1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an approach to the stereoselective synthesis of branched triols

Article abstract of DOI:10.1016/j.tet.2019.130734

2-(tert-Butyldimethylsilyloxymethyl)-4-(methoxymethoxy)pent-2-enyl(tributyl)stannane is transmetallated by tin(IV) chloride stereoselectively to give a pent-1-en-3-yltin trichloride that reacts with aldehydes with excellent (E)-1,5-syn-stereocontrol, e.g.

Full text of DOI:10.1016/j.tet.2019.130734

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
1,5-Stereocontrol in reactions of 2,4-disubstituted
alk-2-enylstannanes with aldehydes; an approach to the
stereoselective synthesis of branched triols*
Eric J. Thomas*, Daniel R. Tray
The Department of Chemistry, The 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:
2-(tert-Butyldimethylsilyloxymethyl)-4-(methoxymethoxy)pent-2-enyl(tributyl)stannane
is
trans-
Received 9 September 2019
Received in revised form
18 October 2019
Accepted 23 October 2019
Available online xxx
metallated by tin(IV) chloride stereoselectively to give a pent-1-en-3-yltin trichloride that reacts with
aldehydes with excellent (E)-1,5-syn-stereocontrol, e.g. (3E)-1,5-syn-3-(tert-butyldimethylsilylox-
ymethyl)-5-(methoxymethoxy)-1-phenylhex-3-en-1-ol was the dominant product with benzaldehyde.
The products from these reactions were taken through to more complex 2-substituted alk-2-
enyl(tributyl)stannanes but only very low yields of the expected products were obtained from tin(IV)
chloride mediated reactions of these stannanes and aldehydes. Nevertheless a stereoselective synthesis
of 2-substituted 4-[(E)-2-alkoxypropylidene]tetrahydrofurans was developed.
Keywords:
Allystannane
Remote stereocontrol
Polyols
© 2019 Elsevier Ltd. All rights reserved.
Transmetallation
Diastereoselectivity
1. Introduction
products from syn-selective reactions between allylstannanes 7
and aldehydes mediated by tin(IV) halides, see Scheme 2.
Lewis acid mediated reactions of alk-2-enyl(trialkyl)stannanes
with aldehydes have been widely investigated [1]. Reactions of 4-,
5- and 6-alkoxy-alk-2-enyl(tributyl)stannanes with aldehydes
when promoted by transmetallation using tin(IV) halides proceed
with effective 1,5-, 1,6- and 1,7-(Z)-stereocontrol [2]. For example,
4-benzyloxypent-2-enyl(tributyl)stannane (1) reacts with alde-
hydes to give the (Z)-alkenols 2 with excellent 1,5-syn-stereo-
selectivity following stereoselective transmetallation with tin(IV)
chloride, see Scheme 1.
It was decided to study the scope of this chemistry using more
complex allylstannanes. In this context, the branched differentially
protected triols 3 were identified as challenging targets for ster-
eoselective synthesis since they could be useful as novel molecular
scaffolds. They should be accessible by hydrogenation of the al-
kenes 4 which were expected to be available from tin(IV) halide
mediated reactions of allylstannanes 5 with aldehydes. The allyl-
stannanes 5 would be prepared from the homoallylic alcohols 6,
In this synthesis, the protecting group (P) in the allylstannanes 5
and 7 will be selected so that it will co-ordinate to the tin in the
reactive allyltin trihalide intermediates, so directing stereoselective
reactions with aldehydes to give 1,5-syn-5-alkoxyalk-3-enols 4 and
6 as the major products, cf. the example shown in Scheme 1 [3]. The
trialkylsilyloxy groups should not participate in these reactions
since they should not compete as ligands for the tin [4]. It is known
that the (E,Z)-geometry of the 4-alkoxyalk-2-enylstannanes does
not affect the (Z)-1,5-stereoselectivity of their reactions with al-
dehydes [2] and so mixtures of the geometrical isomers of stan-
nanes 5 and 7 may be used. All of the stereogenic centres in the final
alkene 4 should be 1,5-syn-disposed due to the expected 1,5-syn-
stereoselectivities of the reactions of stannanes 5 and 7 with al-
dehydes. Therefore, racemic stannanes can be used in this work to
deliver racemic products diastereoselectively.
The central tertiary carbon of the target compounds 3 is ster-
eogenic and hydrogenation of the alkenol 4 could give rise to two
diastereoisomers. However, the free hydroxyl group may influence
the stereoselectivity of this process. As an aside, the central tertiary
carbon in triols prepared by deprotection of the final products 3
will not be stereogenic if any two of the alkyl groups R1 , R2 or R3 are
identical.
*
This paper is dedicated to Stephen G. Davies in recognition of his outstanding
contributions to organic chemistry.
* Corresponding author.
E-mail address: e.j.thomas@manchester.ac.uk (E.J. Thomas).
https://doi.org/10.1016/j.tet.2019.130734
0040-4020/© 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

2
E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
Scheme 1. 1,5-syn-(Z)-Stereoselectivity in the reactions of 4-alkoxypent-2-
enylstannanes and aldehydes.
Scheme 4. Reagents and conditions: i, LDA, THF, ꢀ78 ꢁC, 45 min, then RCHO, ꢀ78 ꢁC,
10 min (R ¼ Me, 45%; R ¼ Ph, 23%).
conditions were also unsuccessful and so dehydration of the aldol
adduct 14 or a Wadsworth-Emmons-Horner reaction of phospho-
nate 16 could not be investigated for the synthesis of the allyl-
stannane 17 en route to the SEM-analogue of the target stannane 7
(R1 ¼ Me) see Scheme 4.
In previous work, the allylic displacement of a phenylsulfonyl
group by a tributyltin moiety under free-radical conditions has
proved to be a useful procedure for the synthesis of substituted
allylstannanes [9]. 2-(Hydroxymethyl)propenyl phenyl sulfone (18)
[10] was therefore protected as its tert-butyldimethylsilyl ether 19.
Addition of the lithiated sulfone 19 to freshly distilled acetaldehyde
gave the adduct 20 as a mixture of diastereoisomers. A little sur-
prisingly, the free-radical mediated allylic displacement of the
mixture of sulfones 20 using tributyltin hydride in the presence of a
sub-stoichiometric amount of azo-bis-isobutyronitrile (AIBN) gave
the pent-2-enylstannane 21 predominantly as its (Z)-diastereo-
isomer, (Z) : (E) ¼ 90 : 10 (1H NMR), see Scheme 5.
Scheme 2. Proposed stereoselective synthesis of derivatives of branched triols using
complex allylstannanes.
Apart from hoping that this work would lead to the potentially
interesting products 3, the initial objective was to see whether the
stereoselectivity of the tin(IV) halide mediated reactions of 4-
alkoxyalk-2-enylstannanes was compatible with substituents at
the 2-position. At the onset of the work, (Z)-1,5-anti-selectivity had
been shown for reactions of the 5-(methoxymethoxy)-2,4-
The (Z)-geometry of the major allylstannane 21 was established
by nOe studies. It has been suggested that the free-radical
displacement of an allylic sulfone by a tributyltin radical is a
concerted process in which allylic 1,3-strain is minimised [11]. In
the present case, the formation of the major isomer (Z)-21 by this
mechanism is consistent with the transition structure 24, see Fig. 1,
being preferred over the alternative 25. A non-concerted process
with the tributyltin group of an intermediate tributyltin radical
adduct co-ordinated to the hydroxyl group, see structure 26, is also
consistent with the observed stereoselectivity, but hydroxyl groups
do not usually co-ordinate to tetralkylstannanes [12], see Fig. 1.
The 4-hydroxypent-2-enyl(tributyl)stannane 21 was alkylated
using methoxymethyl chloride to give the required 4-alkoxypent-
2-enylstannane 22. Transmetallation of this allylstannane with
tin(IV) chloride at ꢀ78 ꢁC generated an allyltin trichloride that
reacted with aldehydes highly stereoselectively to give major
dimethylpent-2-enyl(tributyl)stannanes
8 with aldehydes, see
Scheme 3.[2a,5] However, in these reactions the 2-substituent in
the stannane is an unfunctionalised methyl group and so it was not
clear whether or not the stereoselectivity of the reaction would
tolerate a more bulky, functionalised, alkyl group at this site.
It was therefore decided to prepare
alkylsilyloxymethyl)pent-2-enyl(tributyl)stannane
and to study its reactions with aldehydes mediated by tin(IV)
chloride. If successful, the products would be used to prepare more
complex allylstannanes, cf. 5, and the reactivities of these would be
investigated. The results of this study are reported herein [6].
a 4-alkoxy-2-(tri-
7
(R1 ¼ Me),
2. Results and discussion
Preliminary studies of the aldol reactions of ethyl 3-
tributyltinpropanoate 10 [7] with acetaldehyde and benzaldehyde
gave modest yields of the expected adducts 11 and 12, but the
analogous reaction with 2-(trimethylsilylethoxymethoxy)propanal
13 gave only unreacted starting material, see Scheme 4.
Attempts to effect a conjugate addition of tributyltin hydride to
the 2-substituted acrylate 15 [8] under basic and free-radical
Scheme 5. Synthesis and reactions with aldehydes of the 4-alkoxypent-2-
enyl(tributyl)stannane 22. Reagents and conditions: i, TBSCl, imid., CH2Cl2, 0 ꢁC to rt,
15 h (73%); ii, LDA, ꢀ78 ꢁC, 45 min, MeCHO, ꢀ78 ꢁC, 30 min (68%, 55:45 mixture of
diastereoisomers); iii, Bu3SnH, AIBN (cat.), benzene, reflux, 2 h [69%, (Z) : (E) ¼ 90 :10];
i
Scheme 3. (Z)-1,5-anti-stereoselective reactions of aldehydes with 2,4-dimethyl-5-
(methoxymethoxy)pent-2-enylstannane 8.
iv, MOMCl. Pr2NEt, CH2Cl2, 0 ꢁC to rt, 15 h (82%); v, SnCl4, CH2Cl2, ꢀ78 ꢁC, 5 min, add
RCHO, ꢀ78 ꢁC, 30 min (23a, 69%; 23b, 57%; 23c, 62%; 23d, 59%).
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
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E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
3
1,5-syn-products 23, see Fig. 2.
The products 23 correspond to the intermediates 6 in the pro-
posed synthesis of the branched triol derivatives 3. The next stage
was to convert these into the alkenylstannanes 5. To effect this
transformation, the hydroxyl group would need protection as a
trialkylsilyl ether, and the tert-butyldimethylsilyloxy group con-
verted into a tributylstannane.
Fig. 1. Possible transition structures for the selective formation of the (Z)-4-
hydroxypent-2-enylstannane (Z)-21.
As interim protection, the alcohol 23a was converted into its
acetate 33, but removal of the tert-butyldimethylsilyl group was
accompanied by migration of the acetate to give the hydroxyacetate
34, migration of the acetate being confirmed by 1H NMR, see
experimental. Procedures are known for the conversion of primary
allylic acetates into allylstannanes [15] and so the alcohol 34 was
reprotected as its tert-butyldimethylsilyl ether 35, Scheme 7.
However, attempts to convert this allylic acetate into the corre-
sponding tributylstannane were unsuccessful and mixtures of
products were obtained. Saponification of the acetate gave the
primary alcohol 36 which was converted into the mesylate 37 and
hence into the bromide 38, but treatment of these with tributyltin
lithium or bis(tributyltin) oxide, 1,2-dibromoethane and magne-
sium, respectively, under published conditions [16] for the prepa-
ration of allylstannanes gave mixtures of products including
elimination products. The conversion of alcohols into allyl-
stannanes via their xanthates and rearranged dithiocarbonates is
another well recognised procedure [2] and so the alcohol 36 was
converted into the rearranged dithiocarbonate 40 via its xanthate
39. In this case, reaction of the dithiocarbonate with tributyltin
hydride under free-radical conditions gave the required allyl-
stannane 41 in an acceptable yield of 58%, as a 94 : 6 mixture of
geometrical isomers, Scheme 7. Again the major allylstannane 41
was shown to have the (Z)-configuration by nOe possibly due to
some co-ordination of the tributyltin moiety by the MOM-group in
free-radical intermediates, cf. Fig. 1.
products identified as the (E)-1,5-syn-isomers 23 [3], see Scheme 5.
Less than 3% of any other diastereoisomer was detected in the
product mixtures from these reactions.
Structures were assigned to the products 23 on the basis of
precedent and spectroscopic data. To show that the 1,5-syn- and
1,5-anti-diastereoisomers could be distinguished by NMR, the
major reaction product 23b was converted into the inverted 4-
nitrobenzoate 27 using a Mitsunobu reaction, and saponification
gave the 1,5-anti-epimer 28, Scheme 6. The syn- and anti-isomers
23b and 28 were clearly distinguished by 1H NMR, see experi-
mental. The (E)-configuration [3] of the alkenol 23a was confirmed
by 1H nOe. For example, irradiation of the 2-H2 and 3-CH2 caused
significant enhancements of H-5 and H-4, respectively.
Following confirmation of the high (E)-stereoselectivity in the
formation of the major product 23a, the 1,5-syn-configuration was
assigned on the basis of well precedented mechanistic consider-
ations, see Fig. 2. Transmetallation of 4-alkoxyalk-2-enylstannanes
has been shown to be highly stereoselective for the formation of
allyltin trichloride intermediates in which the adjacent vinyl and
methyl substituents are in a trans-relationship with respect to the
four-membered oxastannane ring [2,4]. In the case of the MOM-
protected stannane 22, the expected transmetallation intermedi-
ate would be the epimer 31 formed via transition structure 29. This
stereoselectivity would be expected irrespective of which oxygen of
the MOM-group was co-ordinated to the trichlorotin group [13,14].
