Stereochemical aspects of the chemistry of 2-[trialkyl(aryl)silyloxy]alkyl- 4-alkoxyalk-2-enylstannanes

Article abstract of DOI:10.1016/j.tetlet.2010.10.096

2-tert-Butyldimethylsilyloxymethyl-4-(methoxymethoxy)pent-2-enyl(tributyl) stannane, prepared predominantly as the (Z)-isomer, is transmetallated by tin(IV) chloride to generate an allyltin trichloride which reacts with aldehydes with excellent stereocont

Full text of DOI:10.1016/j.tetlet.2010.10.096

Tetrahedron Letters 52 (2011) 2065–2068
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Stereochemical aspects of the chemistry
of 2-[trialkyl(aryl)silyloxy]alkyl-4-alkoxyalk-2-enylstannanes
⇑
Eric J. Thomas , Daniel R. Tray
School of Chemistry, University of Manchester, Manchester, M13 9PL, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 26 October 2010
2-tert-Butyldimethylsilyloxymethyl-4-(methoxymethoxy)pent-2-enyl(tributyl)stannane, prepared pre-
dominantly as the (Z)-isomer, is transmetallated by tin(IV) chloride to generate an allyltin trichloride which
reacts with aldehydes with excellent stereocontrol in favour of (E)-1,5-syn-3-tert-butyldimethylsilyloxym-
ethyl-5-(methoxymethoxy)alk-3-en-1-ols. These were taken through to 3-[(E)-2-(methoxymethoxy)
propylidenyl]-5-alkyl(aryl)tetrahydrofurans and used to prepare more complex 4-(methoxymethoxy)
pent-2-enylstannanes.
Keywords:
Allylstannane
Allylsulfone
Remote stereocontrol
Homoallylic alcohol
Stereoselectivity
Ó 2010 Elsevier Ltd. All rights reserved.
Alkoxyalk-2-enylstannanes are transmetalled by tin(IV) halides
to give allyltin trihalides which react with aldehydes with useful
levels of remote stereocontrol; for example, the 4-benzyloxypent-
The racemic 2-(tert-butyldimethylsilyloxy)methylpent-2-enyl-
stannane 9 was synthesized as outlined in Scheme 1. Thus lithia-
tion of the 2-(tert-butyldimethylsilyloxy)methylpropenyl-sulfone
1
4
2
-enylstannane 1 reacts with aldehydes to give (Z)-1,5-syn-hex-3-
6, which is available from the alcohol 5, followed by addition of
2
en-1-ols 2 containing less than 3% of any other stereoisomer. Useful
remote stereocontrol was also observed for analogous reactions of
the 5-alkoxy-2,4-dimethylpent-2-enylstannane 3, which gave the
ethanal gave the hydroxyalkylsulfone 7 as a mixture of diastereo-
isomers. Treatment of this mixture with tri-n-butyltin hydride
5
under free-radical conditions gave the racemic (Z)-4-hydroxy-
(
Z)-1,5-anti-3,5-dimethylhex-3-en-1-ols 4 with excellent stereose-
pent-2-enylstannane 8 together with a small amount of the
(E)- isomer, (2Z)-8:(2E)-8 = 90:10, and the alcohol 8 was converted
into its methoxymethyl ether 9.
lectivity showing that this chemistry is compatible with an alkyl
substituent at C(2) in the stannane.3
The stereoselective formation of the (2Z)-isomer of the
1
4
-hydroxypent-2-enylstannane 8 was established by H NOE
OH
Me
OBn
SnCl4, -78 o
C
Bu3Sn
observations, for example, the significant enhancement of 3-H on
irradiation of 2-CH but not on irradiation of 1-H . This level of
Me
OBn
R
then RCHO, -78 o
2
2
C
1
2
4
stereoselectivity, (2Z):(2E) = 90:10, was unexpected. Whether it
was due to kinetic or thermodynamic control was not investigated
but either way may be due to co-ordination of the hydroxyl group
with the tributyltin moiety either during the tributyltin radical dis-
placement of the phenylsulfonyl group or in the final product.
