1,5-Stereocontrol in tin(IV) halide mediated reactions between N- and S-substituted pent-2-enylstannanes and aldehydes or imines

Article abstract of DOI:10.1016/j.tet.2012.05.032

Following transmetalation of (4S)-4-(dibenzylamino)pent-2-enyl(tributyl) stannane with tin(IV) bromide, reactions of the resulting allyltin tribromide with aldehydes gave (3Z)-1,5-syn-5-(dibenzylamino)hex-3-en-1-ols with excellent, ca. 98:2, stereocontrol. (4R)-5-Benzylthio-4-methylpent-2-enyl(tributyl) stannane similarly reacted with aldehydes to give (3Z)-1,5-anti-6-benzylthio-5- methylhex-3-en-1-ols with 87:13 stereocontrol. Although the analogous reaction of (4R)-4-benzylthiopent-2-enyl(tributyl)stannane with benzaldehyde proceeded with some stereoselectivity, 80-90:20-10, in favour of the (3Z)-1,5-syn- diastereoisomer, the yield was low due to a competing Lewis acid catalysed 1,4-elimination. N-Acylamino- and S-acylthio-pent-2-enylstannanes reacted with aldehydes with variable syn/anti-stereoselectivities. Tin(IV) chloride promoted reactions of the 4-(dibenzylamino)pent-2-enylstannane with 1- alkoxycarbonylimines gave (E)-alk-4-enoates with a modest preference for the 2,6-anti-products, 2,6-anti/2,6-syn=75:25.

Full text of DOI:10.1016/j.tet.2012.05.032

Tetrahedron 68 (2012) 5998e6009
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Tetrahedron
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1,5-Stereocontrol in tin(IV) halide mediated reactions between N- and
S-substituted pent-2-enylstannanes and aldehydes or imines
*
Steven J. Stanway, Eric J. Thomas
The School 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:
Following transmetalation of (4S)-4-(dibenzylamino)pent-2-enyl(tributyl)stannane with tin(IV) bromide,
reactions of the resulting allyltin tribromide with aldehydes gave (3Z)-1,5-syn-5-(dibenzylamino)hex-3-
en-1-ols with excellent, ca. 98:2, stereocontrol. (4R)-5-Benzylthio-4-methylpent-2-enyl(tributyl)stan-
nane similarly reacted with aldehydes to give (3Z)-1,5-anti-6-benzylthio-5-methylhex-3-en-1-ols with
87:13 stereocontrol. Although the analogous reaction of (4R)-4-benzylthiopent-2-enyl(tributyl)stannane
with benzaldehyde proceeded with some stereoselectivity, 80e90:20e10, in favour of the (3Z)-1,5-syn-
diastereoisomer, the yield was low due to a competing Lewis acid catalysed 1,4-elimination. N-Acyla-
mino- and S-acylthio-pent-2-enylstannanes reacted with aldehydes with variable syn/anti-stereo-
selectivities. Tin(IV) chloride promoted reactions of the 4-(dibenzylamino)pent-2-enylstannane with 1-
alkoxycarbonylimines gave (E)-alk-4-enoates with a modest preference for the 2,6-anti-products, 2,6-
anti/2,6-syn¼75:25.
Received 16 February 2012
Received in revised form 24 April 2012
Accepted 8 May 2012
Available online 14 May 2012
Keywords:
Allylstannane
Remote stereocontrol
Transmetalation
Homoallylic alcohol
Chelation control
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
It was of interest to study the analogous reactions of pent-2-
enylstannanes that had N- and S-containing substituents. We re-
Remote stereocontrol has been found for tin(IV) halide medi-
ated reactions between alk-2-enylstannanes with an alkoxy sub-
stituent at the 4-, 5- or 6-position and aldehydes or imines.1 For
example, transmetalation of the (4S)-4-benzyloxypent-2-
enyl(tributyl)stannane 1 using tin(IV) chloride generated an allyl-
tin trichloride that reacted with aldehydes to give the (3Z)-1,5-syn-
diastereoisomers 22 and with 1-alkoxycarbonylimines to give the
(4E)-2,6-anti-products 3;3 useful levels of remote stereocontrol
were observed in both cases.
port here in full the results of this investigation.4,5
2. Results and discussion
2.1. 1,5-Stereocontrol in tin(IV) halide promoted reactions of
N-substituted pent-2-enylstannanes and aldehydes
By analogy with the stannane 1, the (4S)-4-(dibenzylamino)
pent-2-enyl(tributyl)stannane 9 was selected for initial study and
was prepared as outlined in Scheme 1. Oxidation of alcohol 46 and
condensation of the resulting aldehyde with triethyl phosphonoa-
cetate gave ester 5. Reduction gave alcohol 6 and thermolysis of the
derived zanthate 7 gave the dithiocarbonate 8 as a mixture of
epimers. These were reacted with tributyltin hydride to give the
required stannane 9 mainly as its (E)-isomer.7
The NMR spectra of the (R)- and (S)-Mosher’s derivatives of the
4-(dibenzylamino)pent-2-enol 6 were very similar and so the op-
tical purity of this alcohol and hence of the pent-2-enylstannane 9
could not be checked at this stage. However, later functionalization
of products prepared using this stannane confirmed that its enan-
tiomeric excess was ca. 94%.8
Reactions of the stannane 9 with aldehydes were carried out
using tin(IV) bromide to effect transmetalation. Better yields were
obtained allowing 10 min for the transmetalation step with the
reactions of the intermediate allyltin tribromide being carried out
* Corresponding author. E-mail address: e.j.thomas@manchester.ac.uk (E.J.
Thomas).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.032

S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
5999
p-nitrobenzoates 15 and 17 could also be distinguished by NMR.
The configuration of the alcohol 10 at C(1) was initially assigned on
the basis of the relative chemical shifts of the corresponding (R)-
and (S)-O-acetylmandelates 18 and 1910,11 and was confirmed by
ozonolysis of its acetate 20. This gave the (R)-enantiomer 21 of 3-
acetoxy-3-phenylpropan-1-ol.2 The structures of the products 11
and 12 from the other aromatic aldehydes were assigned by
analogy.
Similar correlations were used to confirm the structure of the
product 14 from the reaction between stannane
9 and 2-
methylpropanal, see Scheme 3. The NOE enhancement of H-7 ob-
served on irradiation of the 4-H2 confirmed the (Z)-geometry of the
alkenol. A Mitsunobu inversion followed by saponification con-
verted alkenol 14 into its epimer 23. The alcohols 14 and 23 were
distinguished by 1H NMR as were the corresponding 4-
nitrobenzoates 22 and 24. The configuration of the alcohol 14 at
C(3) was established by comparison of the 1H NMR spectra of the
(R)- and (S)-O-acetylmandelates 25 and 26 and the (R)- and (S)-
Mosher’s derivatives 27 and 28.10,11 The Mosher’s derivatives also
indicated that the optical purity of the alcohol 14, and hence of the
stannane 9, corresponded to an enantiomeric excess of ca. 94%. The
structure of the product 13 from propanal was assigned by analogy.
Scheme 1. Synthesis of the 4-(dibenzylamino)pent-2-enylstannane 9. Reagents and
conditions: (i) (a) DMSO, (COCl)2, DCM, ꢀ55 ꢁC, 15 min, Et3N, 5 min; (b) KOtBu,
(EtO)2P(O)CH2CO2Et, THF, 0 ꢁC, 1 h, add aldehyde, ꢀ78 ꢁC, 20 min (82% from 4); (ii)
DIBALeH, DCM, hexane, ꢀ78 ꢁC, 40 min (83%); (iii) NaN(SiMe3)2, THF, 0 ꢁC, 10 min, CS2,
rt, 3 h, MeI, rt, 2 h (85%); (iv) toluene, heat under reflux, 15 h (81%); (v) Bu3SnH, AIBN
(trace), benzene, heat under reflux, 3 h [79%; (E)/(Z)¼95:5].
at ꢀ78 to ꢀ55 ꢁC typically for 1 h. It was important to add base
during the work-up and triethylamine followed by aqueous sodium
bicarbonate were added to quench the reactions. Under these
conditions, modest to reasonable yields were obtained for several
aldehydes and excellent 1,5-stereoselectivities. Indeed the (3Z)-1,5-
syn-alkenols 10e14 were the only products isolated together with
minor side-products at the 1e2% level that were not characterized.
Lower yields were obtained using tin(IV) chloride.
Scheme 3. Confirmation of the structure of (Z)-7-(dibenzyl)amino-2-methyloct-5-en-
3-ol 14. Reagents and conditions: (i) 4-NO2C6H4CO2H, DEAD, Ph3P, toluene, ꢀ35 ꢁC to
rt, 90 min (31%); (ii) aq NaOH, MeOH, rt, 3 h (48%); (iii) 4-NO2C6H4COCl, Et3N, DMAP
(cat.) DCM, rt, 6 h (58%); (iv) (R)- or (S)-O-acetylmandelic acid, DCC, DMAP (cat.), DCM,
rt, 18 h (25, 44%; 26, 76%); (v) (S)- or (R)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoyl
chloride, py, CCl4, rt, 2 h (27, 78%; 28, 49%).
The (3Z)-1,5-syn-product 10 from benzaldehyde was identified
on the basis of the correlations outlined in Scheme 2. The (Z)-
configuration of the double-bond followed from its vinylic 1H NMR
coupling constant of ca. 10.5 Hz. To show that the epimers at C(1)
could be distinguished, the 1,5-syn-product 10 was converted into
its 1,5-anti-epimer 16 via a Mitsunobu reaction9 and saponification
of the resulting p-nitrobenzoate 15. The epimeric alcohols 10 and
16 could be distinguished by 1H NMR and it appeared that just ca.
2% of the 1,5-anti-epimer 16 was present in the product mixture
from the allylstannane reaction with benzaldehyde. The epimeric
Tin(IV) halide promoted reactions of 4-(dibenzylamino)pent-2-
enyl(tributyl)stannane 9 with aldehydes would appear to proceed
with useful 1,5-stereoselectivity in favour of the (3Z)-1,5-syn-alk-3-
enols reminiscent of the stereoselectivity observed for the analo-
gous reactions of the 4-benzyloxypent-2-enylstannane 1.2 To see
whether varying the substituent on the nitrogen would affect the
stereoselectivity of these reactions, the 4-(N-trimethylsilylethox-
ycarbonylamino)- and 4-(N-benzyloxycarbonylamino)-pent-2-
enylstannanes 38 and 39 were synthesized and their reactions
with benzaldehyde were investigated. The stannanes 38 and 39
were prepared from the corresponding alcohols 32 and 33 via the
xanthates 34 and 35 and the dithiocarbonates 36 and 37. Alcohol 32
was prepared from the protected alanine 29 by reduction to the
alcohol 30, oxidation with a phosphonate condensation to give the
ester 31 followed by reduction, see Scheme 4.
However, both stannanes 38 and 39 reacted with benzaldehyde,
using either tin(IV) bromide or chloride to effect the trans-
metalation, to give 60:40 mixtures of the epimeric (3Z)-hex-3-
enols 40a,b and 41a,b. The configurations of these products at
C(1) were not established, but the minor epimer 40b was converted
into the major 40a by a Mitsunobu esterification and saponification.
The minor epimers were shown to be (Z)-alkenes by 1H NMR. It
would appear that tin(IV) halide promoted reactions of 4-
acylaminopent-2-enylstannanes with aldehydes do not proceed
with useful 1,5-stereocontrol.
Scheme 2. Confirmation of the structure of (Z)-5-(dibenzylamino)-1-phenylhex-3-en-
1-ol 10. Reagents and conditions: (i) 4-NO2C6H4CO2H, DEAD, Ph3P, ꢀ35 ꢁC, 1.5 h (45%);
(ii) aq NaOH, MeOH, rt, 50 min (63%); (iii) 4-NO2C6H4COCl, Et3N, DMAP, 0 ꢁC, rt, 6 h
(56%); (iv) (R)- or (S)-O-acetylmandelic acid, DCC, DMAP (cat.), DCM, rt, 18 h (18, 58%;
19, 64%); (v) Ac2O, Et3N, DMAP (cat.), rt, 18 h (79%); (vi) O3, DCM, w78 ꢁC, 40 min, then
Me2S, rt, followed by NaBH4, MeOH, rt, 2 h (18%).