Reaction of this intermediate allyltin trichloride with an aldehyde
via the six-membered transition structure 32 that would introduce
the (E)-double-bond into the product, would then give rise to the
This chemistry had led to the synthesis of the complex 2-
substituted alk-2-enylstannane 41, but attempts to effect tin(IV)
chloride promoted reactions of this with aldehydes, including
benzaldehyde and acetaldehyde, were unsuccessful and polymeric
materials were the only products isolated.
It was decided to prepare a second allylstannane corresponding
Scheme 6. Conversion of the 1,5-syn-alkenol 23b into its 1,5-anti-epimer 28. Reagents
and conditions: i, Ph3P, 4-NO2C6H4CO2H, DEAD, THF, rt, 2 h (79%); ii, NaOH, MeOH, rt,
2 h (66%).
Scheme 7. Synthesis and preliminary studies of the pent-2-enyl(tributyl)stannane 41.
Reagents and conditions: i, Ac2O, Et3N, DMAP, CH2Cl2, 0 ꢁC to rt, 1 h (94%); ii, TBAF, THF,
rt, 1 h (60%); iii, TBSOTf, Et3N, CH2Cl2, 0 ꢁC to rt, 90 min (85%); iv, NaOH, MeOH, rt, 1 h
(96%); v, mesyl anhydride, Et3N, CH2Cl2, 0 ꢁC to rt, 3 h (89%); vi, NaBr, DMF, rt, 6 h
(85%); vii, NaH, tol., 0 ꢁC to rt, 90 min, cooled to 0 ꢁC, CS2, 0 ꢁC to rt, 3 h, MeI, rt, 18 h
(63%); viii, tol., reflux, 6 h (ca. 100%); ix, Bu3SnH, AIBN (cat.), tol., reflux, 90 min [58%,
(Z) : (E) ¼ 94:6].
Fig. 2. Participation of the allyltin trichloride 31 in the stereoselective formation of the
homoallylic alcohols 23.
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
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E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
to intermediate 5 to investigate further the proposed stereo-
selective synthesis of the branched target compounds 3. It wasn't
clear why the reactions of the stannane 41 with aldehydes had not
been successful but it was decided to use the acetaldehyde-derived
product 23b to prepare the next allylstannane and the more hin-
dered tert-butyldiphenylsilyl ether for protection of the non-
participating hydroxyl group.
Acetylation of the homoallylic alcohol 23b gave the acetate 43
but on desilylation only partial migration of the acetate group was
observed and attempts to drive it to completion using base were
unsuccessful. However, protection of the alcohol 23b using tert-
butyldiphenylsilyl chloride gave the bis-silylated diol 44 and se-
lective removal of the tert-butyldimethylsilyl group using pyr-
idinium toluene p-sulfonate [17] gave the required primary alcohol
45. This was converted into its xanthate 46 that on heating in
toluene rearranged to give the dithiocarbonate 47 as a mixture of
epimers. The reaction with tributyltin hydride under free-radical
conditions then gave the required allylstannane 48, see Scheme 8.
The geometry of the double-bond in this alkenylstannane was not
confirmed but is shown as the (Z)-isomer by analogy with the
stereoselectivity observed during the formation of the stannanes
22 and 41.
Studies of the tin(IV) chloride mediated reactions of the stan-
nane 48 with aldehydes were not encouraging. Generally polymeric
materials were the main products, and only the attempted reaction
with acetaldehyde gave a very low yield of the alcohol 49. This
product was provisionally identified on the basis of its 1H NMR
spectrum and MS data and by analogy with the earlier work, but
the relative configurations of the stereogenic centres and the ge-
ometry of the double-bond were not formally established, see
Scheme 8.
Scheme 9. Synthesis of tetrahydrofurans 51. Reagents and conditions: i, mesyl anhy-
dride, Et3N, CH2Cl2, 0 ꢁC to rt, 2 h (50b, 91%; 50d, 37%); ii, TBAF, THF, rt, 15 min (51b,
36%; 51d, 43%); iii, mesyl anhydride, Et3N, CH2Cl2, 0 ꢁC to rt, 18 h (51a, 33%; 51c, 24%).
aldehydes that were promoted by tin(IV) chloride have been
investigated. During their syntheses, the free-radical mediated
allylic displacements of sulfur-based leaving groups by the tribu-
tyltin moiety were surprisingly stereoselective for formation of (Z)-
pent-2-enyl(tributyl)stannanes. The 2-(tert-butyldimethylsilylox-
ymethyl)pent-2-enylstannane 22 reacted with aldehydes with
excellent stereoselectivity in favour of formation of (E)-1,5-syn-
alkenols 23 on transmetallation with tin(IV) chloride [3]. However,
the analogous reactions using the 2-(2-tert-butyldimethyl- and 2-
(2-tert-butyldiphenyl-silyloxyalkyl)pent-2-enylstannanes 41 and
48 were unsuccessful and unidentifiable polymeric products were
isolated. Only a trace of the required product 49 was isolated in just
one case.
The different behaviour of these stannanes is difficult to ratio-
nalise. Steric hindrance may be a factor. Another consideration may
be the additional co-ordination of the electron deficient tin in the
trichlorotin intermediates generated by transmetallation of these
stannanes, see Fig. 3. If the tin trichloride is hexa-co-ordinated it
will be unable to co-ordinate to an aldehyde and so unable to react
to give the required products. It is conceivable that the equilibrium
of penta- and hexa-co-ordinated tin trichlorides is biased towards
hexaco-ordination for the allyltin trichlorides 52 but less so for the
allyltin trichloride 31 perhaps because the co-ordination by the
silyloxy groups would involve a five-membered co-ordinated spe-
cies in the latter intermediate. If this is the case, then it is the po-
sition of the silyloxy group that determines the usefulness of the
reactions of the stannanes 22, 41 and 48 with aldehydes [18].
Clearly further work is required to resolve this dichotomy.
Alternative protecting groups will need to be investigated for the
non-participating hydroxyl groups. Perhaps other reaction
Notwithstanding the difficulties in using the complex stannanes
41 and 48 in reactions with aldehydes, aspects of the chemistry of
the homoallylic alcohols 23 prepared from the earlier allylstannane
22 were briefly investigated. In particular, the alcohols 23b and 23d
were converted into their mesylates 50b and 50d. On desilylation
these gave the tetrahydrofurans 51b and 51d, respectively. The
mesylates from the benzylic and allylic alcohols 23a and 23c were
unstable. In these cases the mesylation, desilylation and cyclisation
were carried out in one pot over a period of 18 h, see Scheme 9.
3. Summary and conclusions
The 2-substituted 4-alkoxypent-2-enyl(tributyl)stannanes 22,
41 and 48 have been synthesised and their reactions with
Scheme 8. Synthesis and preliminary study of the pent-2-enyl(tributyl)stannane 48.
Reagents and conditions: i, Ac2O, Et3N, DMAP, CH2Cl2, 0 ꢁC to rt, 1 h (76%); ii, TBDPSCl,
imid., CH2Cl2, rt, 18 h (83%); iii, PPTS, EtOH, rt, 40 ꢁC, 4 h (72%); iv, NaH, THF, rt, 90 min,
CS2, 2 h, MeI, rt, 18 h (70%); v, tol., reflux, 2 h (ca. 100%, 55 : 45 mixture of di-
astereoisomers), vi, Bu3SnH, AIBN (cat.), benzene, reflux 1 h (77%, 70 : 30 mixture of
geometrical isomers); vii, SnCl4, CH2Cl2, ꢀ78 ꢁC, 5 min, MeCHO, CH2Cl2, ꢀ78 ꢁC, 45 min
(1e2%).
Fig. 3. Organotin trichlorides from transmetallation of pent-2-enylstannanes 22, 41
and 48.
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E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
5
conditions will also be investigated, e.g. transmetallation using
tin(IV) bromide. However, the reactions with aldehydes of the
stannane 22 have led to the stereoselective synthesis of the useful
products 23 with control of the geometry of trisubstituted double-
bonds as illustrated in the subsequent syntheses of the 2-
substituted 4-(2-alkoxyalkylidene)tetrahydrofurans 51.
CO2CH2CH3), 1.16 (3H, d, J 6.5, 4-H3) and 1.00e0.66 (17H, m,
3 ꢂ SnCH2CH2CH2CH3 and 2-CH2); dC (75 MHz; CDCl3) 176.3, 71.0,
60.6, 50.0, 29.0, 27.3, 21.2, 14.1, 13.6, 9.2 and 8.5; m/z (CI) 437
(Mþ þ 1, 8%), 379 (Mþ ꢀ 57, 100) and 308 (33).
4.2.2. Ethyl 3-hydroxy-3-phenyl-2-(tri-n-butylstannylmethyl)
propanoate (12)
4. Experimental
Following the procedure given for the preparation of 11, n-
butyllithium (1.4 M in hexanes, 1.0 mL, 1.4 mmol), di-
4.1. General experimental details
isopropylamine (0.2 mL, 1.4 mmol), the b-stannyl ester 10 (0.5 g,
1.28 mmol) and benzaldehyde (0.14 mL, 1.4 mmol) gave the title
compound 12 (147 mg, 23%, a 60 : 40 mixture of diastereoisomers)
as a colourless oil; major diastereoisomer: RF [ether-light petro-
leum (1 : 10)] 0.2 (Found: Mþ ꢀ C4H9, 441.1455. C20H33O1320Sn re-
quires M, 441.1451); nmax (neat)/cmꢀ1 3468, 1720, 1455, 1374, 1339,
1250, 1183, 1156, 1040, 1027 and 699; dH (300 MHz; CDCl3) 7.34 (5H,
m, ArH), 4.97 (1H, dd, J 5.0, 3.2, 3-H), 4.07 (2H, m, CO2CH2), 2.91 (1H,
m, 2-H), 2.74 (1H, d, J 3.2, OH), 1.44 (6H, m, 3 ꢂ SnCH2CH2), 1.29 (6H,
m, 3 ꢂ SnCH2CH2CH2), 1.17 (3H, t, J 7.1, CO2CH2CH3) and 1.16e0.68
(17H, m, 3 ꢂ SnCH2CH2CH2CH3 and 2-CH2); dC (75 MHz; CDCl3)
175.7, 141.7, 128.1, 127.5, 126.1, 75.9, 60.6, 50.5, 29.0, 27.3, 13.9, 13.6,
9.3 and 5.4; m/z (CI) 499 (Mþ þ 1, 25%), 481 (Mþ ꢀ 17, 53), 441
(Mþ ꢀ 57, 100), 335 (75) and 308 (93); minor diastereoisomer: RF
[ether-light petroleum (1 : 10)] 0.1 (Found: Mþ ꢀ C4H9, 441.1444.
Chromatography refers to flash column chromatography using
Merck silica gel 60H (40e63 m, 230e300 mesh). Light petroleum
refers to the fraction boiling between 40 and 60 ꢁC and was redis-
tilled before use. THF was dried over sodium-benzophenone and
distilled under nitrogen prior to use. CH2Cl2 was dried over CaH2
and distilled before use. Ether refers to diethyl ether. Reactions
under non-aqueous conditions were carried out under an atmo-
sphere of nitrogen or argon. Low resolution electron impact (EIþ)
and chemical ionisation mass spectra using ammonia (CIþ) were
recorded using a Micromass Trio 2010 quadrupole mass spec-
trometer. Low resolution electrospray (ES) mass spectra were
recorded on a Micromass Platform mass spectrometer. High solu-
tion mass spectra were recorded on a Kratos Concept-IS spec-
trometer. For organostannanes, peaks corresponding to the 120Sn
isotope are given. Infra-red spectra were measured using an ATI
Mattson Genesis FTIR spectrometer on NaCl plates, either neat or in
nujol. Nuclear magnetic resonance spectra were recorded using
Varian Unity 500 (500 MHz) and Varian INOVA 300 (300 MHz)
spectrometers. Coupling constants (J) are given in Hertz (Hz) and
chemical shifts are relative to tetramethylsilane. Residual non-
deuterated solvent was used as the internal standard.
C
20H33O1320Sn requires M, 441.1451); nmax (neat)/cmꢀ1 3443, 1731,
1455, 1375, 1250, 1180, 1160, 1040 and 700; dH (300 MHz; CDCl3)
7.36 (5H, m, ArH), 4.72 (1H, dd, J 7.3, 5.6, 3-H), 4.15 (2H, m, CO2CH2),
3.08 (1H, d, J 5.6, OH), 2.93 (1H, ddd, J 10.6, 7.3, 5.0, 2-H), 1.43 (6H,
m, 3 ꢂ SnCH2CH2), 1.28 (9H, m, 3 ꢂ SnCH2CH2CH2 and CO2CH2CH3)
and 1.06e0.68 (17H, m, 3 ꢂ SnCH2CH2CH2CH3 and 2-CH2); dC
(75 MHz; CDCl3) 176.2, 142.1, 128.3, 127.7, 126.5, 77.9, 60.7, 50.3,
28.9, 27.3, 14.0, 13.6, 9.1 and 8.6; m/z (CI) 481 (Mþ ꢀ 17, 46%), 441
(Mþ ꢀ 57, 31) and 308 (100).
