Stereospecific α-methallylation of hydroxyaldehydes by silatropic ene cyclisation

Article abstract of DOI:10.1016/j.tet.2009.01.117

We describe the thermal rearrangement of aldehydes bearing an α-(allyl- or crotylsilyl)oxy substituent. The transformations are best described mechanistically as intramolecular silatropic ene reactions based on stereoselectivity, kinetic and computed transition state data. The overall process constitutes a stereospecific (meth)allylation of α-hydroxyaldehydes, under neutral conditions, in which the hydroxyl protecting group is also the (meth)allylating agent.

Full text of DOI:10.1016/j.tet.2009.01.117

Tetrahedron 65 (2009) 5541–5551
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereospecific
a
-methallylation of hydroxyaldehydes by silatropic ene cyclisation
,
b
c
Jeremy Robertson a , Michael J. Hall , Stuart P. Green
*
a Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
b School of Chemistry, Bedson Building, Newcastle University, Newcastle NE1 7RU, UK
c Pfizer Global Research and Development, Ramsgate Road, Sandwich CT13 9NJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2009
Received in revised form 30 January 2009
Accepted 31 January 2009
Available online 14 April 2009
We describe the thermal rearrangement of aldehydes bearing an a-(allyl- or crotylsilyl)oxy substituent.
The transformations are best described mechanistically as intramolecular silatropic ene reactions based
on stereoselectivity, kinetic and computed transition state data. The overall process constitutes a ste-
reospecific (meth)allylation of
a-hydroxyaldehydes, under neutral conditions, in which the hydroxyl
protecting group is also the (meth)allylating agent.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
2. Synthesis of crotyl precursors
Our group has been involved in a long-running investigation
of alternative methodology for producing stereodefined polyols
based on silicon-tethered carbonyl ene cyclisation and oxidative
We selected substrates 6 and 10 (Scheme 2) for initial study since
our previous work had shown that phenyl substituents on silicon
conferred a reasonable degree of stability (in contrast to methyl)
without hampering oxidative cleavage of the C–Si bond (in contrast
to tert-butyl).5 Piers’ method6 for hydroxyl silylationwas found to be
reliable, even with allylic silanes, therefore access to the Z-crotyl
derivative 6 required the preparation of Z-crotyldiphenylsilane (4).
This silane was prepared by reduction7 of 2-butynyldiphenylsilane
(3)8 and, following purification by chromatography, was found to be
free of the E-isomer as judged by examination of the 600 MHz 1H
NMR spectrum.9 This reagent was then used to silylate (ꢀ)-ethyl
mandelate and the resulting ester (5) reduced to provide the desired
Z-crotyl precursor (6) in acceptable yield.
cleavage. As part of this study we observed that a-prenylsilyloxy
aldehyde precursors (1a, Scheme 1) cyclised rapidly in the
presence of Me2AlCl to give 1,2-oxasilinanes (2) with the
trans,trans-diastereomer predominating in all cases, although
the dr was usually only moderate.1 Based on the results of all-
carbon substrates2 we decided to investigate the stereospecific-
ity of the reactions of E- and Z-a-crotylsilyloxy aldehydes (1b),
expecting improved ratios of diastereomeric products.3 We now
describe full details4 of the preparation and reactivity of suitable
test substrates, and report further kinetic and computational
studies that add to our mechanistic understanding of the ob-
served cyclisations.
At the time of this study, existing methods10 for the preparation
of a suitable E-crotyl silane were either inapplicable to our specific
requirements or gave poor results in our hands. However, based on
Hodgson’s11 report that the double bond in 1,1-bis(trialkylsilyl)-
alkenes could be migrated into the presumably more stable allylic
position we expected that it would be possible to isomerise the
double bond in readily-prepared 3-butenyl (i.e., homoallylic) si-
lanes into the allylic position. Good precedent for this idea was
provided by Matsuda’s evaluation of a range of Ir(I) and Rh(I)
complexes for their potential to isomerise several simple tetraalkyl-
silanes.12 We soon established that commercially-available
[(COD)Ir(PPh2Me)2]þPF6ꢁ, although not identified as the optimum
pre-catalyst in Matsuda’s study, was an effective reagent for com-
plete C]C isomerisation of the product (8) of silylation of ethyl
mandelate with 3-butenyldiphenylsilane (7).13 DIBAL reduction of
the so-formed ester (9) gave aldehyde 10 to complete a practical,
efficient synthesis of the E-crotyl precursor (Scheme 2).
O
OH
OH
R1
R1
R1
Me2AlCl
H
R2
Me
Me
O
O
O
(from 1a)
Si
R3
Si
Si
Ph Ph
Ph Ph
Ph Ph
R1 = Ph, i-Pr, t-Bu
1a, R2 = R3 = Me
1b, R2,R3 = Me,H
trans,trans-2
cis,cis-2
Scheme 1. 1,2-Oxasilinanes by silicon-tethered Type I ene cyclisations.
* Corresponding author. Tel.: þ44 1865 275660.
E-mail address: jeremy.robertson@chem.ox.ac.uk (J. Robertson).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.117

5542
J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
O
O
Me
Ph
Ph
H
(i)
(ii)
(i)
OEt Me
H
Me
H
Si
Si
78%
67%
O
56%
O
Ph Ph
Me
Ph Ph
Si
Si
Ph Ph
5
Ph Ph
6
3
4
O
O
O
Ph
Ph
O
Ph
(ii)
(iii)
(i)
74%
H
OEt
OEt
H
Si
O
O
82%
97%
Ph Ph
Si
Ph Ph
8
Si
Me
Si
Ph Ph
10
Me
Ph Ph
9
7
Scheme 2. Reagents: (i) DIBAL then H3Oþ; (ii) ethyl mandelate, cat. B(C6F5)3; (iii) cat. [(COD)Ir(PPh2Me)2]þ PFꢁ6
.
3. Ene cyclisations
H
O
H
O
MesN
NMes
Ph
With short, efficient routes to both E- and Z-crotyl precursors it
was disappointing to find that these substrates decomposed or
generated complex product mixtures either under the ‘standard’
conditions (Me2AlCl, CH2Cl2, rt) or with a variety of alternative
Lewis acids at various temperatures. This increased sensitivity to-
wards Lewis acids led us to attempt ene cyclisations under neutral
conditions; accordingly, aldehydes 6 and 10 were heated at 80 ꢂC in
CDCl3 and the reactions monitored by 1H NMR spectroscopy. In
H
H
t-Bu
i-Pr
Cl
Cl
Ru
PCy3
O
O
Si
Si
Ph Ph
23
Ph Ph
24
25
Figure 1. Diagnostic NOE enhancements supporting trans-stereochemistry in 23 and
24 (only small enhancements were observed between the allylic CH2 and the t-Bu or
i-Pr substituents). Grubbs II catalyst 25 for Scheme 5.
each case, there was a smooth progression from the
a-silyloxy-
aldehyde to a pair of 1,3,2-dioxasilolanes (11 or 14, Scheme 3),
which were assigned as epimers at the benzylic position. The ste-
reochemistry at the allylic position (Me/O anti in 11, syn in 14) was
dictated by that of the crotyl unit in the starting material. On
a preparative scale these intermediates could be desilylated to give
a high yield of diols 12 and 13 (from 11) and 15 and 16 (from 14) that
could be readily separated by chromatography.
We sought to confirm the stereochemistry in these com-
pounds by correlation with simpler analogues and, initially,
simple allyl substrates were examined to establish the trend of
predominant formation of 1,3,2-dioxasilolane precursors of the
syn-diols. Preparation of test substrates was readily achieved by
silylation of cyanohydrins 17–2014 (Scheme 4) with allyldiphenyl-
chlorosilane (prepared in situ from dichlorodiphenylsilane and
allylmagnesium bromide)15 followed by DIBAL reduction. Al-
though this sequence worked well for cyanohydrins 17 and 18,
derived, respectively, from pivalaldehyde and isobutyraldehyde,
the DIBAL reductions were not productive in generating the more
labile aldehydes derived from propionaldehyde- and benzalde-
hyde-cyanohydrin (19 and 20, respectively). However, substrates
21 and 22 proved sufficient for the purposes of this study and,
when heated to 80 ꢂC for 16 h, a single compound was obtained in
each case (23 and 24, respectively), the stereochemistry being
confirmed by NOE experiments as indicated in Figure 1.
The tert-butyl-substituted compounds were stable, easy to
handle and gave essentially perfect stereocontrol during the rear-
rangement step, and showed simple NMR spectra with minimal
1H–1H coupling to the ring protons. For these reasons, tert-butyl
variants (28 and 33, Scheme 5) of the Z- and E-crotyl precursors
were then prepared. Once again, cyclisation proceeded extremely
cleanly to give single diastereoisomers of the 1,3,2-dioxasilolane
intermediates (not shown), which were desilylated with hydrogen
peroxide added to ease separation of the diols from phenylsilyl
residues.
The relative stereochemistry at the two hydroxylated positions
was clear by 1H NMR analysis of the intermediate 1,3,2-dioxasi-
lolanes but, to secure the stereochemistry at the allylic position,
the diallyl ethers of diols 29 and 34 were subjected to ring closing
metathesis with the second generation Grubbs catalyst (25, Fig. 1)
to give samples of the dihydropyrans 30 and 35. Seven-mem-
bered ring products (not shown) formed the majority of the mass
balance in these metatheses.16 The coupling constant between
the allylic and ring-oxygen methine protons was large (J 9.4 Hz)
in the case of 30 and small (J 2.7 Hz) in the case of 35 in support
of anti and syn assignments, respectively, of the precursor diols
29 and 34.
Me
OH
OH
(i)
Ph
(ii)
Ph
Ph
6
O
O
Si
OH Me
OH Me
Ph
Ph
11
12, 60%
13, 27%
Me
OH
OH
(i)
Ph
(ii)
Ph
Ph
10
O
O
Si
OH Me
OH Me
Ph
Ph
14
15, 64%
16, 26%
Scheme 3. Thermal rearrangement of (Z)- and (E)-crotylsilyloxyaldehydes; stereo-
specific silatropic ene cyclisation. Reagents: (i) CHCl3, 80 ꢂC; (ii) KF, KHCO3, aq MeOH.
O
R
R
H
(i),(ii)
R
CN
OH
(iii)
O
O
O
Si
Ph Ph
Si
Ph
Ph
23, R = t-Bu, 92%
24, R = i-Pr, 89%
17, R = t-Bu
18, R = i-Pr
19, R = Et
20, R = Ph
21, R = t-Bu, 70%
22, R = i-Pr, 45%
4. Kinetics and mechanism
An intramolecular rearrangement involving Si–O bond forma-
tion in concert with allylation can be drawn (Fig. 5) that accounts
for the connectivity and stereochemistry in the product. However,
Scheme 4. Complete stereoselectivity in the silatropic ene cyclisations of simple iso-
propyl and tert-butyl-substituted allylsilyloxy aldehydes. Reagents: (i) Ph2(allyl)SiCl,
imidazole; (ii) DIBAL; (iii) C6H6, 80 ꢂC.

J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
5543
O
O
O
OH
O
H
t-Bu
t-Bu
(iv), (v)
28%
(i)
(ii)
(iii)
t-Bu
OMe Me
H
Me
OMe
t-Bu
t-Bu
AllO
O
O
OH
52%
71%
88%
H
Si
Ph Ph
27
Si
Ph Ph
28
OH Me
26
Me
29
30
(vi) 79%
O
9.4 Hz
O
O
OH
O
H
t-Bu
t-Bu
t-Bu
(iv), (v)
43%
(vii)
(ii)
(iii)
OMe
OMe
H
t-Bu
t-Bu
AllO
O
O
O
H
91%
81%
74%
Si
Ph Ph
31
Si
Me
Si
Me
OH Me
Me
Ph Ph
32
Ph Ph
33
2.7 Hz
34
35
Scheme 5. Stereospecific alkenyl diol synthesis in tert-butyl substrates and confirmation of OH/Me relative stereochemistry. Reagents: (i) 4, cat. B(C6F5)3, (ii) DIBAL then Swern
oxidation; (iii) C6H6, 80 ꢂC then KF, H2O2, aq MeOH; (iv) NaH, excess allyl bromide (All-Br); (v) cat. 25; (vi) 7, cat. B(C6F5)3; (vii) cat. [(COD)Ir(PPh2Me)2]þPFꢁ6
.