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S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
give the 5-hydroxy-4-methylpent-2-enylstannnane 48. This was
converted into the thioester 49 under Mitsunobu conditions and
hydrolysis of the thioester with in situ alkylation of the resulting
thiol gave the 5-benzylthio-4-methylpent-2-enylstannane 50.
Better results for the reactions of the S-substituted pentenyl-
stannane 50 with aldehydes were obtained using tin(IV) bromide to
effect transmetalation. Under the usual conditions reasonable to
good yields were obtained of the (3Z)-6-benzylthio-5-methylhex-3-
en-1-ols with a useful stereoselectivity in favour of the 1,5-anti-(Z)-
diastereoisomers, typically 1,5-anti-(Z)/1,5-syn-(Z)¼85:15. Minor
amounts, ca. 5%, of an (E)-isomer were also formed. Using tin(IV)
chloride to effect transmetalation, a lower yield, 49%, albeit with
similar 1,5-stereoselectivity, 87:13, was observed for benzaldehyde.
Scheme 4. Synthesis and reactions of stannanes 38 and 39. Reagents and conditions:
(i) (a) NaBH4, LiCl, EtOH, THF, rt, 18 h (96%); (ii) DMSO, (COCl)2, DCM, w55 ꢁC, 5 min,
add 30, ꢀ55 ꢁC, 15 min, Et3N, 5 min; (b) (EtO)2P(O)CH2CO2Et, KOtBu, 0 ꢁC, rt, 1 h,
ꢀ78 ꢁC, add aldehyde, 40 min (57%); (iii) DIBALeH, hexane, ꢀ78 ꢁC, 40 min (63%); (iv)
nBuLi, THF, CS2, rt, 3 h, add MeI, rt, 18 h (34, 99%; 35, 82%); (v) toluene, heat under
reflux, 18 h (36, 84%; 37, 89%); (vi) Bu3SnH, AIBN (cat.), benzene, heat under reflux 3 h
(38, 76%; 39, 86%); (vii) SnBr4, ꢀ78 ꢁC, 10 min, PhCHO, ꢀ55 ꢁC, 12 h (40, 59%; 41, 62%;
60:40 both cases).
The ratios of the 1,5-anti/1,5-syn-products were estimated by 1H
NMR. The major product from the reaction with benzaldehyde was
identified as the (3Z)-1,5-anti-isomer 51 on the basis of spectroscopic
data and the correlations outlined in Scheme 6. The vinylic coupling
constant of 10 Hz indicated the cis-geometry of its double-bond. The
relative chemical shifts of the (R)- and (S)-O-acetylmandelates 55
and 56 were consistent with the 1,5-anti-configuration shown.10,11
The acetate of the major product gave the (S)-enantiomer of 3-
acetoxy-3-phenylpropan-1-ol (S)-21 together with (S)-3-acetoxy-1-
phenylpropan-1-ol (S)-59, the product of acetyl migration, on ozo-
nolysis.2,12 A Mitsunobu reaction followed by saponification of the
ester 60 converted the major product 51 into the 1,5-syn-epimer 61
the 1H NMR spectrum of which corresponded to that of the slightly
less polar minor product. A second minor product, ca. 5%, was be-
lieved to be an (E)-isomer but its structure was not confirmed. The
1H NMR spectra of the Mosher’s derivatives 57 and 58 showed that
the major product had an ee of ca. 80% and were consistent with the
assigned configuration at C(1).11
2.2. 1,5-Stereocontrol in tin(IV) halide promoted reactions of
S-substituted pent-2-enylstannanes and aldehydes
Transmetalation of the 5-benzyloxy-4-methylpent-2-enylstan-
nane 42 generates an allyltin trichloride that reacts with aldehydes
with useful 1,5-stereocontrol in favour of the (3Z)-1,5-anti-di-
astereoisomers 43.12 It was decided to prepare the analogous 5-
benzylthiopent-2-enylstannane 50 and to study its reactions with
aldehydes.
5-Benzylthio-4-methylpent-2-enyl(tributyl)stannane 50 was
synthesized as outlined in Scheme 5. The xanthate 45, prepared
from the alcohol 44,13 was converted into the isomeric dithiocar-
bonate 46 by heating in toluene under reflux. Reaction of the
dithiocarbonate with tributyltin hydride under free radical condi-
tions then gave the pent-2-enylstannane 47 that was desilylated to
Scheme 6. Confirmation of the structures of the products 51 and 53 from reactions of
the stannane 50. Reagents and conditions: (i) (R)- or (S)-O-acetylmandelic acid, DCC,
DMAP (cat.), DCM, rt, 18 h (55, 57%; 56, 70%; 62, 94%; 63, 95%); (ii) (S)- or (R)-2-
methoxy-2-phenyl-3,3,3-trifluoropropanoyl chloride, py, CCl4, rt, 2 h (57, 68%; 58,
64%); (iii) (a) Ac2O, Et3N, DMAP (cat.) (73%); (b) O3, then Me2S, followed by NaBH4
(91%); (iv) 4-NO2C6H4CO2H, DEAD, Ph3P (60, 77%; 64, 42%); (ii) aq NaOH, MeOH (61,
45%; 65, 91%).
Scheme 5. Preparation of the 5-benzylthiopent-2-enylstannane 50. Reagents and
conditions: (i) BuLi, THF, 0 ꢁC, 30 min, CS2, rt, 3 h, MeI, rt, 18 h (76%); (ii) toluene, heat
under reflux, 18 h (87%); (iii) Bu3SnH, AIBN (cat.), benzene, heat under reflux, 3 h
(73%); (iv) TBAF, THF, rt, 18 h (89%); (v) DIAD, Ph3P, THF, 0 ꢁC, 30 min, 48, MeCOSH, THF,
0
ꢁCert, 2 h (72%); (vi) KOH, EtOH, rt, 10 min, BnCl, rt, 1 h (98%).

S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
6001
The structure of the major product from the reaction of the
2.3. 1,5-Stereocontrol in tin(IV) halide promoted reactions of
stannane 50 with 2-methylpropanal was shown to correspond to
the (5Z)-3,7-anti-isomer 53 by comparison of the 1H NMR
spectra of its (R)- and (S)-O-acetylmandelates 62 and 63, which
were consistent with the (R)-configuration at C(3).10,11 The major
product 53 was converted into its syn-epimer 65 via the inverted
p-nitrobenzoate 64 showing that the two C(1)-epimers could be
distinguished and that the syn-epimer 65 corresponded to
a minor product from the reaction with the stannane 50, see
Scheme 6.
N-substituted pent-2-enylstannanes and imines
The tin(IV) halide promoted reactions of alkoxyalk-2-
enylstannanes with imines prepared from glyoxalates have been
shown to proceed with useful stereoselectivity in favour of (E)-alk-4-
enoates. The 2,6-anti-isomers
3 were obtained using the 4-
benzyloxystannane 1.3 Based on this precedent, reactions of the 4-
(dibenzylamino)pent-2-enylstannane 9 with 1-alkoxycarbonylimines
were selected for study.
Although mixed results had been obtained for the tin(IV) halide
mediated reactions between the N-acylaminopent-2-enyl stan-
nanes 38 and 39 and benzaldehyde, it was decided to check the
stereoselectivity of the analogous reaction of the S-acetylpent-2-
enylstannane 49. In the event good yields of two products were
obtained but the ratio of the products was not reproducible varying
from 90:10 to 66:34. The configurations of these products at C(1)
were not established but the major product was shown to be a (3Z)-
isomer, either 66 or 67 by 1H NMR. The alkene geometry of the
minor product was not confirmed.
The tin(IV) chloride promoted reactions of the stannane 9 with
both chiral and achiral 1-alkoxycarbonylimines3 gave similar results.
In all cases a ca. 3:1 mixture of two products identified as the (4E)-
2,6-anti- and (4E)-2,6-syn-epimers were obtained, see Scheme 8.
To study the effect of a thio-ether substituent at C(4) in an alk-
2-enylstannane, the 4-phenylthiopent-2-enyl(tributyl)-stannane
73 was prepared from the 5-acetoxypent-3-en-2-ol 6814 by sub-
stitution of the hydroxyl group with inversion using diphenyl
disulfide and tributylphosphine15 followed by conversion of the
resulting acetoxyalkyl sulfide 69 into the xanthate 71 via the
corresponding alcohol 70. Thermolysis of the xanthate gave the
dithiocarbonate 72 that was converted into the 4-phenylthiopent-
2-enylstannane 73 by reaction with tributyltin hydride, see
Scheme 7.
Scheme 8. Reactions between the 4-(N,N-dibenzylamino)pent-2-enylstannane 9 and
1-alkoxycarbonylimines. Reagents and conditions: (i) 9, SnCl4, ꢀ78 ꢁC, 15 min, add
imine, ꢀ45 ꢁC, 12 h (77/78, 60%, 77/78¼70:30; 79/80, 63%, 79/80¼75:25; 82/83, 60%,
82/83¼75:25; 85/86, 62%, 85/86¼70:30).
The epimeric products from the (R)-imine (R)-76 were separated
and were shown to be (E)-alkenes by 1H NMR. The chemical shifts
of H(2) were used to establish the configurations of these products
at C(2). The epimer with H(2) more shielded was assigned the 1,3-
like configuration between C(2) and the imine derived stereogenic
centre (major product 77, 2-H,
d
d 3.12; minor product 78, 2-H,
Scheme 7. Synthesis and chemistry of the 4-phenylthiopent-2-enylstannane 73. Re-
agents and conditions: (i) Bu3P, (PhS)2, THF, rt, 18 h (86%); (ii) KOH, EtOH, rt, 2 h (81%);
(iii) BuLi, THF, hexane, 0 ꢁC, 30 min, CS2, rt, 3 h, MeI, rt, 18 h (91%); (iv) toluene, heat
under reflux, 18 h (79%); (v) Bu3SnH, AIBN (cat.), benzene, heat under reflux, 1 h (46%);
(vi) SnBr4, DCM, ꢀ78 ꢁC, 10 min, benzaldehyde, ꢀ78 ꢁC, 1 h (40%; 74/75¼80: 20).
3.41).3 The products from the (S)-imine (S)-76 could not be sep-
arated but they too were assigned the configurations shown on the
basis of the H(2) chemical shifts of the major and minor products in
the reaction mixture (major product 79, 2-H,
80, 2-H,
d 3.42; minor product
d
3.12). The products from the achiral imines 81 and 84
However, tin(IV) bromide promoted reactions of the 4-
phenylthiopent-2-enylstannane 73 with benzaldehyde under the
usual conditions tended to give low yields, typically 30e40%. Sig-
nificant amounts, ca. 20% of the product, of a (3E)-5-phenyl-thio-
hex-3-en-1-ol 75 were isolated along with the major (3Z)-
diastereoisomer 74. Similar results were found using tin(IV) chlo-
ride. The 1,5-syn-configuration was assigned to the (3Z)-product 74
by analogy with the stereoselectivity of the analogous reactions of
the 4-benzyloxy- and 4-(dibenzylamino)-pent-2-enylstannanes 1
and 9. The configuration at C(1) of the (3E)-isomer was not estab-
lished but its (E)-configuration was indicated by its vinylic coupling
constant of 15 Hz.
could not be separated. 1H NMR was used to estimate their ratio
and to confirm their (E)-stereochemistry. Their configurations at
C(1) were assigned by analogy with the structures assigned to the
products formed using the chiral imines (R)- and (S)-76.
3. Summary and conclusions
This work has shown that amino and sulfur containing sub-
stituents can direct the stereoselectivity of tin(IV) halide mediated
reactions of pent-2-enylstannanes. The regioselectivity of all of
these reactions is consistent with transmetalation via an SE0

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S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
process to generate a pent-1-en-3-yltin trihalide that then reacts
with the aldehyde to give the product of an overall ipso re-
placement of the tin.1
halide promoted reactions of the acylamino- and acetylthio-
pentenylstannanes 38, 39 and 49 with aldehydes means that ei-
ther the acylated substituents are less effective at controlling the
stereoselectivity of the initial transmetalation process, or that the
resulting allyltin trihalides are more prone to epimerize at the
stereogenic centre next to the tin.
The lower yield observed for the tin(IV) halide promoted re-
action of the 4-phenylthiopent-2-enylstannane 73 with benzalde-
hyde may be due to a Lewis acid catalysed 1,4-elimination that
competes with the transmetalation process, see structure 91. The
formation of a significant amount of (E)-alkenol 75 in this reaction
may be due to participation of a competing process that proceeds
via an open-chain transition structure.
Under the low temperature conditions used the steroselectivity
of the initial transmetalation is believed to be due to kinetic con-
trol.16 For the tin(IV) mediated reactions of the stannane 9, the
selective formation of the (3Z)-1,5-syn-products 10e14 is consis-
tent with participation of the allyltin tribromide 87, in which the
vinyl and methyl substituents are trans-disposed about the four-
membered ring. Reaction with aldehydes via the chair-like six-
membered transition structure 88, in which the group next to tin
adopts an axial position, then gives rise to the observed products,
see Fig. 1.
It is not certain whether cyclic six-membered or open-chain tran-
sition structures are involved in the tin(IV) halide promoted reactions
of 4-alkoxypent-2-enylstannanes with 1-alkoxycarbonylimines.3
However, 1-substituted allyltin trihalides are known to epimerize on
standing even at ꢀ78 ꢁC and the reactions of the allyltin trichloride
derived from the 4-(dibenzylamino)pent-2-enylstannane 9 with 1-
alkoxycarbonylimines took 12 h at ꢀ45 ꢁC to reach completion. It
may be that the modest stereoselectivities observed for the reactions
with imines are due to epimerization at C(3) of the intermediate
allyltin trichloride under the reaction conditions. Nevertheless the
consistent preference for formation of the 2,6-anti-epimer observed
for both enantiomers of the chiral imine is of note.
Notwithstanding the modest stereoselectivities observed for the
acylamino and acylthio substituted pentenylstannanes, and for the
reactions with imines, the highly effective 1,5-stereocontrol ob-
served for 4- and 5-alkoxy-pent-2-enylstannanes has now been
found for tin(IV) halide promoted reactions of 4-alkylamino- and 5-
alkylthio-pent-2-enylstannanes with aldehydes and this may be
useful in synthesis.
Fig. 1. Outline mechanism for the formation of the (3Z)-alkenols 10e14.
The formation of the 1,5-anti-products 51e54 in the tin(IV)
mediated reactions of the stannane 50 is consistent with partici-
pation of the allyltin tribromide 89 that reacts with aldehydes via
the chair-like transition structure 90, see Fig. 2.
4. Experimental
4.1. General
All non-aqueous reactions were performed under an atmo-
sphere of dry nitrogen or argon at ambient temperature unless
otherwise stated.
Proton nuclear magnetic resonance spectroscopy was performed
on Varian Unity 500 (500 MHz), Bruker AC-300 or Varian XL 300
(300 MHz) and Varian Gemini 200 (200 MHz) spectrometers. Car-
bon nuclear magnetic resonance spectroscopy was performed on
Bruker AC-300 or Varian XL 300 (75 MHz) and Varian Gemini 200
(50 MHz) spectrometers. Coupling constants in hertz are rounded to
the nearest 0.5 Hz. Fluorine nuclear magnetic resonance spectros-
copy was performed on a Varian Unity 500 (470 MHz) spectrometer.
Infra-red spectroscopy was performed on a PerkineElmer 1710FTor
an ATI Matteson Genesis FTIR spectrometer. All samples were run as
evaporated discs (from chloroform) on sodium chloride plates. Ab-
sorption maxima were recorded in wavenumbers (cmꢀ1). Low-
resolution electron impact (EI) and chemical ionisation (CI) mass
spectroscopy were performed on a Kratos MS25 or a Fisons TRIO
2000 quadrupole mass spectrometer. High-resolution spectroscopy
was performed on a Kratos Concept-1S mass spectrometer coupled
to a Mach 3 data system. Compounds containing tin displayed
characteristic peak clusters, only those associated to 120Sn are
Fig. 2. Outline mechanism for the formation of the (3Z)-alkenols 51e54.
Analogous allyltin trihalides have been postulated for the tin(IV)
halide promoted reactions of the alkoxy-substituted stannanes 1
and 42 with aldehydes.1,2,12 Chair-like transition structures analo-
gous to 88 and 90, in which the substituents next to tin are in axial
positions, have been invoked for the uncatalysed reactions of 1-
substituted but-2-enyl(tributyl)stannanes with aldehydes under
high temperature conditions.17
(Z)-Alkene formation from 1-substituted allylstannanes is be-
lieved to be indicative of six-membered cyclic transition structures
for the reactions of the intermediate allyltin trihalides with alde-
hydes.16 These processes are believed to be highly stereoselective
so that the 1,5-stereoselectivity in the (Z)-alkenol manifold is an
accurate reflection of the configurations of the participating allyltin
trihalides. The lower 1,5-stereoselectivity observed for the tin(IV)

