the reaction and enhances both
the ²-diketo esters in 47 90% yield (eq 8). For monosubstituted
regioselectivity and diastereoselectivity (eq 12). For reactions in
alkenes to be successful, they must first be treated with ozone in the
DMSO H2O, the ratio of syn:anti products can be controlled by
presence of methanol to generate methoxy hydroperoxides, which
the amount of water added to the reaction.20 SnF2 and Sn(OAc)2
can subsequently be reduced to the ²-diketo esters in 47 74%
cannot replace SnCl2 in this allylation reaction.
yield.17 1,3-Diketones can be prepared in 42 90% yield by SnCl2-
catalyzed reaction of Ä…-diazo ketones with aldehydes (eq 9).18
PdCl2(PhCN)2
R1 OH
+ R2CHO
O2, SnCl2 SnCl2, 25 °C
TBDMSO
N2=CHCO2Et
85% OH
OH
+
R2
R2 (12)
O O
R1
R1
TBDMSO (8)
syn anti
OEt
Solvent Yield (%) syn:anti
R1 R2
p-MeO2CC6H4 DMSO H2O 90 77:23
O SnCl2 O O Me
(9)
p-MeO2CC6H4 DMF 99 22:78
Me
N2=CHCOPh
Bn H
Bn Ph Ph THF H2O 82 20:80
Pr
90%
Ph DMSO H2O 83 70:30
Pr
Ph THF 81 9:91
Me
Ph DMSO 34 65:35
Me
Diastereoselective Carbonyl Allylation. High regio- and
diastereoselectivity can be achieved in the reaction of cinnamyl This reaction has been extended to the synthesis of Ä…-methylene-
chloride with aldehydes using SnCl2 and Aluminum.19 The reac- Å‚-hydroxy lactones by allylation of carbonyl compounds with
tion proceeds through zerovalent tin and affords the anti-adducts ethyl Ä…-(hydroxymethyl)acrylate in DMI/H2O (eq 13).21 When
with high selectivity (eq 10). Under the same conditions, enals the hydroxymethyl group bears an alkyl substituent, the product
provide 1,2-adducts. is obtained with high syn selectivity (eq 14).
A list of General Abbreviations appears on the front Endpapers
TIN(II) CHLORIDE 3
O
Alkenes and (E)-1,3-Dienes. vic-Dinitro compounds can be
denitrated to yield alkenes using either anhydrous SnCl2 or the
CHO O
CO2Et
PdII, SnCl2
dihydrate. This method fails for aliphatic vic-dinitro
+ (13)
44%
compounds.27 Alkenes can also be obtained in good yield
CH2OH Ph
Ph
from the vic-dibromo compounds using SnCl2 and DIBAL
(eq 18).16
CO2Et
+
MeO2C CHO
X
OH
40%
Ph Ph
(18)
Ph Ph
O
X
X = NO2, SnCl2, EtOH 96%
(14)
O
X = Br, SnCl2, 2 DIBAL, THF, TMEDA 88%
C6H4-p-CO2Me
Reaction of a variety of aldehydes with 1-bromo-3-iodopropene
syn:anti = 95:5
in the presence of 2 equiv of SnCl2 yields the corresponding
(E)-1,3-dienes in 40 70% yield (eq 19).28 When an enal is
employed a terminal conjugated triene is obtained. Treatment
C C Bond Formation. Acetals, aldehydes, orthoesters, and
of 1-chloro-3-iodopropene with 1 equiv of SnCl2 in DMF, and
Ä…,²-unsaturated ketones are sufficiently activated by a combina-
reaction with an aldehyde followed by NaOMe yieldes cis-
tion of SnCl2 and Chlorotrimethylsilane22 or SnCl2 and trityl
vinyloxiranes in 51 53% yield (eq 20).29
chloride23 to react with silyl enol ethers to give the correspond-
ing addition products in 70 97% yield (eq 15). These reagents
R H
2 equiv SnCl2
are also effective in facilitating the reaction of activated alkenes,
RCHO + BrCH=CHCH2I (19)
such as 3,4-dihydro-2H-pyran, vinyl ethers, and styrene, with
DMF, toluene
H
acetals to afford the corresponding adducts in 55 85% yield under
R = Ph, 62%; PhCH=CH, 70%
extremely mild conditions.24 SnCl2 facilitates the workup in the
Titanium(IV) Chloride-catalyzed reaction of aldehydes with silyl
R Cl
SnCl2
NaOMe
enol ethers by inhibiting ²-elimination and formation of polymers RCHO + ClCH=CHCH2I
DMF
(eq 16).25 ICl2SnO
RCHO
RCH(OH)CHR2COR1 O
R
+ trans-isomer (20)
H
H
RCH(OMe)2
RCH(OMe)CHR2COR1
OSiR2
SnCl2
3
Propargylic iodides form an adduct with SnCl2, which can
(15)
R2
R1 TrCl or TMSCl HC(OMe)3 react with aldehydes to form a mixture of Ä…-hydroxy allenes and
HC(OMe)2CHR2COR1
²-hydroxy alkynes, in which the former usually predominates.