Me
The resulting data gave a good straight-line fit in a plot of
t-Bu
ln(relative concentration 21) versus time for each temperature run,
indicating first order kinetics with respect to the substrate. This was
confirmed by additional experiments performed at 70 ꢂC, with
only,
°C
36 h
no crossover
products
24
22
+
33
O
O
Si
Ph Ph
36
10ꢀ2, 20ꢀ2 and 30ꢀ2 mg of aldehyde 21 in 700
mL of toluene-d8,
which showed the rate constant for the rearrangement to have
a negligible dependence on concentration. From these experi-
ments, the Arrhenius activation energy (Ea) was calculated (Fig. 3)
Scheme 6. Crossover experiment to confirm the intramolecular nature of the observed
rearrangements.
to be 70.0 kJ molꢁ118
.
to confirm that intermolecular processes were not operating
a mixture of isopropyl/allyl substrate 22 and tert-butyl/E-crotyl
substrate 33 was heated for 36 h at 80 ꢂC. Analysis of the reaction
mixture both by high field 1H NMR spectroscopy and high resolu-
tion GC mass spectrometry revealed the production of only two
siladioxolanes (24 and 36, Scheme 6) in support of a purely intra-
molecular reaction.
-8.6
-8.8
-9
-9.2
-9.4
-9.6
-9.8
-10
To gain further insight into this rearrangement, a series of NMR
experiments were performed in which an 84ꢀ8 mM solution
(20ꢀ2 mg in 700
mL of toluene-d8) of substrate 21 was heated
within the NMR probe whilst the reaction was followed by 1H NMR
spectroscopy. Experiments were performed at 5 ꢂC intervals from
60 to 80 ꢂC whilst the ratios of aldehyde/1,3,2-dioxasilolane (21/23)
were established at 10–30 min intervals by integration17 of the
well-separated CH]CH2 methine resonances in each component
(Fig. 2).
-10.2
-10.4
-10.6
y = –8.415x + 14.895
2.82
2.87
2.92
1000/T (K–1
2.97
3.02
)
Figure 3. Plot of ln(rate constant) versus reciprocal temperature for the activation
energy calculation.
By way of comparison, a conformer distribution for aldehyde 21
was obtained19 (AM1) and key members of the 99 lowest energy
conformers were selected for higher-level geometry optimisations
(B3LYP/6-31G*). At this level of theory the first conformer (in the
original list) to approximate a five-membered Si–O–C–C]O cyclic
arrangement was 4.3 kJ molꢁ1 higher in energy than the first con-
former to contain a cisoid O–C–C]O arrangement. A transition
state was calculated using this conformation as a starting point that
showed a similar degree of C–C and O–Si bond formation, with the
forming and breaking C–C bonds being of roughly equal length
(Fig. 4). This transition state was calculated to be 84 kJ molꢁ1 higher
than the low energy cisoid aldehyde (21) conformer.
In our original working model for these reactions we envisaged
a cooperative20 pre-activation of both the aldehyde and silicon
atom by their mutual coordination, and subsequent allylic transfer
through a chair-like assembly from the face opposite the alkyl sub-
stituent (path a, Fig. 5). This arrangement results in anti-Felkin–Anh
1
Figure 2. Stack plot of typical 500 MHz H NMR experiment (21/23 at 70 ꢂC; plots
shown at 30 min intervals).

5544
J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
H
solution was stirred for 30 min at ꢁ78 ꢂC, rt for 30 min and then
partitioned between water (20 mL) and ether (40 mL). The aqueous
layer was extracted with ether (40 mL) and the combined organic
extracts were washed with brine (20 mL) then dried over MgSO4.
The solvent was removed under reduced pressure and the resulting
oil was purified by flash column chromatography on silica gel
(petrol) to give the product (3) as a colourless oil (2.92 g, 62%). Rf
0.13 (petrol); Found C 81.35, H 6.99, C16H16Si requires C 81.30, H
6.82%; nmax/cmꢁ1 (thin film) 3069m, 3049m, 2916m, 2135s (SiH),
1428s, 1179m, 1117s, 818br s, 734s, 698s, 675s; dH (200 MHz, CDCl3)
1.77 (3H, t, J 2.7, CH3), 2.08 (2H, dq, J 3.3, 2.7, SiCH2), 5.00 (1H, t, J 3.3,
SiH), 7.36–7.47 (6H, m) and 7.64–7.69 (4H, m, 2ꢃPh); dC (50 MHz,
CDCl3) 0.0, 0.6, 71.9, 72.7, 124.9, 126.9, 130.0, 132.4; m/z (EIþ) 236
(Mþ, 18%), 183 (100), 105 (52); HRMS (EIþ) found 236.1022, C16H16Si
[Mþ] requires 236.1016.
2.06
t-Bu
O
1.97
O
Si
2.09
Ph
Ph
Figure 4. Calculated transition state for the cyclisation of 21/23 showing partial-
bond lengths and vibrations.
R
H
Ph
Ph
δŠ O
Si δ+
O
R
E
Z
Δ
a
O
H
E
O
Si
Ph
6.2. (Z-But-2-enyl)diphenylsilane (4)
Ph
Z
Silane 3 (1.22 g, 5.18 mmol) was dissolved in a solution of DIBAL
(10.4 mL,1 M in hexanes,10.4 mmol) and the mixture was heated to
reflux for 4 h. The reaction mixture was then poured into a mixture
of ice (50 mL), 1 M hydrochloric acid (25 mL) and ether (50 mL) and
stirred for 15 min. The aqueous layer was extracted with ether
(50 mL) and the combined organic extracts were washed with 1 M
hydrochloric acid (25 mL), brine (50 mL) and dried over MgSO4. The
solvent was removed under reduced pressure and the resulting oil
was purified byflashcolumnchromatographyonsilica gel(petrol) to
give the product (4) as a colourless oil (965 mg, 78%). Rf 0.25 (petrol);
nmax/cmꢁ1 (thin film) 3069m, 3017m, 2125s (SiH), 1429s, 1151m,
1118s, 990m, 846s, 808s, 731m, 711s, 698s, 647m; dH (200 MHz,
CDCl3) 1.54 (3H, d, J 5.6, CHCH3), 2.15 (2H, dd, J 6.7, 3.6, SiCH2), 4.90
(1H, t, J 3.6, SiH), 5.40–5.48 (1H, m) and 5.51–5.58 (1H, m, CH]CH),
7.37–7.46 (6H, m) and 7.47–7.65 (4H, m, 2ꢃPh); dC (100 MHz, CDCl3)
12.6, 13.5, 123.3, 124.7, 128.0, 129.7, 134.1, 135.2; m/z (CIþ) 256
(MNHþ4 , 42%), 239 (MHþ,16),183 (100); HRMS (CIþ) found 256.1520,
C16H22NSi [MNHþ4 ] requires 256.1516.
b
E
R
Ph
Ph
Z
O
Si
R
O
H
E
O
O
Si
Ph
Ph
Z
Figure 5. Silatropic ene cyclisation by pre-association of the carbonyl oxygen and
silicon atoms (path a) or by concerted Si–O and C–C bond formation (path b).
selectivity and, because the CHR group is forced into a pseudoaxial
position, the usual sense of stereoselectivity between the allylic and
newly-formed hydroxylated positions (E/anti, Z/syn) is re-
versed.21 This model predicts that the level of facial selectivity
should be determined by the effective size of the alkyl group and,
indeed, the t-Bu and i-Pr cases proceeded with excellent stereo-
selectivity in contrast to the Ph cases. Subsequent experiments22
showed that di(isopropyl)-substituted silyl precursors cyclise at
a comparable rate to the diphenyl analogues discussed above,
suggesting that pre-coordination may not be important and that
the reaction follows a concerted pathway (path b, Fig. 5).23
6.3. ( )-Ethyl [(Z-but-2-enyl)diphenylsilanyloxy]-
phenylacetate (5)
Silane 4 (456 mg, 1.93 mmol) and ethyl mandelate (347 mg,
1.93 mmol) were dissolved in dichloromethane (8 mL). Tris(penta-
fluorophenyl)borane (49 mg, 0.097 mmol) was added and the
resulting solutionwas heated at reflux for 1 h, thenallowed to coolto
rt and poured into a mixture of water (10 mL) and ether (10 mL). The
aqueous layer was extracted with ether (2ꢃ10 mL) and the com-
bined organic extracts were washed with brine (10 mL) and then
dried over MgSO4. The solvent was removed under reduced pressure
and the resulting oil was purified by flash column chromatography
on silica gel (petrol/ether, 25:1) togive the product (5) as a colourless
oil (532 mg, 67%). Rf 0.44 (petrol/ether, 5:1); nmax/cmꢁ1 (thin film)
3069m, 3049m, 3016m, 2980m, 2915m, 1753s, 1429s, 1369m,
1263m,1177s,1118s,1072m,1029m, 880m, 838m, 738s, 699s, 650m;
dH (300 MHz, CDCl3) 1.12 (3H, t, J 7.1, CH2CH3), 1.41 (3H, d, J 6.6,
CHCH3), 2.18 (2H, d, J 8.1, SiCH2), 4.02–4.10 (2H, m, CH2O), 5.27 (1H, s,
CHO), 5.33–5.53 (2H, m, CH]CH), 7.31–7.49 (11H, m) and 7.59–7.66
(4H, m, 3ꢃPh); dC (50 MHz, CDCl3) 12.6, 14.0, 15.7, 61.1, 74.8, 123.6,
123.9, 126.7, 127.8, 128.4, 130.1, 133.9, 135.0, 138.7, 138.8, 171.7; m/z
(ESþ) 855 (M2Naþ, 8%), 439 (MNaþ, 73), 361 (100); HRMS (ESIþ)
found 439.1733, C26H28NaO3Si [MNaþ] requires 439.1700.
5. Summary
This process represents an addition to the known allylations
that proceed in the absence of added catalysts. In other systems, the
silicon atom may be rendered Lewis acidic, either by virtue of at-
tached electronegative substituents24 or constraint within a four-
membered ring;20,25 in these cases, complexation to an aldehyde
precedes allyl delivery and an ordered intramolecular reaction
follows with consequently high stereocontrol. Leighton has been
very active in this general field and has reported, inter alia, a variety
of elegant systems for intramolecular carbonyl allylation from sil-
icon intermediates.26 Nevertheless, our examples appear to be the
first in which a simple diarylsilyloxy substituent activates the
proximal carbonyl group in this way.
6. Experimental
6.1. (But-2-ynyl)diphenylsilane (3)
tert-Butyllithium (13.2 mL, 1.7 M in hexanes, 22 mmol) was
added dropwise to a solution of 2-butyne (1.56 mL, 20 mmol) and
TMEDA (3.01 mL, 20 mmol) in THF (20 mL) at ꢁ78 ꢂC and the
mixture was stirred for 30 min. The reaction mixture was allowed
to warm to rt over 30 min, re-cooled to ꢁ78 ꢂC and chloro-
diphenylsilane (3.9 mL, 20 mmol) was added. The resulting
6.4. ( )-[(Z-But-2-enyl)diphenylsilanyloxy]-
phenylacetaldehyde (6)
Ester 5 (522 mg, 1.25 mmol) was dissolved in a mixture of
dichloromethane (2.5 mL) and heptane (3.75 mL) and cooled to

J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
5545
ꢁ78 ꢂC. DIBAL (1.88 mL, 1 M in hexanes, 1.88 mmol) was added
dropwise and the resulting solution was stirred for 1 h. Methanol
(5 mL) and aqueous pH 7.4 buffer solution (5 mL) were added, then
the reaction mixture was warmed to rt and added to 60% aqueous
tartaric acid solution (10 mL) and ether (10 mL). The aqueous layer
was extracted with ether (3ꢃ20 mL) and the combined organic
extracts were washed with brine (20 mL) and dried over MgSO4.
