Stereocontrolled asymmetric synthesis of syn-E-1,4-diol-2-enes using allyl boronates and its application in the total synthesis of solandelactone F

Article abstract of DOI:10.1039/c2ob06975j

The solandelactones A-H comprise a novel class of oxygenated fatty acids bearing an eight-membered lactone, trans cyclopropane, and a 2-ene-1,4-diol subunit. The relative stereochemistry of the 1,4-diol subunit is anti in solandelactones A, C, E & G, and

Full text of DOI:10.1039/c2ob06975j

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Organic &
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2012, 10, 1795
www.rsc.org/obc
PAPER
Stereocontrolled asymmetric synthesis of syn-E-1,4-diol-2-enes using allyl
boronates and its application in the total synthesis of solandelactone F†
Anna Robinson and Varinder K. Aggarwal*
Received 23rd November 2011, Accepted 2nd December 2011
DOI: 10.1039/c2ob06975j
The solandelactones A–H comprise a novel class of oxygenated fatty acids bearing an eight-membered
lactone, trans cyclopropane, and a 2-ene-1,4-diol subunit. The relative stereochemistry of the 1,4-diol
subunit is anti in solandelactones A, C, E & G, and syn in solandelactones B, D, F & H. Having prepared
one member of the solandelactones bearing anti stereochemistry (solandelactone E), we have targeted the
syn series and developed methodology for the synthesis of enantioenriched syn-2-ene-1,4-diols. The
methodology comprises asymmetric deprotonation of an alkyl 2,4,6-triisopropylbenzoate using sBuLi/
sparteine, followed by addition of the α-lithiobenzoate to β-silyl vinyl boronic acid ethylene glycol ester.
The boron-ate complex generated undergoes a 1,2-metallate rearrangement furnishing an intermediate
allyl boronic ester which is trapped by an aldehyde in the presence of MgBr2 to furnish anti-β-hydroxy
E-allylsilanes in good yields, high diastereoselectivity and high enantioselectivity. These sensitive
products were oxidized using mCPBA to the corresponding epoxides and subsequently treated with acid
to furnish syn-E-2-ene-1,4-diols (∼4 : 1 d.r.). Application of the methodology to appropriately
functionalized aldehyde and ω-alkenyl 2,4,6-triisopropylbenzoate coupling partners, led to a short, highly
selective route to solandelactone F (bearing a syn-E-2-ene-1,4-diol).
Martin through total synthesis, the original assignment having
Introduction
incorrect stereochemistry at C11.2
The solandelactones comprise a novel class of oxygenated fatty
acids first isolated and characterised by Shin in 1996.1 (Fig. 1)
Their general structure features an eight-membered lactone, trans
cyclopropane, a 2-ene-1,4-diol subunit, and numerous stereo-
genic centers, making them challenging synthetic targets. Their
correct structure, however, has only recently been validated by
The syntheses of all solandelactones A–H have been
reported.2–5 Martin completed the first synthesis of solandelac-
tone E in 2007, which was highly stereoselective, but linear and
therefore somewhat lengthy.2 Syntheses of the remaining solan-
delactones were subsequently reported by White3 and Pie-
truszka,4 who both opted for disconnections at C11–C12 and
utilized a Nozaki–Hiyama–Kishi (NHK) reaction to complete
the syntheses. However, the NHK reaction between the required
vinyl organometallic reagent and cyclopropyl aldehyde
(Scheme 1) proceeded with poor stereocontrol, leading to a
∼2 : 1 mixture of epimers at C11, in favour of the anti diol.3,4
Thus, solandelactones A, C, E & G were prepared as the major
products but solandelactones B, D, F & H were only isolated as
School of Chemistry, University of Bristol, Cantock’s Close, Bristol, UK,
BS8 1TS. E-mail: V.Aggarwal@Bristol.ac.uk
†Electronic supplementary information (ESI) available: Materials
including experimental procedures, NMR spectra of all new products.
See DOI: 10.1039/c2ob06975j
Fig. 1 Structure of the solandelactones, halicholactone and constanolactones.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 1795–1801 | 1795