4.2. Experimental procedures
4.2.3. (S)-2-(2-Trimethylsilylethoxymethoxy)propanal (13)
4.2.1. Ethyl 3-hydroxy-2-(tri-n-butylstannylmethyl)butanoate (11)
n-Butyllithium (1.4 M in hexanes, 1.0 mL, 1.4 mmol) was added
to di-isopropylamine (0.2 mL, 1.4 mmol) in THF (5 mL) at 0 ꢁC and
the mixture stirred for 30 min. The mixture was cooled to ꢀ78 ꢁC,
Powdered activated 4 Å molecular sieves (450 mg), N-methyl-
morpholine N-oxide (222 mg, 1.89 mmol) and TPAP (33 mg,
0.095 mmol) were added to (S)-2-(2-trimethylsilylethoxymethoxy)
propan-1-ol (0.3 g, 1.46 mmol) in CH2Cl2 (5 mL) at rt. After 2 h, the
mixture was filtered through a pad of Celite®, the pad thoroughly
washed with CH2Cl2, and the filtrate concentrated under reduced
pressure. Chromatography of the residue, eluting with ether-light
petroleum (1 : 3), gave the title compound 13 (184 mg, 60%) as a
the b-stannyl ester 10 (0.5 g, 1.28 mmol) in THF (2 mL) was added,
and the mixture was stirred for 45 min at ꢀ78 ꢁC. Freshly distilled
acetaldehyde (79
m
L, 1.41 mmol) in THF (2 mL) was added at ꢀ78 ꢁC
and the mixture stirred for 10 min. Methanol (1 mL) followed by
saturated aqueous ammonium chloride (2 mL) were added, and the
mixture allowed to warm to rt. The mixture was poured into water
(20 mL) and extracted with ether (3 ꢂ 20 mL). The combined
organic extracts were dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue, eluting with
ether-light petroleum (1 : 10), gave the title compound 11 (250 mg,
45%, a 60 : 40 mixture of diastereoisomers) as a colourless oil;
major diastereoisomer: RF [ether-light petroleum (1 : 10)] 0.33
(Found: Mþ ꢀ C4H9, 379.1291. C15H31O1320Sn requires M, 379.1294);
nmax (neat)/cmꢀ1 3442, 1730, 1462, 1374, 1253, 1184, 1105 and 1037;
dH (300 MHz; CDCl3) 4.19 (2H, m, CO2CH2), 3.97 (1H, m, 3-H), 2.63
(1H, dt, J 10.6, 4.8, 2-H), 2.42 (1H, d, J 5.6, OH), 1.49 (6H, m,
3 ꢂ SnCH2CH2), 1.33 (9H, m, 3 ꢂ SnCH2CH2CH2 and CO2CH2CH3),
1.22 (3H, d, J 6.5, 4-H3) and 0.92 (17H, m, 3 ꢂ SnCH2CH2CH2CH3 and
2-CH2); dC (75 MHz; CDCl3) 175.9, 70.2, 60.6, 49.5, 29.0, 27.3, 19.7,
14.1, 13.6, 9.3 and 5.6; m/z (CI) 379 (Mþ ꢀ 57, 100%) and 308 (13);
minor diastereoisomer: RF [ether-light petroleum (1 : 10)] 0.30
(Found: Mþ ꢀ C4H9, 379.1293. C15H31O1320Sn requires M, 379.1294);
nmax (neat)/cmꢀ1 3438,1730,1462,1376,1260,1184, 1136,1112,1070
and 1040; dH (300 MHz; CDCl3) 4.09 (2H, m, CO2CH2), 3.72 (1H, m,
3-H), 2.56 (1H, d, J 6.9, OH), 2.47 (1H, ddd, J 8.4, 7.1, 5.9, 2-H), 1.39
(6H, m, 3 ꢂ SnCH2CH2), 1.23 (9H, m, 3 ꢂ SnCH2CH2CH2 and
colourless oil, RF [ether-light petroleum (1 : 3)] 0.4; [
a
]
20ꢀ18.6 (c
D
1.4, CH2Cl2); nmax (neat)/cmꢀ1 1737, 1378, 1250, 1109, 1061, 1033,
860 and 836; dH (300 MHz; CDCl3) 9.61 (1H, d, J 1.5, CHO), 4.77 and
4,74 (each 1H, d, J 7.1, OCHHO), 4.01 (1H, qd, J 7.0, 1.5, 2-H), 3.66 (2H,
m, OCH2CH2SiMe3), 1.29 (3H, d, J 7.0, 3-H3), 0.91 (2H, m, CH2Si) and
0.00 (9H, s, 3 ꢂ SiCH3); dC (75 MHz; CDCl3) 202.6, 94.3, 78.0, 65.7,
17.9, 15.2 and ꢀ1.6.
4.2.4. 2-(tert-Butyldimethylsilyloxymethyl)-1-(phenylsulfonyl)
prop-2-ene (19)
Imidazole (8.1 g, 0.12 mol) and tert-butyldimethylsilyl chloride
(14.4 g, 95 mmol) were added to 2-(phenylsulfonylmethyl)prop-2-
en-1-ol 18 (16.8 g, 79 mmol) in CH2Cl2 (200 mL) at 0 ꢁC. The
mixture was allowed to warm to rt and left to stir for ca. 15 h. It was
poured into water (200 mL) and the aqueous layer extracted with
CH2Cl2 (1 ꢂ 200 mL). The organic extracts were dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
residue, eluting with ethyl acetate-light petroleum (1 : 10), gave the
title compound 19 (18.8 g, 73%) as a colourless oil (Found: Mþ þ H,
327.1446. C16H27O3SSi requires M, 327.1450); nmax (neat)/cmꢀ1
1652,1586,1471,1463,1447,1320,1310,1255,1156,1129,1103,1085,
838, 778 and 689; dH (300 MHz; CDCl3) 7.82 (2H, m, ArH), 7.59 (1H,
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

6
E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
m, ArH), 7.49 (2H, m, ArH), 5.28 and 4.82 (each 1H, s, 3-H), 4.09 (2H,
s, 2-CH2), 3.77 (2H, s, 1-H2), 0.83 [9H, s, SiC(CH3)3] and 0.00 (6H, s,
2 ꢂ SiCH3); dC (75 MHz; CDCl3) 138.3, 136.4, 133.6, 128.9, 128.4,
119.1, 64.9, 59.4, 25.8, 18.2 and ꢀ5.5; m/z (CI) 344 (Mþ þ 18, 65%)
and 327 (Mþ þ 1, 100).
21 (2.8 g, 5.4 mmol) in CH2Cl2 (60 mL) at 0 ꢁC. The mixture was
allowed to warm to rt and stirred for 15 h. Saturated aqueous
ammonium chloride (5 mL) was added and the mixture stirred for
15 min then diluted with water (50 mL). The aqueous layer was
extracted with CH2Cl2 (1 ꢂ 50 mL) and the organic extracts were
dried (MgSO4) and concentrated under reduced pressure. Chro-
matography of the residue, eluting with ether-light petroleum-
triethylamine (1 : 30 : 0.3), gave the title compound 22 [2.5 g, 82%,
(Z) : (E) ¼ 90 : 10] as a colourless oil (Found: Mþ þ H, 565.3096.
4.2.5. 4-(tert-Butyldimethylsilyloxymethyl)-3-(phenylsulfonyl)
pent-4-en-2-ol (20)
n-Butyllithium (1.65 M in hexanes, 7.0 mL, 11.5 mmol) was
added to di-isopropylamine (1.6 mL, 11.5 mmol) in THF (20 mL) at
0 ꢁC and the mixture stirred for 30 min. The mixture was cooled
to ꢀ78 ꢁC and the sulfone 19 (3.12 g, 9.6 mmol) in THF (30 mL) was
added. After 45 min at ꢀ78 ꢁC, freshly distilled acetaldehyde
(5.4 mL, 96 mmol) was added dropwise. After stirring for 30 min,
methanol (5 mL) was added and the reaction mixture allowed to
warm to rt. The mixture was diluted with water (50 mL) and ether
(50 mL), the aqueous layer was extracted with ether (2 ꢂ 20 mL),
and the organic extracts were dried (MgSO4) and concentrated
under reduced pressure. Chromatography of the residue, eluting
with ethyl acetate-light petroleum (1 : 5), gave the title compound
20 (2.42 g, 68%, an inseparable 55 : 45 mixture of diastereoisomers)
as a colourless viscous oil which solidified slowly on standing, RF
[ethyl acetate-light petroleum (1 : 5)] 0.3 (Found: Mþ þ H, 371.1715.
C
26H57O3Si120Sn requires M, 565.3098); nmax (neat)/cmꢀ1 1657,
1463, 1376, 1252, 1158, 1097, 1031, 838, 777 and 667; dH [300 MHz;
CDCl3; (Z)-isomer]] 5.01 (1H, br d, J 9.1, 3-H), 4.62 and 4.43 (each
1H, d, J 6.6, OCHHO), 4.40 (1H, dq, J 9.1, 6.5, 2-H), 3.89 (2H, m, 5-H2),
3.31 (3H, s, OCH3), 1.92 and 1.51 (each 1H, d, J 11.8, 4-CHH), 1.42 (6H,
m, 3 ꢂ SnCH2CH2), 1.25 (6H, sextet, J 7.5, 3 ꢂ SnCH2CH2CH2), 1.18
(3H, d,
J
6.5, 1-H3), 0.82 [24H, m, SiC(CH3)3 and
3 ꢂ SnCH2CH2CH2CH3] and 0.00 (6H, s, 2 ꢂ SiCH3); dC [75 MHz;
CDCl3; major (Z)-isomer] 143.1, 119.6, 93.1, 67.6, 67.3, 54.9, 29.0,
27.3, 25.9, 21.4, 18.3, 13.6, 10.2, 9.7 and ꢀ5.3; m/z (EI) 445 (2%), 265
(33), 155 (54), 75 (97) and 49 (100).
4.2.8. (3E,1RS,5SR)-3-(tert-Butyldimethylsilyloxymethyl)-5-
methoxymethoxy-1-phenylhex-3-en-1-ol (23a)
C
18H31O4SSi requires M, 371.1712); nmax (nujol)/cmꢀ1 3488, 1639,
Tin(IV) chloride (1.0 M in CH2Cl2, 2.8 mL, 2.8 mmol) was added
to the allylstannane 22 (1.32 g, 2.35 mmol) in CH2Cl2 (25 mL)
at ꢀ78 ꢁC and the mixture stirred for 5 min. Benzaldehyde (0.29 mL
2.8 mmol) in CH2Cl2 (5 mL) was added at ꢀ78 ꢁC and the mixture
stirred for 30 min. Saturated aqueous sodium hydrogen carbonate
(2 mL) was added, and the mixture allowed to warm to rt then
diluted with water (30 mL). The aqueous layer was extracted with
CH2Cl2 (1 ꢂ 30 mL) and the organic extracts dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
residue, eluting with ether-light petroleum-triethylamine (25 : 75:
1), gave the title compound 23a (618 mg, 69%) as a colourless oil, RF
[ether-light petroleum (1 : 3)] 0.3 (Found: Mþ ꢀ CH2OCH3,
336.2129. C19H31O3Si requires M, 336.2121); nmax (neat)/cmꢀ1 3427,
1673, 1603, 1471, 1463, 1453, 1255, 1156, 1098, 1029, 837, 777 and
700; dH (300 MHz; CDCl3) 7.20 (5H, m, ArH), 5.36 (1H, br d, J 9.1, 4-
H), 4.64 (1H, dm, J 9.8, 1-H), 4.58 and 4.44 (each 1H, d, J 6.8,
OCHHO), 4.40 (1H, dq, J 9.1, 6.3, 5-H), 4.10 and 4.00 (each 1H, dd, J
12.5, 1.0, 3-CHH), 3.84 (1H, br d, J 3.5, OH), 3.26 (3H, s, OCH3), 2.50
(1H, br dd, J 14.1, 3.5, 2-H), 2.36 (1H, dd, J 14.1, 9.8, 2-H0),1.12 (3H, d, J
6.3, 6-H3), 0.83 [9H, s, SiC(CH3)3] and 0.01 and 0.00 (each 3H, s,
SiCH3); dC (75 MHz; CDCl3) 144.9, 138.4, 130.5, 128.3, 127.1, 125.4,
93.6, 72.8, 67.6(2), 55.1, 39.7, 25.9, 21.3, 18.3 and ꢀ5.4(2); m/z (CI)
336 (Mþ ꢀ 45, 26%), 213 (60) and 187 (100).
1461,1377,1304,1283,1253,1145,1111,1083, 858, 838, 776 and 686;
dH (500 MHz; CDCl3; major diastereoisomer) 7.87 (2H, m, ArH), 7.67
(1H, m, ArH), 7.56 (2H, m, ArH), 5.38 and 4.97 (each 1H, s, 5-H), 4.53
(1H, m, 2-H), 4.07 (1H, br s, OH), 3.86 and 3.81 (each 1H, br d, J 14.3,
4-CHH), 3.63 (1H, d, J 2.0, 3-H), 1.26 (3H, d, J 6.2, 1-H3), 0.87 [9H, s,
SiC(CH3)3] and 0.00 and ꢀ0.01 (each 3H, s, SiCH3); dH (500 MHz;
CDCl3; minor diastereoisomer) 7.87 (2H, m, ArH), 7.67 (1H, m, ArH),
7.56 (2H, m, ArH), 5.49 (2H, 2 ꢂ s, each 5-H), 4.62 (1H, m, 2-H), 4.12
and 3.93 (each 1H, d, J 13.5, 4-CHH), 3.64 (1H, d, J 3.5, 3-H), 3.50 (1H,
d, J 3.5, OH), 1.29 (3H, d, J 6.5, 1-H3), 0.88 [9H, s, SiC(CH3)3] and 0.04
(6H, 2 ꢂ s, each SiCH3); dC (75 MHz; CDCl3; mixture of di-
astereoisomers) 139.3, 138.1, 137.1, 133.9, 133.8, 129.3, 129.0, 128.9,
128.8, 121.4, 118.0, 73.0, 72.1, 66.9, 65.9, 65.7, 65.0, 25.8, 21.0, 20.9,
18.2, ꢀ5.5 and ꢀ5.6; m/z (CI) 388 (Mþ þ 18, 72%), 371 (Mþ þ 1, 100),
213 (100) and 132 (52).