The solvent was removed under reduced pressure and the resulting
oil was purified by flash column chromatography on silica gel
(petrol/ether, 15:1) to give the product (6) as a colourless oil
(260 mg, 56%), which solidified to give a waxy solid on standing. Rf
0.30 [petrol/ether, 5:1 (streaks)]; mp 69–76 ꢂC; nmax/cmꢁ1 (thin
film) 3070m, 3050m, 3017m, 2917m, 2858m, 2806m, 1737s, 1590m,
1490m, 1453m, 1429s, 1192m, 1118s, 1074s, 1049m, 1028m, 966m,
923m, 857m, 763m, 740s, 699s; dH (200 MHz, CDCl3) 1.39 (3H, d, J
5.1, CHCH3), 2.16 (2H, dd, J 6.8, 0.9, SiCH2), 5.10 (1H, d, J 1.7, CHO),
5.33–5.43 (2H, m, CH]CH), 7.31–7.49 (11H, m) and 7.54–7.65 (4H,
m, 3ꢃPh), 9.55 (1H, d, J 1.7, CH]O); dC (75 MHz, CDCl3) 12.9, 15.9,
80.8, 123.6, 124.4, 127.0, 128.2, 129.0, 130.5, 133.9, 135.1, 136.3, 138.2,
199.0; m/z (CIþ) 390 (MNH4þ, 50%), 373 (MHþ, 81), 355 (30), 317
[Mꢁ(C4H7)þ, 100]; HRMS (CIþ) found 373.1631, C24H25O2Si [MHþ]
requires 373.1618.
nmax/cmꢁ1 (thin film) 3070m, 2979m, 2910m,1753s, 1639m,1454m,
1429s, 1370m, 1264s, 1178br s, 1117br s, 1028s, 894s, 836s, 699s; dH
(200 MHz, CDCl3) 1.12 (3H, t, J 7.2, CH2CH3), 1.21–1.34 (2H, m,
SiCH2), 2.09–2.23 (2H, m, CH2CH2CH), 3.94–4.11 (2H, m, CH2O), 4.89
(1H, dd, J 10.1, 3.5) and 4.96 (1H, dd, J 17.0, 3.5, ]CH2), 5.23 (1H, s,
CHO), 5.87 (1H, ddt, J 17.0, 10.1, 6.2, CH]CH2), 7.30–7.67 (15H, m,
3ꢃPh); dC (50 MHz, CDCl3) 13.2, 14.0, 26.9, 61.1, 74.7, 113.0, 126.7,
127.9, 128.4, 128.9, 130.1, 134.1, 134.9, 138.8, 141.0, 171.7; m/z (CIþ)
434 (MNHþ4 , 40%), 361 (30), 339 (100), 196 (33), 182 (31); HRMS
(CIþ) found 434.2142, C26H32NO3Si [MNHþ4 ] requires 434.2146.
6.7. ( )-Ethyl [(E-but-2-enyl)diphenylsilanyloxy]-
phenylacetate (9)
(1,5-Cyclooctadiene)-bis(methyldiphenylphosphine) iridium(I)
hexafluorophosphate (14 mg, 0.016 mmol) was dissolved in
degassed dichloromethane (1 mL) and the solution cooled to
ꢁ78 ꢂC. The catalyst was activated under an atmosphere of hy-
drogen (balloon) until a colour change from clear blood-red to
colourless or clear yellow was observed. The remaining hydrogen
was removed and the solution placed under an atmosphere of ar-
gon and warmed to 0 ꢂC. A solution of ester 8 (664 mg, 1.60 mmol)
in degassed dichloromethane (7 mL) was added by cannula and the
resulting solution was stirred for a further 45 min at 0 ꢂC, moni-
toring by 1H NMR. Upon completion, the solvent was removed
under reduced pressure, the resulting material was triturated with
ether (20 mL) and the extract filtered though a silica pad. The sol-
vent was removed under reduced pressure and the resulting oil was
purified by flash column chromatography on silica gel (petrol/ether,
20:1/15:1) to give the product (9) as a colourless oil (647 mg,
97%). Rf 0.40 (petrol/ether, 10:1); Found C 74.81, H 6.90, C26H28O3Si
requires C 74.96, H 6.77%; nmax/cmꢁ1 (thin film) 3070m, 3015m,
2934m, 2916m, 1753s, 1454m, 1429s, 1394m, 1370m, 1264s, 1177br
s,1118br s,1072s,1029s, 965m, 838s, 763s, 727s, 699s; dH (200 MHz,
CDCl3) 1.14 (3H, t, J 7.2, CH2CH3), 1.57 (3H, d, J 5.7, CHCH3), 2.15 (2H,
d, J 6.8, SiCH2), 3.97–4.13 (2H, m, CH2O), 5.32 (1H, s, CHO), 5.25–5.47
(2H, m, CH]CH), 7.33–7.51 (11H, m) and 7.58–7.68 (4H, m, 3ꢃPh);
dC (50 MHz, CDCl3) 14.0, 18.1, 20.1, 61.1, 74.8, 124.3, 126.0, 126.7,
127.8, 128.4, 128.5, 130.1, 134.1, 135.0, 138.8, 171.7; m/z (CIþ) 434
(MNHþ4 , 35%), 361 (100), 341 (27), 196 (31), 182 (43), 165 (15), 105
(21); HRMS (CIþ) found 434.2137, C26H32NO3Si [MNHþ4 ] requires
434.2146.
6.5. (But-3-enyl)diphenylsilane (7)
Magnesium powder (243 mg, 10 mmol), a few crystals of iodine
and ether (5 mL) were heated together at reflux for 15 min. A few
drops of neat 1-bromobut-3-ene were added to initiate the reaction
and then a solution of the remaining 1-bromobut-3-ene (1.02 mL,
10 mmol in total) in ether (5 mL) was added dropwise over 5 min.
The mixture was heated at reflux for a further 90 min then chloro-
diphenylsilane (1.76 mL, 9.0 mmol) was added dropwise. The
mixture was heated at reflux for a further 15 min then cooled to rt,
filtered through a plug of silica gel, washing through with ether
(2ꢃ50 mL). The combined organic portions were washed succes-
sively with water (50 mL) and brine (50 mL) then dried over
MgSO4. The solvent was removed under reduced pressure and the
resulting oil was purified by flash column chromatography on silica
gel (petrol/ether, 20:1) to give the product (7) as a colourless oil
(1.68 g, 78%). Rf 0.30 (petrol); Found C 80.36, H 7.72, C16H18Si re-
quires C 80.61, H 7.61%; nmax/cmꢁ1 (thin film) 3069s, 3001m,
2914m, 2120s (SiH), 1639m, 1428s, 1117s, 996m, 904s, 807s, 732s,
699s; dH (200 MHz, CDCl3) 1.33 (2H, td, J 8.2, 3.6, SiCH2), 2.28 (2H,
td, J 8.2, 6.2, CH2CH2CH), 4.97 (1H, t, J 3.6, SiH), 4.96–5.05 (1H, m)
and 5.03–5.14 (1H, m, ]CH2), 5.98 (1H, ddt, J 16.8, 10.3, 6.2,
CH]CH2), 7.39–7.53 (6H, m) and 7.60–7.68 (4H, m, 2ꢃPh); dC
(50 MHz, CDCl3) 11.4, 28.5, 113.5, 128.0, 129.7, 134.3, 135.3, 140.7;
m/z (EIþ) 238 (Mþ, 9%), 210 (23), 183 (100), 160 (25), 132 (17), 105
(78), 78 (97); HRMS (EIþ) found 238.1171, C16H18Si [Mþ] requires
238.1172.
6.8. ( )-[(E-But-2-enyl)diphenylsilanyloxy]-
phenylacetaldehyde (10)
Ester 9 (758 mg, 1.82 mmol) was dissolved in a mixture of
dichloromethane (4 mL) and heptane (6 mL) and cooled to ꢁ78 ꢂC.
DIBAL (2.73 mL, 1 M in hexanes, 2.73 mmol) was added dropwise
and the resulting solution was stirred at ꢁ78 ꢂC for 1 h. Methanol
(5 mL) and aqueous pH 7.4 buffer solution (5 mL) were added, the
mixture warmed to rt and then added to a mixture of 60% aqueous
tartaric acid solution (10 mL) and ether (10 mL). The aqueous layer
was extracted with ether (3ꢃ20 mL) and the combined organic
extracts were washed with brine (20 mL) and dried over MgSO4.
The solvent was removed under reduced pressure and the resulting
oil was purified by flash column chromatography on silica gel
(petrol/ether, 15:1) to give the product (10) as a colourless oil
(499 mg, 74%). Rf 0.31 [petrol/ether, 15:1 (streaks)]; nmax/cmꢁ1 (thin
film) 3070m, 3016m, 2933m, 2856m, 2806m, 1737s, 1453s, 1429m,
1118s, 957s, 923s, 857s, 740m, 699s; dH (200 MHz, CDCl3) 1.55 (3H,
d, J 5.9, CHCH3), 2.13 (2H, d, J 5.2, SiCH2), 5.12 (1H, d, J 1.7, CHO),
5.19–5.46 (2H, m, CH]CH), 7.31–7.50 (11H, m) and 7.55–7.64 (4H,
m, 3ꢃPh), 9.58 (1H, d, J 1.7, CH]O); dC (50 MHz, CDCl3) 18.1, 20.1,
80.4, 124.0, 126.4, 126.8, 128.0, 128.5, 128.8, 130.3, 133.8, 134.8,
136.2, 199.0; m/z (CIþ) 390 (MNHþ4 , 50%), 373 (73), 355 (33), 317
6.6. ( )-Ethyl [(but-3-enyl)diphenylsilanyloxy]-
phenylacetate (8)
Silane (7) (1.51 g, 6.34 mmol) and ethyl mandelate (1.14 g,
6.34 mmol) were dissolved in dichloromethane (10 mL). Tris-
(pentafluorophenyl)borane (162 mg, 0.317 mmol) was added and
the resulting solution was heated at reflux for 2 h. The mixture was
allowed to cool to rt and then partitioned between water (10 mL)
and ether (10 mL). The aqueous layer was extracted with ether
(2ꢃ10 mL) and the combined organic extracts were washed with
brine (10 mL) and dried over MgSO4. The solvent was removed
under reduced pressure and the resulting oil was purified by flash
column chromatography on silica gel (petrol/ether, 25:1) to give the
product (8) as a colourless oil (2.15 g, 82%). Rf 0.32 (petrol/ether,
10:1); Found C 74.93, H 6.74, C26H28O3Si requires C 74.96, H 6.77%;

5546
J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
(100), 299 (10); HRMS (CIþ) found 373.1624, C24H25O2Si [MHþ]
requires 373.1618.
dH (400 MHz, CDCl3) 1.09 (3H, d, J 7.0, CH3), 2.40–2.49 (1H, m,
CHCH3), 3.64–3.67 (1H, m, CH(CH3)CH(OH)), 4.66 (1H, d, J 6.1,
PhCH), 5.09–5.16 (2H, m, ]CH2), 5.92 (1H, ddd, J 17.3, 10.4, 8.4,
CH]CH2), 7.31–7.43 (5H, m, Ph).
6.9. ( )-(3SR,4SR,5SR)-3-Methyl-5-phenylpent-1-en-4,5-diol
(12) and ( )-(3SR,4SR,5RS)-3-methyl-5-phenylpent-1-en-4,5-
diol (13)
6.11. General procedure for cyanohydrin synthesis14
Aldehyde 6 (171 mg, 0.46 mmol) was dissolved in chloroform
(10 mL) and the solution was heated at 80 ꢂC for 36 h in a sealed
tube. The solvent was removed under reduced pressure and the
resulting oil was dissolved in a mixture of methanol (3 mL), ether
(3 mL) and water (3 mL). KF (145 mg, 2.5 mmol) and KHCO3
(100 mg, 1.0 mmol) were added and the resulting mixture was
stirred at rt for a further 16 h. Water was added (10 mL) and the
reaction mixture was extracted with ether (3ꢃ20 mL). The com-
bined organic extracts were washed with brine (20 mL) and dried
over MgSO4. The solvent was removed under reduced pressure and
the resulting oil was purified by flash column chromatography on
silica gel (petrol/ether, 3:2) to give the major product (12) as
a white crystalline solid (59 mg, 67%) and the minor product (13) as
a white crystalline solid (26 mg, 29%). Data for 12: Rf 0.22 (petrol/
ether, 1:1); mp 72–76 ꢂC; nmax/cmꢁ1 (KBr) 3371br s, 2970m, 2965s,
2962m, 1450m, 1430m, 1199m, 1122s, 1078m, 1008s, 915m, 912m,
845m, 769m, 699m, 521m; dH (200 MHz, CDCl3) 1.08 (3H, d, J 6.9,
CH3), 2.16–2.26 (1H, m, CHCH3), 2.46 (1H, d, J 3.6, PhCH(OH)), 2.83
(1H, d, J 4.0, CH(CH3)CH(OH)), 3.54–3.61 (1H, m, CH(CH3)CH(OH)),
4.59 (1H, dd, J 6.5, 3.6, PhCH), 5.11 (1H, dd, J 17.2, 1.8) and 5.16 (1H,
dd, J 10.4, 1.8, ]CH2), 5.91 (1H, ddd, J 17.2, 10.4, 8.4, CH]CH2), 7.30–
7.41 (5H, m, Ph); dC (100 MHz, CDCl3) 17.7, 39.6, 75.2, 78.9, 116.6,
126.8, 128.0, 128.5, 139.1, 141.2; m/z (CIþ) 210 (MNH4þ, 8%), 193
(MHþ, 100), 175 (39), 157 (30), 120 (32), 91 (16); HRMS (CIþ) found
210.1494, C12H20NO2 [MNHþ4 ] requires 210.1489. Data for 13: Rf 0.30
(petrol/ether,1:1); dH (200 MHz, CDCl3) 1.10 (3H, d, J 6.9, CH3), 2.40–
2.50 (1H, m, CHCH3), 3.67 (1H, dd, J 6.3, 5.0, CH(CH3)CH(OH)), 4.65
(1H, d, J 6.3, PhCH), 5.07–5.19 (2H, m, ]CH2), 5.93 (1H, ddd, J 17.0,
10.7, 8.4, CH]CH2), 7.28–7.51 (5H, m, Ph).