O
DMI is the preferred solvent (eq 21).30
R3 R4
R4CH=CHCR3(OH)CHR2COR1
SnCl2
"
OH O
O OTMS
+ PhCHO +
Ph
Ph
I
79%
+ (16)
HO
R H HO
R H H R = Pr
(21)
97:3
TiCl4 68%
TiCl4 + SnCl2 81%
Deoxygenation of 1,4-Endoperoxides of 1,3-Dienes.31 1,4-
Endoperoxides are converted to the corresponding 1,3-dienes in
Ä…
Ä…
Ä…-Glycosidation.26 Ä…-Glycosides are formed predominantly
15 70% yield using SnCl2 (eq 22).
by reaction of an alcohol with 2,3,4,6-tetra-O-benzyl-²-glucosyl
fluoride in the presence of Tin(II) Chloride Silver(I) Perchlorate
Ph Ph
(eq 17).
SnCl2
O
( )n (22)
ROH
O( )n
CH2OBn
n = 1, 70%
SnCl2, AgClO4
O
BnO
F n = 2, 48%
Ph Ph
BnO
cholesterol, ether
BnO
76%
Rearrangements of 2-Hydroxy-3-trimethylsilylpropyl
CH2OBn
O Selenides.32 Addition of Trimethylsilylmethyllithium to Ä…-
BnO
+ ²-anomer (17)
BnO phenylseleno aldehydes generates 2-hydroxy-3-trimethylsilyl-
BnO
propyl selenides which rearrange in the presence of SnCl2 to
OR
89:11 allylic selenides (eq 23).
Avoid Skin Contact with All Reagents
4 TIN(II) CHLORIDE
SePh
TMSCH2Li R1SePh The reaction of aldehydes with enol esters in the presence of
SnCl2
R1
H H
alcohols, N-chlorosuccinimide (NCS), and tin(II) chloride pro-
R2
R2
ether,  78 °C
HO TMS duces ²-alkoxy ketones (eq 28). Alkyl and aryl aldehydes can be
70 90%
O
used; suitable alcohols include ethanol, allyl alcohol, and ben-
R1
zyl alcohol. No reaction is observed in the absence of the alco-
(23)
hol component. The reaction probably proceeds via the formation
R2 SePh
of hemiacetals or alkoxycarbenium ions, derived from aldehydes
and alcohols with NCS/SnCl2.36 The scope of the reaction was
Direct Conversion of Carboxylic Acids into 1,3-Dithianes.33 expanded by applying the aldol reaction with enol esters to lactols,
cyclic tautomers of É-hydroxyaldehydes. Five- and six-membered
Reactions of carboxylic acids with 1,3,2-dithiaborinane dimethyl
lactols were utilized successfully in the reaction.37
sulfide in the presence of SnCl2 in THF affords the correspond-
ing 1,3-dithianes in high yields. This method is also sufficient to
distinguish between carboxylic acids and isolated double bonds
NCS/SnCl2
(eq 24).
