Application of silacyclic allylsilanes to the synthesis of β-hydroxy-δ-lactones: synthesis of Prelactone B

Article abstract of DOI:10.1016/j.tet.2009.01.116

Silacyclic allylsilanes generated through a silene-diene Diels-Alder cycloaddition represent versatile bifunctional reagents for organic synthesis. This is demonstrated in a short stereocontrolled synthesis of (±)-Prelactone B.

Full text of DOI:10.1016/j.tet.2009.01.116

Tetrahedron 65 (2009) 5588–5595
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Application of silacyclic allylsilanes to the synthesis of
synthesis of Prelactone B
b-hydroxy-d-lactones:
*
Jonathan D. Sellars, Patrick G. Steel
Department of Chemistry, Science Laboratories, South Road, Durham DH1 3LE, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
Silacyclic allylsilanes generated through a silene–diene Diels–Alder cycloaddition represent versatile
bifunctional reagents for organic synthesis. This is demonstrated in a short stereocontrolled synthesis of
(ꢀ)-Prelactone B.
Received 18 December 2008
Received in revised form 21 January 2009
Accepted 22 January 2009
Available online 14 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
bafilomycin. As with all the prelactones it has become a popular
synthetic target to highlight new methodologies and a number of
Allylsilanes are valuable and versatile intermediates for organic
synthesis that enable a multitude of transformations notably the
allylation of aldehydes, ketones and acetals.1 Whilst the presence of
the weakly polar C–Si bond is essential for this chemistry, this
functionality is commonly lost during the reaction. In contrast, with
cyclic allylsilanes the C–Si bond is retained in the product for fur-
ther elaboration and thus these represent simple bifunctional re-
agents that permit two directional synthetic strategies to be
developed.
other synthetic routes have been reported.9–25
HO
HO
HO
O
O
O
O
O
O
1 Prelactone B
2 Prelactone C
3 Prelactone V
HO
C9H19
As a component of a project exploring new silicon mediated
synthetic methodology we have been exploring the chemistry of
silacyclic allylsilanes generated through the cycloaddition of
a transient silene.2 As with acyclic allylsilanes these undergo ally-
lation reactions to produce homoallylic alcohols but with the sili-
con functionality retained. This can subsequently be elaborated to
provide an additional oxygen functionality and we have exploited
this to produce butane-1,4-diols and aryltetralols.3–5 Alternatively,
electrophilic addition to the alkene enables functionalisation of the
silacycle prior to activation and oxidation of the silicon unit. We
HO
O
O
O
O
4 3-hydroxy-5-tetradecanolide
5 3-hydroxy-2,4-dimethyl-5-heptanolide
HO
O
O
O
O
OH
OH
6 (+)-Discodermolide
NH2
first demonstrated this in the preparation of
paper present the full details of the extension of this approach to
produce -hydroxy-
-lactones.7 This structural motif is found in
d
-lactones6 and in this
OH
b
d
a wide range of natural products, Figure 1. In this exemplification of
our new methodology we focused on the relatively simple sub-
Figure 1. Selected examples of naturally occurring b-hydroxy-d-lactones.
group of b-hydroxy-d-lactone natural products represented by the
2. Results and discussion
prelactones and in particular Prelactone B. Isolated from Strepto-
myces griseus, by Bindseil and Zeeck in 1993,8 Prelactone B 1 is
Our initial retrosynthetic analysis of
b-hydroxy-d-lactones is
a
shunt product of the biosynthetic pathway to macrolide
shown in Scheme 1. The key intermediate was the silacyclohexene
10, which would be generated through the Diels–Alder reaction of
a suitably substituted butadiene and a transient silene. The latter
could be generated in situ through the modified Peterson reaction
of the ‘silyl alcohol’ 13. At the outset of the project we envisaged
* Corresponding author. Tel.: þ44 (0)191 334 2131; fax: þ44 (0)191 384 4737.
E-mail address: p.g.steel@durham.ac.uk (P.G. Steel).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.116

J.D. Sellars, P.G. Steel / Tetrahedron 65 (2009) 5588–5595
5589
RO
R
HO
HO
R
RO
R
i. BH3 SMe2, THF
ii. aq. NaOH, aq. H2O2,
34%
OH
Si SiMe3
Ph
Si SiMe3
Ph
Δ
O
Si SiMe3
Ph
10a
OH
8
15
O
7
9
Scheme 3.
White had previously reported that epoxidation of silacyclo-
hexene 16 could be efficiently achieved using classical Payne con-
ditions, Figure 2.30 Our intention was to utilise this, or other
epoxidation methods, to provide access to the silacyclic oxirane 18,
which, when subjected to the Fleming–Tamao oxidation condi-
tions, would undergo a regioselective fragmentation reaction, di-
rected by the silicon atom, to produce the diol 21, Scheme 4.
OH
H
R
R
SiMe3
SiMe3
+
R
Si
Ph
Si
Si SiMe3
Ph
Ph
SiMe3
13
12
Scheme 1.
11
10
MeCN, MeOH, H2O2
O
80%
Si
Si
that the desired b-hydroxy group could be introduced by simple
hydroboration directed by the presence of the silicon atom.26 Fol-
lowing this, simple activation of the silyl centre and subsequent
two-step oxidation, following the precedents of our earlier studies,
would afford the desired lactone. With this in mind we commenced
our studies by preparing the requisite silacycles.
16
17
Figure 2.
Condensation of the hypersilyl magnesium reagent, generated
from phenyltris(trimethylsilyl)silane 1427 by reaction with KOtBu in
THF followed by transmetallation with freshly prepared magnesium
bromide in ether, with isobutyraldehyde or benzaldehyde afforded
the silyl alcohols 13a and 13b, respectively. Treatment of a mixture of
the silyl alcohol and excess 1,3-pentadiene with BuLi followed by the
addition of LiBr afforded the key silacyclohexenes as an inseparable
mixture of stereoisomers (ds 70:20:10) favouring the desired endo
product 10 as ascertained by a combination of 1H, 29Si NMR, GC–MS
analysis and subsequent chemical conversions, Scheme 2.28
R
Si SiMe3
Ph
10
Epoxidation
R
HO
R
O
t
i. KO Bu
OH
Si SiMe3
Ph
OH
SiMe3
Ph Si SiMe3
SiMe3
ii. MgBr2 OEt2
Me3Si
Me3Si
Si
Ph
R
18
21
iii. RCHO
14
F-
Oxidation
R
13
i. BuLi
ii. LiBr
HO
R
O
Si SiMe3
Ph
Si SiMe3
Ph
F
R
Ph
11
F
Si
SiMe3
12
R
Si SiMe3
Ph
19
20
Scheme 4.
10
i
a
R = Pr 50%
R = Ph 45%
b
Whilst many epoxidation reagents either failed to react or led to
extensive loss of material, successful epoxidation was ultimately
realised through the use of (methyl)trifluoromethyldioxirane, al-
beit at low levels of conversion (w25%). This epoxide proved to be
highly labile undergoing silicon induced ring fragmentation on
passage through silica gel, Scheme 5. Interestingly this afforded
a single diastereoisomer of the silanol 22 indicating that both ep-
oxidation and nucleophilic attack at the silicon centre were highly
stereoselective events. Whilst the stereochemistry at the latter
position could not be unambiguously assigned we speculate that it
is as shown in Scheme 5 reflecting inversion on substitution at
silicon. Whilst the yield was disappointing, the selectivity of the
reaction was promising and attention turned to dihydroxylation as
this would also lead to intermediate 21 on silicon mediated ring
fragmentation. Although the dihydroxylation of allylsilanes in-
cluding silacyclic allylsilanes is well documented in the litera-
ture,31–33 the dihydroxylation of silacyclohex-4-enes has not been
Scheme 2.