S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
6003
quoted. Optical rotations were recorded on an Optical Activity AA-
100 polarimeter operating at 589 nm using either chloroform or
methanol as a solvent at ambient temperature.
(40 mL) at ꢀ78 ꢁC. After 40 min, methanol (3 mL), saturated
aqueous ammonium chloride (12 mL) and ether (40 mL) were
added and the mixture was allowed to warm to room temperature.
After filtration and extraction into ethyl acetate (150 mL), the or-
ganic extracts were washed with water (50 mL) and brine (50 mL),
then dried (MgSO4). After concentration under reduced pressure,
chromatography (1:1 petrol/ether) of the residue afforded the title
Analytical high performance liquid chromatography was per-
formed on a Waters Z module, 10 cmꢂ8 mm cartridge containing
C18 5m stationary phase (reverse phase chromatography). De-
tection was by ultraviolet (UV) absorption using a PerkineElmer IC-
480 detector at 255 nm. Semi-preparative HPLC was carried out
using a Gilson 303 pump (manometric module) attached to
compound 6 as a colourless oil (2.26 g, 83%), [
a
]D ꢀ52 (c 1.1, CHCl3);
nmax/cmꢀ1 3332 (br), 3027, 2967, 1494, 1453, 977, 731 and 699; dH
(300 MHz, CDCl3) 1.20 (3H, d, J 6.5, 5-H3), 3.35 (1H, m, 4-H), 3.57
and 3.65 (each 2H, d, J 14.0, PhHCH), 4.16 (2H, d, J 4.5, 1-H2),
5.65e5.90 (2H, m, 2-H, 3-H) and 7.20e7.45 (10H, m, ArH); dC
(75 MHz, CDCl3) 15.1, 53.7, 63.5, 77.2,126.8,128.2,128.6,130.3,133.6
and 140.5; m/z (EI) 281 (Mþ, 4%), 266 (60) and 91 (100); HRMS (CI,
NH3): Mþ, found 281.1784. C19H23ON requires 281.1780.
a Dynamax 83-211-C column 25 cmꢂ10 mm containing C18 8
m
stationary phase (reverse phase chromatography). Detection was
by either UV absorption at 254 nm (Gilson 115 UV detector) or re-
fractive index (RI) (Gilson 131 RI detector). Chromatography refers
to flash column chromatography. The stationary phase was either
silica (Merck, silica 60H, 40e63m or aluminium oxide (Phase Sep-
arations, Act. Alumina UGI-100S)).
Petrol refers to the fraction of petroleum ether, which boils be-
tween 40 and 60 ꢁC and was redistilled prior to use. Other solvents
were dried by standard techniques. Brine refers to saturated aque-
ous sodium chloride. n-Butyllithium was obtained as a solution in
hexanes and titrated against a solution of 2,5-dimethoxybenzyl al-
cohol in tetrahydrofuran prior to use.
4.2.3. S-Methyl-O-[(4S,2E)-4-(N,N-Dibenzylamino)pent-3-en-1-yl]
dithiocarbonate (7). Sodium bis(trimethylsilyl)amide (8.7 mL, 1 M
in THF, 8.7 mmol) was added dropwise to the pent-2-enol 6 (2.45 g,
8.7 mmol) in THF (150 mL) at 0 ꢁC. The mixture was stirred at this
temperature for 10 min, carbon disulphide (2.1 mL, 34.9 mmol) was
added and the mixture stirred at room temperature for 3 h. Iodo-
methane (2.2 mL, 34.9 mmol) was then added and the stirring
continued for 2 h. Aqueous saturated ammonium chloride (20 mL)
was added and the mixture extracted with DCM (200 mL). The
organic extracts were washed with brine (50 mL), dried (MgSO4)
and concentrated under reduced pressure. Chromatography (8:1
petrol/ether) of the residue afforded the title compound 7 as a pale
(R)-5-tert-Butyldimethylsilyloxy-4-methylpent-2-enol 44, [a]
D
þ6.1 (c 3.5, CHCl3) [lit.13 þ10.7 (c 0.65, CHCl3)] was prepared by re-
duction of the corresponding ethyl pent-2-enoate using DIBALeH.13
4.2. Experimental procedures
4.2.1. Ethyl (4S,2E)-4-(N,N-dibenzylamino)pent-2-enoate
(5). Dimethylsulfoxide (3.7 mL, 51.7 mmol) in DCM (15 mL) was
added to oxalyl chloride (2.2 mL, 25.9 mmol) in DCM (40 mL) at
ꢀ55 ꢁC. After 5 min, alcohol 4 (6 g, 23.5 mmol) in DCM (30 mL) was
added followed, after 15 min, by triethylamine (16.5 mL,
117.5 mmol). The solution was stirred for 5 min, then allowed to
warm to room temperature. Water (50 mL) was added and the
aqueous phase was extracted with DCM (50 mL). The organic phase
was washed with brine (50 mL) and dried (MgSO4). Removal of the
solvent under reduced pressure gave the corresponding aldehyde.
Chromatography (3:1 petrol/ether) of a small sample gave (S)-2-
yellow oil (2.75 g, 85%), [
a
]
D
ꢀ43 (c 1.6, CHCl3); nmax/cmꢀ1 3401,
2927, 1216, 1059 and 699; dH (200 MHz, CDCl3) 1.20 (3H, d, J 7.5, 5-
H3), 2.55 (3H, s, SCH3), 3.35e3.65 (5H, m, 2ꢂPhCH2, 4-H), 5.10 (2H,
d, J 7.5, 1-H2), 5.55e6.05 (2H, m, 2-H, 3-H) and 7.20e7.50 (10H, m,
ArH); m/z (CI, NH3) 372 (Mþþ1, 21%), 106 (74) and 91 (l00); HRMS
(CI, NH3): MHþ, found 372.1459. C21H26NOS2 requires 372.1456.
4.2.4. S-Methyl-S-[(4S)-4-(N,N-Dibenzylamino)pent-1-en-3-yl]di-
thiocarbonate (8). The xanthate 7 (2.75 g, 7.4 mmol) was heated in
anhydrous degassed toluene (100 mL) under reflux for 15 h. After
concentration under reduced pressure, chromatography (8:1 pet-
rol/ether) of the residue afforded the title compound 8 as a white
(N,N-dibenzylamino)propanal, [
a
]
D ꢀ24.5 (c, 5.2, CHCl3); nmax/cmꢀ1
3410, 3028, 2925, 1726, 1453, 1028, 747 and 699; dH (200 MHz,
CDCl3) 1.20 (3H, d, J 7.0, 3-H3), 3.35 (1H, m, 2-H), 3.60 and 3.75 (each
2H, d, J 15.0, PhHCH), 7.20e7.50 (10H, m, ArH) and 9.80 (1H, s, CHO);
m/z (CI, NH3) 254 (Mþþ1, 100%) and 91 (59).
solid (2.23 g, 81%), a
2:1 mixture of epimers (1H NMR),
mp¼108e111 ꢁC (DCM, acetone). Found: C, 67.5; H, 7.3; N, 4.2.
C21H25ONS2 requires C, 67.9; H, 6.75; N, 3.75%. [
a
]
ꢀ90 (c 1.0,
D
CHCl3); nmax/cmꢀ1 3400, 2927, 1722, 1643, 1453, 863 and 747; dH
(300 MHz, CDCl3) major epimer 1.10 (3H, d, J 6.5, 5-H3), 2.40 (3H, s,
SCH3), 2.85e3.00 (1H, m, 4-H), 3.35 and 3.85 (each 2H, d, J 14,
2ꢂPhHCH), 4.40 (1H, t, J 10.0, 3-H), 5.10 (1H, d, J 10.0, 1-H), 5.31 (1H,
d, J 15.0, 1-H), 5.60 (1H, m, 2-H) and 7.20e7.50 (10H, m, ArH); m/z
(CI, NH3) 372 (Mþþ1, 100%), 266 (45), 224 (60), 106 (59) and 91
(60); HRMS (CI, NH3): MHþ, found 372.1442. C21H26NOS2 requires
372.1456.
Potassium tert-butoxide (8.51 g, 76.14 mmol) was added to tri-
ethyl phosphonoacetate (17 mL, 84.6 mmol) in THF (250 mL) at 0 ꢁC
and solution stirred at room temperature for 1 h, before cooling to
ꢀ78 ꢁC. The N,N-(dibenzylamino)propanal (21.2 mmol) in THF
(20 mL) was added dropwise and the solution stirred at ꢀ78 ꢁC for
20 min. The solution was poured into a mixture of ether (100 mL)
and aqueous saturated ammonium chloride (100 mL). The aqueous
phase was extracted with ether (50 mL) and the organic extracts
were washed with brine (50 mL) and dried (MgSO4). Concentration
reduced pressure and chromatography (10:1 petrol/ether) of the
residue afforded the title compound 5 as a colourless oil (6.24 g,
4.2.5. (4S,2E)-4-(N,N-Dibenzylamino)pent-2-enyl(tributyl)stannane
(9). Tributyltin hydride (1.1 mL, 3.77 mmol) and AIBN (5 mg) were
added to an anhydrous degassed solution of the dithiocarbonate 8
(1.12 g, 3.02 mmol) in benzene (50 mL) and the solution was heated
under reflux for 3 h. After concentration under reduced pressure,
chromatography (petrol, 1% triethylamine followed by 100:2:1
petrol/ether/triethylamine) of the residue gave the title compound 9
as a colourless oil (1.22 g, 79%), ca. a 95:5 mixture of (E)- and (Z)-
82%), [
a]
D ꢀ95 (c 0.7, CHCl3); nmax/cmꢀ1 2977, 1719, 1269, 1183 and
699; dH (300 MHz, CDCl3) 1.25 (3H, d, J 7.0, 5-H3), 1.32 (3H, t, J 7.0,
CH2CH3), 3.48 (1H, m, 4-H), 3.57 and 3.65 (each 2H, d, J 15.0,
PhHCH), 4.22 (2H, q, J 7.0, CH2CH3), 5.90 (1H, dd, J 16.0, l.5, 2-H),
7.05 (1H, dd, J 16.0, 6, 3-H) and 7.20e7.40 (10H, m, ArH); dC
(75 MHz, CDCl3) 14.1, 14.3, 28.4, 53.8, 60.4, 121.9, 126.9, 128.3, 128.5,
139.9, 150.3 and 166.6; m/z (CI, NH3) 324 (Mþþ1, 100%) and 91 (25).
isomers (1H NMR), [
a
]
D ꢀ36.5 (c 0.8, CHCl3); nmax/cmꢀ1 2958, 2926,
1643,1603,1454,1073,1029, 965, 744 and 698; dH (300 MHz, CDCl3)
(E)-isomer 0.85e0.95 (15H, m, 3ꢂCH2, 3ꢂCH3), 1.15 (3H, d, J 7.5, 5-
H3), 1.25e1.60 (12H, m, 6ꢂCH2), 1.75 (2H, d, J 8, 1-H2), 3.20 (1H, qn, J
7.0, 4-H), 3.45 and 3.65 (each 2H, d, J 14.0, 2ꢂPhHCH), 5.30 (1H, dd, J
15.0, 7.0, 3-H), 5.60 (1H, dt, J 15, 8.5, 4-H) and 7.20e7.45 (15H, m,
4.2.2. (4S,2E)-4-(N,N-Dibenzylamino)pent-2-en-1-ol
(6). Di-iso-
butylaluminium hydride (29 mL, 1 M in hexane, 29 mmol) was
added to the ester 5 (3.13 g, 9.7 mmol) in DCM (40 mL) and hexane