Tin(IV) chloride mediated reactions of the (2EZ)-pentenylstann-
ane 9 with aldehydes were carried out under the usual conditions,
that is, by stirring a mixture of the allylstannane and tin(IV) chlo-
ride at ꢀ78 °C for 5 min to generate the allyltin trihalide before
addition of the aldehyde. After a further 30 min at ꢀ78 °C, and an
aqueous work-up, the (E)-1,5-syn-homoallylic alcohols 10a–d
were obtained, see Scheme 2. In all cases the reactions proceeded
with excellent stereoselectivity, less than 3% of any other diaste-
OH Me
2
SnCl4, -78 o
C
Bu3Sn
OMOM
then RCHO, -78 o
C
R
OMOM
Me
Me
Me
3
It was of interest to see whether this chemistry was compatible
with a functionalised alkyl group at C(2) in the stannane or whether
such functionalisation would disrupt the remote stereocontrol. We
now report aspects of the chemistry of 4-(methoxymethoxy)pent-
2
-enylstannanes with a trialkyl(aryl)silyloxyalkyl substituent at
C(2).
1
13
6,7
reoisomeric product being detected by H or C NMR.
The structures shown were assigned to the major products 10a–
d by analogy with the earlier work on remote stereocontrol using
allylstannanes, for example, the formation of the 1,5-syn-products
⇑
Corresponding author. Tel.: +44 161 275 4614; fax: +44 161 275 4939.
E-mail address: e.j.thomas@manchester.ac.uk (E.J. Thomas).
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.096

2
066
E. J. Thomas, D. R. Tray / Tetrahedron Letters 52 (2011) 2065–2068
S(O)2Ph
S(O)2Ph
Me
an aldehyde via the six-membered, chair-like transition structure
ii
15 to give the (E)-1,5-syn-product 10 after an aqueous work-up,
RO
TBSO
1,2
see Figure 1. Transition structure 15 involving a penta-co-ordi-
OH
nated tin is suggested by analogy with reactions of 1-substituted
allylstannanes with aldehydes under high temperature, non-cata-
lysed, conditions. These are believed to involve transition struc-
tures analogous to 15 in which the group next to tin adopts an
axial position leading to the formation of cis-double-bonds in the
product and relaying the stereochemical information from C(1) in
the stannane to the hydroxyl bearing stereogenic centre in the
5
6
R = H
R = TBS
7
i
iii
2
3
Me
OMOM
Me
OH
TBSO
iv
TBSO
Bu3Sn
1
Bu Sn
3
10
product
9
(2Z)-8
Having prepared the homoallylic alcohols 10, it was of interest
to study the aspects of their chemistry. Mesylation of the homoal-
cohols 10b and 10d gave the corresponding mesylates 16b,d,
which on desilylation using TBAF were converted into the (E)-3-
alkylidenetetrahydrofurans 17b,d, see Scheme 3. In a one-step pro-
cedure, the homoallylic alcohols 16a and 16c were treated with
methane sulfonic anhydride for 18 h. Under these conditions,
mesylation, desilylation and tetrahydrofuran formation occurred
to give the 3-alkylidenetetrahydrofurans 17a and 17c directly,
albeit only in modest, unoptimised yields.
The homoallylic alcohols 10 were also identified as precursors
of more complex 2-substituted 4-alkoxypent-2-enylstannanes.