R1CHO + R2OH
CH2Cl2
+
S S
Me2S

RCO2H + (24)
B R
R1 OSnCl3
H
S S
R = Bn, 84%; Cy, 82%
H OR2
R1
OAc
(28)
or
OR2 O
R1
Deprotection.34 p-Methoxybenzyl (PMB) ethers can be
O+
cleaved selectively in the presence of benzyl ethers by employing
H R2
TMSCl/anisole and a catalytic amount of SnCl2 (eq 25).
PMBO HO R1 = alkyl, aryl
3.0 equiv TMSCl
R2 = C2H5, C6H5CH2, C3H5
O O
1.5 equiv anisole
OBn OBn (25)
0.1 equiv SnCl2
BnO OMe BnO OMe
87%
OBn OBn
A similar reaction manifold was explored in the ring closure of
homoallyl hemiacetals, or oxycarbenium ions, derived from ho-
moallylic alcohols and aldehydes with NCS/SnCl2 (eq 29).38 Both
aromatic and aliphatic aldehydes participate in the reaction pro-
viding products in moderate to good yields (37 61%). Mixtures
First Update
of diastereomers were formed in all reactions.
Oliver R. Thiel
Amgen Inc., Thousand Oaks, CA, USA
Cl
R2 NCS/SnCl2
Aldol-type Reactions. Aldehydes react with enol esters to
CH2Cl2
+
R1CHO (29)
form aldol-condensation products when PdCl2(PhCN)2 is used
OH
as catalyst in combination with stochiometric amounts of tin(II) R2 O R1
R1 = aryl, alkyl
chloride (eq 26).35 Interestingly, the reaction also proceeds, al-
R2 = H, Ph
beit at lower rates in the absence of the palladium catalyst. Aro-
matic aldehydes provide good yields of the desired products, while
reactions with aliphatic and Ä…,²-unsaturated aldehydes proceed
in lower yield. Ä…-Angelica lactone affords Å‚-butyrolactones when
The addition of chelated tin amino acid ester enolates to alde-
used in the reaction with aromatic aldehydes under similar condi-
hydes proceeds in good yields and excellent diastereoselectiv-
tions (eq 27).
ities (eq 30).39 The enolates are generated by double deproto-
nation of Ts-protected amino acid esters with LDA, followed by
PdCl2(PhCN)2
transmetallation with tin(II) chloride. The reaction is applicable to
SnCl2, CH3CN
R
(26)
+ RCHO
both aliphatic and aromatic aldehydes supplying the anti-product
OCOMe
O
with excellent diastereoselectivities (up to 99:1). The syntheti-
cally more useful 2-trimethylsilylethanesulfonyl (SES) protecting
O
group can be used instead of the Ts-protecting group.
O
PdCl2(PhCN)2
The reaction was also successfully applied to Ä…-alkoxy and Ä…-
O
SnCl2, CH3CN (27)
O
siloxy aldehydes (eq 31).40 Excellent diastereoselectivities can
+ PhCHO
be obtained with the chelated tin enolates, while the addition of
Ph
the corresponding zinc enolates resulted in mixtures of all four
O
52% possible stereoisomers.
A list of General Abbreviations appears on the front Endpapers
TIN(II) CHLORIDE 5
2.5 equiv LDA
OH
2.5 equiv SnCl2 SnCl2
O2N
Cl3CNO2 + RCHO
THF
TsHN CO2Bn R
(34)
Cl Cl
CHO
52 92 %
OH
OBn
R
CO2Bn
(30)
R
TsN O
NHTs
² ² ²
² Sulfone, ² Phosphine Oxide, and ² Phos-
²-Keto ²-Keto ²-Keto
Sn
phonate Synthesis. Diazosulfones, diazo phosphine oxides, and
60 91%
diazo phosphonates add to aliphatic aldehydes in the presence of
anti:syn > 97:3
SnCl2 to yield ²-keto sulfones, ²-keto phosphine oxides, and ²-
keto phosphonates, respectively (eq 35).45 Yields for primary and
R = H, 4-Me, 4-MeO, 4-Br, 4-Cl, 4-NO2, 2-NO2
secondary aldehydes range from 42 to 79%. Tertiary aldehydes
OH
lead to low yields in the synthesis of sulfones and the reaction
1. LDA, THF
CO2Bn fails when applied to the synthesis of phosphine oxides and phos-
2. SnCl2
TsHN CO2Bn
phonates.