6004
S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
ArH); dC (75 MHz, CDCl3) 9.2, 13.8, 14.3, 17.2, 27.4, 29.1, 53.5, 55.0,
125.9, 126.5, 128.0, 1285, 131.5 and 141.1; m/z (EI) 498 (Mþꢀ57, 2%),
430 (4), 291 (14), 224 (48) and 91 (100); HRMS (CI, NH3): MꢀC4Hþ9 ,
found 498.2185. C27H40N120Sn requires 498.2183.
DCM, 0.254 mmol) after chromatography (2:1 petrol/ether, 1% trie-
thylamine) gave the title compound 12 as a colourless oil (24 mg, 35%),
a minor product was detected at the 2% level (1H NMR), [
a]D þ31 (c
2.9, CHCl3); nmax/cmꢀ1 3395 (br), 3027, 2963, 1611, 1512, 1454, 1364,
1303,1247,1031, 745 and 699; dH (300 MHz, CDCl3) major product 12
1.15 (3H, d, J 7, 6-H3), 2.30 (2H, m, 2-H2), 2.85 (1H, br s, OH), 3.60 (1H,
m, 5-H), 3.65 (3H, s, OCH3), 3.88 (4H, s, 2ꢂPhCH2), 4.62 (1H, dd, J 8.0,
5.0, 1-H), 5.65 (2H, m, 3-H, 4-H) and 6.90e7.45 (14H, m, ArH); minor
poduct 1.18 (d, J 7.0, 6-H3); dC (75 MHz, CDCl3) 15.7, 38.0, 49.8, 53.8,
55.3, 73.2,113.7,126.9,127.2,128.2,128.5,129.0,133.9,136.6,139.9and
158.9; m/z (CI, NH3) 402 (Mþþ1,19%) and 198 (100); HRMS (CI, NH3):
MHþ, found 402.2435. C27H32NO2 requires 402.2433.
4.2.6. (1R,5S,3Z)-5-(N,N-Dibenzylamino)-1-phenylhex-3-en-1-ol
(10). Tin(IV) bromide (168 mL, 1.027 M in DCM, 0.173 mmol) was
added to the stannane 9 (96 mg, 0.173 mmol) in DCM (2 mL) at
ꢀ55 ꢁC. After 10 min, benzaldehyde (59
mL, 2.95 M in DCM,
0.173 mmol, cooled to ꢀ55 ꢁC) was added and the mixture was
stirred at ꢀ55 ꢁC for 1 h. Triethylamine (103
mL, 0.692 mmol) was
added followed by saturated aqueous sodium hydrogen carbonate
(2 mL) and the mixture was allowed to warm to room temperature.
The mixture was partitioned between water (30 mL) and DCM
(30 mL) and the aqueous phase was extracted with DCM (20 mL).
The organic extracts were washed with brine (20 mL), dried (MgSO4)
and concentrated under reduced pressure. Chromatography (6:1
petrol/etherþ1% triethylamine) of the residue afforded the title
compound 10 as a colourless oil (35 mg, 55%), the minor product 16
4.2.9. (3R,7S,5Z)-7-(N,N-Dibenzylamino)oct-5-en-3-ol (13). Following
the procedure outlined for alkenol 11, stannane
0.151 mmol), tin(IV) bromide (147 L, 1.027 M in DCM, 0.151 mmol),
and propanal (44 L, 3.47 M in DCM, 0.151 mmol) after chromatog-
9 (84 mg,
m
m
raphy (4:1 petrol/ether, 1% triethylamine) gave the title compound 13
as a colourless oil (14 mg, 30%), [
a
]
þ29 (c 1.2, CHCl3); nmax/cmꢀ1
D
being detected at the 2% level (1H NMR) [
a
]D þ98 (c 2.9, CHCl3); nmax
/
3372 (br), 3027, 2964, 1603, 1494, 1454, 1365, 1137, 1073, 1029, 746
and 699; dH (300 MHz, CDCl3) 0.95 (3H, t, J 7.0,1-H3), 1.24 (3H, d, J 7.0,
8-H3), 1.45 (2H, m, 2-H2), 2.00 (2H, m, 4-H2), 3.35 (6H, m, 3-H,
2ꢂPhCH2, 7-H), 5.65 (2H, m, 5-H, 6-H) and 7.20e7.50 (10H, m, ArH);
dC (75 MHz, CDCl3) 10.0, 15.3, 15.8, 30.2, 35.3, 53.8, 65.9, 72.6, 126.9,
127.4, 128.2, 129.1 and 139.9; m/z (EI) 323 (Mþ, 6%) and 91 (100);
HRMS (CI, NH3): Mþ, found 323.2233. C22H29NO requires 323.2249.
cmꢀ1 3400 (br), 3027, 1603, 1494, 1453, 1109, 1029, 745 and 699; dH
(300 MHz, C6D6) major isomer 10 1.00 (3H, d, J 7.0, 6-H3), 2.15e2.40
(2H, m, 2-H2), 3.55 (2H, d, J 13.0, 2ꢂPhHCH), 3.57e3.70 (3H, m,
2ꢂPhHCH, 5-H), 4.53 (1H, dd, J 8.5, 5.0, 1-H), 5.50 (1H, dd, J 10.0, 9.0,
4-H), 5.60 (1H, dt, J 10.0, 7, 3-H) and 7.10e7.60 (10H, m, ArH); minor
isomer 16 1.08 (d, J 7, 6-H3); dC (75 MHz, CDCl3) 15.6, 38.0, 49.9, 53.8,
73.6, 125.9, 126.8, 127.3, 128.0, 128.2, 128.4, 129.0, 134.1, 139.9 and
144.4; m/z (CI, NH3) 372 (Mþþ1, 100%); HRMS (CI, NH3): MHþ, found
372.2325. C26H30NO requires 372.2327.
4.2.10. (3R,7S,5Z)-7-(N,N-Dibenzylamino)-2-methyloct-5-en-3-ol
(14). Following the procedure outlined for alkenol 11, stannane 9
4-Nitrobenzoyl chloride (18 mg, 0.095 mmol) was added to the
(120 mg, 0.216 mmol), tin(IV) bromide (207 L, 1.044 M in DCM,
m
pentenol 10 (16 mg, 0.043 mmol), triethylamine (13
mL, 0.086 mmol)
0.216 mmol) and 2-methylpropanal (65 mL, 3.31 M in DCM,
and DMAP (5 mg) in DCM (0.5 mL) at 0 ꢁC and the mixture was stirred
for 6 h at room temperature. After concentration under reduced
pressure, chromatography (10:1 petrol/ether) of the residue afforded
the 4-nitrobenzoate 17 as a colourlessoil (12.5 mg, 56%); dH (300 MHz,
CDCl3) 1.05 (3H, d, J 6.5, 6-H3), 2.50e2.75 (2H, m, 2-H2), 3.45 (2H, d, J
14.0, 2ꢂPhHCH), 3.47 (1H, m, 5-H), 3.70 (2H, d, J 14.0, 2ꢂPhHCH), 5.55
(2H, m, 3-H, 4-H), 5.95 (1H, t, J 7.0,1-H), 7.20e8.35 (19H, m, ArH); m/z
(CI, NH3) 521 (Mþþ1, 5%), 491 (20), 196 (100) and 106 (91).
0.216 mmol) after chromatography (4:1 petrol/ether, 1% triethyl-
amine) gave the title compound 14 as a colourless oil (42 mg, 58%),
[a
]
D þ46 (c 1.5, CHCl3); nmax/cmꢀ1 3413 (br), 3027, 2962, 1603, 1494,
1453, 1366, 1139, 1029, 744 and 699; dH (300 MHz, CDCl3) 0.89 and
0.92 (each 3H, t, J 6.0, 1-H3 or 2-CH3), 1.20 (3H, d, J 7.0, 8-H3), 1.65
(1H, m, 2-H), 2.00 (2H, m, 4-H2), 2.25 (1H, br s, OH), 3.35 (1H, m, 3-
H), 3.63 (5H, m, 2ꢂPhCH2, 7-H), 5.65 (2H, m, 5-H, 6-H) and
7.20e7.50 (10H, m, ArH); dC (75 MHz, CDCl3) 16.1, 17.6, 18.6, 32.6,
33.6, 49.8, 53.8, 76.2, 126.8, 128.2, 129.0, 129.2, 133.3 and 140.0; m/z
(CI, NH3) 338 (Mþþ1, 68%) and 106 (100); HRMS (CI, NH3): MHþ,
found 338.2485. C23H32NO requires 338.2484.
4.2.7. (1R,5S,3Z)-5-(N,N-Dibenzylamino)-1-(4-chlorophenyl)hex-3-
en-1-ol (11). Tin(IV) bromide (158 mL,1.027 M in DCM, 0.162 mmol)
was added to the stannane 9 (90 mg, 0.162 mmol) in DCM (2 mL) at
ꢀ78 ꢁC. After 10 min, 4-chlorobenzaldehyde (76
m
L, 3.2 M in DCM,
4.2.11. (1S,5S,3Z)-5-(N,N-Dibenzylamino)-1-phenylhex-3-en-1-yl 4-
nitrobenzoate (15). DEAD (23 mL, 0.142 mmol) was added to the
0.243 mmol, cooled to ꢀ78 ꢁC) was added and the mixture stirred
at ꢀ78 ꢁC for 1 h. Triethylamine (95
m
L, 0.648 mmol) was added
pentenol 10 (35 mg, 0.094 mmol), triphenylphosphine (37 mg,
0.142 mmol) and 4-nitrobenzoic acid (24 mg, 0.142 mmol) in tolu-
ene (2 mL) at ꢀ35 ꢁC. The orange-red colour disappeared imme-
diately and the reaction mixture was stirred for 1.5 h allowing the
solution to warm to room temperature. The mixture was parti-
tioned between ether (15 mL) and water (15 mL) and the aqueous
phase was extracted with ether (15 mL). The organic extracts were
washed with brine (20 mL), dried (MgSO4) and concentrated under
reduced pressure. Chromatography (50:1 petrol/ether) of the resi-
due afforded the title compound 15 as a colourless oil (20 mg, 41%),
followed by saturated aqueous sodium hydrogen carbonate (2 mL).
The mixture was allowed to warm to ambient temperature and the
aqueous phase extracted with DCM. The organic extracts were
washed with brine, dried (MgSO4) and concentrated under reduced
pressure. Chromatography (4:1 petrol/ether, 1% triethylamine) of
the residue gave the title compound 11 as a colourless oil (27 mg,
59%), no minor product was evident (1H NMR), [
a]
þ48 (c 3.2,
D
MeOH); nmax/cmꢀ1 3395 (br), 2967, 1492, 1453, 1091, 1071, 1014, 745
and 699; dH (300 MHz, CDCl3) 1.15 (3H, d, J 7.0, 6-H3), 2.25 (2H, m, 2-
H2), 3.35 (1H, br s, OH), 3.58 (1H, m, 5-H), 3.60 and 3.70 (each 2H, d,
J 14.0, PhHCH), 4.63 (1H, m, 1-H), 5.68 (2H, m, 3-H, 4-H) and
7.15e7.50 (14H, m, ArH); dC (75 MHz, CDCl3) 14.8, 38.2, 49.5, 53.8,
72.7, 127.0, 127.3, 128.0, 128.3, 128.4, 129.2, 132.9, 134.8, 139.5 and
143.0; m/z (CI, NH3) 406 (Mþþ1, 100%); HRMS (CI, NH3): MHþ,
found 406.1945. C26H2935ClNO requires 406.1938.
[
a D
l
þ57 (c 1.8, CHCl3); nmax/cmꢀ1 3028, 2967, 1726, 1605, 1529,
1494, 1454, 1343, 1272, 1075, 1015 and 699; dH (300 MHz, CDCl3)
1.10 (3H, d, J 7.0, 6-H3), 2.45e2.80 (2H, m, 2-H2), 3.50 (2H, d, J 14.0,
2ꢂPhHCH), 3.62 (1H, qn, J 7.0, 5-H), 3.70 (2H, d, J 14.0, 2ꢂPhHCH),
5.60 (2H, m, 3-H, 4-H), 6.00 (1H, dd, J 8.5, 5.0, 1-H) and 7.20e8.35
(19H, m, ArH); dC (75 MHz, CDCl3) 17.3, 34.7, 50.3, 53.7, 77.2, 123.5,
126.1, 126.5, 126.7, 128.2, 128.3, 128.6 (2), 130.7, 134.1, 135.7, 139.6,
140.5, 150.6 and 163.8; m/z (CI, NH3) 491 (10%) and 196 (100).
4.2.8. (1R,5S,3Z)-5-(N,N-Dibenzylamino)-1-(4-methoxyphenyl)hex-
3-en-1-ol (12). Following the procedure outlined for alkenol 11,
stannane 9 (94 mg, 0.169 mmol), tin(IV) bromide (165
mL, 1.027 M in
4.2.12. (1S,5S,3Z)-5-(N,N-Dibenzylamino)-1-phenylhex-3-en-1-ol
DCM, 0.169 mmol) and 4-methoxybenzaldehyde (86
mL, 2.88 M in
(16). Nitrobenzoate ester 15 (20 mg, 0.038 mmol) was added to