To a solution of NaHSO3 (7.6 g, 73.1 mmol) in water (20 mL) at
0 ꢂC was added the requisite aldehyde (20 mmol) and the mixture
was stirred for 30 min. A solution of KCN (5.2 g, 80.0 mmol) in
water (100 mL) was added dropwise over 10 min and the resulting
solution was stirred at rt for 2 h. The reaction mixture was extracted
with ether (3ꢃ50 mL) and the combined organic extracts were
washed successively with 5 M hydrochloric acid (50 mL), brine
(50 mL) and dried over MgSO4. The solvent was removed under
reduced pressure and the product was used without further
purification.
6.12. ( )-2-Hydroxy-3,3-dimethylbutyronitrile (17)
Clear waxy solid (1.96 g, 87%); mp 43–45 ꢂC (lit.27 42.5–44 ꢂC);
nmax/cmꢁ1 (thin film) 3445br s, 2967s, 2912m, 2876m, 2247w,
1479m,1467m,1398m,1370s,1243m,1076s,1023s, 949m, 934m; dH
(200 MHz, CDCl3) 1.07 (9H, s, C(CH3)3), 2.96 (1H, br s, OH), 4.13 (1H,
s, CH(OH)); dC (50 MHz, CDCl3) 24.9, 35.4, 70.6, 119.2.
6.13. ( )-2-Hydroxy-3-methylbutyronitrile (18)
Yellow oil (1.88 g, 95%); nmax/cmꢁ1 (thin film) 3436br s, 2970s,
2937s, 2879s, 2248w, 1639m, 1470s, 1391m, 1373m, 1064s, 1017m,
973m, 954m; dH (200 MHz, CDCl3) 1.06 (3H, d, J 5.7) and 1.10 (3H, d,
J 5.7, CH(CH3)2), 2.03 (1H, dhept, J 5.9, 5.7, CH(CH3)2), 3.21 (1H, br s,
OH), 4.27 (1H, d, J 5.9, CH(OH)); dC (50 MHz, CDCl3) 17.2, 17.7, 33.1,
67.0, 119.2.
6.14. General procedure for cyanohydrin silylation
6.10. ( )-(3RS,4SR,5SR)-3-Methyl-5-phenylpent-1-en-4,5-diol
(15) and ( )-(3RS,4SR,5RS)-3-methyl-5-phenylpent-1-en-4,5-
diol (16)
To a solution of dichlorodiphenylsilane (2.03 g, 8.0 mmol) in
ether (20 mL) at 0 ꢂC was added allylmagnesium bromide (8.0 mL,
1 M in ether, 8.0 mmol) and the resulting solution was stirred at rt
for 1 h. The solvent was removed under reduced pressure and the
resulting oil was dissolved in DMF (10 mL). This solution was then
added via cannula to a solution of imidazole (545 mg, 8.0 mmol)
and the requisite cyanohydrin (17 or 18, 4.0 mmol) in DMF (10 mL)
and the mixture stirred for 16 h at rt. The reaction was quenched
with water (30 mL) and the mixture extracted with ether
(3ꢃ30 mL). The combined organic extracts were washed with brine
(20 mL) and dried over MgSO4. The solvent was removed under
reduced pressure and the resulting oil was purified by flash column
chromatography on silica gel (petrol/ether, 25:1).
Aldehyde 10 (95 mg, 0.26 mmol) was dissolved in chloroform
(10 mL) and the solution heated at 80 ꢂC for 36 h in a sealed tube.
The solvent was removed under reduced pressure and the resulting
oil was dissolved in a mixture of methanol (3 mL), ether (3 mL) and
water (3 mL). KF (44 mg, 0.8 mmol) was added and the resulting
mixture was stirred at rt for a further 16 h. Water was added
(10 mL) and the reaction mixture was extracted with ether
(3ꢃ20 mL). The combined organic extracts were washed with brine
(20 mL) and dried over MgSO4. The solvent was removed under
reduced pressure and the resulting oil was purified by flash column
chromatography on silica gel (petrol/ether, 3:2) to give a major
product (15) as a white crystalline solid (35 mg, 71%) and a minor
product (16) as a white crystalline solid (14 mg, 28%). Data for 15: Rf
0.24 (petrol/ether, 1:1); mp 67–68 ꢂC; nmax/cmꢁ1 (KBr) 3368br s,
2972m, 1453m, 1430m, 1199m, 1126s, 1073m, 1008s, 911m, 760m,
718m, 699s, 520m; dH (400 MHz, CDCl3) 1.07 (3H, d, J 6.8, CH3), 2.26
(1H, dqd, J 7.4, 6.8, 5.2, CHCH3), 2.42 (1H, d, J 4.4, CH(CH3)CH(OH)),
2.89 (1H, d, J 4.2, PhCH(OH)), 3.59 (1H, ddd, J 5.2, 4.6, 4.4,
CH(CH3)CH(OH)), 4.67 (1H, dd, J 4.6, 4.2, PhCH), 5.02–5.06 (1H, m)
and 5.09–5.13 (1H, m, ]CH2), 5.82 (1H, ddd, J 17.5, 10.1, 7.4,
CH]CH2), 7.29–7.41 (5H, m, Ph); dC (50 MHz, CDCl3) 14.0, 39.5, 74.5,
78.6, 115.2, 126.6, 127.9, 128.6, 141.2, 141.5; m/z (CIþ) 210 (MNH4þ,
7%), 193 (MHþ, 20), 192 (Mþ, 100), 175 (37), 157 (33), 143 (15), 120
(35), 105 (16), 91 (28); HRMS (CIþ) found 210.1496, C12H20NO2
[MNHþ4 ] requires 210.1489. Data for 16: Rf 0.24 (petrol/ether, 1:1);
6.15. ( )-2-(Allyldiphenylsilanyloxy)-3,3-
dimethylbutyronitrile
Colourless oil (963 mg, 72%); Rf 0.57 (petrol/ether, 10:1); Found
C 75.14, H 7.58, C21H25NOSi requires C 75.18, H 7.51%; nmax/cmꢁ1
(thin film) 3072m, 2966m, 1631m, 1478m, 1429s, 1368m, 1161m,
1111s, 1035m, 902m, 831s, 775m, 738s, 699s; dH (400 MHz, CDCl3)
1.03 (9H, s, Si(CH3)3), 2.29 (1H, ddt, J 14.3, 7.8, 1.2) and 2.35 (1H, ddt,
J 14.3, 7.8, 1.2, SiCH2), 4.01 (1H, s, CHO), 4.95 (1H, ddt, J 10.1, 1.8, 1.2)
and 5.00 (1H, ddt, J 17.0,1.8, 1.2, ]CH2), 5.83 (1H, ddt, J 17.0,10.1, 7.8,
CH]CH2), 7.40–7.51 (6H, m) and 7.62–7.64 (4H, m, 2ꢃPh); dC
(100 MHz, CDCl3) 21.4, 25.1, 36.3, 71.5, 116.1, 118.8, 128.0, 128.1,
130.6, 131.9, 132.4, 132.5, 134.4, 134.8, 135.1; m/z (CIþ) 353 (MNH4þ,
100%), 311 (34), 294 (23), 267 (14), 225 (5), 215 (10), 198 (11); HRMS
(CIþ) found 353.2053, C21H29N2OSi [MNHþ4 ] requires 353.2044.

J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
5547
6.16. ( )-2-(Allyldiphenylsilanyloxy)-3-methylbutyronitrile
Colourless oil (925 mg, 72%); Rf 0.51 (petrol/ether, 10:1); nmax
6.20. General procedure for silatropic ene reaction
/
A solution of aldehyde 21 or 22 (0.48–0.83 mmol) in either
benzene (10 mL) or toluene (10 mL) was heated for 18 h at 80 ꢂC in
a base-washed sealed tube. The solvent was removed under re-
duced pressure to give the product, which was used without fur-
ther purification.
cmꢁ1 (thin film) 3072m, 3052m, 2967s, 2932m, 2876m, 2240w,
1631s, 1590m, 1468m, 1429s, 1390m, 1371m, 1354m, 1186m, 1161s,
1118s, 1063s, 1028m, 998m, 902m, 834m, 809m, 769m, 738s, 699s;
dH (400 MHz, CDCl3) 0.99 (3H, d, J 7.0) and 1.09 (3H, d, J 6.7,
CH(CH3)2), 2.03 (1H, app. heptd, J 7.0, 5.3, CH(CH3)2), 2.30 (1H, ddt, J
15.6, 7.7, 1.2) and 2.35 (1H, ddt, J 15.6, 7.7, 1.2, SiCH2), 4.27 (1H, d, J
5.3, CHO), 4.98 (1H, ddt, J 10.1, 1.7, 1.2) and 5.05 (1H, ddt, J 17.0, 1.7,
1.2, ]CH2), 5.87 (1H, ddt, J 17.0, 10.1, 7.7, CH]CH2), 7.41–7.51 (6H,
m) and 7.62–7.65 (4H, m, 2ꢃPh); dC (100 MHz, CDCl3) 17.1, 17.6, 21.5,
33.9, 68.0, 116.0, 118.6, 127.9, 128.0, 130.6, 131.9, 132.4, 132.5, 134.4,
134.8, 134.9; m/z (CIþ) 339 (MNHþ4 , 100%), 297 (43), 270 (18), 253
(14), 198 (13); HRMS (CIþ) found 339.1893, C20H27N2OSi [MNHþ4 ]
requires 339.1887.
6.21. ( )-4,5-trans-4-Allyl-5-tert-butyl-2,2-diphenyl-[1,3,2]-
dioxasilolane (23)
On a 0.83 mmol scale the reaction gave 23 as a colourless oil
(258 mg, 92%); nmax/cmꢁ1 (thin film) 3072m, 2958s, 2908m,
2870m, 1479m, 1430s, 1365m, 1126s, 1117s, 1053s, 1018s, 997m,
908m, 862m, 806m, 794s, 719s, 699s; dH (400 MHz, CDCl3) 0.97
(9H, s, C(CH3)3), 2.33–2.48 (2H, m, CH2), 3.74 (1H, d, J 5.9, t-BuCHO),
4.28 (1H, ddd, J 7.6, 5.9, 4.4, CH2CHO), 5.10–5.15 (2H, m, ]CH2),
5.92–6.02 (1H, m, CH]CH2), 7.39–7.52 (6H, m) and 7.69–7.73 (4H,
m, 2ꢃPh); dC (100 MHz, CDCl3) 25.8, 37.7, 42.7, 76.1, 87.6, 117.4,
127.8, 128.0, 130.8, 130.9, 131.9, 133.2, 134.5, 135.0, 135.1; dSi
(99 MHz, toluene-d8) ꢁ5.02; m/z (CIþ) 356 (MNH4þ, 66%), 339 (MHþ,
61), 297 (100), 281 (43), 216 (34); HRMS (CIþ) found 339.1792,
C21H27SiO2 [MHþ] requires 339.1775.
6.17. General procedure for silylcyanohydrin reduction
To a solution of the requisite silylcyanohydrin (1.0 mmol) in
dichloromethane (10 mL) at ꢁ78 ꢂC was added DIBAL (1.5 mL, 1 M
in pentane, 1.5 mmol) and the mixture was stirred for 1 h. A satu-
rated solution of tartaric acid in methanol (5 mL) was added and
the reaction mixture partitioned between water (20 mL) and ether
(40 mL). The aqueous layer was extracted with ether (40 mL) and
the combined organic extracts were washed with saturated aque-
ous tartaric acid (30 mL) and brine (20 mL) then dried over MgSO4.
The solvent was removed under reduced pressure and the resulting
oil was purified by flash column chromatography on silica gel
(petrol/ether, 25:1).