(31)
NHTs
3.
CHO TBSO
0.1 equiv SnCl2, RCHO
85%
O
OTBS O O O O
CH2Cl2, rt
N2
S S
Tol Tol R
The addition of tin enolates derived from glycine to simple
aliphatic aldehydes provides 1:1 mixtures of diastereomers. In
(35)
contrast, synthetically useful levels of anti-stereoselection were
O 0.1 equiv SnCl2, RCHO O O
observed in the addition to conjugated ynals and ynones (eq 32).41
N2 CH2Cl2, rt
P P
R2 R2
Slightly lower diastereoselectivities were obtained in the addition R
R2 R2
to enones and enals.
R2 = Ph, OEt
R OH
1. LDA, THF
CO2Et
2. SnCl2
TsHN CO2Et
(32)
3. O
Allylation of Carbonyl Compounds. Tin(II) chloride can
Ph NHTs
be used as a reducing agent in the allylation of aldehydes with
R
allylic halides under aqueous conditions (Barbier-type reaction).46
Ph
R = H: 76%; anti:syn 94:6 The addition of allyl bromide to aldehydes in the presence of
R = Me: 79%; anti:syn 92:8
tin(II) chloride tolerates only the presence of small amounts of
water. Different catalytic or stochiometric additives are required
in order to conduct the reaction in fully aqueous media. These
Michael Addition. Tin enolates generated by transmetallation
include: copper,47 titanium(III) chloride,48 palladium(II) chlo-
of deprotonated glycine esters with tin(II) chloride can also be
ride,49 copper(II) chloride,50 and potassium iodide.51 Alterna-
used in the Michael addition to nitroolefins (eq 33). The products
tively, the use of ultrasonication has been reported in the tin(II)
are obtained in good yields and stereoselectivities. Replacement of
chloride-mediated allylation of aldehydes and ketones with allyl
the trifluoroacetate group by other protecting groups (Ac, Bz, Boc,
bromide in water in the absence of further additives.52 In the addi-
Z) led to an erosion in selectivity. In situ quench of the reaction
tion of cinnamyl bromide to aldehydes, higher Ä…-selectivities were
products with acetyl chloride affords amino acid nitriles.42
obtained in the presence of additives (CuCl2, PdCl2, TiCl3) than
with SnCl2 alone (eq 36). The anti-isomers were formed predom-
inantly, indicating a cyclic transition state.
1. LDA, THF
TFAHN NO2
2. SnCl2
TFAHN CO2t-Bu
(33)
O
3.