S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
6005
sodium hydroxide (14 mg, 0.56 mmol) in methanol (2 mL) and the
solution stirred at room temperature for 50 min. DCM (10 mL) was
added and the aqueous phase was extracted with DCM (20 mL). The
organic extracts were washed using brine (20 mL) and dried
(MgSO4). After concentration under reduced pressure, chromatog-
raphy (6:1 petrol/ether) afforded the title compound 16 as a col-
d, J 7.0, 6-H3), 2.10 (3H, s, O2CCH3), 2.30e2.65 (2H, m, 2-H2), 3.55
(1H, m, 5-H), 3.57 and 3.75 (each 2H, d, J 14.0, 2ꢂPhHCH), 5.55 (2H,
m, 3-H, 4-H), 5.75 (1H, t, J 6.5, 1-H) and 7.15e7.45 (I5H, m, ArH); m/z
(CI, NH3) 414 (Mþþ1, 16%) and 121 (100); HRMS (CI, NH3): MHþ,
found 414.2438. C28H32NO2 requires 414.2433.
Ozone was bubbled through a solution of acetate 20 (86 mg,
0.2 mmol) in DCM (10 mL) over a period of 40 min at ꢀ78 ꢁC and
the solution was then purged with oxygen for 10 min. Methyl sul-
ourless oil (8 mg, 57%), [
a
]
D ꢀ37 (c 0.6, CHCl3); nmax/cmꢀ1 3400 (br),
3027, 2925,1603,1494,1453,1365,1029, 745 and 699; dH (300 MHz,
CDCl3) 1.20 (3H, d, J 6.5, 6-H3), 2.30 (2H, t, J 6.5, 2-H2), 2.80 (1H, br s,
OH), 3.55 (1H, m, 5-H), 3.60 and 3.65 (each 2H, d, J 14.0, 2ꢂPhHCH),
4.70 (1H, t, J 6.5, 5-H), 5.50e5.75 (2H, m, 3-H, 4-H) and 7.20e7.50
(15H, m, ArH); dC (75 MHz, CDCl3) 16.2, 37.2, 50.0, 53.8, 73.3, 125.9,
126.8, 127.3, 127.4, 128.2 (2), 128.9, 134.3, 140.0 and 144.1; m/z (CI,
NH3) 372 (Mþþ1, 45 %), 198 (77) and 91 (86); HRMS (CI, NH3): MHþ,
found 372.2329. C26H30NO requires 372.2327.
phide (146 mL, 2.0 mmol) was added and the mixture warmed to
ambient temperature. After concentration under reduced pressure
the residue was dissolved in DCM (5 mL). Sodium borohydride
(32 mg, 0.8 mmol) in methanol (5 mL) was added and the solution
stirred for 2 h. Water (3 mL) was added and the aqueous phase
extracted with DCM. The organic extracts were washed with brine,
dried (MgSO4) and concentrated under reduced pressure. Chro-
matography of the residue (3:1 petrol/ether) afforded (R)-3-
acetoxy-3-phenylpropan-1-ol [(R)-21] as a colourless oil (7 mg,
4.2.13. (1R,5S,3Z)-1-[(R)-2-Acetoxy-2-phenylacetoxy]-5-(N,N-di-
benzylamino)-1-phenylhex-3-ene (18). Dicyclohexylcarbodiimide
(25 mg, 0.121 mmol) was added to a solution of (R)-2-acetoxy-2-
phenylacetic acid (24 mg, 0.121 mmol), 4-N,N-dimethylaminopyr-
idine (5 mg) and the alcohol 10 (30 mg, 0.081 mmol) in DCM (2 mL)
and the solution stirred for 18 h at ambient temperature. After
concentration under reduced pressure, hexane (5 mL) was added
and the mixture filtered. The filtrate was washed with aqueous
hydrogen chloride (1 M) and saturated aqueous sodium hydrogen
carbonate then dried (MgSO4). After concentration under reduced
pressure, chromatography of the residue (4:1 petrol/ether) afforded
18%), [
a
]
D þ78 (c 0.7, CHCl3) [lit.2 þ79.2 (c 1, CHCl3)].
4.2.16. (3S,7S,5Z)-7-(N,N-Dibenzylamino)-2-methyloct-5-en-3-yl 4-
nitrobenzoate (22). Diethyl azodicarboxylate (55 L, 0.34 mmol)
m
was added to the alcohol 14 (42 mg, 0.113 mmol), triphenylphos-
phine (89 mg, 0.340 mmol) and 4-nitrobenzoic acid (58 mg,
0.340 mmol) in toluene (2 mL) at ꢀ35 ꢁC. The orange-red colour
disappeared immediately and the reaction mixture was stirred for
90 min allowing the solution to warm to ambient temperature. The
mixture was partitioned between ether and water and the aqueous
phase extracted with ether. The organic extracts were washed with
brine, dried (MgSO4) and concentrated under reduced pressure.
Chromatography (80:1 petrol/ether) of the residue gave the title
the title compound 18 as a colourless oil (26 mg, 58%), [
a
]
þ7.1 (c
D
1.6, CHCl3); nmax/cmꢀ1 2929, 1744, 1d, J 7, 6-H3), 2.22 (3496, 1455,
1373, 1232, 1208, 1175, 1057, 750 and 699; dH (300 MHz, CDCl3) 1.00
(3H, H, s, O2CCH3), 2.40 (2H, m, 2-H2), 3.37 (1H, m, 5-H), 3.45 and
3.73 (each 2H, d, J 14.0, 2ꢂPhHCH), 5.55 (2H, m, 3-H and 4-H), 5.70
(1H, t, J 7.0, 1-H), 6.05 (1H, s, O2CCH) and 6.75e7.50 (20H, m, ArH);
dC (75 MHz, CDCl3) 17.7, 20.8, 34.5, 50.3, 53.6, 74.5, 77.2,125.9,126.2,
126.7, 127.8, 128.0, 128.1, 128.6, 128.7, 129.2, 133.2, 133.6, 139.1,
140.6, 167.9 and 170.3; m/z (CI, NH3) 548 (Mþþ1, 52%) and 106
(100); HRMS (CI, NH3): MHþ, found 548.2794. C36H38NO4 requires
548.2801.
compound 22 as a colourless oil (19 mg, 31%), [
a
]
þ49 (c 0.7,
D
CHCl3); nmax/cmꢀ1 2965, 1722, 1606, 1528, 1274, 1102, 720 and 699;
dH (300 MHz, CDCl3) 0.91 and 0.93 (each 3H, d, J 7.0, CH3), 1.05 (3H,
d, J 7.0, 8-H3), 1.90 (1H, m, 2-H), 2.25 (2H, m, 4-H2), 3.45 (2H, d, J
14.0, 2ꢂPhHCH), 3.60 (1H, m, 7-H), 3.70 (2H, d, J 14.0, 2ꢂPhHCH),
5.00 (1H, dt, J 9.0, 7.0, 3-H), 5.55 (2H, m, 5-H, 6-H), 7.20e7.45 (10H,
m, ArH) and 8.13 and 8.30 (each 2H, d, J 8.5, ArH); dC (75 MHz,
CDCl3) 17.7, 18.6, 29.7, 29.9, 31.7, 50.0, 53.7, 123.5, 126.7, 127.1, 128.2,
128.5, 130.6, 133.0, 140.6, 150.5 and 164.2; m/z (CI, NH3) 487 (Mþþ1,
100%) and 457 (80); HRMS (CI, NH3): MHþ, found 487.2593.
C30H35N2O4 requires 487.2597.
4.2.14. (1R,5S,3Z)-1-[(S)-2-Acetoxy-2-phenylacetoxy]-5-(N,N-di-
benzylamino)-1-phenylhex-3-ene (19). Following the procedure
outlined for ester 18, alcohol 10 (30 mg, 0.081 mmol) and (S)-2-
acetoxy-2-phenylacetic acid, after chromatography (4:1 petrol/
ether) gave the title compound 19 as a colourless oil (29 mg, 64%),
4.2.17. (3S,7S,5Z)-7-(N,N-Dibenzylamino)-2-methyloct-5-en-3-ol
(23). Nitrobenzoate 22 (9 mg, 0.019 mmol) was added to sodium
hydroxide (1% w/v in MeOH, 1 mL) and the solution stirred at
ambient temperature for 3 h. DCM and water were added and the
aqueous phase was extracted with DCM. The organic extracts were
washed with brine, dried (MgSO4) and concentrated under reduced
pressure. Chromatography (6:1 petrol/ether) of the residue affor-
ded the title compound 23 as a colourless oil (3 mg, 48%); nmax/cmꢀ1
3415 (br), 2956, 1494, 1453, 1028, 745 and 699; dH (200 MHz, CDCl3)
0.81 and 0.87 (each 3H, d, J 6.0, 1-H3 or 2-CH3), 1.20 (3H, d, J 7.0, 8-
H3), 1.55 (1H, m, 2-H), 1.70 (1H, br s, OH), 2.00 (2H, m, 4-H2), 3.30
(1H, m, 3-H), 3.45 (2H, d, J 14.0, 2ꢂPhHCH), 3.55 (1H, m, 7-H), 3.70
(2H, d, J 14.0, 2ꢂPhHCH), 5.65 (2H, m, 5-H, 6-H) and 7.20e7.45 (10H,
m, ArH); m/z (CI, NH3) 338 (Mþþ1, 75%) and 106 (100); HRMS (CI,
NH3): MHþ, found 338.2487. C23H32NO requires 338.2484.
[
a]
D þ74 (c 2.8, CHCl3); nmax/cmꢀ1 3031,1744,1495,1454,1372,1231,
1208,1175,1057, 749 and 699; dH (300 MHz, CDCl3) 0.95 (3H, d, J 7.0,
6-H3), 2.20 (3H, s, O2CCH3), 2.35 (2H, m, 2-H2), 3.30 (1H, m, 5-H),
3.32 and 3.65 (each 2H, d, J 14.0, PhHCH), 5.25 (1H, dt, J 10.0, 7, 3-H),
5.40 (1H, t, J 10.0, 4-H), 5.70 (1H, t, J 7.0, 1-H), 6.05 (1H, s, O2CCH),
7.10e7.50 (20H, m, ArH); dC (75 MHz, CDCl3) 17.5, 20.8, 34.3, 50.2,
53.6, 74.6, 125.9, 126.4, 126.7, 127.9, 128.1, 128.3, 128.6, 128.8, 129.3,
133.0, 134.0, 139.1, 140.5, 168.2 and 170.2; m/z (CI, NH3) 548 (Mþþ1,
58%) and 106 (100) HRMS (CI, NH3): MHþ, found 548.2800.
C36H38NO4 requires 548.2801.
4.2.15. (lR,5S,3Z)-1-Acetoxy-5-(N,N-dibenzylamino)-1-phenylhex-3-
ene (20). Triethylamine (166
mL, 1.12 mmol), DMAP (2 mg) and
acetic anhydride (56 L, 0.659 mmol) were added to the pentenol
m
10 (83 mg, 0.224 mmol) in DCM (3 mL) and the mixture was stirred
at room temperature for 18 h. Water (5 mL) was added and the
aqueous phase extracted with DCM (10 mL). The organic extracts
were washed with brine (l0 mL), dried (MgSO4) and concentrated
under reduced pressure. Chromatography (3:1, petrol/ether) of the
residue afforded the title compound 20 as a colourless oil (78 mg,
4.2.18. (3R,7S,5Z)-7-(N,N-Dibenzylamino)-2-methyloct-5-en-3-yl 4-
nitrobenzoate (24). 4-Nitrobenzoyl chloride (46 mg, 0.242 mmol)
was added to the alcohol 14 (31 mg, 0.110 mmol), triethylamine
(33 m
L, 0.220 mmol) and DMAP (5 mg) in DCM (1 mL) at 0 ꢁC. The
mixture was stirred for 6 h at ambient temperature and then con-
centrated under reduced pressure. Chromatography (10:1 petrol/
ether) of the residue gave the title compound 24 as a colourless oil
85%), [
a]
þ51 (c 1.3, CHCl3); nmax/cmꢀ1 2964, 2927, 1739, 1529,
D
1494, 1453, 1371, 1236, 1027 and 699; dH (200 MHz, CDCl3) 1.05 (3H,
(26 mg, 58%), [
a]
þ23 (c 2.7, CHCl3); nmax/cmꢀ1 3027, 2966, 1723,
D