Thus the monosilylated diol 10a was converted into its regioisomer
21 by acetylation and fluoride induced desilylation of the resulting
acetate 18 which was accompanied by migration of the acetyl
group from the secondary to the primary alcohol to give the pri-
mary acetate 19, see Scheme 4. Silylation of the secondary alcohol
and saponification gave the secondary mono-silylated diol 21
which was converted into xanthate 22. This rearranged on heating
to give a mixture of the epimeric dithiocarbonates 23 and reaction
of this mixture with tributyltin hydride under free-radical
Scheme 1. Reagents and conditions: (i) TBSCl, imid., DCM, rt, 15 h (73%); (ii) LDA,
THF, ꢀ78 °C, 45 min, ethanal, ꢀ78 °C, 30 min (68%, a 55:45 mixture of diastereo-
n
isomers); (iii) Bu
3
SnH, AIBN (cat.), benzene, reflux, 2 h [69%; (2Z)-8:(2E)-
i
8
= 90:10]; (iv) Pr
2
NEt, MeOCH
2
Cl, DCM, 0 °C, rt, 15 h (82%).
OTBS
OH
Me
TBSO
Bu3Sn
i
2
5
Me
R
OMOM
OMOM
10a R = Ph, 69%
9
1
1
1
0b R = Me, 57%
0c R = (E)-MeCH=CH, 62%
i
0d R = Pr, 59%
ii
OTBS
OTBS
OH
iii
ArCO2
Me
Me
Me
Me
OMOM
OMOM
12
11 Ar = 4-NO2C6H4
Scheme 2. Reagents and conditions: (i) SnCl
78 °C, 30 min (57–69%); (ii) Ph P, 4-nitrobenzoic acid, DEAD, THF, rt, 2 h (79%);
iii) NaOH, MeOH, rt, 2 h (66%).
4
, DCM, ꢀ78 °C, 5 min, aldehyde,
ꢀ
3
Cl
(
Me
Me
Cl Sn
O
3
O
SnCl4
H
Cl Sn
3
9
from reactions of the allylstannanes 1 with aldehydes.1,2 To check
O
2
O
H
TBSO
Bu Sn
Me
TBSO
that the 1,5-syn-products 10 were distinguishable from their 1,5-
anti-epimers, the product 10b from the reaction of the stannane
H
H
Me
3
1
3
14
RCHO
–
9
1
with ethanal was converted into the 1,5-anti-diastereoisomer
2 by reaction with 4-nitrobenzoic acid under Mitsunobu condi-
Cl
tions and saponification of the resulting ester 11. Although the
,5-syn- and -anti-epimers 10b and 12, were indistinguishable by
H
OTBS
OTBS
H
1
SnCl3
1
TLC, there were small but definite differences in their H NMR
R
OH
H2O
R
O
H
H
Me
0
spectra, for example, 3-H and 3-H were observed at d2.18 and at
2
.33 for the 1,5-syn-isomer 10b and were coincident at d2.28 for
MOMO
Me
MOMO
1
H
H
the 1,5-anti-isomer 12. Examination of the H NMR spectrum of
the product 10b from the reaction of stannane 9 with ethanal
showed that only a small amount, less than 3%, of the 1,5-anti-epi-
10
15
Figure 1. Outline of a mechanism that is consistent with the observed stereocon-
trol of tin(IV) chloride promoted reactions of allylstannane 9 with aldehydes.8
mer 12 was present. Similar minor products were detected at the
,9
1
<
3% level in the H NMR spectra of the products from the reactions
of the other aldehydes with stannane 9.
The (E)-geometry of the product 10a from the reaction with
benzaldehyde was confirmed by NOE observations, for example,
a significant enhancement of the peak due to H-5 was observed
on irradiation of 2-H . The geometry of the double-bond in the
2
other products, 10a, 10cd, was assigned by analogy.
10a-d
iii
Me
OMOM
i
ii
OTBS
OMs
The selective formation of the homoallylic alcohols 10a–d from
the reactions of the allylstannane 9 with aldehydes is consistent
with stereoselective transmetallation of the allylstannane, which
O
R
Me
H
R
1
7a-d
OMOM
8
16b,d
is believed to be subjected to kinetic control, to generate the allyl-
tin trihalide 14 in which the vicinal methyl and propenyl groups
are trans and pseudoequatorial with respect to the six-membered
oxastannane ring. The allyltin trichloride 14 can then react with
Scheme 3. Reagents and conditions: (i) Ms
7%); (ii) TBAF, THF, rt, 15 min (17b, 36%); 17d, 43%); (iii) Ms
(17a, 33%; 17c, 24%).