4.2.6. (E)- and (Z)-5-tert-Butyldimethylsilyloxy-4-(tri-n-
butylstannylmethyl)pent-3-en-2-ol (21)
Pentenol 20 (3.76 g, 10.16 mmol), tri-n-butyltin hydride (5.5 mL,
20.32 mmol) and azobisisobutyronitrile (83 mg, 0.51 mmol) were
taken up benzene (80 mL). The mixture was degassed for 15 min
using argon and then heated under reflux for 2 h under argon. After
being allowed to cool to rt, the mixture was concentrated under
reduced pressure and chromatography of the residue, eluting with
ether-light petroleum-triethylamine (25 : 125: 3), gave the title
compound 21 [3.63 g, 69%, (Z) : (E) ¼ 90 : 10] as a colourless oil, RF
4.2.9. (3E,2SR,6SR)-4-(tert-Butyldimethylsilyloxymethyl)-2-
methoxymethoxyhept-3-en-6-ol (23b)
Following the procedure given for the synthesis of 23a, the
allylstannane 22 (0.5 g, 0.89 mmol), tin(IV) chloride (1.0 M in
CH2Cl2, 1.06 mL, 1.06 mmol) and freshly distilled acetaldehyde
[ether-light petroleum (1
24H52O2Si120Sn requires M, 520.2757); nmax (neat)/cmꢀ1 3358,
:
5)] 0.4 (Found: Mþ, 520.2768.
C
1653, 1463, 1376, 1362, 1253, 1117, 1082, 1050, 1005, 858, 838, 777
and 668; dH [300 MHz; CDCl3; (Z)-isomer] 5.17 (1H, br d, J 8.7, 3-H),
4.46 (1H, m, 2-H), 3.87 (2H, m, 5-H2), 1.76 and 1.61 (each 1H, d, J
11.7, 4-CHH), 1.41 (6H, m, 3 ꢂ SnCH2CH2), 1.23 (9H, m,
3 ꢂ SnCH2CH2CH2 and 1-H3), 0.82 [24H, m, 3 ꢂ SnCH2CH2CH2CH3
and SiC(CH3)3] and 0.00 (6H, s, 2 ꢂ SiCH3); dC [75 MHz; CDCl3; (Z)-
isomer] 141.7, 122.4, 67.5, 64.5, 29.0, 27.3, 25.9, 23.4, 18.4, 13.6, 10.5,
9.7 and ꢀ5.3; m/z (CI) 366 (32%), 213 (100) and 132 (35).
(75 mL, 1.33 mmol) gave the title compound 23b (160 mg, 57%) as a
colourless oil, RF [ether-light petroleum (1 : 2)] 0.2 (Found: Mþ ꢀ
CH3OCH2O, 257.1941. C14H29O2Si requires M, 257.1937); nmax (neat)/
cmꢀ1 3450, 1672, 1463, 1372, 1255, 1157, 1100, 1030, 838, 777 and
670; dH (300 MHz; CDCl3) 5.45 (1H, dm, J 9.5, 3-H), 4.66 and 4.55
(each 1H, d, J 6.8, OCHHO), 4.49 (1H, dq, J 9.5, 6.3, 2-H), 4.13 and
4.06 (each 1H, dd, J 12.5, 1.0, 4-CHH), 3.82 (1H, m, 6-H), 3.54 (1H, br
d, J 3.6, OH), 3.36 (3H, s, OCH3), 2.33 (1H, dd, J 14.1, 2.7, 5-H), 2.18
(1H, dd, J 14.1, 9.5, 5-H0), 1.26 (3H, d, J 6.3, 1-H3), 1.21 (3H, d, J 6.0, 7-
H3), 0.91 [9H, s, SiC(CH3)3] and 0.09 and 0.08 (each 3H, s, SiCH3); dC
(75 MHz; CDCl3) 138.5, 130.2, 93.5, 67.7, 67.6, 66.6, 55.0, 38.9, 25.7,
23.7, 21.2, 18.1, ꢀ5.5 and ꢀ5.6; m/z (CI) 274 (9%) and 125 (100).
4.2.7. (E)- and (Z)-5-tert-Butyldimethylsilyloxy-2-
methoxymethoxy-4-(tri-n-butylstannylmethyl)pent-3-ene (22)
Di-isopropylethylamine (1.88 mL, 10.8 mmol) and chloromethyl
methyl ether (0.61 mL, 8.1 mmol) were added to the allylstannane
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
7
4.2.10. (3E,7E,2SR,6RS)-4-(tert-Butyldimethylsilyloxymethyl)-2-
4.2.13. (3E,2SR,6RS)-4-(tert-Butyldimethylsilyloxymethyl)-2-
methoxymethoxynona-3,7-dien-6-ol (23c)
methoxymethoxyhept-3-en-6-ol (28)
Following the procedure given for the synthesis of 23a, the
allylstannane 22 (250 mg, 0.45 mmol), tin(IV) chloride (1.0 M in
CH2Cl2, 0.53 mL, 0.53 mmol) and (E)-crotonaldehyde (44 mL,
Sodium hydroxide (4 mg, 0.1 mmol) in methanol (0.4 mL) was
added to the 4-nitrobenzoate 27 (40 mg, 0.086 mmol) in methanol
(2 mL) at rt and the mixture stirred for 2 h then concentrated under
reduced pressure. The residue was partitioned between water
(10 mL) and ether (10 mL) and the aqueous layer was extracted
with ether (2 ꢂ 10 mL). The organic extracts were dried (MgSO4)
and concentrated under reduced pressure. Chromatography of the
residue, eluting with ether-light petroleum (1 : 2), gave the title
compound 28 (18 mg, 66%) as a colourless oil, RF [ether-light pe-
troleum (1 : 2)] 0.1 (Found: Mþ þ H, 319.2305. C16H35O4Si requires
M, 319.2304); nmax (neat)/cmꢀ1 3450, 1671, 1463, 1371, 1255, 1157,
1100, 1030, 838, 777 and 669; dH (300 MHz; CDCl3) 5.45 (1H, br d, J
9.3, 3-H), 4.61 and 4.51 (each 1H, d, J 6.8, OCHHO), 4.51 (1H, dq, J 9.3,
6.3, 2-H), 4.09 (2H, br. s, 4-CH2), 3.94 (1H, m, 6-H), 3.35 (3H, s,
OCH3), 2.95 (1H, br d, J 3.6, OH), 2.28 (2H, d, J 6.0, 5-H2), 1.25 and
1.20 (each 3H, d, J 6.3, either 1-H3 or 7-H3), 0.90 [9H, s, SiC(CH3)3]
and 0.08 (6H, s, 2 ꢂ SiCH3); dC (75 MHz; CDCl3) 138.1, 130.8, 93.1,
67.9, 67.1, 66.1, 54.9, 38.7, 25.7, 23.1, 21.1, 18.1 and ꢀ5.6; m/z (CI) 319
(Mþ þ 1, 3%) and 125 (100).
0.53 mmol) gave the title compound 23c (94 mg, 62%) as a colourless
oil, RF [ether-light petroleum (1 : 3)] 0.2 (Found: Mþ þ H, 345.2467.
C
18H37O4Si requires M, 345.2461); nmax (neat)/cmꢀ1 3443, 1672,
1463, 1449, 1388, 1372, 1362, 1254, 1156, 1098, 1030, 836, 776 and
666; dH (300 MHz; CDCl3) 5.69 (1H, dq, J 15.3, 6.5, 8-H), 5.50 (1H,
dd, J 15.3, 1.2, 7-H), 5.44 (1H, d, J 9.4, 3-H), 4.67 and 4.53 (each 1H, d,
J 6.9, OCHHO), 4.49 (1H, dq, J 9.4, 6.3, 2-H), 4.14 (1H, d, J 12.5, 4-
CHH), 4.07 (1H, m, 6-H), 4.07 (1H, d, J 12.5, 4-CHH), 3.36 (3H, s,
OCH3), 2.38 (1H, dd, J 13.9, 3.8, 5-H), 2.25 (1H, dd, J 13.9, 9.3, 5-H0),
1.69 (3H, d, J 6.5, 9-H3), 1.26 (3H, d, J 6.3, 1-H3), 0.91 [9H, s,
SiC(CH3)3] and 0.08 (6H, s, 2 ꢂ SiCH3); dC (75 MHz; CDCl3) 138.2,
134.0, 130.1, 125.9, 93.6, 71.3, 67.7, 67.5, 55.1, 37.4, 25.8, 21.3, 18.3,
17.6, ꢀ5.4 and ꢀ5.5; m/z (CI) 362 (Mþ þ 18, 1%), 345 (Mþ þ 1, 1), 327
(Mþ ꢀ 17, 1) and 151 (100).
4.2.11. (5E,3SR,7RS)-5-(tert-Butyldimethylsilyloxymethyl)-7-
methoxymethoxy-2-methyloct-5-en-3-ol (23d)
4.2.14. (3E,1RS,5SR)-1-Acetoxy-3-(tert-
Following the procedure given for the synthesis of 23a, the
allylstannane 22 (250 mg, 0.44 mmol), tin(IV) chloride (1.0 M
butyldimethylsilyloxymethyl)-5-methoxymethoxy-1-phenylhex-3-
ene (33)
CH2Cl2, 0.53 mL, 0.53 mmol) and 2-methylpropanal (48
m
L,
Acetic anhydride (0.47 mL, 4.97 mmol) was added to the
homoallylic alcohol 23a (894 mg, 2.35 mmol), triethylamine
(2.08 mL, 14.9 mmol) and 4-dimethylaminopyridine (30 mg,
0.25 mmol) in CH2Cl2 (20 mL) at 0 ꢁC. The mixture was allowed to
warm to rt, stirred for 1 h, and then poured into saturated aqueous
sodium hydrogen carbonate (20 mL). The aqueous layer was
extracted with CH2Cl2 (1 ꢂ 20 mL) and the organic extracts were
dried (MgSO4) and concentrated under reduced pressure. Chro-
matography of the residue, eluting with ether-light petroleum (1 :
4), gave the title compound 33 (936 mg, 94%) as a colourless oil, RF
[ether-light petroleum (1 : 4)] 0.3 (Found: Mþ þ NH4, 440.2850.
0.53 mmol) gave the title compound 23d (90 mg, 59%) as a colour-
less oil, RF [ether-light petroleum (1 : 3)] 0.3 (Found: Mþ ꢀ
CH3OCH2O, 285.2250. C16H33O2Si requires M, 285.2250); nmax
(neat)/cmꢀ1 3469, 1672, 1466, 1386, 1364, 1255, 1156, 1099, 1031,
838, 777 and 670; dH (300 MHz; CDCl3) 5.42 (1H, dm, J 9.5, 6-H),
4.70 and 4.54 (each 1H, d, J 6.7, OCHHO), 4.49 (1H, dq, J 9.5, 6.4, 7-
H), 4.17 and 4.07 (each 1H, dd, J 12.5, 1.0, 5-CHH), 3.41 (2H, m, 3-H
and OH), 3.36 (3H, s, OCH3), 2.36 and 2.15 (each 1H, m, 4-H), 1.70
(1H, m, 2-H), 1.28 (3H, d, J 6.4, 8-H3), 0.96 and 0.95 (each 3H, d, J 6.8,
either 1-H3 or 2-CH3), 0.91 [9H, s, SiC(CH3)3] and 0.09 (6H, 2 ꢂ s,
each SiCH3); dC (75 MHz; CDCl3) 139.6, 129.4, 93.4, 75.0, 67.5(2),
55.0, 34.2, 33.2, 25.8, 21.3, 18.3, 18.2, 17.6, ꢀ5.4 and ꢀ5.5; m/z (CI)
302 (7%) and 153 (100).
C
23H42NO5Si requires M, 440.2832); nmax (neat)/cmꢀ1 1742, 1470,
1463, 1454, 1371, 1234, 1156, 1098, 1029, 838, 777 and 700; dH
(500 MHz; CDCl3) 7.31 (5H, m, ArH), 5.86 (1H, t, J 7.5, 1-H), 5.39 (1H,
br d, J 9.5, 4-H), 4.65 and 4.51 (each 1H, d, J 7.0, OCHHO), 4.38 (1H,
dq, J 9.5, 6.1, 5-H), 4.07 and 3.96 (each 1H, dd, J 13.8, 1.3, 3-CHH),
3.38 (3H, s, OCH3), 2.65 (2H, d, J 7.5, 2-H2), 2.07 (3H, s, COCH3), 0.97
(3H, d, J 6.1, 6-H3), 0.91 [9H, s, SiC(CH3)3] and 0.06 (6H, s, 2 ꢂ SiCH3);
dC (75 MHz; CDCl3) 170.0, 140.2, 136.7, 129.0, 128.4, 128.0, 126.5,
93.3, 74.7, 67.1, 66.3, 55.0, 35.3, 25.9, 21.2, 21.0, 18.3 and ꢀ5.4; m/z
(CI) 440 (Mþ þ 18, 33%), 361 (Mþ ꢀ 61, 18) and 301 (100).
4.2.12. (3E,2SR,6RS)-4-(tert-Butyldimethylsilyloxymethyl)-2-
methoxymethoxy-6-(4-nitrophenylcarbonyloxy)hept-3-ene (27)
Triphenylphosphine (62 mg, 0.27 mmol) and the alcohol 23b
(50 mg, 0.16 mmol) in THF (2 mL) were added to 4-nitrobenzoic
acid (29 mg, 0.17 mmol) and diethyl azodicarboxylate (37 mL,
0.24 mmol) in THF (2 mL) at rt. The mixture was stirred for 2 h then
poured into water (10 mL) and extracted with ether (3 ꢂ 10 mL).