6.22. ( )-4,5-trans-4-Allyl-5-isopropyl-2,2-diphenyl-[1,3,2]-
dioxasilolane (24)
On a 0.48 mmol scale the reaction gave 24 as a colourless oil
(137 mg, 89%); nmax/cmꢁ1 (thin film) 3072m, 2962s, 2874m, 1469m,
1430s, 1388m, 1125s, 1059s, 1027s, 917m, 741m, 718s, 700s; dH
(400 MHz, CDCl3) 1.06 (3H, d, J 6.8) and 1.07 (3H, d, J 6.5, CH(CH3)2),
1.82–1.90 (1H, m, CH(CH3)2), 2.47 (2H, app. dd, J 7.2, 6.4, CH2), 3.82
(1H, dd, J 5.8, 5.8, i-PrCHO), 4.21 (1H, td, J 6.4, 5.8, CH2CHO), 5.15–
5.22 (2H, m, ]CH2), 6.00 (1H, ddt, J 17.7, 10.4, 7.2, CH]CH2), 7.42–
7.52 (6H, m) and 7.73–7.76 (4H, m, 2ꢃPh); dC (100 MHz, CDCl3) 17.5,
19.5, 32.2, 40.9, 77.7, 84.8, 117.6, 127.8, 127.9, 130.4, 130.9, 132.4,
132.7,134.5,135.0,135.3; m/z (CIþ) 342 (MNH4þ, 21%) 325 (MHþ, 54),
283 (100), 216 (45), 199 (16), 183 (15), 109 (13); HRMS (CIþ) found
325.1625, C20H25O2Si [MHþ] requires 325.1618.
6.18. ( )-2-(Allyldiphenylsilanyloxy)-3,3-dimethyl-
butyraldehyde (21)
Colourless oil (328 mg, 97%); Rf 0.52 (petrol/ether, 10:1); nmax
/
cmꢁ1 (thin film) 3071s, 3001m, 2962s, 2871s, 1733s, 1631m,
1590m, 1478m, 1421s, 1396m, 1366s, 1158s, 1118s, 1307s, 998m,
900s, 847s, 770s, 737s, 598s; dH (400 MHz, CDCl3) 0.99 (9H, s,
C(CH3)3), 2.22 (1H, ddt, J 14.4, 7.6, 1.4) and 2.27 (1H, ddt, J 14.4, 7.6,
1.4, SiCH2), 3.69 (1H, d, J 2.8, CHO), 4.90–4.98 (2H, m, ]CH2), 5.81
(1H, ddt, J 17.0, 10.1, 7.6, CH]CH2), 7.38–7.48 (6H, m) and 7.61–
7.66 (4H, m, 2ꢃPh), 9.60 (1H, d, J 2.8, CH]O); dC (100 MHz, CDCl3)
21.9, 25.8, 36.1, 84.9, 115.6, 127.8, 128.0, 130.2, 130.2, 132.5, 133.7,
134.8, 134.8, 134.9, 203.6; dSi (99 MHz, toluene-d8) ꢁ6.35; m/z
(CIþ) 356 (MNHþ4 , 100%), 339 (MHþ, 63), 297 (96), 281 (38), 216
(29); HRMS (CIþ) found 339.1781, C21H27O2Si [MHþ] requires
339.1775.
6.23. ( )-2-Hydroxy-3,3-dimethylbutyric acid28
A solution of cyanohydrin 17 (2.26 g, 20 mmol) in 35% hydro-
chloric acid (20 mL) was stirred for 16 h at rt and then heated at
reflux for 4 h. The solution was allowed to cool to rt, then NaCl
(1.0 g) was added and the reaction mixture extracted with ether
(3ꢃ20 mL). The combined organic extracts were dried over MgSO4
and the solvent was removed under reduced pressure to give the
acid as a white crystalline solid (2.56 g, 97%). nmax/cmꢁ1 (KBr)
3426br s, 2965br s, 1714s, 1481s, 1371s, 1283m, 1225s, 1184m,
1085s, 1025m; dH (200 MHz, CDCl3) 1.00 (9H, s, C(CH3)3), 3.87 (1H,
s, CH(OH)); dC (50 MHz, CDCl3) 26.2, 35.7, 78.7, 178.7.
6.19. ( )-2-(Allyldiphenylsilanyloxy)-3-methyl-
butyraldehyde (22)
Colourless oil (206 mg, 64%); Rf 0.45 (petrol/ether, 10:1); nmax
/
cmꢁ1 (thin film) 3071m, 3001m, 2965s, 2875m, 1736s, 1630m,
1467m, 1428s, 1388m, 1368m, 1188m, 1161s, 1118s, 1069s, 1028m,
998m, 928m, 901s, 846m, 770m, 737s, 699s; dH (400 MHz, CDCl3)
0.96 (3H, d, J 6.8) and 0.97 (3H, d, J 6.8, CH(CH3)2), 2.05–2.12 (1H,
m, CH(CH3)2), 2.23 (1H, ddt, J 14.0, 7.9, 1.2) and 2.28 (1H, ddt, J
14.0, 7.9, 1.2, SiCH2), 3.93 (1H, dd, J 4.4, 1.6, CHO), 4.90–4.94 (1H,
m) and 4.93–4.99 (1H, m, ]CH2), 5.83 (1H, ddt, J 17.2, 10.1, 7.9,
CH]CH2), 7.38–7.48 (6H, m) and 7.61–7.64 (4H, m, 2ꢃPh), 9.58
(1H, d, J 1.6, CH]O); dC (100 MHz, CDCl3) 16.9, 18.6, 22.0, 31.7,
82.4, 115.6, 127.8, 127.9, 130.2, 130.2, 132.6, 133.8, 133.9, 134.8,
134.9, 203.9; m/z (CIþ) 342 (MNHþ4 , 91%), 325 (MHþ, 70), 283
(100); HRMS (CIþ) found 325.1626, C20H25O2Si [MHþ] requires
325.1618.
6.24. ( )-Methyl (2-hydroxy-3,3-dimethyl)butyrate (26)
To a solution of 2-hydroxy-3,3-dimethylbutyric acid (2.30 g,
17.0 mmol) in methanol (20 mL) was added acetyl chloride (120 mL,
1.7 mmol) and the reaction mixture was heated at reflux for 16 h.
The solvent was removed under reduced pressure and the resulting
oil was dissolved in ethyl acetate (40 mL). The solution was washed
with saturated aqueous NaHCO3 solution (3ꢃ40 mL) and brine
(40 mL) then dried over MgSO4. The solvent was removed under
reduced pressure to give the product (26) as a colourless oil (1.66 g,
66%). Rf 0.13 (petrol/ether, 10:1); nmax/cmꢁ1 (thin film) 3504br s,
2959s, 2909s, 2873s, 1736s, 1480s, 1439s, 1397m, 1368s, 1275s,
1222s, 1173s, 1089s, 1024s, 987m, 802m, 749m; dH (200 MHz,

5548
J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
CDCl3) 0.91 (9H, s, C(CH3)3), 2.83 (1H, br s, OH), 3.73 (3H, s, OCH3),
3.77 (1H, s, CH(OH)); dC (50 MHz, CDCl3) 26.1, 35.6, 52.4, 78.9, 175.2;
m/z (CIþ) 164 (MNHþ4 , 100%), 147 (MHþ, 62), 99 (11); HRMS (CIþ)
found 147.1019, C7H15O3 [MHþ] requires 147.1016.
10 min triethylamine (860 mL, 6.2 mmol) was added and the
resulting cloudy solution was stirred for 15 min at ꢁ78 ꢂC and then
allowed to warm to rt over 1 h. The reaction mixture was parti-
tioned between water (20 mL) and ether (40 mL) and the aqueous
layer was extracted with ether (40 mL). The combined organic ex-
tracts were washed with brine (20 mL) and dried over MgSO4. The
solvent was removed under reduced pressure and the resulting oil
was purified by flash column chromatography on silica gel (petrol/
ether, 25:1) to give the product (28) as a colourless oil (469 mg,
86%). Rf 0.58 (petrol/ether, 10:1); nmax/cmꢁ1 (thin film) 3071m,
3017m, 2961s, 2871m, 1732s, 1590m, 1478m, 1429s, 1396m, 1365m,
1154s, 1118s, 1037m, 991m, 899m, 847m, 779s, 738s, 699s, 648s; dH
(400 MHz, CDCl3) 0.98 (9H, s, C(CH3)3), 1.41 (3H, dd, J 6.5, 1.2,
]CHCH3), 2.11–2.21 (2H, m, SiCH2), 3.65 (1H, d, J 2.8, CHO), 5.35–
5.51 (2H, m, CH]CH), 7.37–7.47 (6H, m) and 7.60–7.64 (4H, m,
2ꢃPh), 9.58 (1H, d, J 2.8, CH]O); dC (100 MHz, CDCl3) 12.6, 15.4,
25.9, 36.0, 84.8, 123.4, 124.0, 126.9, 127.8, 130.1, 130.2, 133.9, 134.1,
134.9, 135.0, 203.8; m/z (CIþ) 370 (MNHþ4 , 8%), 353 (MHþ, 19), 297
(100), 216 (36), 155 (11), 137 (17), 78 (16); HRMS (CIþ) found
353.1941, C22H29O2Si [MHþ] requires 353.1931.
6.25. ( )-Methyl 2-[(Z-but-2-enyl)diphenylsilanyloxy]-3,3-
dimethylbutyrate (27)
Silane 4 (827 mg, 3.47 mmol) and hydroxyester 26 (507 mg,
3.47 mmol) were dissolved in dichloromethane (10 mL). Tris-
(pentafluorophenyl)borane (89 mg, 0.17 mmol) was added and the
reaction mixture was heated at reflux for 3 h. The reaction mixture
was allowed to cool to rt and then poured into water (10 mL) and
ether (20 mL). The aqueous layer was extracted with ether
(2ꢃ30 mL) and the combined organic extracts were washed with
brine (20 mL) and then dried over MgSO4. The solvent was removed
under reduced pressure and the resulting oil was purified by flash
column chromatography on silica gel (petrol/ether, 25:1) to give the
product (27) as a colourless oil (695 mg, 52%). Rf 0.44 (petrol/ether,
10:1); Found C 72.22, H 7.99, C23H30O3Si requires C 72.21, H 7.90%;
nmax/cmꢁ1 (thin film) 2957m, 1752s, 1429m, 1364m, 1272m, 1218m,
1162m, 1118s, 1037m, 993m, 846m, 780m, 739m, 700s, 647m; dH
(400 MHz, CDCl3) 0.96 (9H, s, C(CH3)3), 1.40 (3H, dd, J 6.8, 1.2,
]CHCH3), 2.14 (2H, app. dd, J 8.1, 1.4, SiCH2), 3.41 (3H, s, OCH3), 3.93
(1H, s, CHO), 5.33–5.41 (1H, m, ]CHCH3), 5.45–5.52 (1H, m,
CH2CH]), 7.34–7.46 (6H, m) and 7.59–7.64 (4H, m, 2ꢃPh); dC
(100 MHz, CDCl3) 12.6, 15.1, 25.9, 35.4, 50.9, 80.4, 123.7, 125.6, 127.6,
127.6, 129.9, 132.0, 134.0, 134.1, 135.1, 135.1, 172.4; m/z (CIþ) 400
(MNHþ4 , 59%), 327 (100), 305 (42), 299 (30), 213 (33); HRMS (CIþ)
found 400.2306, C23H34NO3Si [MNHþ4 ] requires 400.2302.
6.28. ( )-(4SR,5SR,30SR)-5-tert-Butyl-4-(but-10-en-30-yl)-2,2-
diphenyl-[1,3,2]-dioxasilolane
A solution of aldehyde 28 (466 mg, 1.3 mmol) in benzene
(10 mL) was heated for 36 h at 80 ꢂC in a base-washed sealed tube.
After cooling, the solvent was removed under reduced pressure to
give the product, which was used without further purification, as
a colourless oil (459 mg, 99%). nmax/cmꢁ1 (thin film) 3071m, 2960s,
2907m, 2870m, 1479m, 1430s, 1365m, 1117s, 1061s, 1012s, 996s,
970m, 932m, 916m, 854s, 812m, 740s, 699s; dH (400 MHz, CDCl3)
0.93 (9H, s, C(CH3)3), 1.17 (3H, d, J 6.9, CHCH3), 2.21–2.29 (1H, m,
CHCH3), 3.88 (1H, d, J 5.6, t-BuCHO), 4.12 (1H, dd, J 5.6, 4.0, CHCHO),
4.93 (1H, ddd, J 17.2, 2.0, 0.8) and 4.98 (1H, dd, J 10.0, 2.0, ]CH2),
5.71 (1H, ddd, J 17.2, 10.0, 8.6, CH]CH2), 7.37–7.50 (6H, m) and
7.65–7.70 (4H, m, 2ꢃPh); dC (100 MHz, CDCl3) 18.3, 25.9, 34.8, 44.2,
80.1, 85.8, 116.0, 127.7, 127.7, 130.0, 130.7, 132.4, 132.9, 135.2, 135.3,
139.6; m/z (CIþ) 370 (MNHþ4 , 4%), 353 (MHþ,14), 297 (100), 216 (46),
137 (17), 94 (12), 78 (13); HRMS (CIþ) found 370.2208, C22H32NO2Si
[MNHþ4 ] requires 370.2197.