2
O, Et
3
N, DCM, rt, 2 h (16b, 91%; 16d,
3
2
O, Et N, DCM, rt, 18 h
3
9

E. J. Thomas, D. R. Tray / Tetrahedron Letters 52 (2011) 2065–2068
OAc
2067
OTBS
OR
OTBS
OR
OR
TBDPSO
Me
OR
ii, iii
ii, iii
Me
Me
OMOM
Me
Me
OMOM
Ph
Me
Ph
OMOM
OMOM
1
0a R = H
8 R = Ac
19 R = H
20 R = TBS
10b R = H
26 R = H
27 R = C(S)SMe
i
i
1
25 R = TBDPS
iv, v
iv
Me
OR
OTBDPS
TBSO
Ph
TBSO
Ph
SC(O)SMe
Me
vi
TBDPSO
Me
v
SC(O)SMe
Me
Bu3Sn
Me
Me
OMOM
OMOM
OMOM
OMOM
23
21 R = H
(
Z)-29
28
2
2 R = C(S)SMe
vii
Ph
Scheme 5. Reagents and conditions: (i) TBDPSCl, imid., DCM, rt, 18 h (83%); (ii)
PPTS, EtOH, 40 °C, 4 h (72%); (iii) NaH, toluene, rt, 90 min, CS , rt, 2 h, MeI, rt, 18 h
2
n
(
70%); (iv) toluene, heat, 2 h (ca. 100%); (v) Bu
3
SnH, AIBN (cat.), benzene, rt, 1 h
OTBS
[77%, (E):(Z) = 30:70].
Bu Sn
Me
3
Me
O
Me
TBS
OMOM
(
Z)-24
O
O
Cl3Sn
H
M
H
SnCl4
Scheme 4. Reagents and conditions: (i) Ac
TBAF, THF, rt, 1 h (60%); (iii) TBSOTf, Et N, DCM, rt, 90 min (85%); (iv) NaOH, MeOH,
rt, 1 h (96%); (v) NaH, toluene, rt, 90 min, CS , rt, 3 h, MeI, rt, 18 h (63%); (vi) toluene,
SnH, AIBN (cat.), toluene, heat, 90 min [58%;
2
O, Et
3
N, DMAP, DCM, rt, 1 h (94%); (ii)
9
O
H
O
H
TBSO
3
Me
2
Me
n
heat, 6 h (ca. 100%); (vii) Bu
E):(Z) = 6:94].
3
14a
14b
(
Me
O
R2
Me
O
R1
O
Cl3Sn
H
M
H
2
conditions gave the pent-2-enyl-stannane 24, again predomi-
nately, 94:6, as the (Z)-isomer.
R O
O
H
O
H
SnCl4
24, 29
R1
Me
Stannane 29 was prepared from the monoprotected diol 10b as
outlined in Scheme 5. In this case, following protection of the sec-
ondary alcohol as it is tert-butyldiphenylsilyl ether 25, selective re-
moval of the tert-butyldimethylsilyl group gave the primary
alcohol 26. This was converted into xanthate 27 which rearranged
to give the dithiocarbonates 28 on heating. These reacted with tri-
butyltin hydride under free-radical conditions to give the pent-2-
enylstannane 29, again mainly as the (Z)-isomer.
Me
31a
3
1b
R1 = Me, Ph; R2 = TBDPS, TBS; M = SnCl3
Figure 2. Options for co-ordination of the tin in allyltin trichlorides from
transmetallation of pent-2-enylstanannes.
trihalide 31 the equilibrium lies in favour of the less reactive hexa
co-ordinated species 31b. However, more work is required to
delineate fully the reasons behind the differing reactivities of
allylstannane 9 and the homologues 24 and 29.