View Article Online
C13–C14 bonds we were able to use our novel stereocontrolled
methodology for the synthesis of anti-2-ene-1,4-diols
(Scheme 2).9 Thus, treatment of lithiated carbamate 1 with vinyl
borane 2 and aldehyde 3 led to anti-β-hydroxy Z-allylsilane 4
via 6-membered chair TS1 with high stereoselectivity, which
was subsequently converted into the required anti-1,4-diol
(Scheme 3).5
In order to specifically target the other series of solandelac-
tones we needed a method that would deliver syn-1,4-diols.
These could possibly be prepared from oxidation of either syn-
β-hydroxy Z-allylsilanes or anti-β-hydroxy E-allylsilanes, com-
pounds which are potentially accessible from the allylboration
reaction.10 Stereocontrol in the allylboration reaction is ulti-
mately dictated by the geometry of the allyl boron reagent and
by the nature of the ligands on boron.11 However, all the possible
isomers of syn-β-hydroxy Z-allylsilanes are not accessible from
any boron reagent, but anti-β-hydroxy E-allylsilanes are.9d,12
These could potentially be obtained from the reaction of the
allylboron reagent 7 bearing small substituents on boron,9d so
that upon reaction with an aldehyde, the R1 substituent would
occupy a pseudoequatorial position in the 6-membered chair
TS2 (Scheme 3). Allylboron reagent 7 could in turn be obtained
from reaction of the same lithiated carbamate 1 with vinyl
boronic ester 6. Although this appears to represent a small
modification, there were a number of major challenges inherent
in the realization of this plan. Ultimately, we were able to over-
come these hurdles and thus develop a new protocol for the syn-
thesis of syn 2-ene-1,4-diols which enabled us to craft a
stereocontrolled synthesis of solandelactone F.
Scheme 1 Common bond construction (NHK reaction) in the synth-
eses of solandelactones, halicholactone and constanolactones.
Scheme 2 Retrosynthetic analysis of solandelactones E.
the minor components from the NHK reaction. Indeed, the same
selectivity issue has been observed in numerous syntheses of
related natural products including halicholactone6 and the con-
stanolactones.7 For example, there are currently five published
syntheses of halicholactone, four of which use the poorly selec-
tive NHK coupling reaction. The alternative route by Takemoto,
avoids this strategy, but is also the longest synthesis to date.8
Three of the four syntheses of constanolactones A–D also
involve a poorly selective NHK reaction as the key step.7
Results & Discussion
Synthesis of anti E/Z-alkyl-substituted β-hydroxy allylsilanes
Our strategy for the synthesis of solandelactone E addressed
both the issue of stereocontrol and convergence simultaneously.
Through disconnection of solandelactone E at the C11–C12 and
The synthesis of syn or anti E/Z-alkyl-substituted β-hydroxy
allylsilanes, key components in our targeted synthesis of
Scheme 3 Synthesis of solandelactone E and proposed synthesis of solandelactone F.
1796 | Org. Biomol. Chem., 2012, 10, 1795–1801
This journal is © The Royal Society of Chemistry 2012

View Article Online
Table 1 Optimization of the allylboration reaction
Entry
Lewis acid (equiv.)
T/°C
Time/h
Yield 15 (%)
Yield 16 (%)
Yield 12c (%)
1a
2
3
4
5
MgBr2·Et2O (1 equiv.)
MgBr2·Et2O (1 equiv.)
MgBr2·Et2O (1 equiv.)
MgBr2·Et2O (1 equiv.)
MgBr2·Et2O (1 equiv.)
MgBr2·Et2O (2 equiv.)
−20
−20
−30
−40
−40
−60
18
18
24
18
36
19
50
—
—
26
28
46
—
75
12
—
—
9
29
—
75
43
58
30
6
a Complete reaction conducted in Et2O, without solvent exchange
solandelactone F, is not straightforward and usually requires mul-
tiple steps.13 Whilst routes have been developed for the synthesis
of β-hydroxy allylsilanes bearing terminal alkenes,13a–d,f,k those
bearing substituted alkenes have scarcely been documented.13e,f,h
In our synthesis of solandelactone E, the key step in the for-
mation of the anti-β-hydroxy Z-allylsilane was achieved by reac-
tion of the required Hoppe-type lithiated carbamate14 with vinyl
borane 2 followed by addition of an aldehyde (Scheme 3). The
key allylborane intermediate was formed after 1,2-metallate
rearrangement of the intermediate boron-ate complex, a reaction
pioneered by Matteson15 and subsequently developed by
Kocienski,16 Blakemore17 and ourselves.9b This furnished the
anti-β-hydroxy Z-allylsilane 4 in high yield and very high dia-
stereo- and enantioselectivity. Subsequent epoxidation and acid
catalyzed rearrangement gave the anti-1,4-diol, again with very
high selectivity. In order to target the syn-1,4-diol, we needed
the anti-β-hydroxy E-allylsilane which could potentially be
obtained from reaction of allylboronic ester 7 with a suitable
aldehyde. In turn, allylboronic ester 7 could be obtained from
reaction of a lithiated carbamate with vinyl boronic ester 6.24
However, compared to the anti-1,4-diols, the preparation of the
syn-1,4-diol series suffers from the following significant
challenges:
Lewis acids can also promote Peterson elimination of β-hydroxy
allylsilanes to give dienes.
These challenges proved insurmountable when we employed
vinyl boronic ester 6 in the lithiation–borylation reaction with
carbamate 5 (Scheme 4).25 Although the boronate complex 9
easily formed, we were unable to effect both the 1,2-migration
and subsequent allylboration reactions cleanly. The use of Lewis
acids (e.g. MgBr2) to promote 1,2-migration resulted in Peterson
elimination of the β-hydroxy E-allylsilane 11. In contrast, the use
of thermal conditions to promote the 1,2-migration resulted in a
subsequent 1,3-borotropic shift of the intermediate allyl boronic
ester 10 (for a full discussion of this investigation see ESI†).26
We therefore sought a better leaving group than the carbamate
for the 1,2-metallate rearrangement and focused on the 2,4,6-trii-
sopropyl benzoyl group, which we had found to be effective in
lithiation–borylation reactions involving slow migrating
substituents.27
(i) The diastereoselectivity in epoxidation of E-allylsilanes is
considerably lower than for Z-allylsilanes.18,19
(ii) The 1,2-metallate rearrangement is much slower with
boronic esters compared to boranes.20
Scheme 4 Attempted synthesis of anti-E-allylsilanes.
(iii) The allylic boronic ester is also much slower at allylbora-
tion compared to the allyl borane.21,9d
(iv) Although both the 1,2-metallate rearrangement9b,22 and
allylboration reaction23 can both be accelerated by Lewis acids,
Beak first showed that the position α to an alkyl 2,4,6-triiso-
propylbenzoate could be deprotonated and trapped with
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 1795–1801 | 1797