The organic extracts were dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue, eluting with
ether-light petroleum (1 : 3), gave the title compound 27 (58 mg,
79%) as a yellow oil, RF [ether-light petroleum (1 : 2)] 0.5 (Found:
Mþ þ NH4, 485.2677. C23H41N2O7Si requires M, 485.2683); nmax
(neat)/cmꢀ11780,1724,1607,1530,1463,1349,1274,1101,1030, 919,
838, 779 and 720; dH (300 MHz; CDCl3) 8.27 and 8.16 (each 2H, m,
ArH), 5.41 (1H, br d, J 9.6, 3-H), 5.36 (1H, m, 6-H), 4.62 (1H, d, J 6.9,
OCHHO), 4.58 (1H, dq, J 9.6, 6.5, 2-H), 4.50 (1H, d, J 6.9, OCHHO),
4.17 and 4.10 (each 1H, dd, J 13.5, 1.5, 4-CHH), 3.37 (3H, s, OCH3),
2.71 (1H, dd, J 14.1, 8.3, 5-H), 2.37 (1H, dd, J 14.1, 5.1, 5-H0), 1.38 (3H,
d, J 6.3, 7-H3), 1.10 (3H, d, J 6.5, 1-H3), 0.89 [9H, s, SiC(CH3)3] 0.04
(6H, 2 ꢂ s, each SiCH3); dC (75 MHz; CDCl3) 163.7, 150.3, 137.5, 135.8,
130.4, 128.6, 123.3, 93.0, 71.1, 66.5, 66.1, 55.0, 34.2, 25.6, 21.3, 20.1,
18.1, ꢀ5.56 and ꢀ5.59; m/z (CI) 485 (Mþ þ 18, 37%), 406 (Mþ ꢀ 61,
60) and 376 (100).
4.2.15. (3E,1RS,5SR)-3-Acetoxymethyl-5-methoxymethoxy-1-
phenylhex-3-en-1-ol (34)
Tetra-n-butylammonium fluoride (1.0 M in THF, 4.4 mL,
4.4 mmol) was added to the acetate 33 (936 mg, 2.22 mmol) in THF
(20 mL) at rt and the mixture stirred for 1 h then poured into water
(20 mL). The mixture was extracted with ether (3 ꢂ 20 mL) and the
organic extracts were dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue, eluting with
ether-light petroleum (1 : 1), gave the title compound 34 (414 mg,
60%) as a colourless oil, RF [ether-light petroleum (1 : 1)] 0.2
(Found: Mþ þ NH4, 326.1960. C17H28NO5 requires M, 326.1967);
nmax (neat)/cmꢀ1 3437, 1736, 1674, 1452, 1372, 1231, 1156, 1094,
1028, 917, 758 and 703; dH (300 MHz; CDCl3) 7.29 (5H, m, ArH), 5.50
(1H, br d, J 9.3, 4-H), 4.80 (1H, dt, J 9.5, 4.5, 1-H), 4.71 (1H, d, J 7.1,
OCHHO), 4.66 (1H, dd, J 13.1, 1.1, 3-CHH), 4.57 (1H, d, J 7.1, OCHHO),
4.53 (1H, dd, J 13.1, 1.1, 3-CHH), 4.45 (1H, dq, J 9.3, 6.3, 5-H), 3.36
(3H, s, OCH3), 3.21 (1H, br d, J 4.5, OH), 2.59 (1H, dd, J 14.4, 9.5, 2-H),
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

8
E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
purification (Found: Mþ þ NH4, 476.2499. C22H42NO6SSi requires
M, 476.2502); nmax (neat)/cmꢀ1 1672, 1604, 1471, 1454, 1359, 1256,
1176, 1157, 1094, 1067, 1031, 936, 919, 836, 778 and 702; dH
(300 MHz; CDCl3) 7.27 (5H, m, ArH), 5.51 (1H, br d, J 9.3, 4-H), 4.79
(1H, t, J 6.6, 1-H), 4.58 and 4.48 (each 1H, d, J 6.9, OCHHO), 4.47 and
4.41 (each 1H, dd, J 11.7, 1.1, 3-CHH), 4.39 (1H, dq, J 9.3, 6.5, 5-H),
3.34 (3H, s, OCH3), 2.95 (3H, s, SO2CH3), 2.60 and 2.50 (each 1H, dd, J
13.8, 6.6, 2-H), 1.07 (3H, d, J 6.5, 6-H3), 0.86 [9H, s, SiC(CH3)3] and
0.00 and ꢀ0.16 (each 3H, s, SiCH3); dC (75 MHz; CDCl3) 144.1, 135.1,
132.1, 128.3, 127.5, 125.9, 93.5, 74.7, 73.7, 67.0, 55.2, 39.1, 37.7, 25.8,
20.8, 18.1, ꢀ4.8 and ꢀ5.1; m/z (CI) 476 (Mþ þ 18, 14%) and 221 (100).
2.44 (1H, dd, J 14.4, 4.5, 2-H0), 2.08 (3H, s, OCOCH3) and 1.12 (3H, d, J
6.3, 6-H3); dC (75 MHz; CDCl3) 170.7, 144.4, 133.6,133.2, 128.4, 127.5,
125.4, 93.9, 72.0, 67.9, 67.4, 55.2, 39.0, 21.1 and 20.9; m/z (CI) 326
(Mþ þ 18, 26%), 264 (40) and 141 (100).
4.2.16. (3E,1RS,5SR)-3-Acetoxymethyl-1-tert-
butyldimethylsilyloxy-5-methoxymethoxy-1-phenylhex-3-ene (35)
Triethylamine (0.56 mL, 4.03 mmol) and tert-butyldimethylsilyl
trifluoromethanesulfonate (0.46 mL, 2.02 mmol) were added to the
alcohol 34 (414 mg, 1.34 mmol) in CH2Cl2 (5 mL) at 0 ꢁC and the
mixture was allowed to warm to rt and stirred for 90 min. Saturated
aqueous ammonium chloride (2 mL), water (20 mL) and CH2Cl2
(20 mL) were added and the aqueous layer extracted with CH2Cl2
(1 ꢂ 20 mL). The organic extracts were dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
residue, eluting with ether-light petroleum (1 : 4), gave the title
compound 35 (483 mg, 85%) as a colourless viscous oil, RF [ether-
light petroleum (1 : 1)] 0.6 (Found: Mþ þ NH4, 440.2846.
4.2.19. (3E,1RS,5SR)-3-Bromomethyl-1-tert-butyldimethylsilyloxy-
5-methoxymethoxy-1-phenylhex-3-ene (38)
Sodium bromide (40 mg, 0.59 mmol) was added in one portion
to the allylic mesylate 37 (67 mg, 0.15 mmol) in N,N-dime-
thylformamide (3 mL) at rt and the reaction mixture stirred for 6 h
then being poured into water (30 mL) and extracted with ether
(3 ꢂ 20 mL). The organic extracts were washed with water
(2 ꢂ 20 mL), dried (MgSO4) and concentrated under reduced pres-
sure to give the title compound 38 (55 mg, 85%) as a colourless oil
which was used without further purification (Found: Mþ þ NH4,
460.1889. C21H39NO739BrSi requires M, 460.1883); nmax (neat)/cmꢀ1
1472, 1463, 1453, 1371, 1255, 1205, 1156, 1094, 1066, 1030, 918, 836,
777 and 701; dH (300 MHz; CDCl3) 7.28 (5H, m, ArH), 5.51 (1H, d, J
9.3, 4-H), 4.80 (1H, t, J 6.7, 1-H), 4.60 and 4.47 (each 1H, d, J 6.7,
OCHHO), 4.35 (1H, dq, J 9.3, 6.3, 5-H), 3.88 and 3.77 (each 1H, d, J
9.6, 3-CHH), 3.35 (3H, s, OCH3), 2.67 (2H, d, J 6.7, 2-H2), 1.06 (3H, d, J
6.3, 6-H3), 0.87 [9H, s, SiC(CH3)3] and 0.02 and ꢀ0.14 (each 3H, s,
SiCH3); dC (75 MHz; CDCl3) 144.3, 136.1, 134.6, 128.1, 127.3, 125.9,
93.4, 74.7, 67.1, 55.1, 39.5, 39.1, 25.7, 20.7, 18.1, ꢀ4.8 and ꢀ5.1; m/z
(CI) 462 (Mþ þ 18, 9%), 460 (Mþ þ 18, 9) and 221 (100).
C
23H42NO5Si requires M, 440.2832); nmax (neat)/cmꢀ1 1744, 1673,
1471, 1453, 1370, 1250, 1227, 1156, 1094, 1067, 1029, 836, 777 and
701; dH (300 MHz; CDCl3) 7.26 (5H, m, ArH), 5.33 (1H, br d, J 9.3, 4-
H), 4.76 (1H, t, J 7.0, 1-H), 4.57 (1H, d, J 6.7, OCHHO), 4.43 (3H, m, 3-
CH2 and OCHHO), 4.29 (1H, dq, J 9.3, 6.3, 5-H), 3.33 (3H, s, OCH3),
2.62 and 2.45 (each 1H, dd, J 13.7, 7.0, 2-H), 2.09 (3H, s, COCH3), 0.92
(3H, d, J 6.3, 6-H3), 0.84 [9H, s, SiC(CH3)3], 0.00 and ꢀ0.15 (each 3H,
s, SiCH3); dC (75 MHz; CDCl3) 170.5, 144.3, 133.8, 131.6, 128.1, 127.3,
125.9, 93.3, 74.5, 67.9, 66.9, 55.0, 39.9, 25.7, 20.9, 20.8, 18.1, ꢀ4.8
and ꢀ5.2; m/z (CI) 440 (Mþ þ 18, 46%) and 221 (100).
4.2.17. (3E,1RS,5SR)-1-tert-Butyldimethylsilyloxy-3-
hydroxymethyl-5-methoxymethoxy-1-phenylhex-3-ene (36)
Sodium hydroxide (44 mg, 1.1 mmol) in methanol (4.4 mL) was
added to the allylic acetate 35 (380 mg, 0.9 mmol) in methanol
(10 mL) at rt and the solution stirred for 60 min then concentrated
under reduced pressure. Water (20 mL) and ether (20 mL) were
added, the aqueous layer was extracted with ether (2 ꢂ 20 mL) and
the organic extracts were dried (MgSO4) and then concentrated
under reduced pressure. Chromatography of the residue, eluting
with ether-light petroleum (1 : 1), gave the title compound 36
(330 mg, 96%) as a colourless oil, RF [ether-light petroleum (1 : 1)]
0.3 (Found: Mþ þ H, 381.2465. C21H37O4Si requires M, 381.2461);
nmax (neat)/cmꢀ1 3447, 1671, 1471, 1453, 1371, 1255, 1156, 1092,
1066,1030, 919, 836, 777 and 701; dH (300 MHz; CDCl3) 7.30 (5H, m,
ArH), 5.36 (1H, br d, J 9.4, 4-H), 4.75 (1H, dd, J 7.7, 5.6, 1-H), 4.54 and
4.45 (each 1H, d, J 6.7, OCHHO), 4.40 (1H, dq, J 9.4, 6.3, 5-H), 4.02
and 3.95 (each 1H, dd, J 14.0, 6.0, 3-CHH), 3.28 (3H, s, OCH3), 2.64
(1H, dd, J 13.9, 5.6, 2-H), 2.50 (1H, dd, J 13.9, 7.7, 2-H0), 2.29 (1H, t, J
6.0, OH), 1.12 (3H, d, J 6.3, 6-H3), 0.87 [9H, s, SiC(CH3)3] and 0.00
and ꢀ0.16 (each 3H, s, SiCH3); dC (75 MHz; CDCl3) 144.4, 139.1, 129.1,
128.1, 127.4, 125.9, 93.3, 75.7, 67.3, 67.1, 55.0, 39.7, 25.7, 21.1,
18.1, ꢀ4.7 and ꢀ5.1; m/z (CI) 381 (Mþ þ 1, 1%), 319 (Mþ ꢀ 61, 1) and
187 (100).
4.2.20. (3E,1RS,5SR)-1-tert-Butyldimethylsilyloxy-5-
methoxymethoxy-3-(methyldithiocarbonyloxy)methyl-1-
phenylhex-3-ene (39)
The allylic alcohol 36 (394 mg, 1.04 mmol) in toluene (5 mL) was
added to a vigorously stirred suspension of sodium hydride (60%
dispersion in mineral oil, 62 mg dispersion, 1.56 mmol) in toluene
(5 mL) at 0 ꢁC. The mixture was allowed to warm to rt, stirred for
90 min, and then cooled to 0 ꢁC. Carbon disulfide (0.25 mL,
4.15 mmol) was added and the mixture allowed to warm to rt then
stirred for 3 h. Iodomethane (0.26 mL, 4.15 mmol) was added, the
mixture was stirred for ca. 18 h and then water (2 mL) was added
cautiously. Water (50 mL) and CH2Cl2 (50 mL) were added and the
aqueous layer was extracted with CH2Cl2 (2 ꢂ 50 mL). The organic
extracts were dried (MgSO4) and concentrated under reduced
pressure. Chromatography of the residue, eluting with ether-light
petroleum (1 : 10), gave the title compound 39 (306 mg, 63%) as a
pale yellow oil, RF [ether-light petroleum (1 : 10)] 0.4 (Found:
Mþ þ NH4, 488.2319). C23H42NO4S2Si requires M, 488.2324); nmax
(neat)/cmꢀ1 1492, 1471, 1453, 1254, 1200, 1156, 1094, 1064, 1031,
836, 777 and 701; dH (300 MHz; CDCl3) 7.27 (5H, m, ArH), 5.41 (1H,
d, J 9.3, 4-H), 5.00 and 4.92 (each 1H, d, J 12.6, 3-CHH), 4.78 (1H, t, J
6.8,1-H), 4.57 and 4.45 (each 1H, d, J 6.7, OCHHO), 4.30 (1H, dq, J 9.3,
6.3, 5-H), 3.34 (3H, s, OCH3), 2.67 (1H, dd, J 13.7, 6.8, 2-H), 2.58 (3H,
s, SCH3), 2.50 (1H, dd, J 13.7, 6.8, 2-H0), 0.93 (3H, d, J 6.3, 6-H3), 0.86
([9H, s, SiC(CH3)3] and 0.00 and ꢀ0.15 (each 3H, s, SiCH3); dC
(75 MHz; CDCl3) 215.3, 144.2, 133.7, 133.0, 128.1, 127.3, 126.0, 93.4,
77.4, 74.5, 66.8, 55.1, 40.0, 25.8, 20.7, 19.0, 18.1, ꢀ4.8 and ꢀ5.1; m/z
(CI) 488 (Mþ þ 18, 2%), 409 (Mþ ꢀ 61, 6) and 221 (100).