However, preliminary studies of the tin(IV) chloride mediated
reactions of the pent-2-enylstannanes 24 and 29 with aldehydes
were not successful. Generally only complex mixtures of products
were obtained and only in one case, the reaction of stannane 29
1
This work has shown that 4-alkoxypent-2-enylstannanes with
functionality at the 2-position can undergo tin(IV) halide mediated
reaction with aldehydes with remote stereocontrol. However the
difference in reactivity between the 2-silyloxymethylpentenylst-
annane 9 and the 2-silyloxypropylpent-2-enylstannanes 24 and
29, which may be due to additional co-ordination of the electron
deficient tin in the intermediate allyltin trichlorides 31, is of inter-
est. Also of note in this work, is the stereoselective formation of the
trisubstituted double-bonds of the (Z)-isomers of the stannanes 8,
24 and 25 during the reactions of the sulfone 7 and dithiocarbon-
ates 23 and 28 with tributyltin hydride under free-radical condi-
tions. This may be due to thermodynamic control involving an
interaction between the tin and the 5-heteroatom functionality
in the products.
with ethanal, was a trace of the expected product 30 (R = R =
2
Me, R = TBDPS) isolated.
R1
OR2
SnCl4, -78 o
C
OH
(Z)-24/(Z)-29
then RCHO, -78 o
C
Me
R
OMOM
0 R1 = Ph, Me; R2 = TBS, TBDPS
3
The difficulties in the tin(IV) chloride mediated reactions of the
stannanes 24 and 29 with aldehydes contrasted with the results
obtained using the pent-2-enylstannane 9 which gave the 1,5-
syn-products 10 from tin(IV) chloride mediated reactions with
aldehydes. One explanation for this dichotomy may be due to co-
ordination of the electron deficient tin in the intermediate allyltin
trihalides 14 and 31 by the silyloxy groups as well as by the MOM-
ethers, see Figure 2. Perhaps the penta-co-ordinated allyltin triha-
lides 14a and 31a are in equilibrium with the hexa-co-ordinated
species 14b and 31b. The latter would be unable to co-ordinate
to, that is, to react with, aldehydes. For the allyltin trihalide 14
derived from stannane 9, perhaps the equilibrium lies in favour
of the more reactive allyltin trihalide 14a whereas for the allyltin
Acknowledgements
We thank the EPSRC for a studentship and AstraZeneca for sup-
port through the CASE scheme (to D.R.T.).
References and notes
1.
(a) Thomas, E. J. J. Chem. Soc., Chem. Commun. 1997, 411; (b) Thomas, E. J. Chem.
Rec. 2007, 7, 115.
2. MacNeill, A. H.; Thomas, E. J. Synthesis 1994, 322.

2
068
E. J. Thomas, D. R. Tray / Tetrahedron Letters 52 (2011) 2065–2068
3
.
.
.
.
Teerawutgulrag, A.; Thomas, E. J. J. Chem. Soc., Perkin Trans. I 1993, 2863. 0.00 and 0.01 (each 3H, s, SiCH
3
), 0.83 [9H, s, SiC(CH
3
)
3
], 1.12 (3H, d, J 6.3, 6-H
3
).
),
0
4
5
6
Breuilles, P.; Uguen, D. Tetrahedron Lett. 1987, 28, 6053.
2.36 (1H, dd, J 14.1, 9.8, 2-H), 2.50 (1H, dd, J 14.1, 3.5, 2-H ), 3.26 (3H, s, OCH
3
Ueno, Y.; Aoki, S.; Okawara, M. J. Am. Chem. Soc. 1979, 101, 5414.