With these silacyclic allylsilanes in hand attention then turned
to the hydroboration sequence. Following precedents established
by Soderquist, who had previously demonstrated that silacycles
could be employed in these transformations with no significant
side reactions at silicon,29 10a was treated with borane–dime-
thylsulfide complex to afford after oxidation the desired alcohol in
a modest 34% yield, accompanied by a significant amount of the
putative alternative regioisomer (ꢁ20%), Scheme 3. Attempts to
enhance this process through the use of alternative borane sources
or oxidation conditions proved to be unsuccessful. Moreover, all
attempts to oxidise the C–Si bonds, either directly or following
protection of the newly formed hydroxyl group, failed to provide
the expected triol and alternative strategies for the elaboration of
the silacycle were considered.

5590
J.D. Sellars, P.G. Steel / Tetrahedron 65 (2009) 5588–5595
HO
Ph
Si SiMe3
Ph
Si SiMe3
Ph
HO
10a
23b
BF3 2AcOH
DCM
82%
O
O
CF3
BF3 2AcOH
HO
Ph
SiO2
20%
HO
Ph
O
Si
O
Si SiMe3
Ph
Ph
Si SiMe3
Ph
Si SiMe3
Ph
HO
22
Me3Si
F
27
26
H2O2, KHCO3
THF-H2O
18a
90%
21%
Scheme 5.
HO
Ph
described. Despite this, treatment of silacycle 10b using the clas-
sical Upjohn conditions (cat. OsO4, NMO, acetone/H2O 20:1) affor-
ded the corresponding diols 23b–25b in a combined 82% yield in
a ratio of isomers reflecting that found in the starting material.
Flash chromatography enabled the major diastereoisomer 23b to be
separated with subsequent NOESY experiments showing correla-
tions consistent with the 4-hydroxy group being trans to the methyl
group, Scheme 6.
OH
21b
Scheme 7.
of this intermediate with hydrogen peroxide afforded the desired
diol 21b in 72% yield as a single diastereoisomer, Scheme 7.
On the basis of our earlier studies exploring the Hosomi Sakurai
reaction in which the formation of a single silyl fluoride di-
astereoisomer could be observed,3 the generation of a 1:1 isomeric
mixture was unusual and merited further investigation. Whilst two
possible reaction pathways could account for the formation of the
cyclic siloxane neither is fully consistent with the production of
a 1:1 isomeric mixture. Whilst a formal intramolecular SN2 reaction
of the allylic alcohol with silyl fluoride 27 leads to the observed
product this might be expected to afford a single stereoisomer.
Although scrambling of stereochemistry during substitution at
silicon is possible via Berry pseudorotation the cyclic nature of this
substrate might be expected to inhibit such a process. Similarly,
whilst the observed product mixture could arise through a disso-
ciative SN1 type process the requirement for a ‘silyl cation’ renders
this less likely. Consequently, in order to probe this transformation,
further experiments were undertaken. Since both pathways require
the intermediacy of the acyclic silyl fluoride 27, the cyclic siloxane
26 was treated with BF3$2AcOH complex. This afforded a new
highly labile species, which resisted purification but on oxidation
using hydrogen peroxide allowed isolation of the diol 21b, albeit in
a low (21%) yield. Curiously, 1H and 19F NMR analyses revealed it to
be a single diastereoisomeric species possessing one fluorine atom.
This was proposed to be the silyl fluoride 27 based on a character-
Ph
Si SiMe3
Ph
10b
ds, 70:20:10
OsO4 (cat.), NMO
Acetone/H2O (20:1)
HO
HO
Ph
HO
HO
Ph
HO
HO
Ph
Si SiMe3
Ph
Si Ph
SiMe3
Si SiMe3
Ph
24b
23b
25b
82% (7:2:1)
H
H
Ph
H
Si
istic doublet (
d
¼ꢂ140.8) observed in the 19F NMR spectrum. At-
Ph
H
tempts to reverse the ring opening with base were not successful,
leading to extensive decomposition, suggesting that the silyl fluo-
ride is possibly not the original product of the fragmentation in
these processes.
H
R
HO
H
OH
Selected NOESY Correlations for 23b (R = SiMe3)
Returning to the synthesis of the prelactones, having identified
an efficient method for the generation of diol 21b, it remained to
oxidise the alkene to a carboxylic acid and cyclise to form the lac-
tone ring. Initial attempts to achieve this directly via hydroboration
with in-situ oxidation proved not to be viable. Whilst simple
hydroboration–oxidation did afford the desired triol 28 attempts to
oxidise this proved not to be selective resulting in complex mix-
tures of products. Since the oxidative cyclisation of 1,6-diols to give
lactones had been achieved using similar conditions in our earlier
studies it was felt that protection of the allylic alcohol was required.
Fortunately, this could be achieved by simple treatment with TBSCl
and imidazole. Confirmation of the desired regiochemistry was
Scheme 6.
Having developed an efficient oxidation protocol it was then
necessary to promote ring fragmentation. Treatment of the diol 23b
with BF3$2AcOH complex afforded
a 1:1 mixture of di-
astereoisomers that showed a complete absence of a fluorine signal
as ascertained by 1H and 19F NMR spectroscopy, respectively. ESMS
analysis suggested a molecular ion of m/z¼352, which coupled with
a characteristic siloxane peak at
spectrum suggested this intermediate to be the cyclic siloxane 26.
d
¼ꢂ21 ppm in the 29Si NMR
Importantly, in the context of prelactone synthesis, direct oxidation

J.D. Sellars, P.G. Steel / Tetrahedron 65 (2009) 5588–5595
5591
HO
Ph
OH
OH
HO
Ph
HO
Ph
OH
i. BH3 SMe2
ii. H2O2, NaOH
64%
TPAP, NMO
O
O
29
21b
28
TBSCl, Imidazole, DCM
70%
TBSO
Ph
OH
TBSO
Ph
OH
TBSO
Ph
i. BH3 SMe2
ii. H2O2, NaOH
64%
OH
OH
OH
31b
60%
30
i. Cy2BH
32
1 : 1
ii. H2O2, NaOH
60%
TBSO
Ph
Ph
O
H
O
O
B
B
H
H
TBSO
Ph
33
34
OH
Ph
H
O
H
H
OH
31b
TBSO
B
33
Scheme 8.
TBSO
Ph
OH
TBSO
Ph
HO
Ph
Et3N.3HF
TPAP, NMO
O
O
OH
31b
O
35
O
29
Scheme 9.
obtained through NOESY studies of the resultant silyl ether 30,
which revealed correlations between the methyl group of the TBS
unit and the allylic, rather than the benzylic methine, hydrogen.
Whilst, with the interfering alcohol now masked, alkene hydro-
boration using BH3$SMe2 complex followed by hydrogen peroxide
oxidation proceeded smoothly this led to a 1:1 regioisomeric
mixture of diols 31b and 32 in 60% yield. This result differed to that
obtained previously for the hydroboration of diol 21b suggesting
that the TBS group forces the allyl group in 30 into close proximity
with a coordinated borane molecule leading to an intramolecular
delivery of borane to the alkene. In contrast, with 21b the borane
reagent can coordinate both hydroxyl groups, locking the molecule
and enabling selective hydroboration at the least hindered position,
cf. structures 33 and 34. In support of such a proposal diol 32 was
isolated as a single, albeit unconfirmed, diastereoisomer consistent
with a cyclic 6-membered ring transition state structure 33z in
which all substituents occupy pseudoequatorial positions. Based on
this analysis we turned to more hindered boranes and explored the
use of dicyclohexylborane. To our satisfaction, when treated with
an excess of freshly prepared dicyclohexylborane and oxidised
i. BF3•2AcOH
HO
ii. H2O2, KHCO3
HO
OsO4 (cat.), NMO
Acetone/H2O (20:1)
Si SiMe3
Ph
OH
21a
Si SiMe3
Ph
HO
23a
32%
10a
64%
TBSCl, Im.
i. Cy2BH
ii. H2O2, NaOH
i. TPAP, NMO
ii. Et3N.3HF
HO
TBSO
TBSO
O
OH
OH
O
1
OH
31a
30a
52%
90%
70%
Scheme 10.