4.2.18. (3E,1RS,5SR)-1-tert-Butyldimethylsilyloxy-3-
methanesulfonyloxymethyl-5-methoxymethoxy-1-phenylhex-3-ene
(37)
Methanesulfonic anhydride (188 mg, 1.08 mmol) was added to
the allylic alcohol 36 (205 mg, 0.54 mmol) and triethylamine
(0.4 mL, 2.70 mmol) in CH2Cl2 (5 mL) at 0 ꢁC. The mixture was
allowed to warm to rt, stirred for 3 h, then poured into saturated
aqueous sodium hydrogen carbonate (20 mL) and extracted with
CH2Cl2 (2 ꢂ 10 mL). The organic extracts were dried (MgSO4) and
concentrated under reduced pressure to give the title compound 37
(220 mg, 89%) as a brown oil which was used without further
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
9
4.2.21. (1RS,5SR)-1-tert-Butyldimethylsilyloxy-5-methoxymethoxy-
3-methylene-4-(methylthiocarbonyl)thio-1-phenylhexane (40)
The allylic xanthate 39 (70 mg, 0.15 mmol) in toluene (2 mL) was
heated under reflux for 6 h and the solution then allowed to cool to
rt and concentrated under reduced pressure to give the title com-
pound 40 (70 mg, ca. 100%, a 55 : 45 mixture of diastereoisomers) as
requires M, 378.2676); nmax (neat)/cmꢀ1 1739, 1463, 1372, 1241,
1158, 1098, 1032, 838 and 777; dH (300 MHz; CDCl3) 5.44 (1H, br d, J
9.3, 3-H), 5.01 (1H, sextet, J 6.3, 6-H), 4.62 (1H, d, J 6.6, OCHHO), 4.54
(1H, dq, J 9.3, 6.3, 2-H), 4.49 (1H, d, J 6.6, OCHHO), 4.12 and 4.04
(each 1H, dd, J 14.0, 1.5, 4-CHH), 3.36 (3H, s, OCH3), 2.33 (2H, m, 5-
H2), 2.01 (3H, s, CH3CO), 1.26 (3H, d, J 6.3, 1-H3), 1.20 (3H, d, J 6.3, 7-
H3), 0.89 [9H, s, SiC(CH3)3] and 0.05 (6H, s, 2 ꢂ SiCH3); dC (75 MHz;
CDCl3) 170.3, 137.5, 128.2, 93.1, 69.6, 67.0, 66.1, 54.9, 34.2, 25.7, 21.2,
21.1, 19.8, 18.1 and ꢀ5.6(2); m/z (CI) 378 (Mþ þ 18, 21%) and 299
(Mþ ꢀ 61, 100).
a
pale yellow oil used without further purification (Found:
Mþ þ NH4, 488.2330. C23H42NO4S2Si requires M, 488.2324); nmax
(neat)/cmꢀ1 1730, 1644, 1471, 1453, 1375, 1361, 1255, 1151, 1089,
1068, 1035, 863, 837, 777 and 701; dH (300 MHz; CDCl3; major
diastereoisomer) 7.27 (5H, m, ArH), 5.16 and 5.00 (each 1H, br s, 3-
CHH), 4.84 (1H, m,1-H), 4.63 (2H, m, OCH2O), 4.42 (1H, d, J 4.7, 4-H),
3.98 (1H, qd, J 6.3, 4.7, 5-H), 3.38 (3H, s, OCH3), 2.56 (1H, m, 2-H),
2.43 (3H, s, SCH3), 2.42 (1H, m, 2-H0), 1.20 (3H, d, J 6.3, 6-H3), 0.86
[9H, s, SiC(CH3)3] and 0.03 and ꢀ0.21 (each 3H, s, SiCH3); dH
(300 MHz; CDCl3; minor diastereoisomer) 7.27 (5H, m, ArH), 5.09
and 4.97 (each 1H, br s, 3-CHH), 4.84 (1H, m, 1-H), 4.63 (2H, m,
OCH2O), 4.24 (1H, d, J 5.8, 4-H), 3.90 (1H, quin, J 5.8, 5-H), 3.36 (3H,
s, OCH3), 2.56 (1H, m, 2-H), 2.44 (3H, s, SCH3), 2.42 (1H, m, 2-H0),
1.17 (3H, d, J 5.8, 6-H3), 0.85 [9H, s, SiC(CH3)3] and 0.01 and ꢀ0.21
(each 3H, s, SiCH3); dC (75 MHz; CDCl3; mixture of di-
astereoisomers) 189.1, 188.9, 145.1, 144.8, 142.1, 141.3, 128.0, 127.9,
127.1, 127.0, 126.21, 126.18, 117.9, 117.1, 95.3(2), 74.2, 74.0, 73.8, 55.7,
55.6, 55.3, 46.7, 46.2, 25.8, 18.4, 18.1, 17.9, 13.1, ꢀ4.6, ꢀ4.7, ꢀ5.0
and ꢀ5.1; m/z (CI) 488 (Mþ þ 18, 1%), 339 (40) and 221 (100).
4.2.24. (3E,2SR,6SR)-4-tert-Butyldimethylsilyloxymethyl-6-tert-
butyldiphenylsilyloxy-2-methoxymethoxyhept-3-ene (44)
Imidazole (51 mg, 0.76 mmol) and tert-butyldiphenylsilyl chlo-
ride (0.17 mL, 0.65 mmol) were added to the homoallylic alcohol
23b (160 mg, 0.5 mmol) in CH2Cl2 (5 mL) at rt and the mixture
stirred for 18 h before being poured into water (20 mL) and
extracted with CH2Cl2 (2 ꢂ 20 mL). The organic extracts were dried
(MgSO4) and concentrated under reduced pressure. Chromatog-
raphy of the residue, eluting with ether-light petroleum (1 : 10),
gave the title compound 44 (230 mg, 83%) as a colourless oil, RF
[ether-light petroleum (1 : 10)] 0.4 (Found: Mþ þ NH4, 574.3743.
C
32H56NO4Si2 requires M, 574.3748); nmax (neat)/cmꢀ1 1589, 1471,
1463, 1428, 1376, 1362, 1254, 1157, 1104, 1031, 837 and 703; dH
(300 MHz; CDCl3) 7.68 (4H, m, ArH), 7.39 (6H, m, ArH), 5.38 (1H, br
d, J 9.5, 3-H), 4.56 and 4.42 (each 1H, d, J 6.6, OCHHO), 4.39 (1H, dq, J
9.5, 6.1, 2-H), 3.94 (1H, m, 6-H), 3.83 (2H, m, 4-CH2), 3.31 (3H, s,
OCH3), 2.29 (1H, dd, J 13.5, 8.3, 5-H), 2.12 (1H, dd, J 13.5, 5.1, 5-H0),
1.16 (3H, d, J 6.1, 1-H3), 1.06 [9H, s, SiPh2C(CH3)3], 1.02 (3H, d, J 6.1, 7-
H3), 0.86 [9H, s, SiMe2C(CH3)3] and ꢀ0.01 and ꢀ0.02 (each 3H, s,
SiCH3); dC (75 MHz; CDCl3) 138.5, 135.7, 134.3, 134.0, 129.4, 129.3,
127.3(2), 126.6, 93.0, 68.5, 67.0, 65.9, 54.8, 38.2, 26.8, 25.7, 22.7, 21.2,
18.9, 18.1 and ꢀ5.6; m/z (CI) 574 (Mþ þ 18, 27%), 495 (Mþ ꢀ 61, 38)
and 239 (100).
4.2.22. (3E,1RS,5SR)- and (3Z,1RS,5SR)-1-tert-
Butyldimethylsilyloxy-5-methoxymethoxy-1-phenyl-3-(tri-n-
butylstannylmethyl)hex-3-ene (41)
A solution of the dithiocarbonate 40 (150 mg, 0.319 mmol), tri-
n-butyltin hydride (129 mL, 0.479 mmol) and azobisisobutyronitrile
(2.6 mg, 0.016 mmol) in toluene (2 mL) was degassed for 15 min
using argon then heated under reflux for 90 min under nitrogen.
After being allowed to cool to rt, the mixture was concentrated
under reduced pressure and chromatography of the residue, eluting
with ether-light petroleum-triethylamine (1 : 50: 0.5), gave the title
compound 41 [120 mg, 58%, (Z): (E) ¼ 94 : 6] as a colourless oil, RF
[ether-light petroleum (1 : 30)] 0.2; nmax (neat)/cmꢀ1 1642, 1463,
1375, 1362, 1251, 1156, 1096, 1070, 1031, 836, 776, 699 and 664; dH
[500 MHz; C6D6; (Z)-isomer] 7.33 and 7.15 (each 2H, m, ArH), 7.03
(1H, m, ArH), 4.92 (1H, d, J 8.9, 4-H), 4.88 (1H, t, J 6.5, 1-H), 4.66 (1H,
d, J 6.6, OCHHO), 4.59 (1H, dq, J 8.9, 6.5, 5-H), 4.41 (1H, d, J 6.6,
OCHHO), 3.22 (3H, s, OCH3), 2.55 and 2.36 (each 1H, m, 2-H), 2.10
and 1.90 (each 1H, d, J 11.6, 3-CHH),1.56 (6H, m, 3 ꢂ SnCH2CH2),1.35
(9H, m, 3 ꢂ SnCH2CH2CH2 and 6-H3], 0.96 [9H, s, SiC(CH3)3], 0.95
(6H, m, 3 ꢂ SnCH2), 0.93 (9H, t, J 7.2, 3 ꢂ SnCH2CH2CH2CH3) and
0.09 and ꢀ0.12 (each 3H, s, SiCH3); dC [75 MHz; C6D6; (Z)-isomer]
145.1, 139.8, 127.8, 126.9, 125.9, 125.0, 92.7, 75.3, 67.1, 54.3, 51.0,
29.0, 27.3, 25.6, 21.4, 17.8, 14.5, 13.3, 9.5, ꢀ4.9 and ꢀ5.3; m/z (ESþ)
693 (Mþ þ K, 7%) and 111 (100).
4.2.25. (3E,2SR,6SR)-6-tert-Butyldiphenylsilyloxy-4-
hydroxymethyl-2-methoxymethoxyhept-3-ene (45)
Pyridinium toluene p-sulfonate (56 mg, 0.221 mmol) was added
in one portion to the bis-silyl ether 44 (410 mg, 0.74 mmol) in ab-
solute ethanol (5 mL) at rt and the mixture stirred at 40 ꢁC for 4 h.
After being allowed to cool to rt and concentrated under reduced
pressure, water (10 mL) and ether (10 mL) were added, and the
aqueous layer was extracted with ether (2 ꢂ 10 mL). The organic
extracts were dried (MgSO4) and concentrated under reduced
pressure. Chromatography of the residue, eluting with ether-light
petroleum (3 : 2), gave the title compound 45 (236 mg, 72%) as a
colourless viscous oil, RF [ether-light petroleum (3 : 2)] 0.4 (Found:
M
þ ꢀ CH3OCH2 þ H, 398.2283. C24H34O3Si requires M, 398.2277);
nmax (neat)/cmꢀ1 3415, 1671, 1590, 1473, 1428, 1376, 1157, 1104,
1032, 822 and 703; dH (300 MHz; CDCl3) 7.69 (4H, m, ArH), 7.41 (6H,
m, ArH), 5.38 (1H, br d, J 9.3, 3-H), 4.57 and 4.45 (each 1H, d, J 6.6,
OCHHO), 4.38 (1H, dq, J 9.3, 6.3, 2-H), 3.96 (3H, m, 4-CH2 and 6-H),
3.30 (3H, s, OCH3), 2.36 (1H, dd, J 14.0, 6.5, 5-H), 2.26 (1H, dd, J 14.0,
5.9, 5-H0), 2.16 (1H, br s, OH), 1.17 (3H, d, J 6.3, 1-H3), 1.06 [9H, s,
SiC(CH3)3] and 1.04 (3H, d, J 6.3, 7-H3); dC (75 MHz; CDCl3) 138.8,
135.7, 133.9, 133.5, 129.6, 129.5, 129.1, 127.4(2), 93.1, 69.0, 66.9, 54.9,
37.9, 26.8, 22.6, 21.1 and 18.9; m/z (CI) 381 (Mþ ꢀ 61, 33%) and 125
(100).