The tin(IV) halide mediated reactions of 4-alkoxypent-2-enylstannanes with
aldehydes give 1,5-syn-5-alkoxyalk-3-enols with excellent (Z)-stereo-
selectivity, for example, 1 ? 2. The geometry of the products 10 parallels this
stereoselectivity but the products are designated as (E)-isomers simply because
the tert-butyldimethylsilyloxymethyl group has priority according to IUPAC
nomenclature over the hydroxyalkyl fragment.
General procedure for reactions of the pent-2-enylstannane 9 with aldehydes:
preparation of (1RS,5SR,3E)-3-tert-butyldimethylsilyloxymethyl-5-(methoxyme-
thoxy)-1-phenylhex-3-en-1-ol 10a:
3.84 (1H, br d, J 3.5, OH), 4.00 and 4.10 (each 1H, dd, J 12.5, 1.0, 3-CH), 4.40 (1H,
dq, J 9.1, 6.3, 5-H), 4.44 and 4.58 (each 1H, d, J 6.8, OHCHO), 4.64 (1H, m, 1-H),
5.36 (1H, br d, J 9.1, 4-H), and 7.20 (5H, m, ArH); d
C
(75 MHz; CDCl
3
) ꢀ5.41,
ꢀ5.36, 18.30, 21.26, 25.86, 39.75, 55.15, 67.58, 67.62, 72.76, 93.59, 125.41,
+
127.15, 128.28, 130.53, 138.37 and 144.96; m/z (CI) 336 (M ꢀ45, 26%), 301
(15), 230 (19), 213 (60) and 187 (100).
8. (a) Beddoes, R.; Hobson, L. A.; Thomas, E. J. J. Chem. Soc., Chem. Commun. 1997,
1929; (b) Hobson, L.; Vincent, M.; Thomas, E. J.; Hillier, I. H. J. Chem. Soc., Chem.
Commun. 1998, 899.
7
.
9. The intermediate allyltin trichloride 13 has been depicted as having a six-
membered oxastannane ring involving co-ordination of the more remote
oxygen of the methoxymethoxy substituent. There is always the possibility
that the other oxygen of the methoxymethoxy group is involved in which a
case a four-membered oxastannane ring would be formed. However, the
preferred four-membered ring containing intermediate would still have the
methyl and propenyl groups trans-disposed with respect to the oxastannane
ring, that is, the same configuration at the tin bearing stereogenic centre
relative to the configuration of the stereogenic centre bearing the
methoxymethoxy substituent. The same overall stereochemical outcome
would therefore be expected.
Tin(IV) chloride in dichloromethane (1 M, 2.8 ml, 2.8 mmol) was added to the
pentenylstannane 9 (1.32 g, 2.345 mmol) in dichloromethane (25 ml) at ꢀ78 °C
and the solution stirred for 5 min. Benzaldehyde (0.28 ml) in dichloromethane
(
5 ml) was added and the mixture stirred for 30 min at ꢀ78 °C. Saturated
aqueous sodium hydrogen carbonate (2 ml) was added and the mixture
allowed to warm to room temperature. Water (30 ml) was added and the
aqueous phase extracted with dichloromethane (30 ml). The organic extracts
4
were dried (MgSO ) and concentrated under reduced pressure. Chromato-
graphy of the residue using ether/light petroleum (25:75 containing 1%
triethylamine) gave the title compound 10a (620 mg, 69%), as a colourless oil,
+
R
C
F
(ether:light petroleum = 1:3) 0.3 (Found: M ꢀCH
2
OCH
3
,
336.2129;
10. (a) Pratt, A. J.; Thomas, E. J. J. Chem. Soc., Perkin Trans. I 1989, 1521; (b) Jephcote,
V. J.; Pratt, A. J.; Thomas, E. J. J. Chem. Soc., Perkin Trans. I 1989, 1529.
ꢀ
1
19
H
31
O
3
Si requires M, 336.2121);
m
max (film)/cm 3427, 1673, 1603, 1471,
1
463, 1453, 1255, 1156, 1098, 1029, 837, 777 and 700; d
H
(300 MHz; CDCl )
3