6006
S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
1607, 1529, 1494, 1454, 1348, 1274, 1118, 1102, 746, 720 and 699; dH
(300 MHz, CDCl3) 0.89 and 0.91 (each 3H, d, J 7.0, CH3), 1.20 (3H, d, J
7.0, 8-H3), 1.95 (1H, m, 2-H), 2.30 (2H, m, 4-H2), 3.45 (2H, d, J 14.0,
2ꢂPhHCH), 3.60 (1H, qn, J 7.0, 7-H), 3.73 (2H, d, J 14.0, 2ꢂPhHCH),
5.03 (1H, dt, J 8.5. 5.0, 3-H), 5.60 (2H, m, 5-H, 6-H), 7.20e7.40 (10H,
m, ArH) and 8.23 and 8.33 (each 2H, d, J 8.5, ArH); dC (75 MHz,
CDCl3) 17.5, 17.9, 18.7, 29.7, 31.4, 50.6, 53.8, 80.2, 123.6, 126.7, 128.1,
128.6, 130.7, 133.0, 136.0, 140.5, 150.5 and 164.4; m/z (CI, NH3) 486
(Mþ, 100%); HRMS (CI, NH3): Mþ, found 486.2516. C30H34N2O4 re-
quires 486.2519.
HRMS (CI, NH3): Mþ, found 553.2812. C33H38F3NO3 requires
553.2804.
4.2.22. (3R,7S,5Z)-7-(N,N-Dibenzylamino)-2-methyloct-5-en-3-yl
[(S)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoate (28). Following
the procedure outlined for ester 27, alcohol 14 (26 mg, 0.077 mmol)
and (R)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoyl chloride gave
the title compound 28 as a colourless oil (21 mg, 49%); dH (200 MHz,
CDCl3) 0.69 and 0.71 (each 3H, d, J 7.0, CH3), 1.20 (3H, d, J 7.0, 8-H3),
1.75 (1H, m, 2-H), 2.15 (2H, m, 4-H2), 3.40 (2H, d, J 14.0, 2ꢂPhHCH),
3.50 (1H, m, 7-H), 3.55 (3H, s, OCH3), 3.70 (2H, d, J 14.0, 2ꢂPhHCH),
4.95 (1H, dt, J 9.0, 6.0, 3-H), 5.55 (2H, m, 5-H, 6-H) and 7.15e7.60
(15H, m, ArH); dF (470 MHz, CDCl3) ꢀ72.70 (major), ꢀ72.75.
4.2.19. (3R,7S,5Z)-7-(N,N-Dibenzylamino)-3-[(R)-2-acetoxy-2-
phenylacetoxy]-2-methyloct-5-ene (25). Following the procedure
outlined for ester 18, alcohol 14 (21 mg, 0.062 mmol) and (R)-2-
acetoxy-2-phenylacetic acid, after chromatography (4:1 petrol/
ether), gave the title compound 25 as a colourless oil (14 mg,
4.2.23. S-Methyl-O-[(4R)-5-(tert-butyldimethylsilyloxy)-4-methyl
pent-2-en-1-yl]dithiocarbonate (45). n-Butyllithium (25 mL, 1.6 M
solution in hexanes, 39.5 mmol) was added dropwise to the alcohol
44 (7.56 g, 32.9 mmol) in THF (200 mL) at 0 ꢁC. The solution was
stirred for 30 min, then carbon disulphide (8.25 mL, 131.6 mmol)
was added and the mixture was stirred at ambient temperature for
3 h. Iodomethane (8.25 mL, 131.6 mmol) was added and the mix-
ture was stirred for 18 h. Saturated aqueous ammonium chloride
was added and the aqueous phase was extracted with ether. The
organic extracts were washed with brine, dried (MgSO4) and con-
centrated under reduced pressure. Chromatography of the residue
(20:1 petrol/ether) gave the title compound 45 as a yellow oil
(8.02 g, 76%), an 80:20 mixture of (E)- and (Z)-isomers (1H NMR),
44%), [
a
]
ꢀ35 (c 1.6, CHCl3); nmax/cmꢀ1 2965, 1743, 1498, 1457,
D
1373, 1234, 1211, 1179, 1057, 753 and 699; dH (500 MHz, CDCl3)
0.50 (6H, d, J 6.0, 1-H3, 2-CH3), 1.15 (3H, d, J 7.0, 8-H3), 1.55 (1H,
m, 2-H), 2.10 (2H, m, 4-H2), 2.19 (3H, s, O2CCH3), 3.40 (2H, d, J
11.0, 2ꢂPhHCH), 3.50 (1H, m, 7-H), 3.70 (2H, d, J 11.0, 2ꢂPhHCH),
4.70 (1H, m, 3-H), 5.50 (2H, m, 5-H, 6-H), 5.95 (1H, s, O2CCH) and
7.10e7.50 (15H, m, ArH); dC (75 MHz, CDCl3) 16.8, 18.3, 20.9, 29.7,
31.3, 50.4, 53.6, 74.7, 79.8, 126.5, 127.0, 127.6, 128.0, 128.5, 129.0,
132.0, 134.1, 140.6, 168.4 and 169.9; m/z (CI, NH3) 514 (Mþþ1,
100%); HRMS (CI, NH3): MHþ, found 514.2945. C33H40NO4 re-
quires 514.2957.
[
a
]
ꢀ8.1 (c 2.3, CHCl3); nmax/cmꢀ1 2956, 2847, 1471, 1387, 1255,
D
4.2.20. (3R,7S,5Z)-7-(N,N-Dibenzylamino)-3-[(S)-2-acetoxy-2-
phenylacetoxy]-2-methyloct-5-ene (26). Following the procedure
outlined for ester 18, alcohol 14 (19 mg, 0.051 mmol) and (S)-2-
acetoxy-2-phenylacetic acid, after chromatography (4:1 petrol/
ether), gave the title compound 26 as a colourless oil (22 mg, 76%),
1063, 838 and 777; dH (300 MHz, CDCl3) 0.08 (6H, s, 2ꢂCH3Si),
0.90e1.05 [12H, m, 4-CH3, (CH3)3CSi], 2.40 (0.8H, m, 4-H), 2.60 (3H,
s, SCH3), 2.70 (0.2H, m, 4-H), 3.40e3.60 (2H, m, 5-H2), 5.05 (2H, d, J
6.5, 1-H2) and 5.60e5.90 (2H, m, 2-H, 3-H); m/z (CI, NH3) 338
(Mþþ18, 100%) and 321 (Mþþ1, 9); HRMS (CI, NH3): MNH4þ, found
338.1648. C14H32NO2S2Si requires 338.1643.
[
a]
þ57 (c 2.2, CHCl3); nmax/cmꢀ1 2965, 1743, 1498, 1457, 1373,
D
1234, 1180, 1055, 1003, 753 and 700; dH (500 MHz, CDCl3) 0.75 and
0.77 (each 3H, d, J 7.0, CH3), 1.09 (3H, d, J 7.0, 8-H3), 1.70 (1H, oct, J
7.0, 2-H), 1.92 (2H, t, J 7.0, 4-H2), 2.18 (3H, s, O2CCH3), 3.20 (2H, d, J
14.0, 2ꢂPhHCH), 3.35 (1H, m, 7-H), 3.60 (2H, d, J 14.0, 2ꢂPhHCH),
4.70 (1H, q, J 7.0, 3-H), 5.05 (1H, dt, J 10.5, 7.0, 5-H), 5.20 (1H, t, J 10.5,
6-H), 5.88 (1H, s, O2CCH) and 7.10e7.50 (15H, m, ArH); dC (75 MHz,
CDCl3) 17.4, 18.1, 18.4, 20.8, 29.3, 31.5, 50.1, 53.5, 74.8, 80.0, 126.5,
126.8, 127.8, 128.0, 128.4, 128.5, 129.1, 131.7, 133.8, 140.4, 168.5 and
170.1; m/z (CI, NH3) 514 (Mþþ1,100%); HRMS (CI, NH3): MHþ, found
514.2936. C33H40NO4 requires 514.2957.
4.2.24. S-Methyl-S0-[(4S)-5-tert-butyldimethylsilyloxy-4-methyl-
pent-1-en-3-yl]dithiocarbonate (46). The xanthate 45 (8.02 g,
25.1 mmol) in degassed toluene (100 mL) was heated under reflux
for 18 h. After concentration under reduced pressure, chromatog-
raphy (50:1 petrol/ether) gave the title compounds 46 as a colour-
less oil (6.97 g, 87%), [
a
]
D þ3.9 (c 2.1, CHCl3); nmax/cmꢀ1 2956, 1649,
1470, 1256, 1104, 870, 776 and 666; dH (300 MHz, CDCl3) 0.05 (6H, s,
2ꢂCH3Si), 0.95 [12H, m, 4-CH3, (CH3)3CSi], 2.02 (1H, m, 4-H), 2.20
(3H, s, SCH3), 3.55 (2H, m, 5-H2), 4.45 (1H, m, 3-H), 5.20 (2H, m, 1-
H2) and 5.85 (1H, m, 2-H); m/z (CI, NH3) 338 (Mþþ18,100%) and 321
(Mþþ1, 65); HRMS (CI, NH3): MHþ, found 321.1377. C14H29O2S2Si
requires 321.1378.
4.2.21. (3R,7S,5Z)-7-(N,N-Dibenzylamino)-2-methyloct-5-en-3-yl
(R)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoate (27). Alcohol 14
(28 mg, 0.083 mmol) in carbon tetrachloride (0.5
(S)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoyl chloride (32 mg,
0.125 mmol) in pyridine (0.5 L) and the solution stirred for 2 h at
ambient temperature. 3-(N,N-Dimethylamino)propylamine
(0.5 L) was added and, after 10 min, the solution was partitioned
mL) was added to
4.2.25. (4R)-5-tert-Butyldimethylsilyloxy-4-methylpent-2-
enyl(tributyl)stannane (47). Tri-n-butyltin hydride (10.95 mL,
32.7 mmol) was added to the dithiocarbonate 46 (6.97 g,
21.8 mmol) and AIBN (350 mg) in degassed benzene (120 mL) and
the solution was heated under reflux for 3 h. After concentration
under reduced pressure, chromatography (petrol, 0.5% triethyl-
amine) of the residue gave the title compound 47 as a colourless oil
m
m
between ether and water. The aqueous phase was extracted with
ether and the organic extracts were washed with dilute aqueous
aqueous hydrogen chloride (1 M), saturated aqueous sodium hy-
drogen carbonate and brine, then dried (MgSO4). Concentration
under reduced pressure afforded the title compound 27 as a pale
(7.96 g, 73%), [
a
]
D
ꢀ4.6 (c 2.3, CHCl3); nmax/cmꢀ1 2957, 1523, 1377,
1254, 1085, 1006, 835, 775 and 667; dH (300 MHz, CDCl3) 0.05 (6H,
s, 2ꢂCH3Si), 0.85e1.05 [27H, m, (CH3)3CSi, 4-CH3, 3ꢂCH2, 3ꢂCH3],
1.15e1.75 (14H, m, 1-H2, 6ꢂCH2), 2.28 (1H, m, 4-H), 3.30 and 3.52
(each 1H, m, 5-H) and 5.15 and 5.62 (each 1H, m, 2-H or 3-H); mþ/z
yellow oil (36 mg, 78%), [
a]
þ43 (c 2.5, CHCl3); nmax/cmꢀ1 2968,
D
1743, 1494, 1453, 1370, 1260, 1168, 1123, 1079, 1020, 996, 837 and
700; dH (300 MHz, CDCl3) 0.73 and 0.83 (each 3H, d, J 7.0, CH3),
1.17 (3H, d, J 7.0, 8-H3), 1.85 (1H, m, 2-H), 2.10 (2H, m, 4-H2), 3.30
(2H, d, J 14.0, 2ꢂPhHCH), 3.45 (1H, dq, J 11.5, 7.0, 7-H), 3.55 (3H, s,
OCH3), 3.68 (2H, d, J 14.0, 2ꢂPhHCH), 4.90 (1H, dt, J 9.0 6.0, 3-H),
5.35 (1H, dt, J 11.0, 6.0, 5-H), 5.45 (1H, dd, J 11.0, 9.0, 6-H) and
7.15e7.60 (15H, m, ArH); dF (470 MHz, CDCl3) ꢀ72.75 (major) and
ꢀ72.70 (trace); m/z (EI) 553 (Mþ, 3%), 539 (60) and 189 (100);
(EI) 447 (Mþꢀ57, 15%) and 177 (100); HRMS (CI, NH3): MꢀC4H9
,
found 447.2102. C20H43OSi120Sn requires 447.2105.
4.2.26. (4R)-5-Hydroxy-4-methylpent-2-enyl(tributyl)stannane
(48). Tetrabutylammonium fluoride (31.7 mL, 1 M in THF,
31.7 mmol) was added to the stannane 47 (7.96 g, 15.8 mmol) and

S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
6007
the solution was stirred for 18 h. After concentration under reduced
pressure, chromatography (gradient: petrol to 5:1 petrol/etherþ1%
triethylamine) of the residue gave the title compound 48 as a col-
ourless oil (5.48 g, 89%), an 80:20 mixture of (E)- and (Z)-isomers
(br), 3028, 2958, 1602, 1494, 1453, 1049, 760 and 701; dH (500 MHz,
CDCl3) major isomer 51 0.90 (3H, d, J 7.0, 5-CH3), 2.20e2.65 (6H, m,
6-CH2, 5-H, 2-H2, OH), 3.66 (2H, s, PhCH2), 4.70 (1H, dd, J 8.0 and
4.5, 1-H), 5.28 (1H, t, J 10.5, 4-H), 5.42 (1H, m, 3-H) and 7.20e7.40
(10H, m, ArH); minor isomers 0.97 and 1.03 (each d, J 7, 5-CH3), 3.67
and 3.68 (each s, PhCH2), 4.65 (dd, J 9.0, 4.0, 1-H) and 4.73 (t, J 5.5,1-
H); dC (75 MHz, CDCl3) major isomer 51 20.7, 32.2, 36.6, 38.2, 38.6,
73.3, 125.1, 125.7, 126.9, 127.3, 128.2, 128.4, 128.8, 137.6 and 144.0;
m/z (CI, NH3) 330 (Mþþ18, 100%), 295 (Mþꢀ17, 70); HRMS (CI,
NH3): MNH4þ, found 330.1895. C20H28NOS requires 330.1891.
Following the procedures outlined for the alkenol 10, acetyla-
tion of the hexenol 51 (73%) and ozonolysis of the acetate (71 mg,
0.192 mmol) gave, after chromatography (5:2 petrol/ether), (S)-3-
(1H NMR), [
a
]
D þ7.1 (c 1.9, CHCl3); nmax/cmꢀ1 3345 (br), 2957, 2923,
1655, 1460, 1376, 1035, 962 and 868; dH (300 MHz, CDCl3)
0.85e0.95 (15H, m, 3ꢂCH2, 3ꢂCH3), 1.00 (3H, d, J 7.0, 4-CH3),
1.20e1.95 (14H, m, CH2Sn, 6ꢂCH2), 2.30 (1H, qn, J 7.0, 4-H),
3.30e3.55 (2H, m, 5-H2), 4.85 (0.2H, t, J 10.0, 3-H), 5.05 (0.8H, dd, J
15.0, 8, 3-H) and 5.70 (1H, m, 2-H); m/z (EI) 333 (Mþꢀ57, 39%) and
þ
235 (100); HRMS (CI, NH3): MꢀC4H9
,
found 333.1241.
C14H29O120Sn requires 333.1240.
4.2.27. (4R)-5-Acetylthio-4-methylpent-2-enyl(tributyl)stannane
(49). Di-iso-propyl azodicarboxylate (3 mL, 15.4 mmol) was added to
triphenylphosphine (4.03 g,15.4 mmol) in THF (20 mL) at 0 ꢁC and the
mixture stirred for 30 min. The hydroxyalkylstannane 48 (2 g,
5.14 mmol) and thioacetic acid (1.1 mL, 15.4 mmol) in THF (30 mL)
were added and the mixture stirred at 0 ꢁC for 1 h, then at ambient
temperature for 1 h. After concentration under reduced pressure,
chromatography (petrol,1% triethylamine) of the residue gave the title
compound 49 as a colourless oil (1.66 g, 72%), an 80:20 mixture of (E)
acetoxy-3-phenylpropan-1-ol (S)-21 as a colourless oil, [
a
]
ꢀ42
D
(c 1.9, CHCl3) and (S)-3-acetoxy-1-phenylpropan-1-ol 60, [a]
ꢀ12
D
(c 1.5, CHCl3) (lit.12 for the (R)-enantiomer þ15 (c 0.49, CHCl3)
(34 mg, combined yield, 91%)) both with spectroscopic data iden-
tical to those obtained previously.
4.2.30. (1S,5R,3Z)-6-Benzylthio-5-methyl-1-(4-nitrophenyl)hex-3-
en-1-ol (52). Following the procedure outlined for the synthesis of
alkenol 51, stannane 50 (80 mg, 0.16 mmol), tin(IV) bromide (146
1.1 M in DCM, 0.16 mmol) and p-nitrobenzaldehyde (0.244
0.66 M in DCM, 0.16 mmol) after chromatography (4:1 petrol/ether,
m
m
L,
L,
and (Z)-isomers (1H NMR), [
a]
D
þ9.6 (c 4.1, CHCl3); nmax/cmꢀ1 2957,
2925, 2871, 1696, 1457, 1376, 1353, 1136, 960 and 875; dH (300 MHz,
CDCl3) 0.85e0.95 (15H, m, 3ꢂCH2CH3), 1.05 (3H, d, J 7.0, 4-CH3),
1.30e1.65 (12H, m, 3ꢂCH2CH2), 1.70 (2H, d, J 8.0, 1-H2), 2.35 (4H, m, 4-
H, CH3CO), 2.85 (2H, m, 5-H2), 4.90 (0.2H, dd, J 10.5, 9.5, 3-H), 5.10
(0.8H, dd, J 15.0, 7.5, 3-H) and 5.60 (1H, m, 4-H); dC (75 MHz, CDCl3)(E)-
isomer 9.2, 13.7, 14.2, 20.3, 27.4, 29.2, 30.6, 36.4, 36.9, 128.9, 129.7 and
196.0;m/z(EI) 448 (Mþ, 3%), 391(Mþꢀ57, 51)and 179 (100); HRMS (CI,
NH3): MꢀC4H9þ, found 391.1112. C16H31OS120Sn requires 391.1118.
1% triethylamine) gave the title compound 52 as a colourless oil
(38 mg, 66%), an 82:10:8 mixture of diastereoisomers (1H NMR), [
a]
D
ꢀ14 (c 3.7, CHCl3); nmax/cmꢀ1 3429 (br), 2958, 1603,1520,1453,1346,
1068 and 855; dH (500 MHz, CDCl3) major isomer 52 0.90 (3H, d, J
8.5, 5-CH3), 2.25e2.60 (5H, m, 2-H2, 6-H2, 5-H), 2.72 (1H, br s, OH),
3.68 and 3.72 (each 1H, d, J 13.0, PhHCH), 4.80 (1H, dd, J 8.5, 4.0,1-H),
5.32 (1H, t, J 10.0, 4-H), 5.40 (1H, dt, J 9.5, 6.0, 3-H), 7.20e7.30 (5H, m,
ArH) and 7.52 and 8.17 (each 2H, d, J 9.0, ArH); minor isomers 0.94
and 1.05 (each d, J 7.0, 5-CH3), 3.6 (s, PhCH2), 4.73 (dd, J 8.5, 4.0, 1-H),
4.86 (dd, J 6.5, 5.5, 1-H); dC (75 MHz, CDCl3) major isomer 52 20.6,
32.1, 36.8, 38.1, 38.3, 72.4,123.2, 124.1, 126.2, 126.7, 128.2, 128.5, 138.4
and 151.2; m/z (EI) 357 (Mþ, 13%), 340 (Mþꢀ17, 41) and 91 (100);
HRMS (CI, NH3): Mþ, found 357.1398. C20H23NO3S requires 357.1399.
4.2.28. (4R)-5-Benzylthio-4-methylpent-2-enyl(tributyl)stannane
(50). Potassium hydroxide (362
was added to the stannane 49 (219 mg, 0.49 mmol) in ethanol
(8 mL) and the solution stirred for 10 min. Benzyl chloride (139 L,
mL, 10% w/v in EtOH, 0.64 mmol)
m
1.23 mmol) was added and the solution stirred for 1 h. Ether and
water were added and the aqueous phase extracted with ether. The
organic extracts were washed with brine, dried (MgSO4) and con-
centrated under reduced presure. Chromatography (petrol, 1%
triethylamine) of the residue gave the title compound 50 as a col-
ourless oil (238 mg, 98%), as an 80:20 mixture of (E)- and (Z)-iso-
4.2.31. (3S,7R,5Z)-8-Benzylthio-2,7-dimethyloct-5-en-3-ol
(53). Following the procedure outlined for the synthesis of alkenol
51, stannane 50 (202 mg, 0.408 mmol), tin(IV) bromide (0.37
1.1 M in DCM, 0.408 mmol) and 2-methypropanal (38
m
m
L,
L,
mers (1H NMR), [
a
]
D
ꢀ5.6 (c 2.5, CHCl3); nmax/cmꢀ1 2957, 2924,
0.408 mmol) after chromatography (20:1 petrol/ether, 0.5% trie-
1457, 1073 and 962; dH (300 MHz, CDCl3) 0.85e0.95 (15H, m,
3ꢂCH2, 3ꢂCH3), 1.05 (3H, d, J 7.0, 4-CH3), 1.30e1.60 (12H, m,
6ꢂCH2), 1.73 (1.6H, d, J 7.0, 1-H2), 1.82 (0.4H, d, J 7.0, 1-H2),
2.25e2.50 (2H, m, 5-H2), 3.70 (1.6H, s, PhCH2), 3.77 (0.4H, s, PhCH2),
4.90 (0.2H, dd, J 10.5, 9.5, 3-H), 5.10 (0.8H, dd, J 15.0, 8.0, 3-H), 5.55
(1H, m, 2-H) and 7.30 (5H, m, ArH); dC (75 MHz, CDCl3) 9.2, 13.8,
14.2, 20.3, 27.4, 29.2, 36.7, 36.8, 39.4, 126.8, 128.4, 128.8, 128.9, 129.7
and 138.8; m/z (EI) 439 (Mþꢀ57, 2%) and 91 (100); HRMS (CI, NH3):
MꢀC4H9þ, found 439.1498. C21H35S120Sn requires 439.1481.
thylamine) gave the title compound 53 as a colourless oil (80 mg,
71%), an 87:13 mixture of two diastereoisomers (1H NMR), [
a
]
D þ15
(c 3.2, CHCl3); nmax/cmꢀ1 3443 (br), 2958, 1494, 1453, 1238, 1030,
870 and 700; dH (500 MHz, CDCl3) major isomer 53 0.925 and 0.935
(each 3H, d, J 7.0, CH3), 0.96 (3H, d, J 7.0, 7-CH3), 1.70 (1H, oct, J 6.5,
2-H), 2.08 (1H, br s, OH), 2.15 (2H, m, 8-H2), 2.30 (1H, dd, J 13.0, 9.0,
4-H), 2.38 (1H, dd, J 13.0, 5.0, 4-H), 2.65 (1H, m, 7-H), 3.37 (1H, dt, J
8.5, 5.0, 3-H), 3.67 and 3.70 (each 1H, d, J 14.0, PhHCH), 5.28 (1H, t, J
10.5, 6-H), 5.40 (1H, m, 5-H) and 7.20e7.30 (5H, m, ArH); minor
isomer 61 0.99 (d, J 7.0, 7-CH3); dC (75 MHz, CDCl3) major isomer 53
17.6, 18.8, 20.9, 32.1, 32.6, 33.4, 36.9, 38.6, 76.1, 126.4, 126.9, 128.5,
129.0, 137.3 and 138.4; minor isomer 61 17.8, 18.9, 20.8, 33.2, 38.8,
76.2, 125.4, 137.5 and 138.5; m/z (CI, NH3) 296 (Mþþ18, 100%), 279
(Mþþ1, 15) and 261 (Mþꢀ17, 14); HRMS (CI, NH3): MHþ, found
279.1778. C17H27OS requires 279.1783. Repeated chromatography
achieved a partial separation of the two diastereoisomers.
4.2.29. (1S,5R,3Z)-6-Benzylthio-5-methyl-1-phenylhex-3-en-1-ol
(51). Tin(IV) bromide (150 mL, 1.027 M in DCM, 0.154 mmol) was
added to the stannane 50 (76 mg, 0.154 mmol) in DCM (2 mL) at
ꢀ78 ꢁC. After 10 min, benzaldehyde (52
mL, 2.95 M in DCM,
0.154 mmol, cooled to ꢀ78 ꢁC) was added and the mixture stirred at
ꢀ78 ꢁC for 1 h. Saturated aqueous sodium hydrogen carbonate
(2 mL) was added and the mixture allowed to warm to ambient
temperature. The aqueous phase was extracted with DCM and the
organic extracts were washed with brine and dried (MgSO4). After
concentration under reduced pressure chromatography (3:1 petrol/
ether, 1% triethylamine) of the residue gave the title commpound 51
as a colourless oil (28 mg, 58%), a 78:12:10 mixture of di-
4.2.32. (3S,7R,5Z)-8-Benzylthio-7-methyloct-5-en-3-ol
(54). Following the procedure outlined for the synthesis of alkenol
51, stannane 50 (99 mg, 0.20 mmol), tin(IV) bromide (181
DCM, 0.20 mmol) and propanal (15 L, 0.20 mmol) after chroma-
tography (4:1 petrol/ether, 1% triethylamine) gave the title compound
54 as colourless oil (29 mg, 54%), an 82:18 mixture of
mL,1.1 M in
m
astereoisomers (1H NMR), [
a
]
ꢀ10 (c 2.8, CHCl3); nmax/cmꢀ1 3409
a
D