4.2.23. (3E,2SR,6SR)-6-Acetoxy-4-tert-
butyldimethylsilyloxymethyl-2-methoxymethoxyhept-3-ene (43)
Acetic anhydride (73 mL, 0.77 mmol) was added to the homo-
allylic alcohol 23b (120 mg, 0.38 mmol), triethylamine (0.27 mL,
1.9 mmol) and 4-dimethylaminopyridine (5 mg, 0.04 mmol) in
CH2Cl2 (2 mL) at 0 ꢁC and the mixture was allowed to warm to rt
and stirred for 1 h. Saturated aqueous sodium hydrogen carbonate
(10 mL) was added and the mixture extracted with CH2Cl2
(2 ꢂ 10 mL). The organic extracts were dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
residue, eluting with ether-light petroleum (1 : 4), gave the title
compound 43 (105 mg, 76%) as a colourless oil, RF [ether-light pe-
troleum (1 : 4)] 0.3 (Found: Mþ þ NH4, 378.2679. C18H40NO5Si
4.2.26. (3E,2SR,6SR)-6-tert-Butyldiphenylsilyloxy-2-
methoxymethoxy-4-(methyldithiocarbonyloxy)methylhept-3-ene
(46)
Following the procedure outlined for the synthesis of xanthate
39, the allylic alcohol 45 (236 mg, 0.534 mmol) in THF (2 mL),
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

10
E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
sodium hydride (60% dispersion in mineral oil, 32 mg dispersion,
0.8 mmol) in THF (2 mL), carbon disulfide (0.13 mL, 2.14 mmol) and
iodomethane (0.13 mL, 2.14 mmol) with extraction using ether
(3 ꢂ 15 mL) and chromatography, eluting with ether-light petro-
leum (1 : 5), gave the title compound 46 (200 mg, 70%) as a pale
yellow oil, RF [ether-light petroleum (1 : 5)] 0.4 (Found: Mþ þ NH4,
550.2483. C28H44NO4S2Si requires M, 550.2481); nmax (neat)/cmꢀ1
1589, 1471, 1449, 1427, 1376, 1212, 1192, 1103, 1077, 1060, 1031, 918,
822, 739 and 703; dH (300 MHz; CDCl3) 7.68 (4H, m, ArH), 7.40 (6H,
m, ArH), 5.45 (1H, br d, J 9.3, 3-H), 4.92 and 4.85 (each 1H, dd, J 12.8,
1.1, 4-CHH), 4.57 and 4.45 (each 1H, d, J 6.8, OCHHO), 4.41 (1H, dq, J
9.3, 6.3, 2-H), 4.00 (1H, m, 6-H), 3.32 (3H, s, OCH3), 2.51 (3H, s,
SCH3), 2.41 (1H, dd, J 13.7, 7.8, 5-H), 2.28 (1H, dd, J 13.7, 5.7, 5-H0),
1.18 (3H, d, J 6.3, 1-H3), 1.06 [9H, s, SiC(CH3)3] and 1.04 (3H, d, J 7.2,
7-H3); dC (75 MHz; CDCl3) 214.9, 135.7, 135.6, 134.1, 133.7, 133.2,
133.1,129.5,129.4,127.4,127.3, 93.3, 76.8, 68.3, 66.9, 55.0, 38.3, 26.8,
22.8, 20.9, 18.9 and 18.8; m/z (CI) 550 (Mþ þ 18, 100%), 471
(Mþ ꢀ 61, 83), 425 (31) and 283 (76).
4-CHH), 1.31 (9H, m, 3 ꢂ SnCH2CH2CH2 and 1-H3), 1.16 [12H, m,
SiC(CH3)3 and 7-H3] and 0.90 (15H, m, 3 ꢂ SnCH2CH2CH2CH3); dH
[300 MHz; C6D6; (E)-isomer] 7.80 (4H, m, ArH), 7.20 (6H, m, ArH),
5.08 (1H, d, J 9.5, 3-H), 4.78 (1H, d, J 6.8, OCHHO), 4.48 (1H, dq, J 9.5,
6.3, 2-H), 4.44 (1H, d, J 6.8, OCHHO), 4.19 (1H, m, 6-H), 3.16 (3H, s,
OCH3), 2.42 and 2.14 (1H, m, 5-H), 1.79 and 1.72 (each 1H, d, J 11.6,
4-CHH), 1.50 (6H, m, 3 ꢂ SnCH2CH2), 1.31 (9H, m, 3 ꢂ SnCH2CH2CH2
and 1-H3), 1.16 [12H, m, SiC(CH3)3 and 7-H3] and 0.90 (15H, m,
3 ꢂ SnCH2CH2CH2CH3); dC (75 MHz; C6D6; mixture of isomers)
141.2, 140.9, 136.3, 135.1, 134.7, 129.9, 127.9, 125.2, 124.8, 93.2, 93.1,
69.6, 69.2, 67.6, 67.5, 54.8, 50.4, 43.1, 29.6, 29.5, 27.3, 23.54, 23.50,
22.3, 22.0, 21.1, 19.5, 19.4, 14.6, 13.9, 10.0 and 9.8; m/z (ESþ) 739
(Mþ þ Na, 15%), 655 (24) and 332 (100).
4.2.29. (3E,2SR,20SR,6SR)-4-[2-(tert-Butyldiphenylsilyloxy)propyl]-
2-methoxymethoxyhept-3-en-6-ol (49)
Tin(IV) chloride (1.0 M in CH2Cl2, 0.17 mL, 0.17 mmol) was added
to the allylstannane 48 (100 mg, 0.14 mmol) in CH2Cl2 (2 mL)
at ꢀ78 ꢁC and the mixture stirred for 5 min. Freshly distilled acet-
aldehyde (15
m
L, 0.28 mmol) in CH2Cl2 (1 mL) was added at ꢀ78 ꢁC
4.2.27. (2SR,3SR,6SR)- and (2SR,3RS,6SR)-6-tert-
Butyldiphenylsilyloxy-2-methoxymethoxy-4-methylene-3-
(methylthiocarbonyl)thioheptane (47)
and the mixture stirred for 45 min at ꢀ78 ꢁC. Saturated aqueous
sodium hydrogen carbonate (2 mL) was added, and the mixture
allowed to warm to rt, poured into water (10 mL) and extracted
with CH2Cl2 (3 ꢂ 10 mL). The organic extracts were dried (MgSO4)
and concentrated under reduced pressure. Chromatography of the
residue, eluting with ether-light petroleum-triethylamine (50 : 50:
1), gave the title compound 49 (ca. 1 mg, 1%) as a colourless gum, RF
[ether-light petroleum (1 : 1)] 0.2; dH (300 MHz; CDCl3) 7.67 (4H, m,
ArH), 7.40 (6H, m, ArH), 5.16 (1H, br d, J 9.0, 3-H), 4.69 and 4.54
(each 1H, d, J 6.9, OCHHO), 4.43 (1H, dq, J 9.0, 6.3, 2-H), 3.97 (1H,
sextet, J 6.3, either 6-H or 20-H), 3.60 (1H, m, either 6-H or 20-H),
3.34 (3H, s, OCH3), 2.19 (2H, m, either 5-H2 or 10-H2), 2.11 (1H, dd, J
14.0, 9.1, either 5-H or 10-H), 1.97 (1H, dd, J 14.0, 3.8, either 5-H0 or
10-H0), 1.25 (1H, s, OH), 1.19 (3H, d, J 6.3, 1-H3), 1.06 (6H, d, J 6.0, 7-H3
and 30-H3) and 1.04 [9H, s, SiC(CH3)3]; m/z (ESþ) 493 (Mþ þ Na,
100%), 409 (16) and 283 (45).
The allylic xanthate 46 (200 mg, 0.38 mmol) in toluene (5 mL)
was heated under reflux for 2 h and the solution allowed to cool to
rt then concentrated under reduced pressure to give the title
compound 47 (200 mg, ca. 100%, a 55 : 45 mixture of di-
astereoisomers) as a pale yellow oil that was used without further
purification (Found: Mþ þ NH4, 550.2471. C28H44NO4S2Si requires
M, 550.2481); nmax (neat)/cmꢀ1 1645, 1471, 1427, 1377, 1107, 1034,
917, 866, 822, 739 and 703; dH (500 MHz; CDCl3; major diastereo-
isomer) 7.70 (4H, m, ArH), 7.41 (6H, m, ArH), 5.14 and 4.92 (each 1H,
s, 4-CHH), 4.56 and 4.53 (each 1H, d, J 6.9, OCHHO), 4.21 (1H, d, J 4.9,
3-H), 4.12 (1H, m, 6-H), 3.84 (1H, m, 2-H), 3.33 (3H, s, OCH3), 2.40
(3H, s, SCH3), 2.40 and 2.21 (each 1H, m, 5-H), 1.13 (3H, d, J 6.4, 1-
H3), 1.11 (3H, d, J 6.0, 7-H3) and 1.06 [9H, s, SiC(CH3)3]; dH
(500 MHz; CDCl3; minor diastereoisomer) 7.70 (4H, m, ArH), 7.41
(6H, m, ArH), 5.10 and 4.93 (each 1H, s, 4-CHH), 4.61 and 4.57 (each
1H, d, J 6.9, OCHHO), 4.19 (1H, d, J 6.0, 3-H), 4.07 (1H, m, 6-H), 3.84
(1H, m, 2-H), 3.35 (3H, s, OCH3), 2.41 (3H, s, SCH3), 2.40 (1H, m, 5-
H), 2.21 (1H, m, 5-H0), 1.18 (3H, d, J 6.2, 1-H3), 1.09 (3H, d, J 6.2, 7-H3)
and 1.06 [9H, s, SiC(CH3)3]; dC (75 MHz; CDCl3; mixture of di-
astereoisomers) 188.9, 188.8, 142.8, 142.2, 135.8, 134.6(2), 134.3,
134.1, 129.5, 129.4, 129.0, 128.2, 127.5, 127.4, 125.2, 116.9, 116.6, 95.5,
74.3, 73.6, 68.4, 68.1, 56.0, 55.7, 55.6, 55.4, 45.2, 45.0, 27.0, 23.0, 22.9,
19.2, 18.7, 17.9 and 13.1; m/z (CI) 550 (Mþ þ 18, 32%), 533 (Mþ þ 1, 6)
and 283 (100).
4.2.30. (3E,2SR,6SR)-4-tert-Butyldimethylsilyloxymethyl-6-
methanesulfonyloxy-2-methoxymethoxyhept-3-ene (50b)
Methanesulfonic anhydride (66 mg, 0.38 mmol) was added to
the homoallylic alcohol 23b (60 mg, 0.19 mmol) and triethylamine
(0.13 mL, 0.95 mmol) in CH2Cl2 (5 mL) at 0 ꢁC and the mixture
allowed to warm to rt then stirred for 2 h. After concentration
under reduced pressure, saturated aqueous sodium hydrogen car-
bonate (10 mL) and ether (10 mL) were added and the aqueous
layer extracted with ether (2 ꢂ 10 mL). The organic extracts were
dried (MgSO4) and concentrated under reduced pressure to afford
the title compound 50b (68 mg, 91%) as a colourless oil that was
used without further purification, RF [ether-light petroleum (1 : 2)]
0.2 (Found: Mþ þ NH4, 414.2340. C17H40NO6SSi requires M,
414.2345); nmax (neat)/cmꢀ1 1674, 1463, 1358, 1255, 1176, 1099,
1031, 920, 838, 779 and 671; dH (300 MHz; CDCl3) 5.48 (1H, br d, J
9.1, 3-H), 4.96 (1H, m, 6-H), 4.63 and 4.51 (each 1H, d, J 6.9, OCHHO),
4.50 (1H, dq, J 9.1, 6.1, 2-H), 4.13 and 4.06 (each 1H, dd, J 13.3, 1.1, 4-
CHH), 3.35 (3H, s, OCH3), 2.98 (3H, s, SO2CH3), 2.53 (1H, dd, J 14.0,
7.6, 5-H), 2.40 (1H, dd, J 14.0, 6.6, 5-H0), 1.40 (3H, d, J 6.1, 1-H3), 1.26
(3H, d, J 6.6, 7-H3), 0.90 [9H, s, SiC(CH3)3] and 0.06 (6H, s,
2 ꢂ SiCH3); dC (75 MHz; CDCl3) 136.2, 130.1, 93.5, 78.5, 67.4, 66.8,
55.1, 38.3, 35.3, 25.8, 21.3, 18.2, ꢀ5.4 and ꢀ5.5; m/z (CI) 414
(Mþ þ 18, 21%), 335 (Mþ ꢀ 61, 44) and 125 (100).
4.2.28. (3E,2SR,6SR)- and (3Z,2SR,6SR)-6-tert-
Butyldiphenylsilyloxy-2-methoxymethoxy-4-(tri-n-
butylstannylmethyl)hept-3-ene (48)
A solution of the dithiocarbonate 47 (58 mg, 0.11 mmol), tri-n-
butyltin hydride (44 mL, 0.164 mmol) and azobisisobutyronitrile
(2 mg, 0.01 mmol) in benzene (2 mL) was degassed for 15 min using
argon. The mixture was then heated under reflux for 1 h, allowed to
cool to rt and concentrated under reduced pressure. Chromatog-
raphy of the residue, eluting with ether-light petroleum-triethyl-
amine (1 : 30: 0.3), gave the title compound 48 [60 mg, 77%, a 70 : 30
mixture of (Z) and (E)-isomers] as a colourless oil, RF [ether-light
petroleum (1 : 30)] 0.4; nmax (neat)/cmꢀ1 1642, 1590, 1463, 1427,
1375, 1108, 1030, 998, 917, 822, 739 and 702; dH [300 MHz; C6D6;
(Z)-isomer] 7.80 (4H, m, ArH), 7.20 (6H, m, ArH), 4.94 (1H, d, J 9.2, 3-
H), 4.76 (1H, d, J 6.6, OCHHO), 4.57 (1H, dq, J 9.2, 6.3, 2-H), 4.43 (1H,
d, J 6.6, OCHHO), 4.19 (1H, m, 6-H), 3.19 (3H, s, OCH3), 2.42 (1H, m,
5-H), 2.14 (2H, m, 5-H0 and 4-CHH), 1.50 (7H, m, 3 ꢂ SnCH2CH2 and
4.2.31. (3E,2SR,6RS)-4-tert-Butyldimethylsilyloxymethyl-6-
methanesulfonyloxy-2-methoxymethoxy-7-methyloct-3-ene (50d)
Following the procedure outlined for the synthesis of mesylate
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
11
50b, the homoallylic alcohol 23d (76 mg, 0.22 mmol), meth-
anesulfonic anhydride (77 mg, 0.44 mmol) and triethylamine
(0.15 mL, 1.1 mmol) gave the title compound 50d (34 mg, 37%) as a
colourless oil, RF [ether-light petroleum (1 : 2)] 0.4 (Found:
Mþ þ NH4, 442.2650. C19H44NO6SSi requires M, 442.2658); nmax
(neat)/cmꢀ1 1673, 1471, 1359, 1255, 1175, 1098, 1031, 907, 838, 778
and 666; dH (300 MHz; CDCl3) 5.48 (1H, br d, J 9.3, 3-H), 4.74 (1H,
ddd, J 9.2, 5.6, 3.7, 6-H), 4.65 and 4.53 (each 1H, d, J 6.8, OCHHO),
4.50 (1H, dq, J 9.3, 6.3, 2-H), 4.16 and 4.07 (each 1H, dd, J 13.5, 1.2, 4-
CHH), 3.35 (3H, s, OCH3), 2.98 (3H, s, SO2CH3), 2.43 (2H, m, 5-H2),
2.02 (1H, m, 7-H),1.27 (3H, d, J 6.3,1-H3), 1.02 and 0.98 (each 3H, d, J
6.9, either 7-CH3 or 8-H3), 0.90 [9H, s, SiC(CH3)3] and 0.06 (6H, s,
2 ꢂ SiCH3); dC (75 MHz; CDCl3) 136.7, 129.8, 93.6, 86.7, 67.5, 66.6,
55.0, 38.4, 31.9, 29.3, 25.8, 21.3, 18.2,17.7, 17.0 and ꢀ5.4; m/z (CI) 442
(Mþ þ 18, 95%) and 363 (Mþ ꢀ 61, 100).