5592
J.D. Sellars, P.G. Steel / Tetrahedron 65 (2009) 5588–5595
under standard conditions, the desired diol 31b was generated as
the sole product in 60% yield. None of the regioisomeric product
was present by TLC or 1H NMR analysis of the crude material,
Scheme 8.
associated characterisation data for silacyclohexenes 10a and 10b
have previously been reported.28
4.1.1. (1SR,2RS,3SR,4RS/SR) 1-Phenyl-1-trimethylsilyl-2-
With an efficient synthetic strategy in place to gain access to the
1,5-diols, attention turned to the final oxidation. Lactonisation of
diol 31b was undertaken with TPAP and NMO. Pleasingly, the lac-
tone product 35b was generated efficiently and on mild silicon
(isopropyl)-3-methyl-4-hydroxysilacyclohexane 15
Borane–dimethylsulfide complex (0.060 ml, 0.70 mmol) in THF
(4 ml) was cooled to 0 ꢃC and treated with a solution of silacyclo-
hex-4-ene 10a (200 mg, 0.70 mmol) in THF (4 ml). The reaction was
stirred for 2 h at 0 ꢃC, then for 1 h at room temperature and treated
with water (0.40 ml) (H2 gas evolved), followed by 3 M NaOH
(0.20 ml, 0.70 mmol) and a 35% w/w solution of H2O2 in water
(0.20 ml, 2.2 mmol). The mixture was refluxed at 65 ꢃC for 4 h after
which time Na2S2O3 (10 ml) was added. The aqueous layer was
separated and extracted with EtOAc (3ꢄ10 ml). The combined or-
ganic layers were dried over MgSO4, filtered, concentrated and
dried in vacuo. Flash chromatography (pet. ether, pet. ether/ether
[14:1], [9:1], [4:1], [2:1]) afforded the title compound as a white
solid (0.070 g, 34%); mp 118–120 ꢃC; Rf 0.3 (pet. ether/ether 3:2);
nmax (ATR) 3368 (broad-OH), 3067, 2922, 2872, 1726, 1462, 1427,
deprotection utilising Et3N$3HF in THF provided the
b-hydroxy-d-
lactone 29 in quantitative yield from diol 31b, Scheme 9.
Simple repetition of this sequence starting with the isopropyl
substituted silacycle 10a then afforded Prelactone B 1 in compa-
rable yields, Scheme 10. The spectroscopic data for Prelactone B
proved to be identical with those previously reported in the
literature.
3. Conclusions
We have described a concise and flexible approach to the syn-
thesis of the prelactones. This chemistry relies on the bifunctional
nature of the cyclic allylsilanes that can be conveniently generated
through a silene–diene cycloaddition. The modular nature of the
approach will facilitate its future application to more highly
1244, 1102, 1048, 1019, 852, 833, 735, 700 cmꢂ1
; dH (300 MHz,
CDCl3) 7.55–7.51 (2H, m, Ar-H), 7.32–7.29 (3H, m, Ar-H), 3.26 (1H, td,
J 11, 3, 4-H), 2.18 (1H, m, 3-H), 2.05 (1H, m, 2-CH(CH3)2), 1.65 (2H, m,
6-H2), 1.45 (1H, m, 2-H), 1.26 (2H, m, 5-H2), 1.14 (3H, d, J 7, 2-
CH(CH3)2), 1.00 (3H, d, J 7, 3-CH3), 0.75 (3H, d, J 7, 2-CH(CH3)2), 0.29
(9H, s, Si(CH3)3); dC (126 MHz, CDCl3) 139.9 (ipso-Ar-C),134.5 (Ar-C),
128.5 (Ar-C), 127.9 (Ar-C), 77.8 (4-C), 41.9 (3-C), 38.6 (2-C), 35.2 (2-
CH(CH3)2), 33.5 (5-C), 23.5 (2-CH(CH3)2), 22.1 (2-CH(CH3)2), 18.4 (3-
CH3), 9.6 (6-C), 0.3 (Si(CH3)3); m/z (ESþ) 343 (MNaþ), 303
(MþꢂH2O).
substituted
b-hydroxy-d-lactones and work in this regard is in
progress and will be reported in due course.
4. Experimental
4.1. General procedures
4.1.2. (3RS,4SR,5RS,(Si)RS/SR) 3-(1-Hydroxy-2,2,2-trimethyl-1-
phenyldisilanyl)-5-hydroxy-2,4-dimethylhept-6-ene 22
All air and/or moisture sensitive reactions were carried out
under an argon atmosphere. Solvents were purified and dried fol-
lowing established protocols. Petrol refers to petroleum spirit
boiling in the 40–60 ꢃC range. Ether refers to diethyl ether. Alde-
hydes and dienes were distilled, immediately prior to use, from
anhydrous calcium sulfate and sodium borohydride, respectively.
All other commercially available reagents were used as received
unless otherwise stated. Flash column chromatography was per-
formed according to the method of Still et al. using 200–400 mesh
silica gel.34 Yields refer to isolated yields of products of greater than
95% purity as determined by 1Hþ13C NMR spectroscopy. Melting
points were determined using Gallenkamp melting point apparatus
and are uncorrected. Infrared spectra were recorded using a Di-
amond ATR (attenuated total reflection) accessory (Golden Gate) on
a Perkin–Elmer FT-IR 1600 spectrometer. Unless otherwise stated
1H NMR spectra were recorded in CDCl3 on Varian Mercury 200,
Varian Unity-300, Varian VXR-400 or Varian Inova-500 and are
A solution of silacyclohex-4-ene 10a (100 mg, 0.30 mmol) in
acetonitrile (2.5 ml) was cooled to 0 ꢃC and treated with EDTA
disodium salt (1.7 ml, 0.40 mM) and trifluoroacetone (0.30 ml,
3.7 mmol). This solution was then treated with a mixture of
NaHCO3 (0.20 g, 2.6 mmol) and oxone (1.0 g, 1.7 mmol) over a pe-
riod of 1 h and reacted for a further 3 h, after which time the re-
action was poured into water and extracted with DCM (3ꢄ10 ml).