6008
S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
diastereoisomers (1H NMR), [
a]
D þ6.0 (c 1.9, CHCl3); nmax/cmꢀ1 3422
the procedure outlined for the synthesis of ester 57, the alcohol 51
(17 mg, 0.054 mmol) and (S)-2-methoxy-2-phenyl-3,3,3-
trifluoropropanoic acid (35 mg, 0.15 mmol) after chromatography
(30:1 petrol/ether) gave the title compound 58 as a colourless oil
(br), 2960, 1494, 1453, 1238, 1071, 1027, 972 and 700; dH (500 MHz,
CDCl3) major isomer 54 0.95 (3H, t, J 8.0, 1-H3), 0.97 (3H, d, J 7.0, 7-
CH3), 1.50 (1H, m, 2-H2), 1.94 (1H, br s, OH), 2.15 (2H, m, 8-H2), 2.35
(2H, m, 4-H2), 2.65 (1H, m, 7-H), 3.53 (1H, m, 3-H), 3.68 and 3.685
(each 1H, d, J 14.0, PhHCH), 5.28 (1H, t, J 10.5, 6-H), 5.40 (1H, dt, J 10.5,
8.0, 5-H) and 7.20e7.30 (5H, m, ArH); minor isomer 0.94 (t, J 8, 1-H3)
and 0.99 (d, J 7.0, 7-CH3); dC (75 MHz, CDCl3) 10.1, 20.8, 29.9, 32.1, 35.4,
36.9, 38.7, 72.7,125.9,127.0,128.5,129.0,137.4and 138.5; m/z (CI, NH3)
282 (Mþþ18, 100%), 265 (Mþþ1, 14), 247 (Mþꢀ17, 12); HRMS (CI,
NH3): MNH4þ, found 282.1910. C16H28NOS requires 282.1892.
(20 mg, 70%) together with minor isomers, ratio 72:14:14 (1H and 19
F
NMR), [
a
]D ꢀ50 (c 2.4, CHCl3); nmax/cmꢀ1 2956, 1748, 1495, 1453, 1271,
1170,1122,1081,1018, 762 and 699; dH (500 MHz, CDCl3) 0.77 (3H, d, J
7.0, 5-CH3), 2.22 (2H, d, J 5.0, 6-H2), 2.40e2.70 (3H, m, 2-H2, 5-H), 3.43
(3H, s, OCH3), 3.64 (2H, s, PhCH2), 5.15 (2H, m, 3-H, 4-H), 5.93 (1H, t, J
5.5, 1-H) and 7.15e7.40 (15H, m, ArH); dF (470 MHz, CDCl3) ꢀ72.93
(major), ꢀ73.17; m/z (CI, NH3)546(Mþþ18, 22%)and 295(100);HRMS
(CI, NH3): MNHþ4 , found 546.2295. C30H35F3NO3S requires 546.2290.
4.2.33. (1S,5R,3Z)-6-Benzylthio-5-methyl-1-[(R)-2-acetoxy-2-
phenylacetoxy]-1-phenylhex-3-ene (55). Following the procedure
outlined for the synthesis of ester 18, alcohol 51 (19 mg,
0.061 mmol) and (R)-2-acetoxy-2-phenylacetic acid after chroma-
tography (5:1 petrol/ether) gave the title compound 55 as a colour-
4.2.37. (1R,5R,3Z)-6-Benzylthio-5-methyl-1-phenylhex-3-en-1-yl 4-
nitrobenzoate (60). Following the procedure outlined for ester 22,
the alcohol 51 (36 mg, 0.115 mmol) after chromatography (10:1
petrol/ether) gave the title compound 60 as a colourless oil (41 mg,
less oil (20 mg, 68%), [
a
]
D ꢀ66 (c 1.6, CHCl3); nmax/cmꢀ1 2959, 1745,
77%), [
a
]
D
ꢀ2.0 (c 1.9, CHCl3); nmax/cmꢀ1 2961, 1724, 1606, 1528,
1495, 1454, 1372, 1232, 1208, 1175, 1056 and 699; dH (300 MHz,
CDCl3) 0.80 (3H, d, J 7.0, 5-CH3), 2.22 (3H, s, CH3CO2), 2.15e2.60 (5H,
m, 5-H, 6-H2, 2-H2), 3.65 (2H, s, PhCH2), 5.05 (2H, m, 3-H, 4-H), 5.75
(1H, t, J 7.0,1-H), 6.05 (1H, s, O2CCH) and 7.15e7.50 (15H, m, ArH); dC
(75 MHz, CDCl3) 20.0, 20.8, 32.0, 34.2, 36.9, 38.5, 74.6, 123.0, 126.5,
126.9, 127.4, 128.6, 128.7,129.0, 129.3, 133.9,137.2, 139.2, 168.1,170.2
and 213.9; m/z (CI, NH3) 506 (Mþþ18, 100%); HRMS (CI, NH3):
MNH4þ, found 506.2374. C30H36NO4S requires 506.2365.
1344, 1273, 1103, 720 and 700; dH (300 MHz, CDCl3) 0.97 (3H, d, J
7.0, 5-CH3), 2.32 (2H, m, 6-H2), 2.55e2.90 (3H, m, 5-H, 2-H2), 3.70
(2H, s, PhCH2), 5.35 (2H, m, 3-H, 4-H), 6.07 (1H, dd, J 7.0, 6.0, 1-H),
7.15e7.45 (10H, m, ArH) and 8.25e8.35 (4H, m, ArH); dC (75 MHz,
CDCl3) 20.5, 32.3, 34.7, 37.1, 38.7, 123.4, 123.6, 126.5, 127.0, 128.4,
128.5, 128.7, 128.8, 130.8, 135.8, 137.6, 138.5, 139.5, 150.6 and 163.9;
m/z (CI, NH3) 479 (Mþþ18, 15%) and 117 (100).
4.2.38. (1R,5R,3Z)-6-Benzylthio-5-methyl-1-phenylhex-3-en-1-ol
(61). Following the procedure outlined for the synthesis of alcohol
23, the p-nitrobenzoate 60 (23 mg, 0.05 mmol) after chromatog-
raphy (3:1 petrol/ether) gave the title compound 61 as a colourless
oil (7 mg, 45%) a 75:13:12 mixture of 61, 51 and an (E)-isomer (1H
4.2.34. (1S,5R,3Z)-6-Benzylthio-5-methyl-1-[(S)-2-acetoxy-2-
phenylacetoxy]-1-phenylhex-3-ene (56). Following the procedure
outlined for the synthesis of ester 18, alcohol 51 (23 mg,
0.074 mmol) and (S)-2-acetoxy-2-phenylacetic acid after chroma-
tography (4:1 petrol/ether) gave the title compound 56 as a colour-
NMR), [
a]
þ10.5 (c 0.7, CHCl3); nmax/cmꢀ1 3428 (br), 3027, 2919,
D
less oil (23 mg, 64%), [
a]
D þ16 (c 2.3, CHCl3); nmax/cmꢀ1 2959, 1744,
1493, 1452, 1048, 758 and 700; dH (500 MHz, CDCl3) major isomer
61 0.96 (3H, d, J 7.0, 5-CH3), 1.80 (1H, br s, OH), 2.25e2.65 (5H, m, 6-
H2, 5-H, 2-H2,), 3.66 (2H, s, PhCH2), 4.73 (1H, t, J 6.0, 1-H), 5.30 (1H,
1495, 1454, 1372, 1232, 1208, 1175, 1056 and 699; dH (300 MHz,
CDCl3) 0.85 (3H, d, J 7.0, 5-CH3), 2.21 (3H, s, CH3CO2), 2.20e2.70 (5H,
m, 6-CH2, 2-CH2, 5-H), 3.73 (2H, s, PhCH2), 5.25 (2H, m, 3-H, 4-H),
5.75 (1H, t, J 7.0, 1-H), 6.05 (1H, s, O2CCH) and 7.00e7.50 (15H, m,
ArH); m/z (CI, NH3) 506 (Mþþ18, 48%) and 295 (100); HRMS (CI,
NH3): MNH4þ, found 506.2375. C30H36NO4S requires 506.2365.
t, J 10.0, 4-H), 5.36 (1H, dt, J 10.5, 9.0, 3-H) and 7.20e7.35 (10H, m,
þ
ArH); m/z (CI, NH3) 330 (Mþþ18, 100%); HRMS (CI, NH3): MNH4
,
found 330.1892. C20H28NOS requires 330.1891.
4.2.39. (3S,7R,5Z)-8-Benzylthio-2,7-dimethyl-3-[(R)-2-acetoxy-2-
phenylacetoxy]hex-5-ene (62). Following the procedure outlined
for the synthesis of ester 18, the alcohol 53 (24 mg, 0.087 mmol)
and (R)-2-acetoxy-2-phenylacetic acid after chromatography (20:1
petrol/ether) gave the title compound 62 as a colourless oil (37 mg,
4.2.35. (1S,5R,3Z)-6-Benzylthio-5-methyl-1-phenylhex-3-en-1-yl
(R)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoate (57). N,N-Dime-
thylformamide (5
trifluoropropanoic acid (37 mg, 0.16 mmol) and oxalyl chloride
(139 L, 0.80 mmol) in hexane (1 mL) and the solution was stirred
mL) was added to (R)-2-methoxy-2-phenyl-3,3,3-
m
94%), [
a
]
ꢀ65 (c 3.5, CHCl3); nmax/cmꢀ1 2963, 1745, 1454, 1372,
D
for 1 h. Filtration and concentration of the filtrate under reduced
pressure afforded the crude acid chloride as a colourless oil. This
acid chloride (0.16 mmol) in DCM (0.5 mL) was added to the alcohol
1234, 1180, 1055 and 699; dH (500 MHz, CDCl3) major isomer 0.85
(9H, d, J 7.0, 3ꢂCH3), 1.60e2.65 (6H, m, 7-H, 2-H, 4-H2, 8-H2), 2.17
(3H, s, CH3CO2), 3.64 (2H, s, PhCH2), 4.73 (1H, m, 3-H), 4.90 (1H, dt, J
10.5, 7.0, 5-H), 5.00 (1H, t, J 10.5, 6-H), 5.86 (1H, s, O2CCH) and
7.20e7.50 (10H, m, ArH); dC (75 MHz, CDCl3) 17.2, 18.7, 20.2, 20.7,
29.1, 31.0, 32.0, 36.9, 38.7, 74.8, 79.9, 123.8, 126.9, 127.7, 128.5, 128.7,
128.9, 129.2, 133.9, 136.5, 138.6, 168.7 and 170.3; m/z (CI, NH3) 472
(Mþþ18, 100%), 455 (Mþþ1, 5); HRMS (CI, NH3): MNH4þ, found
472.2527. C27H38NO4S requires 472.2522.
51 (25 mg, 0.08 mmol), triethylamine (47 mL, 0.32 mmol) and
DMAP (2 mg) in DCM (0.5 mL) and the solution was stirred for
3.5 h. Ether was added and the solution washed with water and
brine, then dried (MgSO4). Concentration under reduced pressure
and chromatography (20:1 petrol/ether) of the residue gave the
title compound 57 as a colourless oil (24 mg, 57%) together with
minor isomers, ratio 72:14:14 (1H and 19F NMR), [
a]
þ7.3 (c 2.7,
D
CHCl3); nmax/cmꢀ1 2956, 1748, 1495, 1453, 1271, 1170, 1123, 1081,
1018, 763 and 699; dH (500 MHz, CDCl3) major isomer 57 0.79 (3H,
d, J 7.0, 5-CH3), 2.28 (2H, d, J 5.0, 6-H2), 2.40e2.70 (3H, m, 2-H2, 5-
H), 3.43 (3H, s, OCH3), 3.64 (2H, s, PhCH2), 5.10e5.30 (2H, m, 3-H, 4-
H), 5.87 (1H, t, J 5.5, 1-H) and 7.15e7.40 (15H, m, ArH); dF (470 MHz,
CDCl3) ꢀ73.17 (major isomer 57), ꢀ72.93 (minor), ꢀ72.88 (minor);
m/z (CI, NH3) 546 (Mþþ18, 34%), 295 (95) and 205 (100); HRMS (CI,
NH3): MNH4þ, found 546.2303. C30H35F3NO3S requires 546.2290.
4.2.40. (3S,7R,5Z)-8-Benzylthio-2,7-dimethyl-3-[(S)-2-acetoxy-2-
phenylacetoxy]hex-5-ene (63). Following the procedure outlined
for the synthesis of ester 18, the alcohol 53 (20 mg, 0.072 mmol)
and (S)-2-acetoxy-2-phenylacetic acid, after chromatography (20:1
petrol/ether), gave the title compound 63 as a colourless oil (31 mg,
95%), [
a
]
þ33 (c 3.1, CHCl3); nmax/cmꢀ1 2964, 1745, 1495, 1454,
D
1372, 1233, 1212, 1180, 1056 and 699; dH (500 MHz, CDCl3) 0.60 and
0.63 (each 3H, d, J 7.0, CH3), 0.98 (3H, d, J 7.0, 7-CH3), 1.70 (1H, oct, J
5.0, 2-H), 2.17 (3H, s, O2CCH3), 2.28 (2H, t, J 7.5, 8-CH2), 2.33 (1H, dd,
J 13.0, 7.0, 4-H) 2.40 (1H, dd, J 15.0, 7.0, 4-H), 2.60 (1H, m, 7-H), 3.68
(2H, s, PhCH2), 4.73 (1H, q, J 4.0, 3-H), 5.25 (2H, m, 5-H, 6-H), 5.90
4.2.36. (1S,5R,3Z)-6-Benzylthio-5-methyl-1-phenylhex-3-en-1-yl
(S)-2-methoxy-2-phenyl-3,3,3-trifluoropropanoate (58). Following