6.26. ( )-2-[(Z-But-2-enyl)diphenylsilanyloxy]-3,3-
dimethylbutanol
To a stirred solution of ester 27 (666 mg, 1.74 mmol) in
dichloromethane (10 mL) at ꢁ78 ꢂC was added DIBAL (3.66 mL, 1 M
in dichloromethane, 3.66 mmol). The resulting solution was stirred
for 1 h then a saturated solution of tartaric acid in methanol (5 mL)
was added. The reaction mixture was allowed to warm to rt and
then partitioned between ether (30 mL) and 1 M hydrochloric acid
(20 mL). The aqueous layer was extracted with ether (20 mL) and
the combined organic portions were washed with 1 M hydrochloric
acid (20 mL) and brine (20 mL) then dried over MgSO4. The solvent
was removed under reduced pressure and the resulting oil was
purified by flash column chromatography on silica gel (petrol/ether,
10:1) to give the product as a colourless oil (509 mg, 83%). Rf 0.24
(petrol/ether, 10:1); nmax/cmꢁ1 (thin film) 3582br s, 3015m, 2958m,
2870m, 1428m, 1395m, 1362m, 1111s, 1032m, 996m, 951m, 782m,
738m, 700s, 646m; dH (400 MHz, CDCl3) 0.90 (9H, s, C(CH3)3), 1.41
(3H, dd, J 6.4, 1.7, ]CHCH3), 2.15–2.25 (2H, m, SiCH2), 3.48 (1H, dd, J
7.2, 2.5, CHO), 3.57 (1H, dd, J 11.6, 7.2) and 3.64 (1H, dd, J 11.6, 2.5,
CH2OH), 5.38 (1H, dqt, J 11.6, 6.4, 1.6, ]CHCH3), 5.50 (1H, dtq, J 11.6,
8.4, 1.7, CH2CH]), 7.36–7.47 (6H, m) and 7.61–7.69 (4H, m, 2ꢃPh);
dC (100 MHz, CDCl3) 12.8, 15.8, 26.5, 34.6, 64.1, 82.5, 123.8, 124.1,
127.8, 127.9, 129.8, 132.0, 134.9, 134.9, 135.0, 135.1; m/z (ESI–) 353
(MꢁHþ, 100%), 311 (20); HRMS (ESIꢁ) found 353.1935, C22H29O2Si
(MꢁHþ) requires 353.1942.
6.29. ( )-(3SR,4SR,5SR)-3,6,6-Trimethylhept-1-en-4,5-diol (29)
To a stirred solution of (ꢀ)-(4SR,5SR,30SR)-5-tert-butyl-4-(but-
10-en-30-yl)-2,2-diphenyl-[1,3,2]-dioxasilolane (423 mg, 1.2 mmol)
in a mixture of ether (5 mL), water (5 mL) and methanol (5 mL)
were added KF (313 mg, 5.4 mmol) and hydrogen peroxide (2 mL,
30% aq). The resulting solution was stirred at rt for 16 h. The solvent
was removed under reduced pressure and the resulting material
triturated with ether (40 mL) and the extract washed with water
(20 mL). The aqueous layer was extracted with ether (40 mL) and
the combined organic extracts were washed with brine (20 mL) and
then dried over MgSO4. The solvent was removed under reduced
pressure and the resulting oil was purified by flash column chro-
matography on silica gel (petrol/ether, 5:1/1:1) to give the
product (29) as a white solid (181 mg, 88%). Rf 0.15 (petrol/ether,
5:1); nmax/cmꢁ1 (KBr) 3434br s, 3292br s, 3082m, 2963s, 1478m,
1429m, 1127s, 1085s, 1056s, 1013m, 997m, 955m, 909s, 720s, 699s;
dH (400 MHz, CDCl3) 0.93 (9H, s, C(CH3)3), 1.04 (3H, d, J 6.8, CHCH3),
2.26–2.35 (1H, m, CHCH3), 2.47–2.37 (1H, br s, OH), 2.65 (1H, br s,
OH), 3.20 (1H, br d, J 2.4, t-BuCH(OH)), 3.49 (1H, app. br d, J 7.2,
CHCH(OH)), 5.12–5.17 (2H, m, ]CH2), 5.76 (1H, ddd, J 18.0, 9.6, 8.7,
CH]CH2); dC (100 MHz, CDCl3) 16.5, 26.1, 35.0, 43.8, 71.4, 77.4,
116.9, 140.6; m/z (CIþ) 190 (MNHþ4 , 23%), 173 (MHþ, 81), 155 (66),
137 (100), 121 (22), 99 (17), 92 (24); HRMS (CIþ) found 190.1812,
C10H24NO2 [MNHþ4 ] requires 190.1807.
6.27. ( )-2-[(Z-But-2-enyl)diphenylsilanyloxy]-3,3-
dimethylbutyraldehyde (28)
To a stirred solution of oxalyl chloride (170 mL, 1.94 mmol) in
dichloromethane (5 mL) at ꢁ78 ꢂC was added DMSO (220
mL,
3.1 mmol). After 10 min a cooled solution of (ꢀ)-2-[(Z-but-2-enyl)-
diphenylsilanyloxy]-3,3-dimethylbutanol (550 mg, 1.55 mmol) in
dichloromethane (5 mL) was added via cannula. After a further

J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
5549
6.30. ( )-(3SR,4SR,5SR)-4,5-Di(allyloxy)-3,6,6-trimethylhept-
1-ene
2909m, 1752s, 1639m, 1479m, 1429s, 1368m, 1271m, 1218s, 1163s,
1117s, 1037m, 996m, 909m, 890m, 844m, 740s, 700s; dH (400 MHz,
CDCl3) 0.96 (9H, s, C(CH3)3), 1.21–1.30 (2H, m, SiCH2), 2.11–2.19 (2H,
m, CH2CH]), 3.41 (3H, s, OCH3), 3.90 (1H, s, CHO), 4.90 (1H, dtd, J
10.2, 1.7, 1.0) and 5.00 (1H, dtd, J 17.1, 1.7, 1.0, ]CH2), 5.90 (1H, ddt, J
17.1, 10.2, 6.2, CH]CH2), 7.36–7.46 (6H, m) and 7.58–7.63 (4H, m,
2ꢃPh); dC (100 MHz, CDCl3) 12.7, 25.9, 26.9, 35.4, 50.9, 80.3, 112.9,
127.7, 127.7, 129.9, 130.0, 134.0, 134.2, 134.9, 135.0, 141.1, 172.4; m/z
(CIþ) 400 (MNHþ4 , 49%), 327 (41), 305 (100), 230 (14), 213 (13), 183
(13); HRMS (CIþ) found 400.2297, C23H34NO3Si [MNHþ4 ] requires
400.2302.
A mixture of diol 29 (48 mg, 0.3 mmol) and NaH (70 mg, 60% in
mineral oil,1.8 mmol) was stirred for 15 min in THF (2 mL) and DMF
(2 mL). The solution was cooled to 0 ꢂC and allyl bromide (150
mL,
1.8 mmol) was added dropwise. The reaction mixture was allowed
to warm to rt and then stirred for 16 h. The resulting solution was
partitioned between water (30 mL) and ether (30 mL), the aqueous
layer was extracted with ether (30 mL) and the combined organic
extracts were washed with brine (20 mL) and dried over MgSO4.
The solvent was removed under reduced pressure and the resulting
oil was purified by flash column chromatography on silica gel
(petrol/ether, 25:1) to give the title compound as a colourless oil
(54 mg, 72%). Rf 0.68 (petrol/ether, 10:1); nmax/cmꢁ1 (thin film)
2956s, 2926s, 2870s, 2853s, 1480m, 1459m, 1422m, 1362m, 1145m,
1086s, 1002m, 914s; dH (400 MHz, CDCl3) 0.93 (9H, s, C(CH3)3), 1.12
(3H, d, J 6.8, CHCH3), 2.11–2.19 (1H, m, CHCH3), 2.95 (1H, d, J 6.8, t-
BuCHO), 3.26 (1H, dd, J 6.8, 2.7, CHCHO), 3.85 (1H, ddt, J 12.7, 6.1,
1.4), 3.91 (1H, ddt, J 12.7, 6.1, 1.4), 4.28 (1H, ddt, J 9.2, 5.6, 1.8) and
4.31 (1H, ddt, J 9.2, 5.6, 1.8, 2ꢃOCH2), 5.01–5.14 (4H, m), 5.23 (1H,
ddt, J 17.6, 5.6, 1.8) and 5.25 (1H, ddt, J 17.6, 5.6, 1.8, 3ꢃ]CH2), 5.89–
5.98 (3H, m, 3ꢃCH]CH2); dC (100 MHz, CDCl3) 18.8, 26.5, 34.9, 43.7,
72.9, 73.4, 81.1, 86.1, 115.3, 115.5, 115.7, 135.9, 136.0, 140.2; m/z (CIþ)
253 (MHþ, 100%), 127 (66); HRMS (CIþ) found 253.2177, C16H29O2
[MHþ] requires 253.2162.
6.33. ( )-Methyl 2-[(E-but-2-enyl)diphenylsilanyloxy]-3,3-
dimethylbutyrate (32)
(1,5-Cyclooctadiene) bis(methyldiphenylphosphine) iridium(I)
hexafluorophosphate (24 mg, 0.028 mmol) was dissolved in
degassed dichloromethane (5 mL) and the solution cooled to
ꢁ78 ꢂC. The catalyst was activated under an atmosphere of hy-
drogen (balloon) until a colour change from clear blood-red to
colourless or clear yellow was observed. The remaining hydrogen
was removed and the reaction placed under an atmosphere of ar-
gon and warmed to 0 ꢂC. A solution of silyloxyester 31 (1.06 g,
2.78 mmol) in degassed dichloromethane (5 mL) was added via
cannula and the reaction mixture was stirred at 0 ꢂC for 30 min,
with monitoring by 1H NMR. The solvent was removed under re-
duced pressure, the product triturated with ether (30 mL) and the
extract filtered though a silica pad. The solvent was removed under
reduced pressure and the resulting oil was purified by flash column
chromatography on silica gel (petrol/ether,15:1) to give the product
(32) as a colourless oil (960 mg, 91%). Rf 0.33 (petrol/ether, 10:1);
6.31. ( )-(2SR,3SR,10SR)-2-(10-Allyloxy-20,20-dimethylpropyl)-
3-methyl-3,6-dihydro-2H-pyran (30)
To a stirred solution of (ꢀ)-(3SR,4SR,5SR)-4,5-di(allyloxy)-3,6,6-
trimethylhept-1-ene (50 mg, 0.2 mmol) in degassed dichloro-
methane (5 mL) was added Grubbs II catalyst (25, 3 mg,
0.004 mmol). The resulting brown solution was stirred at rt for 4 h.
The solvent was removed under reduced pressure and the resulting
oil was purified by flash column chromatography on silica gel
(petrol/ether, 20:1) to give the product (30) as a colourless oil
(16 mg 35%). Rf 0.32 (petrol/ether, 10:1); nmax/cmꢁ1 (thin film)
3028m, 2958s, 2874s, 2811m, 1481m, 1459m, 1392m, 1360m,
1338m,1261m,1182m,1135s,1113s,1080s,1034m,1013m, 920m; dH
(400 MHz, CDCl3) 0.95 (3H, d, J 7.0, CHCH3), 1.01 (9H, s, C(CH3)3),
2.54–2.64 (1H, m, CHCH3), 3.08 (1H, d, J 0.6, t-BuCHO), 3.22 (1H, dd,
J 9.4, 0.6, CHCHO), 4.01–4.03 (1H, m), 4.05–4.07 (1H, m) and 4.12–
4.24 (2H, m, 2ꢃOCH2), 5.13 (1H, ddt, J 10.0, 1.6, 1.0) and 5.25 (1H,
ddt, J 17.2, 1.6, 1.6, ]CH2), 5.59–5.63 (1H, m) and 5.67–5.71 (1H, m,
CH]CH), 5.99 (1H, ddt, J 17.2, 10.0, 6.0, CH]CH2); dC (100 MHz,
CDCl3) 17.6, 27.6, 34.1, 36.0, 65.6, 76.1, 79.9, 85.4, 116.4, 125.1, 131.5,
135.5; m/z (CIþ) 242 (MNH4þ, 11%), 225 (MHþ, 100), 167 (27), 127
(44), 97 (17); HRMS (CIþ) found 225.1858, C14H25O2 [MHþ] requires
225.1849.