The combined organic layers were dried over MgSO4, filtered,
concentrated and dried in vacuo. Flash chromatography (pet. ether,
pet. ether [99:1], [98:2]) afforded the title silanol as a colourless oil
(25 mg, 22%); Rf 0.6 (pet. ether/ether 9:1); nmax (thin film) 3068
(broad-OH), 2956, 2928, 2892, 2870, 1718, 1427, 1244, 1103, 1004,
855, 835, 699 cmꢂ1
; dH (500 MHz, CDCl3) 7.58–7.55 (2H, m, Ar-H),
7.35–7.34 (3H, m, Ar-H), 5.75 (1H, ddd, J 17, 10, 7, 6-H), 5.21 (1H, d, J
17, 7-HH), 5.08 (1H, d, J 10, 7-HH), 4.53 (1H, t, J 7, 5-H), 2.28 (1H, m,
4-H), 1.99 (1H, septet, J 6, 2-H), 1.26 (1H, m, 3-H), 1.09 (3H, d, J 6, 1-
H), 1.07 (3H, d, J 6, 2-CH3), 0.86 (3H, d, J 6, 4-CH3), 0.17 (9H, s,
Si(CH3)3); dC (126 MHz, CDCl3) 139.6 (ipso-Ar-C), 137.5 (6-C), 133.7
(Ar-C), 128.9 (Ar-C), 127.8 (Ar-C), 116.4 (7-C), 84.3 (5-C), 44.5 (3-C),
40.7 (4-C), 27.5 (2-C), 25.2 (1-C), 23.4 (2-CH3), 16.6 (4-CH3), ꢂ1.4
(Si(CH3)3); m/z (ESþ) 359 (MNaþ); HRMS (ESþ). Found MNaþ,
359.1837 (C18H32O2Si2Na requires 359.1833).
reported as follows; chemical shift
protons, multiplicity, coupling constant J (Hz), assignment). Re-
sidual protic solvent CHCl3
d (parts per million) (number of
(dH¼7.26) was used as the internal ref-
erence. 13C NMR spectra were recorded at 63 MHz or 126 MHz,
using the central resonance of CDCl3 (dC¼77.0 ppm) as the internal
reference. 29Si NMR spectra were recorded at 99 MHz on Varian
Inova-500. All chemical shifts are quoted in parts per million rel-
ative to tetramethylsilane (dH¼0.00 ppm) and coupling constants
are given in hertz. All 13C spectra were proton decoupled. Assign-
ment of spectra was carried out using DEPT, COSY, HSQC, HMBC and
NOESY experiments.
4.1.3. (1SR,2SR,3SR,4SR,5SR) 4,5-Dihydroxy-3-methyl-1,2-diphenyl-
1-(trimethylsilyl)silacyclohexane 23b
A solution of silacyclohex-4-ene 10b (50 mg, 0.15 mmol) in ac-
etone/water (2.1 ml, 20:1) was treated with NMO (35 mg,
0.30 mmol), cooled to 0 ꢃC and treated with a catalytic amount of
osmium tetroxide (1.9 mg, 0.0070 mmol). After stirring for 45 min
the reaction mixture was treated with aq Na2S2O3 and extracted
with EtOAc (3ꢄ5 ml). The combined organic layers were dried over
MgSO4, filtered, concentrated and dried in vacuo gave the crude
diols as a 7:2:1 mixture of diastereoisomers. Flash chromatography
(pet. ether/ether [1:1], [1:2]) afforded the title dihydroxyl silacycle
Gas chromatography-mass spectra (GC–MS, EI or CI) were
obtained using a Thermo TRACE mass spectrometer. Electrospray
(ES) mass spectra were obtained on a Micromass LCT mass spectro-
meter. High-resolution mass spectra were obtained using a Thermo
LTQ mass spectrometer (ES) at the University of Durham, or per-
formed by the EPSRC National Mass Spectrometry Service Centre,
University of Wales, Swansea. Methods for the preparation of and

J.D. Sellars, P.G. Steel / Tetrahedron 65 (2009) 5588–5595
5593
23b as a colourless gum (30 mg, 56%); Rf 0.3 (pet. ether/ether 1:1);
nmax (thin film) 3631–3579 (broad-OH), 3069, 3026, 2955, 2925,
(5-C), 75.1 (3-C), 39.6 (4-C), 30.6 (6-C), 20.0 (7-CH3), 16.0 (6-CH3),
12.2 (4-CH3); m/z (ESþ) 181 (MNaþ); HRMS (ESþ). Found MNaþ,
181.1199 (C9H18O2Na requires 181.1199).
2895, 2871, 1598, 1426, 1256, 1242, 1049, 1021, 896, 835, 781 cmꢂ1
;
dH (500 MHz, CDCl3) 7.31–7.21 (5H, m, Ar-H), 7.18–7.12 (3H, m, Ar-
H), 7.08–7.06 (2H, m, Ar-H), 4.48 (1H, m, 5-H), 3.38 (1H, dd, J 10, 3,
4-H), 2.57 (1H, m, 3-H), 2.15 (1H, d, J 12, 2-H), 1.63 (1H, dd, J 15.5, 6,
6-HH), 1.34 (1H, dd, J 15.5, 6, 6-HH), 0.95 (3H, d, J 7, 3-CH3), 0.03 (9H,
s, Si(CH3)3); dC (126 MHz, CDCl3) 143.2 (ipso-Ar-C), 137.2 (ipso-Ar-C),
134.9 (Ar-C), 128.9 (Ar-C), 128.8 (Ar-C), 128.6 (Ar-C), 127.7 (Ar-C),
125.1 (Ar-C), 79.8 (4-C), 72.2 (5-C), 41.0 (2-C), 36.1 (3-C), 18.1 (3-
CH3), 17.5 (6-C), -0.7 (Si(CH3)3); dSi (100 MHz, CDCl3) ꢂ18.72,
ꢂ21.22; m/z (ESþ) 393 (MNaþ), 425 (MNaþMeOHþ), 763 (2MNaþ);
HRMS (ESþ) Found MNaþ, 393.1676 (C21H30O2Si2Na requires
393.1677). Further elution afforded an inseparable mixture of diols
24b and 25b (24%); key 1H NMR signals (500 MHz, CDCl3) 4.49 (1H,
m, 5-H), 4.37 (1H, m, 5-H), ꢂ0.04 (9H, s, Si(CH3)3), ꢂ0.11 (9H, s,
Si(CH3)3).
4.1.6. (1SR,2SR,3RS) 2-Methyl-1-phenylpent-4-ene-1,3-diol 21b
Following the same procedure outlined above, silacyclic diol 23b
(120 mg, 0.32 mmol) was transformed into the title compound 21b,
which was isolated as a colourless oil (45 mg, 72%); Rf 0.3 (pet.
ether/ether 1:1); nmax (thin film) 3502–3214 (broad-OH), 3064,
2974, 2886, 1721, 1711, 1690, 1601, 1512, 1450, 1332, 1216, 1128,
1080 cmꢂ1
; dH (500 MHz, CDCl3) 7.38–7.36 (4H, m, Ar-H), 7.33–7.28
(1H, m, Ar-H), 6.00 (1H, ddd, J 16, 10, 5, 4-H), 5.33 (1H, d, J 16, 5-HH),
5.26 (1H, d, J 10, 5-HH), 4.69 (1H, d, J 9, 1-H), 4.40 (1H, m, 3-H), 2.95
(1H, br s, –OH), 2.11 (1H, qd, J 9, 3, 2-H), 0.82 (3H, d, J 9, 2-CH3); dC
(126 MHz, CDCl3) 143.7 (ipso-Ar-C), 138.5 (4-C), 128.7 (Ar-C), 128.0
(Ar-C), 126.8 (Ar-C), 115.8 (5-C), 78.3 (1-C), 74.9 (3-C), 44.3 (2-C),
12.5 (2-CH3); m/z (ESþ) 215 (MNaþ); HRMS (ESþ). Found MNaþ,
215.1043 (C12H16O2Na requires 215.1043).