S.J. Stanway, E.J. Thomas / Tetrahedron 68 (2012) 5998e6009
6009
(1H, s, O2CCH) and 7.20e7.50 (10H, m, ArH); dC (75 MHz, CDCl3)
16.6, 18.6, 20.4, 20.8, 29.5, 30.7, 32.2, 37.0, 38.8, 74.7, 79.7, 123.8,
126.9, 127.7, 128.5, 128.7, 128.9, 129.1, 134.3, 136.8, 138.7, 168.6 and
170.2; m/z (CI, NH3) 472 (Mþþ18, 100%) and 455 (Mþþ1, 5); HRMS
(CI, NH3): MNH4þ, found 472.2525. C27H38NO4S requires 472.2522.
7.5, 5.0, 6-H); dC (75 MHz, CDCl3) major isomer 20.2, 30.7, 32.2, 35.9,
37.9, 73.9, 125.7, 125.9, 127.5, 128.4, 136.8, 144.1 and 196.0; m/z (CI,
NH3), 282 (Mþþ18, 100%), 264 (Mþ, 22) and 247 (Mþꢀ17, 78);
HRMS (CI, NH3): MNH4þ, found 282.1535. C15H24NO2S requires
282.1528.
4.2.41. (3R,7R,5Z)-8-Benzylthio-2,7-dimethyloct-5-en-3-ol
(65). Following the procedure outlined for the synthesis of ester
22, the alcohol 53 (29 mg, 0.106 mmol) after chromatography (15:1
petrol/ether) gave the 4-nitrobenzoate 64 as a colourless oil (19 mg,
Acknowledgements
We thank Dr. D.J. Hallett for carrying out the reactions of stan-
nane 9 with imines and the EPSRC for a studentship (to S.J.S.).
42%), [
a]
D ꢀ20 (c 2.0, CHCl3); nmax/cmꢀ1 2965, 1721, 1528, 1275 and
720; dH (200 MHz, CDCl3) 0.90 (3H, d, J 6.5, 7-CH3), 0.99 and 1.01
(each 3H, d, J 6.5, CH3), 2.00 (1H, m, 2-H), 2.30e2.70 (5H, m, 4-H2, 8-
H2, 7-H), 3.70 (2H, s, PhCH2), 5.05 (1H, m, 3-H), 5.30 (2H, m, 5-H, 6-
H), 7.25 (5H, m, ArH) and 8.20 (4H, m, ArH); m/z (CI, NH3) 445
(Mþþ18, 45%) and 194 (100).
Supplementary data
Full experimental procedures and characterization of the
products in Schemes 4, 7 and 8. Supplementary data associated
with this article can be found in the online version, at doi:10.1016/
j.tet.2012.05.032.
Following the procedure outlined for the synthesis of alcohol 23,
the 4-nitrobenzoate 64 (17 mg, 0.04 mmol) after chromatography
(4:1 petrol/ether) gave the title compound 65 as a colourless oil
References and notes
(10 mg, 91%), [
a
]
D
ꢀ8.8 (c 1.5, CHCl3); nmax/cmꢀ1 3422 (br), 2958,
1453, 1237, 1030, 870 and 700; dH (500 MHz, CDCl3) 0.91 and 0.93
(each 3H, d, J 7.0, CH3), 0.99 (3H, d, J 7.0, 7-CH3), 1.58 (1H, br s, OH),
1.67 (1H, oct, J 6.5, 2-H), 2.15 (2H, m, 8-H2), 2.35 (2H, m, 4-H2), 2.65
(1H, m, 7-H), 3.34 (1H, m, 3-H), 3.68 (2H, s, PhCH2), 5.30 (1H, t, J
10.0, 6-H), 5.40 (1H, dt, J 10.5, 7.0, 5-H) and 7.20e7.30 (5H, m, ArH);
dC (75 MHz, CDCl3) 17.8, 18.9, 20.7, 32.1, 32.6, 33.2, 37.0, 38.8, 76.2,
125.7, 126.9, 128.5, 128.9, 137.5 and 138.5; m/z (CI, NH3) 296
(Mþþ18, 100%), 279 (Mþþ1, 15) and 261 (Mþꢀ17, 14); HRMS (CI,
NH3): MHþ, found 279.1776. C17H27OS requires 279.1783.
1. (a) Thomas, E. J. Chem. Rec. 2007, 7, 115; (b) Thomas, E. J. Chem. Commun. 1997,
411.
2. MacNeill, A. H.; Thomas, E. J. Synthesis 1994, 322.
3. (a) Hallett, D. J.; Tanikkul, N.; Thomas, E. J. Org. Biomol. Chem., Available at:
http://xlink.rsc.org/?doi¼C2OB25097G; (b) Hallett, D. J.; Thomas, E. J. J. Chem.
Soc., Chem. Commun. 1995, 657; (c) Hallett, D. J.; Thomas, E. J. Tetrahedron:
Asymmetry 1995, 6, 2575.
4. Stanway, S. J.; Thomas, E. J. J. Chem. Soc., Chem. Commun. 1994, 285.
5. Stanway, S. J.; Thomas, E. J. Synlett 1995, 214.
6. Miller, A. E. G.; Biss, J. W.; Schwartzman, L. H. J. Org. Chem. 1959, 24, 627.
7. Ueno, Y.; Sano, H.; Okawara, M. Tetrahedron Lett. 1980, 21, 1767.
8. The work outlined in this paper is concerned with relative stereocontrol.
Nevertheless, a knowledge of the optical purity of the stannanes and hence of
the products was helpful in establishing the relative configurations of the
products using O-acetoxymandelates, Mosher’s derivatives and in the chemical
correlations via ozonolysis.
4.2.42. 6-Hydroxy-2-methyl-6-phenylhex-3-en-1-yl
thioacetates
(66) and (67). Following the procedure outlined for the synthesis
of alkenol 51, stannane 49 (97 mg, 0.217 mmol), tin(IV) bromide
(197 mL, 1.1 M in DCM, 0.217 mmol) and benzaldehyde (94 mL, 2.3 M
in DCM, 0.217 mmol) after chromatography (3:1 petrol/ether, 1%
triethylamine) gave a mixture of the title compounds 66 and 67 as
9. Mitsunobu, O. Synthesis 1981, 1.
10. Trost, B. M.; Belletire, J. L.; Godleski, S.; McDougal, P. G.; Balkovec, J. M.; Bald-
win, J. L.; Christy, M. E.; Ponticello, G. S.; Varga, S. L.; Springer, J. P. J. Org. Chem.
1986, 51, 2370.
11. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512.
12. Carey, J. S.; MacCormick, S.; Stanway, S. J.; Teerawutgulrag, A.; Thomas, E. J. Org.
Biomol. Chem. 2011, 9, 3896.
a colourless oil (51 mg, 89%), ratio 90:10 (1H NMR), [
a
]
D ꢀ17 (c 2.0,
CHCl3); nmax/cmꢀ1 3442 (br), 2962, 1691, 1453, 1135, 1049, 957 and
701; dH (500 MHz, CDCl3) major isomer 0.92 (3H, d, J 7.0, 2-CH3),
2.20 (1H, s, OH), 2.32 (3H, s, CH3CO), 2.43 and 2.55 (each 1H, m, 1-
H), 2.64 (1H, m, 2-H), 2.76 (1H, dd, J 13.0, 7.5, 5-H), 2.83 (1H, dd, J
13.0, 6.5, 5-H), 4.69 (1H, dd, J 7.5, 5.0, 6-H), 5.28 (1H, t, J 10.5, 3-H),
5.41 (1H, m, 4-H) and 7.20e7.35 (5H, m, ArH); minor isomer 1.025
(d, J 7.0, 2-CH3), 2.30 (s, CH3CO), 2.89 (dd, J 13.0, 6.5, 5-H), 4.65 (dd, J
€
ꢀ
13. Furstner, A.; Bouchez, L. C.; Morency, L.; Funel, J.-A.; Liepins, V.; Poree, F.-H.;
Gilmour, R.; Laurich, D.; Beaufils, F.; Tamiya, M. Chem.dEur. J. 2009, 15, 3983.
14. Genet, J.-P.; Balabane, M.; Charbonnier, F. Tetrahedron Lett. 1982, 23, 5027.
15. Cleary, D. G. Synth. Commun. 1989, 19, 737.
16. (a) Hobson, L. A.; Vincent, M.; Thomas, E. J.; Hillier, I. H. Chem. Commun. 1998,
899; (b) Beddoes, R.; Hobson, L. A.; Thomas, E. J. Chem. Commun. 1997, 1929.
17. (a) Jephcote, V. J.; Pratt, A. J.; Thomas, E. J. J. Chem. Soc., Perkin Trans. 1 1989,
1529; (b) Pratt, A. J.; Thomas, E. J. J. Chem. Soc., Perkin Trans. 1 1989, 1521.