Found C 72.29, H 8.01, C23H30O3Si requires C 72.21, H 7.90%; nmax
/
cmꢁ1 (thin film) 3070m, 3015m, 2957s, 2884m, 1751s, 1479m,
1429s, 1396m, 1368m, 1271m, 1218s, 1163s, 1118s, 1037s, 965m,
871m, 846m, 763m, 739s, 700s; dH (400 MHz, CDCl3) 0.96 (9H, s,
C(CH3)3), 1.59 (3H, d, J 6.8, CHCH3), 2.13 (2H, app. d, J 7.2, SiCH2),
3.41 (3H, s, OCH3), 3.96 (1H, s, CHO), 5.30–5.47 (2H, m, CH]CH),
7.35–7.46 (6H, m) and 7.58–7.65 (4H, m, 2ꢃPh); dC (100 MHz,
CDCl3) 18.1, 19.6, 25.9, 35.4, 50.9, 80.3, 124.5, 125.9, 127.6, 127.7,
129.9, 129.9, 134.1, 134.2, 135.1, 135.5, 172.4; m/z (CIþ) 400 (MNH4þ,
63%), 327 (100), 305 (56), 299 (31), 230 (33), 213 (25), 183 (11);
HRMS (CIþ) found 400.2302, C23H34NO3Si [MNHþ4 ] requires
400.2302.
6.34. ( )-2-[(E-But-2-enyl)diphenylsilanyloxy]-3,3-
dimethylbutanol
To a stirred solution of ester 32 (929 mg, 2.43 mmol) in
dichloromethane (10 mL) at ꢁ78 ꢂC was added DIBAL (5.35 mL, 1 M
in dichloromethane, 5.35 mmol). The resulting solution was stirred
for 1 h then a saturated solution of tartaric acid in methanol (5 mL)
was added. The reaction mixture was allowed to warm to rt and
then partitioned between ether (30 mL) and 1 M hydrochloric acid
(20 mL). The organic layer was washed with 1 M hydrochloric acid
(20 mL) and the aqueous layer was extracted with ether (20 mL).
The organic extracts were combined and the solvent was removed
under reduced pressure. The resulting oil was purified by flash
column chromatography on silica gel (petrol/ether, 10:1) to give the
title compound as a colourless oil (773 mg, 90%). Rf 0.11 (petrol/
ether, 10:1); nmax/cmꢁ1 (thin film) 3580br m, 3070m, 3014m, 2958s,
2871m, 1480m, 1436m, 1428s, 1395m, 1362m, 1159m, 1111s, 1067m,
1032s, 998m, 963m, 934m, 799m, 763m, 738s, 701s; dH (400 MHz,
CDCl3) 0.90 (9H, s, C(CH3)3), 1.60 (3H, dd, J 5.9, 0.7, ]CHCH3), 2.11–
2.24 (2H, m, SiCH2), 3.51 (1H, dd, J 7.3, 2.5, CHO), 3.54–3.66 (2H, m,
CH2OH), 5.33–5.48 (2H, m, CH]CH), 7.36–7.47 (6H, m) and 7.60–
7.68 (4H, m, 2ꢃPh); dC (100 MHz, CDCl3) 18.1, 20.4, 26.4, 34.6, 64.0,
6.32. ( )-Methyl 2-[(but-3-enyl)diphenylsilanyloxy]-3,3-
dimethylbutyrate (31)
To a solution of hydroxyester 26 (584 mg, 4.0 mmol) and silane
7 (952 mg, 4.0 mmol) in dichloromethane (10 mL) was added
tris(pentafluorophenyl)borane (102 mg, 0.2 mmol) and the re-
action mixture was heated at reflux for 3 h. The mixture was
allowed to cool to rt and then poured into water (20 mL) and
extracted with ether (3ꢃ30 mL). The combined organic extracts
were washed with brine (20 mL) and dried over MgSO4. The solvent
was removed under reduced pressure and the resulting oil was
purified by flash column chromatography on silica gel (petrol/ether,
50:1) to give the product (31) as a colourless oil (1.20 g, 78%). Rf 0.41
(petrol/ether, 10:1); Found C 72.32, H 8.00, C23H30O3Si requires C
72.21, H 7.90%; nmax/cmꢁ1 (thin film) 3071m, 3000m, 2976s, 2957s,

5550
J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
82.4,125.0,125.9,127.8,127.9,129.8,130.0,135.0,135.2,135.2,135.8;
m/z (ESI–) 353 (MꢁHþ, 100%), 253 (13); HRMS (ESIꢁ) found
353.1947, C22H29O2Si [MꢁHþ] requires 353.1942.
chromatography on silica gel (petrol/ether, 5:1/1:1) to give the
product (34) as a white solid (228 mg, 74%). Rf 0.50 (petrol/ether,
1:1); nmax/cmꢁ1 (KBr) 3472br m, 3337br m, 2959s, 2908m, 2570m,
2476m, 1429m, 1128s, 1103s, 1054s, 1014m, 996m, 908m, 740m,
718m, 698s, 523m, 490m; dH (400 MHz, CDCl3) 0.92 (9H, s, C(CH3)),
1.07 (3H, d, J 6.7, CHCH3), 2.36–2.29 (1H, m, CHCH3), 3.26 (1H, s, t-
BuCH(OH)), 3.45 (1H, d, J 8.3, CHCH(OH)), 5.02 (1H, ddd, J 10.3, 2.0,
0.4) and 5.08 (1H, ddd, J 17.2, 2.0, 0.9, ]CH2), 5.69 (1H, ddd, J 17.2,
10.3, 8.7, CH]CH2); dC (100 MHz, CDCl3) 16.1, 25.7, 34.8, 44.0, 72.1,
76.4, 114.5, 142.0; m/z (CIþ) 190 (MNHþ4 , 18%), 173 (MHþ, 100), 171
(39), 161 (15), 137 (12); HRMS (CIþ) found 190.1815, C10H24NO2
[MNHþ4 ] requires 190.1802.
6.35. ( )-2-[(E-But-2-enyl)diphenylsilanyloxy]-3,3-
dimethylbutyraldehyde (33)
To a stirred solution of oxalyl chloride (220 mL, 2.5 mmol) in
dichloromethane (5 mL) at ꢁ78 ꢂC was added DMSO (280
mL,
4.0 mmol). After 10 min a cooled solution of (ꢀ)-2-[(E-but-2-
enyl)diphenylsilanyloxy]-3,3-dimethylbutanol (714 mg, 2.0 mmol)
in dichloromethane (5 mL) was added via cannula. After a further
10 min triethylamine (1.11 mL, 8.0 mmol) was added, the resulting
cloudy mixture was stirred for 15 min at ꢁ78 ꢂC and then allowed
to warm to rt over 1 h. The reaction mixture was partitioned be-
tween water (20 mL) and ether (40 mL). The aqueous layer was
extracted with ether (40 mL) and the combined organic extracts
were washed with brine (20 mL) and dried over MgSO4. The solvent
was removed under reduced pressure and the resulting oil was
purified by flash column chromatography on silica gel (petrol/ether,
25:1) to give the product (33) as a colourless oil (646 mg, 91%). Rf
0.51 (petrol/ether, 10:1); Found C 74.62, H 8.09, C22H28O2Si requires
C 74.95, H 8.01%; nmax/cmꢁ1 (thin film) 3070m, 3015m, 2961s,
2935m, 2872m, 1733s, 1478m, 1429s, 1396m, 1366m, 1158m, 1117s,
1077m, 1037m, 966m, 846m, 797m, 764m, 737s, 700s; dH
(400 MHz, CDCl3) 1.00 (9H, s, C(CH3)3), 1.61 (3H, dd, J 5.6, 0.6,
]CHCH3), 2.15–2.17 (2H, m, SiCH2), 3.69 (1H, d, J 2.9, CHO), 5.32–
5.47 (2H, m, CH]CH), 7.39–7.49 (6H, m) and 7.62–7.66 (4H, m,
2ꢃPh), 9.59 (1H, d, J 2.9, CH]O); dC (100 MHz, CDCl3) 10.1, 19.9,
25.9, 36.1, 84.7, 124.0, 125.3, 128.0, 128.2, 130.1, 130.1, 134.1, 134.2,
134.9, 135.1, 203.9; m/z (CIþ) 370 (MNHþ4 , 38%), 353 (MHþ, 58), 297
(98), 285 (19), 216 (100), 157 (22), 137 (43), 94 (23), 78 (61); HRMS
(CIþ) found 353.1934, C22H29O2Si (MHþ) requires 353.1931.
6.38. ( )-(3RS,4SR,5SR)-4,5-Di(allyloxy)-3,6,6-trimethylhept-
1-ene
A mixture of diol 34 (351 mg, 2.04 mmol) and NaH (492 mg, 60%
in mineral oil, 12.3 mmol) in THF (10 mL) and DMF (10 mL) was
stirred for 15 min at rt. The solution was cooled to 0 ꢂC, allyl bro-
mide (1.06 mL, 12.3 mmol) was added dropwise and the reaction
mixture was stirred for 16 h at rt. The resulting mixture was par-
titioned between water (30 mL) and ether (30 mL). The aqueous
layer was extracted with ether (30 mL) and the combined organic
extracts were washed with brine (20 mL) and dried over MgSO4.
The solvent was removed under reduced pressure and the resulting
oil was purified by flash column chromatography on silica gel
(petrol/ether, 25:1) to give the product as a colourless oil (437 mg,
85%). Rf 0.74 (petrol/ether, 10:1); nmax/cmꢁ1 (thin film) 2958s,
2871s, 1646m, 1481m, 1424m, 1394m, 1362m, 1106s, 998s, 914s; dH
(400 MHz, CDCl3) 0.95 (9H, s, C(CH3)3), 1.09 (3H, d, J 6.8, CHCH3),
2.33–2.51 (1H, m, CHCH3), 2.94 (1H, d, J 5.5, t-BuCHO), 3.35 (1H, dd,
J 5.5, 4.1, CHCHO), 3.91–3.99 (2H, m), 4.23 (1H, ddt, J 12.6, 5.2, 1.6)
and 4.33 (1H, ddt, J 12.6, 5.0, 1.6, 2ꢃOCH2), 4.98 (1H, ddd, J 10.3, 1.7,
0.8, CHCH]CH2), 5.02 (1H, ddd, J 17.2, 1.8, 1.4), 5.08–5.13 (2H, m),
5.25 (1H, ddt, J 17.2, 1.9, 1.8) and 5.26 (1H, ddt, J 17.2, 1.9, 1.8,
3ꢃ]CH2), 5.84–5.97 (3H, m, 3ꢃCH]CH2); dC (100 MHz, CDCl3)
14.2, 26.7, 35.3, 41.9, 72.2, 73.9, 80.9, 86.2, 113.5, 115.4, 115.7, 135.8,
135.9, 142.8; m/z (CIþ) 270 (MNHþ4 , 3%), 253 (MHþ, 100), 127 (64);
HRMS (CIþ) found 253.2173, C16H29O2 [MHþ] requires 253.2162.
6.36. ( )-(4SR,5SR,30RS)-5-tert-Butyl-4-(but-10-en-30-yl)-2,2-
diphenyl-[1,3,2]-dioxasilolane
A solution of aldehyde 33 (625 mg, 1.78 mmol) in benzene
(10 mL) was heated for 36 h at 80 ꢂC in a base-washed sealed tube.
The solvent was removed under reduced pressure to give the
product as a colourless oil (602 mg, 96%), which was used without
further purification. nmax/cmꢁ1 (thin film) 3070m, 2958s, 2870m,
1478m,1429m,1364m,1124s,1117s,1056s,1014s, 985m, 917m, 845s,
740m, 717s, 699s, 678m; dH (400 MHz, CDCl3) 0.90 (9H, s, C(CH3)3),
1.02 (3H, d, J 6.4, CHCH3), 2.20–2.29 (1H, m, CHCH3), 3.91 (1H, d, J 4.4,
t-BuCHO), 4.12 (1H, dd, J 5.8, 4.4, CHCHO), 5.04 (1H, ddd, J 10.4, 2.0,
0.8) and 5.08 (1H, ddd, J 17.2, 2.0, 0.8, ]CH2), 5.79 (1H, ddd, J 17.2,
10.4, 8.4, CH]CH2), 7.36–7.49 (6H, m) and 7.65–7.69 (4H, m, 2ꢃPh);
dC (100 MHz, CDCl3) 14.9, 25.9, 34.9, 44.5, 79.5, 85.8, 114.9, 127.7,
127.8, 130.6, 130.7, 132.4, 133.3, 135.0, 135.1, 141.6; m/z (CIþ) 370
(MNHþ4 , 11%), 353 (MHþ, 29), 297 (100), 285 (16), 216 (51), 199 (12);
HRMS (CIþ) found 353.1924, C22H29O2Si [MHþ] requires 353.1931.