4.1.4. (1SR,2RS,3SR,4SR,5SR) 4,5-Dihydroxy-1-phenyl-1-
trimethylsilyl-2-(isopropyl)-3-methylsilacyclohexane 23a
4.1.7. (2SR/RS,3SR,4SR,5SR) 4-Methyl-2,3-diphenyl-2-
Following the same procedure as described for diol 10b, silacy-
clohex-4-ene 10a (170 mg, 0.56 mmol) was transformed into the
title compound, which was isolated as a yellow oil (60 mg, 32%); Rf
0.3 (pet. ether/ether 1:1); nmax (thin film) 3498–3211 (broad-OH),
(trimethylsilyl)-5-vinyl-1,2-oxasilolane 26
To a solution of silacyclic diol 23b (40 mg, 0.11 mmol) in dry
DCM (2 ml) was added trifluoroborane–acetic acid complex
(0.030 ml, 0.22 mmol). The solution was stirred for 15 min at room
temperature then mixed with saturated NaHCO3 solution (5 ml)
and extracted with DCM (3ꢄ5 ml). The combined organic layers
were dried over MgSO4, filtered, concentrated and dried in vacuo.
Flash chromatography (pet. ether, pet. ether/ether [98:2]) gave the
title compound as an opaque oil (27 mg, 72%) as an inseparable
1:1 mixture of diastereoisomers; Rf 0.3 (pet. ether/ether 98:2);
nmax (thin film) 2956, 2923, 1650, 1555, 1427, 1244, 1107, 1003, 835,
2950, 2932, 2898, 2864, 1426, 1096, 1022, 992, 832, 731, 697 cmꢂ1
;
dH (500 MHz, CDCl3) 7.53–7.51 (2H, m, Ar-H), 7.31–7.30 (3H, m, Ar-
H), 4.20 (1H, m, 5-H), 3.49 (1H, m, 4-H), 2.25 (1H, m, 3-H), 2.14 (1H,
m, 2-CH(CH3)2), 1.36 (1H, dd, J 14, 9, 6-HH), 1.18 (1H, m, 6-HH), 1.08
(1H, dd, J 9, 6, 2-H), 1.04 (3H, d, J 7, 2-CH(CH3)2), 0.97 (3H, d, J 7, 3-
CH3), 0.91 (3H, d, J 7, 2-CH(CH3)2), 0.21 (9H, s, Si(CH3)3); dC (126 MHz,
CDCl3) 140.2 (ipso-Ar-C),134.4 (Ar-C),128.5 (Ar-C),128.0 (Ar-C), 78.8
(4-C), 70.2 (5-C), 36.8 (2-C), 35.8 (3-C), 29.1 (2-CH(CH3)2), 23.8 (2-
CH(CH3)2), 19.4 (3-CH3), 16.5 (6-C), ꢂ0.4 (Si(CH3)3); dSi (100 MHz,
CDCl3) ꢂ17.90, ꢂ23.36; m/z (ESþ) 359 (MNaþ); HRMS (ESþ). Found
MNaþ, 359.1834 (C18H32Si2O2Na requires 359.1833). Further elution
afforded an inseparable mixture of diols 24a and 25a; key 1H NMR
signals (300 MHz, CDCl3) 4.15 (1H, m, 5-H), 3.83 (1H, m, 5-H), 0.23
(9H, s, Si(CH3)3), 0.05 (9H, s, Si(CH3)3).
698 cmꢂ1
; dH (500 MHz, CDCl3) 7.62–7.59 (2H, m, Ar-H), 7.43–7.41
(3H, m, Ar-H), 7.34–7.30 (3H, m, Ar-H), 7.24–7.20 (2H, m, Ar-H),
7.17–7.03 (9H, m, Ar-H), 6.74 (1H, d, J 8, Ar-H{B}), 5.95 (1H, ddd, J
17, 9, 6, 5-CH]CH2{B}), 5.84 (1H, ddd, J 17, 11, 8, 5-CH]CH2{A}),
5.41 (1H, d, J 17, 5-CH]CHH{B}), 5.31 (1H, d, J 9, 5-CH]CHH{B}),
5.30 (1H, m, 5-CH]CHH{A}), 5.17 (1H, d, J 11, 5-CH]CHH{A}), 4.92
(1H, t, J 6, 5-H{B}), 4.80 (1H, t, J 7, 5-H{A}), 2.94 (1H, sept, J 7, 4-
H{A}), 2.72 (1H, d, J 12, 3-H{A}), 2.69–2.63 (2H, m, 4-H, 3-H{B}),
0.95 (3H, d, J 7, 4-CH3{A}), 0.91 (3H, d, J 6, 4-CH3{B}), 0.21 (9H, s,
Si(CH3)3{B}), 0.11 (9H, s, Si(CH3)3{A}); dC (126 MHz, CDCl3) 140.9
(ipso-Ar-C), 139.4 (ipso-Ar-C), 138.8 (ipso-Ar-C), 137.2 (5-
CH]CH2{B}), 136.7 (5-CH]CH2{A}), 135.7 (ipso-Ar-C), 133.9 (Ar-C),
133.0 (Ar-C), 129.3 (Ar-C), 129.0 (Ar-C), 128.3 (Ar-C), 128.0 (Ar-C),
127.7 (Ar-C), 127.4 (Ar-C), 126.8 (Ar-C), 124.7 (Ar-C), 124.4 (Ar-C),
116.7 (5-CH]CH2{B}), 116.4 (5-CH]CH2{A}), 84.6 (5-C{A}), 83.4
(5-C{B}), 41.7 (3-C{A}), 41.5 (4-C{A}), 40.27 (3-C{B}), 40.25 (4-
C{B}), 15.3 (4-CH3{A}), 15.1 (4-CH3{B}),-2.1 (Si(CH3)3{A}), ꢂ1.3
(Si(CH3)3{B}); dSi (100 MHz, CDCl3) 19.5, 14.5, ꢂ20.8, ꢂ21.0; m/z
(ESþ) 353 (MHþ); HRMS (ESþ). Found MHþ, 353.1752 (C21H29OSi2
requires 353.1752).
4.1.5. (3RS,4RS,5RS) 4,6-Dimethylhept-1-ene-3,5-diol 21a
To a solution of silacyclic diol 23a (60 mg, 0.18 mmol) in dry
DCM (4 ml) was added trifluoroborane–acetic acid complex
(0.049 ml, 0.36 mmol). The solution was stirred for 15 min at room
temperature then mixed with saturated NaHCO3 solution (5 ml)
and extracted with DCM (3ꢄ10 ml). The combined organic layers
were dried over MgSO4, filtered, concentrated and dried in vacuo to
give a colourless oil, which was used immediately without further
purification.