NO2 SnCl2
t-BuOOC
H2O
H
+
56% (syn:anti 93:7) Br Ph
MeO
(36)
Reformatzky-type Reactions. Trichloronitromethane adds to
OH OH
aldehydes in the presence of tin(II) chloride in a Reformatzky-
Ph
type reaction (eq 34). The reaction proceeds in good yields for
Ph
aliphatic aldehydes (67 92%) and acceptable yields for aromatic
MeO MeO
and heteroaromatic aldehydes (52 61%). Low yields are obtained
no additive: 71% (58:42)
in the presence of other Lewis acids. The proposed mechanism
with CuCl2: 84% (98:2)(anti:syn 84:16)
involves oxidative addition of tin(II) chloride into trichloroni-
tromethane followed by reaction with the aldehyde. The reaction
does not work with ketones as acceptors.43 Acid chlorides can be The addition of allylic alcohols to aldehydes in the presence
used as acceptors using the same protocol, providing access to of equimolar amounts of tin(II) chloride can be catalyzed by
dichloronitroketones.44 rhodium(I) complexes (eq 37).53 Mechanistic studies suggest that
Avoid Skin Contact with All Reagents
6 TIN(II) CHLORIDE
SnCl2
an allylrhodium species serves as the allylating reagent, this is in
Ph Me
MeCN
+
Bu3Sn Ph
contrast to the analogous palladium(II) chloride-catalyzed reac-
O
tion where an allyltin species has been proposed.20
Ph
Me
Ph
Sn
SnCl2
via Ph
OH O
[RhCl(cod)]2 HO Me
O
Ph
THF, H2O
OH
+ (37)
R 83% (anti:syn 92:8)
R H
51 99 %
SnCl2
Ph Me
+ MeCN
Tin(II) chloride can be used to facilitate the allylation of
Bu3Sn
O
carbonyl compounds with allylic tributyltins (eqs 38 and 39).54
Acetonitrile is the preferred solvent for the reaction and the pro-
Me
Ph
posed reaction mechanism involves transmetallation of the tin(IV) Sn
via Ph
species to a tin(II) species. The reaction is applicable to aldehydes,
O
HO Me
Ph
ketones, and imines, providing addition products in high yields.
79% (syn:anti 99:1)
In cases of unsaturated aldehydes and ketones, the 1,2-addition
products are obtained exclusively. The addition of cinnnamyl-
tributyltin to aldehydes proceeds with high stereoselectivities
SnCl2
(anti:syn > 92:8), while the use of crotyltributyltin results in low
Me
MeCN
Bu3Sn Ph MeO
+
selectivities.
O
The addition of cinnamyltributyltin has also been applied
to the allylation of aromatic ketones.55 Good yields and high
Me Ph
selectivities favoring the anti-diastereomer are obtained. Cyclic
O
MeO
(39)
allylic stannanes can also be added to aromatic ketones afford-
Sn
HO Me
ing high syn-selectivities. Low selectivities were obtained with
via Ph
O
crotyltributyltin. The observed stereoselectivities can be explained
99% (ds > 99:1)
Me
by cyclic transition states. The geometry of the double bond in
the allylating species is translated to the stereochemistry of the
product. Simple aliphatic ketones afforded low selectivities, but
NCS/SnCl2
i-Pr i-Pr i-Pr i-Pr
Ä…-O-substituted ketones can be allylated with high selectivities.
CH2Cl2
OH OSnCl3
SnCl2
Ph H MeCN
+
Bu3Sn
OH
O
R1CHO
(40)
SnCl3
Ph
R1
OH
R1 = aryl, alkyl
97%
SnCl2
Ph H
MeCN
+
Bu3Sn Ph
O
Ph
SnCl2
Ph
(38) Ph
+ MeCN
Bu3Sn Br
OH
O
83% (anti:syn 94:6)
Ph
(41)
Ph
O Br
The combination of NCS/SnCl2 can be used for the preparation
Sn O
of allylic trichlorotin reagents from Ä…,Ä…-diisopropylhomoallylic
60%
Cl
alcohols. The allyltin reagents generated in situ can be added to
aldehydes to afford homoallylic alcohols (30 78%) (eq 40).56 The
reaction mechanism involves formation of trichlorotin alkoxides,
which undergo retro-allylation to afford the allylic trichlorotins. The reaction of Ä…-stannyl esters with Ä…,²-unsaturated ketones
The addition of allyltributyltin to Ä…-halogenated aryl ketones in the presence of tin(II) chloride provides the corresponding 1,2-
in the presence of tin(II) chloride results in an interesting allyl- addition product selectively (eq 42).58 Linear and cyclic enones
ation-rearrangement sequence (eq 41).57 The intermediate tin(II) can be employed in the reaction. Complementary selectivity for
alkoxide formed after the allylation is believed to be the key 1,4-addition can be obtained when trimethylsilyl chloride is em-
intermediate for the aryl rearrangement. ployed instead of tin(II) chloride.