6.39. ( )-(2SR,3RS,10SR,)-2-(10-Allyloxy-20,20-dimethylpropyl)-
3-methyl-3,6-dihydro-2H-pyran (35) and ( )-2,3-cis-3,4-trans-
3-allyloxy-2-tert-butyl-4-methyl-2,3,4,7-tetrahydrooxepin
To a solution of (ꢀ)-(3RS,4SR,5SR)-4,5-di(allyloxy)-3,6,6-trime-
thylhept-1-ene (252 mg, 1.0 mmol) in degassed dichloromethane
(10 mL) was added Grubbs II catalyst (25, 17 mg, 0.05 mmol) and
the resulting brown reaction mixture was stirred at rt for 4 h. The
solvent was removed under reduced pressure and the resulting oil
was purified by flash column chromatography on silica gel (petrol/
ether, 20:1) to give the major product (35) as a colourless oil
(111 mg, 49%) and the minor seven-membered ring product as
a colourless oil (66 mg, 29%). Data for 35: Rf 0.44 (petrol/ether,
10:1); nmax/cmꢁ1 (thin film) 3030m, 2958s, 2880s, 2816m, 1482m,
1459m, 1394m, 1372m, 1362m, 1181s, 1143s, 1095s, 1074s, 1019m,
915m, 863m, 841m, 707m; dH (400 MHz, CDCl3) 0.96 (9H, s,
C(CH3)3), 1.10 (3H, d, J 6.4, CHCH3), 2.01–2.08 (1H, m, CHCH3), 2.98
(1H, d, J 5.7, t-BuCHO), 3.64 (1H, dd, J 5.7, 2.7, CHCHO), 4.00 (1H, ddt,
J 12.3, 6.0, 1.4, CHH0CH]CH2), 4.16–4.27 (2H, m, CH2CH]CH), 4.31
(1H, ddt, J 12.3, 5.6, 1.4, CHH0CH]CH2), 5.11 (1H, ddt, J 10.4, 1.9, 1.4)
and 5.24 (1H, ddt, J 17.2, 1.9, 1.4, ]CH2), 5.64 (1H, dddd, J 10.0, 3.0,
1.8, 0.8) and 5.82 (1H, ddt, J 10.0, 5.7, 2.1, CH]CH), 5.97 (1H, dddd, J
17.2, 10.4, 6.0, 5.6, CH]CH2); dC (100 MHz, CDCl3) 14.6, 26.8, 33.5,
35.9, 67.1, 74.8, 76.4, 86.0, 116.0, 125.3, 131.6, 135.8; m/z (CIþ) 242
(MNHþ4 , 3%), 225 (MHþ, 100), 167 (16), 127 (40), 97 (11); HRMS (CIþ)
found 225.1848, C14H25O2 [MHþ] requires 225.1849. Data for minor
6.37. ( )-(3RS,4SR,5SR)-3,6,6-Trimethylhept-1-en-4,5-diol (34)
To a solution of (ꢀ)-(4SR,5SR,30RS)-5-tert-butyl-4-(but-10-en-30-
yl)-2,2-diphenyl-[1,3,2]-dioxasilolane (636 mg, 1.8 mmol) in a mix-
ture of ether (5 mL), water (5 mL) and methanol (5 mL) were added
KF (313 mg, 5.4 mmol) and hydrogen peroxide (2 mL, 30% aq) and
the reaction mixture was stirred at rt for 16 h. The solvent was
removed under reduced pressure and the resulting material tritu-
rated with ether (40 mL) and the extract washed with water
(20 mL). The aqueous layer was re-extracted with ether (40 mL)
and the combined organic extracts were washed with brine (20 mL)
and dried over MgSO4. The solvent was removed under reduced
pressure and the resulting oil was purified by flash column

J. Robertson et al. / Tetrahedron 65 (2009) 5541–5551
5551
component: Rf 0.31 (petrol/ether, 10:1); nmax/cmꢁ1 (thin film)
3014s, 2956s, 2872s, 1647m, 1480m, 1459s, 1425m, 1408m, 1393m,
1360s, 1236m, 1221m, 1194m, 1170s, 1123s, 1098s, 1075s, 1018s,
997s, 922s, 690m; dH (400 MHz, CDCl3) 0.98 (9H, s, C(CH3)3), 1.00
(3H, d, J 7.4, CHCH3), 2.80–2.87 (1H, m, CHCH3), 3.09 (1H, d, J 0.4,
t-BuCHO), 3.66 (1H, dd, J 3.7, 0.4, CHCHO), 3.98 (1H, ddt, J 12.8, 6.0,
1.4, OCHH0CH]CH2), 3.98–4.01 (1H, m, OCHH0CH]CH), 4.14 (1H,
9. See Experimental section for details.
10. E.g., by the deprotonation and silylation of E-but-2-ene: Kno¨lker, H.-J.; Baum,
E.; Schmitt, O. Tetrahedron Lett. 1998, 39, 7705–7708.
11. Hodgson, D. M.; Barker, S. F.; Mace, L. H.; Moran, J. R. Chem. Commun. 2001, 153–
154.
12. Matsuda, I.; Kato, T.; Sato, S.; Izumi, Y. Tetrahedron Lett. 1986, 27, 5747–5750.
13. (a) Kahle, K.; Murphy, P. J.; Scott, J.; Tamagni, R. J. Chem. Soc., Perkin Trans. 11997,
997–999; (b) Kim, C.; Choi, S. K.; Park, E.; Jung, I. J. Korean Chem. Soc. 1997, 41,
88–97.
14. Meerpoel, L.; Hoornaert, G. Synthesis 1990, 905–908 and references cited
therein.
15. Hayashi, M.; Yoshiga, T.; Nakatani, K.; Ono, K.; Oguni, N. Tetrahedron 1994, 50,
2821–2830.
ddt,
J
12.8, 6.0, 1.4, OCHH0CH]CH2), 4.41–4.46 (1H, m,
OCHH0CH]CH), 5.12 (1H, ddt, J 10.3, 1.6, 1.4) and 5.23 (1H, ddt, J
17.2, 1.6, 1.4, ]CH2), 5.49–5.57 (2H, m, CH]CH), 5.97 (1H, ddt, J 17.2,
10.3, 6.0, CH]CH2); dC (100 MHz, CDCl3) 18.9, 27.6, 35.2, 35.9, 70.5,
70.9, 81.3, 85.3,116.8,127.9,132.0,135.7; m/z (CIþ) 242 (MNH4þ,11%),
225 (MHþ, 100), 167 (49); HRMS (CIþ) found 225.1849, C14H25O2
[MHþ] requires 225.1849.
16. Cf. Jafarpour, L.; Heck, M.-P.; Baylon, C.; Lee, H. M.; Mioskowski, C.; Nolan, S. P.
Organometallics 2002, 21, 671–679.
17. To ensure reproducible measurements, the FID file of each 1H NMR experiment
was processed automatically within MestRe-C using a set of preset parameters
followed by automated integration of the methine signals.
18. An Eyring plot was used to calculate
D
Hz (67 kJ molꢁ1
)
and
D
Sz
(ꢁ130 J Kꢁ1 molꢁ1) for the reaction. The large, negative value for the entropy of
activation is consistent with a highly ordered transition state, and is larger than
values typically associated with intramolecular prototropic ene reactions (75–
80 J Kꢁ1 molꢁ1), see: Oppolzer, W.; Snieckus, V. Angew. Chem., Int. Ed. Engl. 1978,
17, 476–486.
Acknowledgements
The authors would like to thank Pfizer Ltd, Oxford University
and Newcastle University for funding, Professor William McFarlane
(Newcastle University) for assistance with 1H NMR kinetic studies
and 29Si INEPT experiments, and Professor Richard Henderson
(Newcastle University) for helpful discussions.
19. Spartan’06, Wavefunction, Irvine, CA: Shao, Y.; Molnar, L. F.; Jung, Y.; Kussmann,
J.; Ochsenfeld, C.; Brown, S. T.; Gilbert, A. T. B.; Slipchenko, L. V.; Levchenko, S.
V.; O’Neill, D. P.; DiStasio, R. A., Jr.; Lochan, R. C.; Wang, T.; Beran, G. J. O.; Besley,
N. A.; Herbert, J. M.; Lin, C. Y.; Van Voorhis, T.; Chien, S. H.; Sodt, A.; Steele, R. P.;
Rassolov, V. A.; Maslen, P. E.; Korambath, P. P.; Adamson, R. D.; Austin, B.; Baker,
J.; Byrd, E. F. C.; Dachsel, H.; Doerksen, R. J.; Dreuw, A.; Dunietz, B. D.; Dutoi, A.
D.; Furlani, T. R.; Gwaltney, S. R.; Heyden, A.; Hirata, S.; Hsu, C.-P.; Kedziora, G.;
Khalliulin, R. Z.; Klunzinger, P.; Lee, A. M.; Lee, M. S.; Liang, W. Z.; Lotan, I.; Nair,
N.; Peters, B.; Proynov, E. I.; Pieniazek, P. A.; Rhee, Y. M.; Ritchie, J.; Rosta, E.;
Sherrill, C. D.; Simmonett, A. C.; Subotnik, J. E.; Woodcock, H. L., III; Zhang, W.;
Bell, A. T.; Chakraborty, A. K.; Chipman, D. M.; Keil, F. J.; Warshel, A.; Hehre, W.
J.; Schaefer, H. F.; Kong, J.; Krylov, A. I.; Gill, P. M. W.; Head-Gordon, M. Phys.
Chem. Chem. Phys. 2006, 8, 3172–3191.
20. Matsumoto, K.; Oshima, K.; Utimoto, K. J. Org. Chem. 1994, 59, 7152–7155.
21. For a summary of aspects of stereocontrol involving reactions between alde-
hydes and allylsilane derivatives, see pp 2112–2118 in Fleming, I.; Barbero, A.;
Walter, D. Chem. Rev. 1997, 97, 2063–2192.
22. Robertson, J.; Stafford, P. M.; Bell, S. J. J. Org. Chem. 2005, 70, 7133–7148.
23. The reaction of 21/23 was also monitored by 29Si NMR (employing a re-
focussed INEPT experiment), however no evidence of a pre-coordinated in-
termediate was observed.
Supplementary data
Structural information from DFT calculations. 1H NMR kinetics
data [plots of relative conc versus time, ln(relative conc) versus
time, calculations of reaction rates and activation parameters].
Supplementary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2009.01.117.
References and notes
1. Robertson, J.; Hall, M. J.; Stafford, P. M.; Green, S. P. Org. Biomol. Chem. 2003, 1,
3758–3767.
24. (a) Kobayashi, S.; Nishio, K. J. Org. Chem. 1994, 59, 6620–6628; (b) Hosomi,
A.; Kohra, S.; Ogata, K.; Yanagi, T.; Tominaga, Y. J. Org. Chem. 1990, 55,
2415–2420; (c) Kira, M.; Hino, T.; Sakurai, H. Tetrahedron Lett. 1989, 30,
1099–1102; (d) Kira, M.; Sato, K.; Sakurai, H. J. Am. Chem. Soc. 1988, 110,
4599–4602; (e) Kira, M.; Kobayashi, M.; Sakurai, H. Tetrahedron Lett. 1987,
28, 4081–4084.
25. For a theoretical study, see: Omoto, K.; Sawada, Y.; Fujimoto, H. J. Am. Chem. Soc.
1996, 118, 1750–1755.
26. See, for example Zacuto, M. J.; O’Malley, S. J.; Leighton, J. L. J. Am. Chem. Soc.
2002, 124, 7890–7891.
2. For pertinent descriptions of carbonyl ene cyclisations containing discussion of
stereochemistry and mechanism under a variety of conditions, see: (a) Wil-
liams, J. T.; Bahia, P. S.; Snaith, J. S. Org. Lett. 2002, 4, 3727–3730; (b) Kocovsky,
P.; Ahmed, G.; Srogl, J.; Malkov, A. V.; Steele, J. J. Org. Chem. 1999, 64, 2765–2775.
3. Snider, B. B.; Karras, M.; Price, R. T.; Rodini, D. J. J. Org. Chem.1982, 47, 4538–4545.
4. Robertson, J.; Hall, M. J.; Green, S. P. Org. Biomol. Chem. 2003, 1, 3635–3638.
5. Review: Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599–7662.
6. Blackwell, J. M.; Foster, K. L.; Beck, V. H.; Piers, W. E. J. Org. Chem. 1999, 64,
4887–4892; See also Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J.-X.; Yamamoto,
Y. J. Org. Chem. 2000, 65, 6179–6186.
27. Roberts, T. G.; Teague, P. C. J. Am. Chem. Soc. 1955, 77, 6258–6261.
28. (a) Hartwig, W.; Scho¨llkopf, U. Liebigs Ann. Chem. 1982, 1952–1970; (b) Bessard,
Y.; Crettaz, R. Tetrahedron 2000, 56, 4739–4745.
7. Rajagopalan, S.; Zweifel, G. Synthesis 1984, 113–115.
8. Prepared by the general procedure described in Rajagopalan, S.; Zweifel, G.
Synthesis 1984, 111–112.