To the colourless oil was added KHCO3 (50 mg, 0.54 mmol) and
KF (21 mg, 0.36 mmol). The mixture was dissolved in methanol/
THF solution (1:1, 4 ml) and a 35% w/w solution of H2O2 in water
(0.21 ml, 2.1 mmol) then added. The mixture was heated to reflux
and stirred for 1 h. The mixture was then allowed to cool to room
temperature and saturated Na2S2O3 solution (5 ml) was added to-
gether with EtOAc (10 ml). The aqueous layer was separated and
extracted with EtOAc (3ꢄ10 ml). The combined organic layers were
dried over MgSO4, filtered, concentrated and dried in vacuo. Flash
chromatography (pet. ether/ether [9:1], [4:1], [3:2], [1:1], [1:2])
afforded the desired diol 21a as a colourless oil (18 mg, 64%); Rf 0.3
(pet. ether/ether 1:1); nmax (thin film) 3525–3134 (broad-OH),
4.1.8. (1SR,2SR,3RS) 2-Methyl-1-phenylpentane-1,3,5-triol 28
A solution of diol 21b (20 mg, 0.10 mmol) in THF (1 ml) was
treated with borane–dimethylsulfide complex (0.035 ml,
0.37 mmol) at 0 ꢃC. The reaction was then warmed to room tem-
perature and reacted for 1 h. The mixture was then treated suc-
cessively with water (0.50 ml), NaOH (0.035 ml, 0.10 mmol) and
H2O2 (0.13 ml, 1.3 mmol). The mixture was then refluxed for 1 h, at
which point the mixture was cooled and poured into Na2S2O3 and
extracted with EtOAc (3ꢄ10 ml). The combined organic layers were
dried over MgSO4, filtered, concentrated and dried in vacuo. Flash
chromatography (DCM/MeOH [98:2], [95:5], [9:1]) afforded the
title triol as a colourless oil (15 mg, 64%); Rf 0.3 (DCM/MeOH 9:1);
nmax (thin film) 3348–3119 (broad-OH), 2962, 2924, 2360, 1684,
2962, 2870, 1459, 1427, 1118, 1081, 974, 919, 844, 697, 639 cmꢂ1
; dH
(500 MHz, CDCl3) 5.94 (1H, ddd, J 16, 10, 5, 2-H), 5.29 (1H, d, J 16, 1-
HH), 5.19 (1H, d, J 10, 1-HH), 4.41 (1H, s, 3-H), 3.39 (1H, m, 5-H), 3.11
(1H, br s, –OH), 2.53 (1H, br s, –OH), 1.89 (1H, qd, J 7, 3, 4-H), 1.82
(1H, m, 6-H), 0.94 (3H, d, J 8, 7-CH3), 0.92 (3H, d, J 8, 6-CH3), 0.87
(3H, d, J 7, 4-CH3); dC (126 MHz, CDCl3) 138.9 (2-C), 115.4 (1-C), 79.8
1437, 1338, 1223, 1077, 907, 730, 650 cmꢂ1
; dH (500 MHz, CDCl3)

5594
J.D. Sellars, P.G. Steel / Tetrahedron 65 (2009) 5588–5595
7.36–7.34 (4H, m, Ar-H), 7.28 (1H, m, Ar-H), 4.68 (1H, d, J 8, 1-H),
4.08 (1H, d, J 11, 3-H), 3.89–3.82 (3H, m, 5-H2, –OH), 1.98–1.93 (3H,
m, 4-HH, 2-H, –OH), 1.55 (1H, d, J 11, 4-HH), 0.83 (3H, d, J 7, 2-CH3);
dC (126 MHz, CDCl3) 143.8 (ipso-Ar-C), 128.7 (Ar-C), 127.9 (Ar-C),
126.7 (Ar-C), 78.5 (1-C), 74.7 (3-C), 63.0 (5-C), 44.4 (2-C), 34.4 (4-C),
12.8 (2-CH3); m/z (ESþ) 233 (MNaþ); HRMS (ESþ). Found MNaþ,
233.1148 (C12H18O3Na requires 233.1148).
7-CH3), 0.90 (9H, s, SiC(CH3)3), 0.84 (3H, d, J 6, 6-CH3), 0.76 (3H,
t
t
d, J 7, 4-CH3), 0.41 (3H, s, Si(CH3)2 Bu), 0.11 (3H, s, Si(CH3)2 Bu); dC
(126 MHz, CDCl3) 75.4 (3-C), 60.2 (1-C), 40.3 (4-C), 34.0 (2-C),
30.0 (6-C), 26.0 (SiC(CH3)3), 20.4 (7-CH3), 18.4 (SiC(CH3)3), 13.83
t
t
(6-CH3), 13.82 (4-CH3), ꢂ4.1 (Si(CH3)2 Bu), ꢂ4.7 (Si(CH3)2 Bu);
m/z (ESþ) 313 (MNaþ), 291 (MHþ); HRMS (ESþ) Found MHþ,
291.2349 (C15H35O3Si requires 291.2350).
4.1.9. (3RS,4RS,5RS) 5-(tert-Butyldimethylsilyloxy)-2,4-
dimethylhept-6-en-3-ol 30a
4.1.12. (1SR,2RS,3RS) 3-(tert-Butyldimethylsilyloxy)-2-methyl-1-
phenylpentane-1,5-diol 31b
To a solution of diol 21a (18 mg, 0.11 mmol) in dry DCM (2 ml)
were added imidazole (31 mg, 0.47 mmol) and tert-butyl-
chlorodimethylsilane (21 mg, 0.14 mmol). The solution was stirred
for 2 h at room temperature then diluted with EtOAc and washed
with water (5 ml) and brine (5 ml). The organic layer was dried over
MgSO4, filtered, concentrated and dried in vacuo. Flash chroma-
tography (pet. ether/ether [95:5], [9:1]) afforded the desired the
title silyl ether 30a as a colourless oil (16 mg, 52%); Rf 0.3 (pet.
ether/ether 95:5); nmax (thin film) 3630–3130 (broad-OH), 2957,
Following the identical procedure as outlined for compound
31a, alkene 30b (20 mg, 0.070 mmol) was transformed into the title
diol 31b, which was isolated as a colourless oil (12 mg, 60%); Rf 0.3
(pet. ether/ether 2:3); nmax (thin film) 3490–3182 (broad-OH),
2956, 2932, 2886, 2860, 1684, 1676, 1560, 1437, 1259, 1202, 1075,
1050, 781 cmꢂ1
; dH (500 MHz, CDCl3) 7.34–7.31 (5H, m, Ar-H), 4.58
(1H, d, J 10, 1-H), 4.14 (1H, dt, J 10, 3, 3-H), 3.85 (1H, m, 5-HH), 3.75
(1H, m, 5-HH), 2.07–1.96 (2H, m, 2-H, 4-HH), 1.89 (1H, m, 4-HH),
0.97 (9H, s, SiC(CH3)3), 0.57 (3H, d, J 7, 2-CH3), 0.22 (3H, s,
t
t
2930, 2857, 1471, 1384, 1254, 1126, 1022, 996, 835, 776 cmꢂ1
;
dH
Si(CH3)2 Bu), 0.16 (3H, s, Si(CH3)2 Bu); dC (126 MHz, CDCl3) 143.9
(ipso-Ar-C), 128.5 (Ar-C), 127.8 (Ar-C), 127.3 (Ar-C), 77.8 (1-C), 74.6
(3-C), 60.1 (5-C), 45.2 (2-C), 34.3 (4-C), 26.1 (SiC(CH3)3), 18.2
(500 MHz, CDCl3) 5.93 (1H, ddd, J 17, 10, 6, 6-H), 5.22 (1H, d, J 17, 7-
HH), 5.19 (1H, d, J 10, 7-HH), 4.30 (1H, m, 5-H), 3.95 (1H, br s, –OH),
3.41 (1H, d, J 9, 3-H), 1.82 (1H, m, 4-H), 1.68 (1H, qd, J 7, 2, 2-H), 0.99
(3H, d, J 7, 1-H), 0.91 (9H, s, SiC(CH3)3), 0.86 (3H, d, J 7, 2-CH3), 0.77
t
t
(SiC(CH3)3), 14.0 (2-CH3), ꢂ4.1 (Si(CH3)2 Bu), ꢂ4.6 (Si(CH3)2 Bu);
m/z (ESþ) 347 (MNaþ); HRMS (ESþ). Found MNaþ, 347.2014
(C18H32O3SiNa requires 347.2013).
t
t
(3H, d, J 7, 4-CH3), 0.09 (3H, s, Si(CH3)2 Bu), 0.06 (3H, s, Si(CH3)2 Bu);
dC (126 MHz, CDCl3) 137.3 (6-C), 116.4 (7-C), 79.1 (5-C), 77.5 (3-C),
41.3 (4-C), 30.1 (2-C), 26.0 (SiC(CH3)3), 20.4 (1-C), 18.4 (SiC(CH3)3),
4.1.13. (1SR,2RS,3SR,4RS) 3-(tert-Butyldimethylsilyloxy)-2-methyl-
1-phenylpentane-1,4-diol 32
t
t
14.2 (2-CH3), 13.1 (4-CH3), ꢂ4.3 (Si(CH3)2 Bu), ꢂ5.0 (Si(CH3)2 Bu);
m/z (ESþ) 295 (MNaþ); HRMS (ESþ) Found MHþ, 273.2245
(C15H33O2Si requires 273.2244).