A list of General Abbreviations appears on the front Endpapers
TIN(II) CHLORIDE 7
SnCl2 · H2O, EtSH
SnCl2
(45)
OMe Ph CH2Cl2
MeCN
Bu3Sn
+
91%
OO OPMB OH
76%
OMe (42)
A catalytic amount of Pd(OAc)2 with tin(II) chloride as cocat-
Ph OH
alyst can be used for the deprotection of hydrazones to carbonyl
O
compounds(eq 46).64 The reaction is believed to proceed com-
petitively via acidic and oxidative mechanisms, since both the
absence of water and air was detrimental to reaction efficiency.
The scope is fairly general, hydrazones derived from aromatic and
Protection. Tin(II) chloride dihydrate can be used as a catalyst
for the THP (tetrahydropyranyl) protection of aliphatic alcohols.59 aliphatic ketones are deprotected in high yields (90 98%), while
hydrazones derived from aliphatic aldehydes result in slightly
PMB-, TBDPS-, MEM-ethers, and nitro-groups are tolerated un-
lower yields (53 87%). Various substituents on the hydrazone
der the reaction conditions. Acetonides and TBDMS ethers are
nitrogen are tolerated (methyl, phenyl, benzyl, cyclic alkyl).
cleaved under these conditions.
Cyclic thioketals can be used as orthogonal protecting groups for
carbonyls under these conditions.
Deprotection. Tin(II) chloride dihydrate converts conjugated
dioxolanes, and dimethoxy or diethoxy acetals to aldehydes (84
NMe2
N
98%). Nonconjugated dimethoxy and diethoxy aldehydes are also
O
Pd(OAc)2, SnCl2
efficiently deprotected to aldehydes (84 94%) (eq 43).60 The
DMF/H2O
(46)
reaction rate can be increased by the addition of naphthalene or
fullerenes.61
98%
OR2 O
SnCl2·2H2O
CH2Cl2, rt
R OR2 R H
1,3-Dioxolanes from Epoxides. Anhydrous tin(II) chloride
is an efficient catalyst for the direct conversion of epoxides to
R = Ph, C3H7; R2 = Me, Et, -CH2CH2-
acetonides (eq 47).65 Terminal epoxides are converted in high
(43)
yields (63 97%), optically pure epoxides provide products with
SnCl2·2H2O
significant erosion of enrichment.
OR2 O
CH2Cl2, rt
SnCl2 (1 mol %)
Ph OR2 Ph H
acetone
O O
reflux
R2 = Me, Et (47)
O
R
R
The use of tin(II) chloride has also been described for the
selective deprotection of benzylidene acetals from sugars Allylic Amination. Primary and secondary amines can be
(eq 44).62 The reaction is performed at room temperature with alkylated with allylic alcohols in the presence of a catalytic amount
catalytic amounts of tin(II) chloride, and the deprotected carbo- of Pd(PPh3)4 and a stochiometric amount of SnCl2 (eq 48).66 No
hydrates are recovered in high yields (86 95%). Other protect- reaction was observed without either palladium catalyst or tin(II)
ing groups such as benzoyl, acetyl, benzyl, and acetonide are not chloride. Nucleophilic aliphatic amines afford higher yields than
affected. aromatic amines, while primary amines are dialkylated. The reac-
tion presumably proceeds via the formation of a Ä„-allylpalladium
complex from the allylic alcohol mediated by tin(II) chloride.