Chromatography of the residue, eluting with ether-light petroleum
(1 : 3), gave the title compound 51a (20 mg, 33%) as a colourless oil,
RF [ether-light petroleum (1 : 3)] 0.4 (Found: Mþ þ NH4, 266.1751.
C
15H24NO3 requires M, 266.1756); nmax (neat)/cmꢀ1 1687, 1605,
1452, 1372, 1216, 1156, 1131, 1096, 1028, 917, 839, 755 and 699; dH
(300 MHz; CDCl3) 7.31 (5H, m, ArH), 5.25 (1H, br d, J 8.9, 10-H), 4.95
(1H, dd, J 9.1, 6.3, 2-H), 4.71 (1H, d, J 6.7, OCHHO), 4.58 (1H, br d, J
13.1, 5-H), 4.55 (1H, d, J 6.7, OCHHO), 4.43 (1H, br d, J 13.1, 5-H0), 4.35
(1H, dq, J 8.9, 6.4, 20-H), 3.37 (3H, s, OCH3), 3.08 (1H, dd, J 15.8, 6.3,
3-H), 2.43 (1H, dd, J 15.8, 9.1, 3-H0) and 1.25 (3H, d, J 6.4, 30-H3); dC
(75 MHz; CDCl3) 142.1, 141.5, 128.3, 127.6, 125.8, 120.8, 93.3, 81.1,
71.3, 69.6, 55.1, 37.7 and 21.0; m/z (CI) 266 (Mþ þ 18, 23%), 244 (99)
and 187 (100).
4.2.35. (2SR)-4-[(E,2SR)-2-(Methoxymethoxypropylidene]-2-[(E)-
prop-1-enyltetrahydrofuran (51c)
Following the procedure outlined for the preparation of the
tetrahydrofuran 51a, the allylic alcohol 23c (70 mg, 0.20 mmol),
methanesulfonic anhydride (71 mg, 0.41 mmol) and triethylamine
(0.14 mL, 1.0 mmol) gave the title compound 51c (11 mg, 24%) as a
colourless oil, RF [ether-light petroleum (1 : 3)] 0.4 (Found:
4.2.32. (2RS)-4-[(E,2SR)-2-Methoxymethoxypropylidene]-2-
methyltetrahydrofuran (51b)
Tetra-n-butylammonium fluoride (1.0 M in THF, 0.18 mL,
0.18 mmol) was added to the homoallylic mesylate 50b (60 mg,
0.15 mmol) in THF (2 mL) at rt, and the mixture stirred for 15 min,
poured into water (10 mL) and extracted with ether (3 ꢂ 10 mL).
The organic extracts were dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue, eluting with
ether-light petroleum (1 : 2), gave the title compound 51b (10 mg,
36%) as a colourless oil, RF [ether-light petroleum (1 : 2)] 0.4
(Found: Mþ þ NH4, 204.1604. C10H22NO3 requires M, 204.1600);
nmax (neat)/cmꢀ1 1446, 1385, 1374, 1216, 1156, 1133, 1097, 1029, 917
and 833; dH (300 MHz; CDCl3) 5.16 (1H, br d, J 9.1, 10-H), 4.65 and
4.51 (each 1H, d, J 6.7, OCHHO), 4.38 (1H, br d, J 13.3, 5-H), 4.32 (1H,
dq, J 9.1, 6.4, 20-H), 4.25 (1H, br d, J 13.3, 5-H0), 4.02 (1H, m, 2-H),
3.36 (3H, s, OCH3), 2.74 (1H, dd, J 16.0, 5.3, 3-H), 2.03 (1H, dd, J 16.0,
9.1, 3-H0), 1.29 (3H, d, J 5.9, 2-CH3) and 1.25 (3H, d, J 6.4, 30-H3); dC
(75 MHz; CDCl3) 142.9, 120.2, 93.1, 75.7, 70.7, 69.4, 54.9, 36.7, 20.8
and 20.1; m/z (CI) 204 (Mþ þ 18, 6%), 142 (27) and 125 (100).
M
þ þ NH4, 230.1737. C12H24NO3 requires M, 230.1756); nmax (neat)/
cmꢀ1 1449, 1371, 1299, 1216, 1156, 1136, 1096, 1029, 966 and 917; dH
(300 MHz; CDCl3) 5.76 (1H, dqd, J 15.3, 6.6, 0.8, 200-H), 5.52 (1H, ddq,
J 15.3, 7.2, 1.5, 100-H), 5.17 (1H, br d, J 9.0, 10-H), 4.66 and 4.52 (each
1H, d, J 6.8, OCHHO), 4.39 (1H, br d, J 12.9, 5-H), 4.33 (2H, m, 2-H and
20-H), 4.27 (1H, br d, J 12.9, 5-H0), 3.36 (3H, s, OCH3), 2.76 (1H, dd, J
16.1, 5.9, 3-H), 2.20 (1H, dd, J 16.1, 8.9, 3-H0), 1.71 (3H, dd, J 6.6, 1.5,
300-H3) and 1.25 (3H, d, J 6.3, 30-H3); dC (75 MHz; CDCl3) 142.3, 130.5,
128.8, 120.4, 93.1, 80.2, 70.5, 69.4, 55.0, 35.4, 20.8 and 17.5; m/z (CI)
230 (Mþ þ 18, 6%) and 151 (100).
Acknowledgements
We thank Astra-Zeneca and the EPSRC for a CASE Award (to D. R.
T.)
4.2.33. (2SR)-4-[(E,2SR)-2-Methoxymethoxypropylidene]-2-prop-
2-yltetrahydrofuran (51d)
Appendix A. Supplementary data
Following the procedure outlined for the preparation of the
tetrahydrofuran 51b, the homoallylic mesylate 50d (20 mg,
0.05 mmol) and tetra-n-butylammonium fluoride (1.0 M in THF,
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2019.130734.
50 mL 0.05 mmol) gave the title compound 51d (4.5 mg, 43%) as a
colourless oil, RF [ether-light petroleum (1 : 3)] 0.3 (Found:
References
M
þ þ NH4, 232.1911. C12H26NO3 requires M, 232.1912); nmax (neat)/
[1] E.J. Thomas, Chem. Rec. 7 (2007) 115.
[2] (a) A.H. MacNeill, E.J. Thomas, Synthesis (1994) 322;
cmꢀ1 1469, 1388, 1372, 1299, 1216, 1157, 1134, 1097, 1029, 918 and
838; dH (300 MHz; CDCl3) 5.17 (1H, br d, J 9.0, 10-H), 4.66 and 4.53
(each 1H, d, J 6.7, OCHHO), 4.37 (1H, br d, J 13.2, 5-H), 4.35 (1H, dq, J
9.0 6.3, 20-H), 4.25 (1H, br d, J 13.2, 5-H0), 3.57 (1H, m, 2-H), 3.37 (3H,
s, OCH3), 2.66 (1H, dd, J 15.9, 5.8, 3-H), 2.11 (1H, dd, J 15.9, 9.3, 3-H0),
1.73 (1H, octet, J 6.8, 2-CH), 1.25 (3H, d, J 6.3, 30-H3) and 0.99 and
0.90 (each 3H, d, J 6.8, 2-CHCH3); dC (75 MHz; CDCl3) 142.7, 120.4,
93.3, 85.4, 71.0, 69.6, 55.1, 33.0, 32.9, 21.0,19.1 and 18.5; m/z (CI) 232
(Mþ þ 18, 5%), 202 (2), 170 (21) and 153 (100).
(b) J.S. Carey, S. MacCormick, S.J. Stanway, A. Teerawutgulrag, E.J. Thomas, Org.
Biomol. Chem. 9 (2011) 3896;
(c) D.J. Hallett, N. Tanikkul, E.J. Thomas, Org. Biomol. Chem. 10 (2012) 6130;
(d) S.J. Stanway, E.J. Thomas, Tetrahedron 68 (2012) 5998.
[3] The double-bonds in the products 6 are assigned the (E)-configuration, even
though the 1,5-syn-substituted hydroxy- and alkoxy-alkyl groups are cis to
each other across the newly introduced double-bond, cf. the original products
2 where they are assigned the (Z)-configuration. This is a consequence of the
IUPAC Priority Rules that give the trialkylsilyloxymethyl group a higher pri-
ority than a 2-hydroxyalkyl group.
[4] L.A. Hobson, E.J. Thomas, Org. Biomol. Chem. 10 (2012) 7510.
[5] A. Teerawutgulrag, E.J. Thomas, J. Chem. Soc. Perkin Trans. I (1993) 2863.
[6] Preliminary communication on part of this work see: E.J. Thomas, D.R. Tray
Tetrahedron Lett. 52 (2011) 2065.
[7] M. Pereyre, G. Colin, J. Valade, Bull. Soc. Chim. Fr. (1968) 3358.
[8] W.A. Kleschick, C.H. Heathcock, J. Org. Chem. 43 (1978) 1256.
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[10] P. Breuilles, D. Uguen, Tetrahedron Lett. 28 (1987) 6053.
[11] C.-S. Hau, C. Tindall, J.B. Sweeney, Synlett (1996) 749.
4.2.34. (2SR)-4-[(E,2SR)-2-Methoxymethoxypropylidene]-2-
phenyltetrahydrofuran (51a)
Methanesulfonic anhydride (85 mg, 0.49 mmol) was added to
the benzylic alcohol 23a (93 mg, 0.25 mmol) and triethylamine
(0.17 mL, 1.22 mmol) in CH2Cl2 (5 mL) at 0 ꢁC and the mixture
allowed to warm to rt and stirred for 18 h. After concentration
under reduced pressure, saturated aqueous sodium hydrogen car-
bonate (10 mL) and ether (10 mL) were added and the aqueous
layer extracted with ether (2 ꢂ 10 mL). The organic extracts were
dried (MgSO4) and concentrated under reduced pressure.
[12] D.C. Deka, E.J. Thomas, Tetrahedron 57 (2001) 10017.
[13] In transmetallation of 4-, 5- and 6-alkoxyalk-2-enyl(tributyl)stannanes with
tin(IV) chloride, the substituent on the tin-bearing carbon is always trans to
any substituent on the adjacent carbon in the oxastannane rings formed by
co-ordination of the electron deficient tin by the alkoxy group, see ref. 4. This
applies to 4-, 5- and 6-membered oxastannane rings.
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734

12
E.J. Thomas, D.R. Tray / Tetrahedron xxx (xxxx) xxx
[14] It has not been confirmed which oxygen in MOMO- and SEMO substituted
alkenyltin trichlorides co-ordinate preferentially to the tin. However, the (Z)-
1,5-syn-stereoselectivity observed for the 4-benzyloxypent-2-enylstannane 1
has also been confirmed for analogous 4-(2-trimethylsilyloxymethoxy)pent-
2-enylstannanes, see: K. Hoegenauer, E.J. Thomas Org. Biomol. Chem. 10
(2012) 6995.
[15] (a) B.M. Trost, J.W. Herndon, J. Am. Chem. Soc. 106 (1984) 6835;
(b) T. Tabuchi, J. Inanaga, M. Yamaguchi, Tetrahedron Lett. 28 (1987) 215.
[16] (a) S. Weigand, R. Bruckner, Synthesis (1996) 475;
(b) A.S.-Y. Lee, W.-C. Dai, Tetrahedron 53 (1997) 859.
[17] C. Prakash, S. Saleh, I.A. Blair, Tetrahedron Lett. 30 (1989) 19.
[18] This explanation is very tenuous. Primary 5-tert-butyldimethylsilyloxy groups
can co-ordinate to allyltin trichlorides and so influence the stereoselectivities
of their reactions with aldehydes. However, secondary 4-tert-butyldime-
thylsilyloxy groups can be less effective in this respect, see ref. 4. In Figure 3, it
is a secondary tert-butyldimethylsilyloxy group that is involved but it may be
that participation of co-ordination via the six-membered ring is important,
see 52b cf. 31b.
Please cite this article as: E.J. Thomas, D.R. Tray, 1,5-Stereocontrol in reactions of 2,4-disubstituted alk-2-enylstannanes with aldehydes; an
approach to the stereoselective synthesis of branched triols, Tetrahedron, https://doi.org/10.1016/j.tet.2019.130734