A solution of mono-protected diol 30b (22 mg, 0.070 mmol) in
THF (1 ml) was treated with borane–dimethylsulfide complex
(0.020 ml, 0.18 mmol) at 0 ꢃC. The reaction was then warmed to
room temperature and stirred for 1 h. The reaction was then
treated successively with water (0.50 ml), NaOH (0.020 ml,
0.070 mmol) and H2O2 (0.090 ml, 0.86 mmol). The mixture was
then refluxed for 1 h, at which point the mixture was cooled and
poured into Na2S2O3 and extracted with Et2O (3ꢄ10 ml). The
combined organic layers were dried over MgSO4, filtered, con-
centrated and dried in vacuo. Flash chromatography (pet. ether,
pet. ether/ether [9:1], [4:1], [1:1], [2:3]) afforded the title com-
pound as a white solid (7 mg, 30%); Rf 0.4 (pet. ether/ether 2:3);
mp 120–122 ꢃC; nmax (ATR) 3518–3190 (broad-OH), 3124, 3030,
4.1.10. (1SR,2RS,3RS) 3-(tert-Butyldimethylsilyloxy)-2-methyl-1-
phenylpent-4-en-1-ol 30b
Following the same procedure as described for 30a, diol 21b
(20 mg, 0.10 mmol) was converted into the title ether, which was
isolated as a colourless oil (22 mg, 70%); Rf 0.3 (pet. ether/ether
95:5); nmax (thin film) 3572–3286 (broad-OH), 2960, 2932, 2894,
2852, 1468, 1368, 1256, 1026, 926, 832, 770 cmꢂ1
; dH (500 MHz,
CDCl3) 7.34–7.27 (5H, m, Ar-H), 6.05 (1H, ddd, J 17, 10, 7, 4-H), 5.33–
5.27 (2H, dd, J 17, 10, 5-H2), 4.54 (1H, d, J 9, 1-H), 4.45–4.43 (1H, m,
3-H), 2.04 (1H, sd, J 9, 3, 2-H), 0.99 (9H, s, SiC(CH3)3), 0.58 (3H, d, J 9,
t
t
2-CH3), 0.17 (3H, s, Si(CH3)2 Bu), 0.12 (3H, s, Si(CH3)2 Bu); dC
(126 MHz, CDCl3) 143.9 (ipso-Ar-C), 137.2 (4-C), 128.4 (Ar-C), 127.7
(Ar-C), 127.3 (Ar-C), 116.7 (5-C), 78.3 (3-C), 77.6 (1-C), 45.7 (2-C),
2962, 2932, 2856, 1606, 1255, 1068, 1024, 896, 835, 716 cmꢂ1
; dH
(500 MHz, CDCl3) 7.38–7.31 (5H, m, Ar-H), 4.46 (1H, d, J 9, 1-H),
4.11 (1H, dd, J 5, 2, 3-H), 3.99 (1H, m, 4-H), 2.53 (1H, s, –OH), 2.19–
2.06 (2H, m, 2-H, –OH), 1.26 (3H, d, J 8, 5-H), 0.99 (9H, s, SiC(CH3)3),
t
26.1 (SiC(CH3)3), 18.3 (SiC(CH3)3), 13.4 (2-CH3), ꢂ4.2 (Si(CH3)2 Bu)
t
t
ꢂ4.9 (Si(CH3)2 Bu); m/z (ESþ) 329.3 (MNaþ), 635 (2MNaþ); HRMS
0.71 (3H, d, J 7, 2-CH3), 0.22 (3H, s, Si(CH3)2 Bu), 0.17 (3H, s,
t
(ESþ). Found MNaþ, 329.1907 (C18H30O2SiNa requires 329.1907).
Si(CH3)2 Bu); dC (126 MHz, CDCl3) 143.9 (ipso-Ar-C), 128.4 (Ar-C),
127.7 (Ar-C), 126.9 (Ar-C), 76.7 (1-C), 75.4 (3-C), 70.3 (4-C), 41.8 (2-
C), 25.9 (SiC(CH3)3), 19.1 (5-C), 18.3 (SiC(CH3)3), 12.0 (2-CH3), ꢂ4.2
4.1.11. (3RS,4RS,5RS) 3-(tert-Butyldimethylsilyloxy)-4,6-
dimethylheptane-1,5-diol 31a
t
t
(Si(CH3)2 Bu), ꢂ4.6 (Si(CH3)2 Bu); m/z (ESþ) 347 (MNaþ); HRMS
(ESþ). Found MNaþ, 347.2011 (C18H32O3SiNa requires 347.2013).
Further elution afforded 3-(tert-butyldimethylsilyloxy)-2-methyl-
1-phenylpentane-1,5-diol 31b (7 mg, 30%) identical with that
described above.
A solution of alkene 30a (16 mg, 0.060 mmol) in THF (2 ml)
was treated with an excess of freshly prepared dicyclohex-
ylborane at 0 ꢃC. The reaction was then warmed to room tem-
perature and reacted for 1 h. The reaction was then treated
successively with water (0.50 ml), 3 M aq NaOH (0.050 ml,
0.15 mmol) and H2O2 (0.070 ml, 0.71 mmol). The mixture was
then refluxed for 1 h, then cooled, poured into Na2S2O3 and
extracted with Et2O (3ꢄ10 ml). The combined organic layers
were dried over MgSO4, filtered, concentrated and dried in
vacuo. Flash chromatography (pet. ether/ether [1:1], [2:3])
afforded the title diol as a colourless oil (12 mg, 70%); Rf 0.3 (pet.
ether/ether 1:1); nmax (thin film) 3562–3356 (broad-OH), 3005,
4.1.14. (ꢀ)-Prelactone B 1
A solution of 1,6-diol 31a (12 mg, 0.041 mmol) in DCM (2 ml)
was treated with NMO (15 mg, 0.12 mmol) and 4 Å molecular
sieves. The mixture was then treated with TPAP (0.70 mg,
0.0020 mmol) at room temperature. After 1 h at room temperature
the mixture was filtered through a pad of silica gel (pet. ether/ether
2:3). The filtrate was concentrated and dried in vacuo to give
a colourless oil, which was then redissolved in THF (2 ml) and
treated with Et3N$3HF (0.070 ml, 0.41 mmol) at room temperature.
The reaction was left overnight and then mixed with water (2 ml)
and extracted with DCM (3ꢄ10 ml). The combined organic layers
2949, 2931, 1713, 1417, 1360, 1223, 1089, 1051, 838, 530 cmꢂ1
; dH
(500 MHz, CDCl3) 4.00 (1H, m, 3-H), 3.79 (1H, m, 1-HH), 3.70
(1H, m, 1-HH), 3.51 (1H, dd, J 10, 2, 5-H), 1.90–1.83 (2H, m, 4-H,
2-HH), 1.78 (1H, m, 2-HH), 1.68 (1H, m, 6-H), 1.00 (3H, d, J 6,

J.D. Sellars, P.G. Steel / Tetrahedron 65 (2009) 5588–5595
5595
were dried over MgSO4, filtered, concentrated and dried in vacuo.
References and notes
Flash chromatography (DCM/ether [9:1], [4:1], [7:3]) afforded the
1. Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004, 3173–3199.