O HO
SnCl2
O O
(44)
Ph Pd(PPh3)4
CH2Cl2
OBn OBn
SnCl2
O
THF
O OMe HO OMe
+
Ph OH
HN
OBn OBn
91%
O
Catalytic amounts of tin(II) chloride hydrate in combination
(48)
Ph N
with ethanethiol can be used for the selective deprotection of
aliphatic and aromatic p-methoxybenzyl (PMB) ethers (eq 45).63
In the latter case, the alkylation of the aromatic ring with PMB
can be an undesired side reaction. Benzyl ethers, methyl ethers, Indole Synthesis. Anilines react with epoxides in the presence
and acetonides are not cleaved under the reaction conditions. Alu- of a ruthenium catalyst along with tin(II) chloride to afford 2-
minum(III) chloride can be used as an alternative to tin(II) chloride substituted indoles (eq 49).67 Various ruthenium catalysts can be
in this reaction. used, but the optimal catalyst system is a mixture of ruthenium(III)
Avoid Skin Contact with All Reagents
8 TIN(II) CHLORIDE
chloride with triphenylphosphine as ligand. The proposed reaction chloride dihydrate and ruthenium(III) chloride affording 2-ethyl-
mechanism involves initial Lewis acid-catalyzed ring opening of 3-methylquinolines (eq 52). Similar to the indole synthesis with
the epoxide, followed by a ruthenium-catalyzed cyclization. The the same catalyst system, the reaction most likely proceeds
indoles are obtained in moderate to good yields (22 98%) when a through an amine exchange reaction followed by heteroannula-
large excess of the aniline is used. In most cases, the 3-subsituted tion.
indoles are formed as minor by-products.
SnCl2·H2O
R
RuCl3, PPh3
RuCl3, PPh3
SnCl2
dioxane, 180 ºC
R2
N +
3
dioxane, 180 °C
R
+
NH2
O
NH2
R = H, Me, OMe, Cl
R = H, Me, OMe, Cl, Bu
R
R2 = Me, Bu, Bn, Ph
(52)
R R2 (49)
N
N
28 61%
H
ortho-Nitrostyrene derivatives undergo palladium-catalyzed
Nitroarenes are reductively cyclized with tris(3-hydroxypropyl)
cyclization affording indoles in the presence of tin(II) chloride
amine in the presence of a ruthenium catalyst, tin(II) chloride
(eq 50).68 In a related reaction, 2H-Indazoles are obtained from N-
dihydrate, and isopropanol to afford the corresponding quinolines
(2-nitrobezylidene)amine derivatives. The role of tin(II) chloride
(eq 53).73 Anilines can be used directly instead of nitroarenes in
in these reactions is not fully understood, since carbon monoxide
the reaction.74
serves as the primary reducing agent for the nitro functionality.
Other Lewis acids (SnCl4, FeCl3, MoCl5, BF3) are not efficient
SnCl2·H2O
R
additives in the reaction.
RuCl3, PPh3, i-PrOH
dioxane, 180 ºC
N(CH2CH2CH2OH)3 +
PdCl2(PPh3)
CO2CH3 SnCl2, CO
NO2
dioxane
CO2CH3
R
N
NO2
H (53)
60%
N
(50)
42 95%
Cl R = H, Me, OMe, Cl, CO2Me, COMe
PdCl2(PPh3)
SnCl2, CO
NCl
THF
N
N
NO2
Benzoxazole Synthesis. The condensation of 2-aminophenols
74%
with carboxylic acids affords 2-substituted benzoxazoles. Tin(II)
Anilines react with trialkanolamines69 or trialkanolammonium chloride is an efficient catalyst for this reaction and higher yields
chlorides70 in the presence of a catalytic amount of ruthenium(III) (37 73%) are obtained than with other Lewis acids (eq 54).75
chloride, together with tin(II) chloride dihydrate, supplying Different aromatic and aliphatic carboxylic acids can be used.