2. Ottosson, H.; Steel, P. G. Chem.dEur. J. 2006, 12, 1576–1585.
3. Sellars, J. D.; Steel, P. G.; Turner, M. J. Chem. Commun. 2006, 2385–2387.
desired lactone as a white solid (5 mg, 90%); Rf 0.3 (DCM/ether 7:3);
10
mp 90–92 ꢃC (lit. mp 97–98 ꢃC);
n
(ATR) 3516–3180 (broad-
max
OH), 2967, 2929, 2876, 2260, 2245, 1731 (C]O), 1600, 1253, 1009,
4. Pullin, R. D. C.; Sellars, J. D.; Steel, P. G. Org. Biomol. Chem. 2007, 5, 3201–3206.
5. Hughes, N. J.; Pullin, R. D. C.; Sanganee, M. J.; Sellars, J. D.; Steel, P. G.; Turner, M.
J. Org. Biomol. Chem. 2007, 5, 2841–2848.
896, 716, 650 cmꢂ1
;
dH (500 MHz, CDCl3) 3.78–3.76 (2H, m, 6-H, 4-
H), 2.93 (1H, dd, J 17, 6, 3-HH), 2.48 (1H, dd, J 17, 6, 3-HH), 2.00 (1H,
qd, J 7, 2, 6-CH(CH3)2), 1.74 (1H, m, 5-H), 1.10 (3H, d, J 7, 6-CH(CH3)2),
1.08 (3H, d, J 7, 5-CH3), 0.92 (3H, d, J 7, 6-CH(CH3)2); dC (126 MHz,
CDCl3) 170.7 (C]O), 86.2 (6-C), 69.9 (4-C), 39.1 (5-C), 39.0 (3-C),
28.9 (6-CH(CH3)2), 20.0 (6-CH(CH3)2), 14.0 (5-CH3), 13.5 (6-
CH(CH3)2); m/z (ESþ) 195 (MNaþ), 227 (MNaþMeOHþ); HRMS
(ESþ). Found MHþ, 173.1173 (C9H17O3 requires 173.1172). All data
agree with those reported in the literature.10
6. Sanganee, M. J.; Steel, P. G.; Whelligan, D. K. Org. Biomol. Chem. 2004, 2,
2393–2402.
7. Sellars, J. D.; Steel, P. G. Org. Biomol. Chem. 2006, 4, 3223–3224.
8. Bindseil, K. U.; Zeeck, A. Helv. Chim. Acta 1993, 76, 150–157.
9. Esumi, T.; Fukuyama, H.; Oribe, R.; Kawazoe, K.; Iwabuchi, Y.; Irie, H.; Hata-
keyama, S. Tetrahedron Lett. 1997, 38, 4823–4826.
10. Hanefeld, U.; Hooper, A. M.; Staunton, J. Synthesis 1999, 401–403.
11. Chakraborty, T. K.; Tapadar, S. Tetrahedron Lett. 2001, 42, 1375–1377.
12. Yamashita, Y.; Saito, S.; Ishitani, H.; Kobayashi, S. Org. Lett. 2002, 4, 1221–1223.
13. Chakraborty, T. K.; Tapadar, S. Tetrahedron Lett. 2003, 44, 2541–2543.
14. Csaky, A. G.; Mba, M.; Plumet, J. Synlett 2003, 2092–2094.
15. Enders, D.; Haas, M. Synlett 2003, 2182–2184.
16. Fournier, L.; Gaudel-Siri, A.; Kocienski, P. J.; Pons, J. M. Synlett 2003, 107–111.
17. Pihko, P. M.; Erkkila, A. Tetrahedron Lett. 2003, 44, 7607–7609.
18. Yamashita, Y.; Saito, S.; Ishitani, H.; Kobayashi, S. J. Am. Chem. Soc. 2003, 125,
3793–3798.
4.1.15. (4RS,5SR,6SR) 4-Hydroxy-5-methyl-6-phenyltetrahydro-2H-
pyran-2-one 29
Following the same protocol as outlined above for Prelactone B,
diol 31b (12 mg, 0.037 mmol) was converted into the title lactone
29, which was isolated as a white solid (8 mg, 100%); Rf 0.3 (DCM/
ether 7:3); mp 118–120 ꢃC; nmax (ATR) 3530–3190 (broad-OH),
2922, 2852, 2359, 2339, 1736 (C]O), 1654, 1245, 1161, 1056, 1022,
19. Aggarwal, V. K.; Bae, I.; Lee, H. Y. Tetrahedron 2004, 60, 9725–9733.
20. Dias, L. C.; Steil, L. J.; Vasconcelos, V. D. Tetrahedron: Asymmetry 2004, 15,
147–150.
21. Yadav, J. S.; Reddy, K. B.; Sabitha, G. Tetrahedron Lett. 2004, 45, 6475–6476.
22. Salaskar, A. A.; Mayekar, N. V.; Sharma, A.; Nayak, S. K.; Chattopadhyaya, A.;
Chattopadhyay, S. Synthesis 2005, 2777–2781.
894, 837 cmꢂ1
; dH (500 MHz, CDCl3) 7.42–7.38 (3H, m, Ar-H), 7.34–
7.27 (2H, m, Ar-H), 4.77 (1H, d, J 11, 6-H), 3.95 (1H, m, 4-H), 3.09 (1H,
dd, J 18, 7, 3-HH), 2.69 (1H, dd, J 18, 7, 3-HH), 2.00 (1H, m, 5-H), 0.94
(3H, s, 5-CH3); dC (126 MHz, CDCl3) 170.1 (C]O), 137.6 (ipso-Ar-C),
129.2 (Ar-C), 128.9 (Ar-C), 127.7 (Ar-C), 85.2 (6-C), 70.1 (4-C), 43.5
(5-C), 39.5 (3-C), 13.9 (5-CH3); m/z (ESþ) 261 (MNaþMeOHþ);
HRMS (ESþ). Found MNaþMeOHþ, 261.1098 (C13H18O4Na requires
261.1097).
23. Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2005, 46, 2133–2136.
24. Sabitha, G.; Padmaja, P.; Reddy, K. B.; Yadav, J. S. Tetrahedron Lett. 2008, 49,
919–922.
25. Srihari, P.; Ravindar, K.; Somaiah, R.; Yadav, J. S. Synth. Commun. 2008, 38,
1389–1397.
26. Soderquist, J. A.; Brown, H. C. J. Org. Chem. 1980, 45, 3571.
27. Sanganee, M. J.; Steel, P. G.; Whelligan, D. K. J. Org. Chem. 2003, 68, 3337–3339.
28. Berry, M. B.; Griffiths, R. J.; Sanganee, M. J.; Steel, P. G.; Whelligan, D. K. Org.
Biomol. Chem. 2004, 2, 2381–2392.
29. Soderquist, J. A.; Negron, A. Tetrahedron Lett. 1998, 39, 9397–9400.
30. Badali, F.; Karalis, A.; Tham, W. Y.; White, J. M. Aust. J. Chem. 1996, 49,
1293–1299.
Acknowledgements
31. Ward, R. A.; Procter, G. Tetrahedron 1995, 51, 12821–12836.
32. Fleming, I.; Lawrence, N. J.; Sarkar, A. K.; Thomas, A. P. J. Chem. Soc., Perkin Trans.
1 1992, 3303–3308.
33. Landais, Y.; Mahieux, C.; Schenk, K.; Surange, S. S. J. Org. Chem. 2003, 68,
2779–2789.
We thank the EPSRC for financial support of this work (stu-
dentship to JDS); Dr. A.M. Kenwright for assistance with NMR ex-
periments; Dr. M. Jones and The EPSRC National Mass Spectrometry
Service, Swansea for mass spectra.
34. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923–2925.