indoles in moderate to good yields (eq 51). The proposed reac-
tion mechanism involves formation of 2-anilinoethanols by an
SnCl2
NH2 Me
amine exchange reaction between the trialkanolamine and ani- dioxane
180 °C
line. Cyclization to the indole derivative is proposed to occur
+
via ruthenium-catalyzed C H activation. The reaction affords
OH COOH
the highest yields with electron-rich anilines (toluidines or
anisidines), while meta-substituted anilines afford mixtures of
N
regioisomeric indoles. Me
(54)
O
SnCl2·H2O
55%
N(CH2CH2OH)3
R
RuCl3, PPh3 R
dioxane, 180 ºC
(51)
NH2
N
Biginelli Reaction. A mixture of tin(II) chloride and lithium
H
chloride has been shown to be an efficient catalyst for the con-
R = H, Me, OMe, Cl
9 99%
densation of an aldehyde, urea, and a ²-keto ester (eq 55).76 The
resulting 3,4-dihydropyrimidin-2(1H)-ones are obtained in good
Quinoline Synthesis. Anilines react with triallylamines71 yields (60 85%). Most Lewis and Bronsted acids promote this
reaction in varying selectivities.
or allylammonium chlorides72 in the presence of tin(II)
A list of General Abbreviations appears on the front Endpapers
TIN(II) CHLORIDE 9
X
SnCl2, LiCl
O O 24. Mukaiyama, T.; Wariishi, K.; Saito, Y.; Hayashi, M.; Kobayashi, S.,
EtOH
Chem. Lett. 1988, 1101.
+
RCHO +
H2N NH2
EtO
25. Kohler, B. A. B., Synth. Commun. 1985, 15, 39.
R = aryl
26. Mukaiyama, T.; Murai, Y.; Shoda, S., Chem. Lett. 1981, 431.
X = O,S
R
27. Fukunaga, K., Synthesis 1975, 442.
EtOOC
28. Augé, J., Tetrahedron Lett. 1985, 26, 753.
NH
(55)
29. Augé, J.; Serge, D., Tetrahedron Lett. 1983, 24, 4009.
N X 30. Mukaiyama, T.; Harada, T., Chem. Lett. 1981, 621.
H
31. Kohmoto, S.; Kasai, S.; Yamamoto, M.; Yamada, K., Chem. Lett. 1988,
60 85%
1477.
32. Nishiyama, H.; Kitajima, T.; Yamamoto, A.; Itoh, K., J. Chem. Soc.,
Chem. Commun. 1982, 1232.
Dehydration of Propynyl Alcohols. Propargylic alcohols can
33. Kim, S.; Kim, S.; Lim, T.; Shim, S., J. Org. Chem. 1987, 52, 2114.
undergo a palladium-catalyzed dehydration in the presence of
34. Akiyama, T.; Shima, H.; Ozaki, S., Synlett 1992, 415.
tin(II) chloride (eq 56).77 The products are obtained as mixtures
35. Masuyama, Y.; Sakai, T.; Kurusu, Y., Tetrahedron Lett. 1993, 34, 653.
of Z- and E-isomers, with the former dominating (3:1 to 5:1).
36. Masuyama, Y.; Kobayashi, Y.; Yanagi, R.; Kurusu, Y., Chem. Lett. 1992,
2039.
OH
SnCl2 (1.5 equiv)
37. Masuyama, Y.; Kobayashi, Y.; Kurusu, Y., J. Chem. Soc., Chem.
PdCl2(PPh3)2 R
R
Commun. 1994, 1123.
(56)
R2
53 79%
R2
38. Masuyama, Y.; Gotoh, S.; Kurusu, Y., Synth. Commun. 1995, 1989.
39. Grandel, R.; Kazmaier, U., Eur. J. Org. Chem. 1998, 409.
R = C6H13, Ph; R2 = C5H11, Me2CH, PhCH2
40. (a) Grandel, R.; Kazmaier, U.; Rominger, F., J. Org. Chem. 1998,
63, 4524. (b) Kazmaier, U.; Grandel, R., Eur. J. Org. Chem. 1998,
Related Reagents. Cerium(III) Chloride Tin(II) Chloride;
1833.
Dichlorobis(triphenylphosphine)Platinum(II) Tin(II) Chloride.
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155.
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Avoid Skin Contact with All Reagents
10 TIN(II) CHLORIDE
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A list of General Abbreviations appears on the front Endpapers