View Article Online
Table 2 Synthesis of E-allyl silanes
Entry R1
R2
Product Yield (%)a d.r.
e.r.b
1
2
3
4
5
6
Ph(CH2)2(13) Ph
Ph(CH2)2(13) nBu 12b
Ph(CH2)2(13) cPr
12a
61
70
75
88
64
64
>20 : 1 95 : 5
>20 : 1 95 : 5
>20 : 1 95 : 5
12c
12d
Me (17)
Me(17)
Me(17)
Ph
20 : 1
19 : 1
10 : 1
91 : 9
91 : 9
91 : 9
nBu 12e
cPr 12f
a Isolated yield. b The e.r. of the product was identical to the e.r. of the
starting stannane. cPr = cyclopropyl
electrophiles.28 Hammerschmidt demonstrated that this reaction
could be performed enantioselectively, through a tin-lithium
exchange and that the lithiated benzoate was configurationally
stable at −78 °C.29 Work within our group has shown that this
lithiated species, formed by transmetallation of the stannane with
n-BuLi, or by deprotonation with s-BuLi/sparteine, undergoes a
lithiation–borylation reaction with a broad range of especially
challenging boronic esters.27
Thus, the benzoate ester 13 was prepared, lithiated and reacted
with boronic ester 6 at −78 °C. Heating the ate complex for just
1 h at 40 °C effected a much more rapid 1,2-metallate rearrange-
ment. Subsequent addition of cyclopropylaldehyde and
MgBr2·OEt2 at −20 °C gave the anti-β-hydroxy E-allylsilane
12c as a single diastereoisomer in 29% yield. However, large
amounts of alcohol 15 were also isolated indicating that the allyl-
boration step had not gone to completion (Table 1, entry 1). We
therefore decided to carry out a solvent exchange from Et2O to
the less coordinating CH2Cl2 in order to maximize the effect of
the Lewis acid.9d Thus, after the boron-ate complex formation,
Et2O was removed and CH2Cl2 added, the reaction was heated at
reflux for 1 h, followed by the aldehyde and MgBr2·OEt2 at
−20 °C, but this now led to the Peterson elimination product 16
in 75% yield (Table 1, Entry 2). This indicated that essentially
complete conversion of 13→14→12c had been achieved, but
that under the reaction conditions the Lewis acid was also pro-
moting elimination. Careful control of temperature and time was
required to produce optimum results (Table 1). Lower tempera-
tures reduced the amount of the elimination side-product 16 but
also led to increased amounts of alcohol 15. Optimum conditions
were the use of just one equivalent of MgBr·Et2O at −30 °C
which gave the anti β-hydroxy E-allylsilane 12c in excellent
yield and with complete diastereoselectivity (Entry 3).
Scheme 5 Selectivity in the epoxidation/elimination reaction of
β-hydroxy E-allylsilanes.
even when a small Me group (R1) was present (entries 4–6). The
enantiomeric excess of the product reflected the e.r. of the start-
ing stannane, which in turn was a reflection of the selectivity in
deprotonation by s-BuLi/sparteine.
Epoxidation of β-hydroxy allylsilanes and conversion to 1,4-diols
β-Hydroxy allylsilanes are versatile building blocks in organic
synthesis, undergoing a range of transformations, including
Fleming–Tamao oxidation,13d,30 fluorination,31 addition to
acetals,32 [3+2] annulations33 and [4+2] annulations.34
Of particular interest to us was epoxidation followed by acid
catalyzed elimination13a,b leading to 1,4-syn diols for application
in the synthesis of the solandelactones. The facial selectivity of
epoxidation of β-hydroxy E-allylsilanes can be influenced by the
oxidizing reagent employed, but the diastereoselectivity is
usually low, in contrast to related Z-allylsilanes which invariably
lead to very high stereoselectivity.15,16,35 As expected, moderate-
low diastereoselectivity was observed with 12d: using mCPBA a
∼4 : 1 ratio E-1,4-diol 18 : Z-1,4-diol 19 was obtained, whilst
using Ti(OiPr)4/tBuOOH the Z-1,4-diol was favored (2 : 1)
(Scheme 5).36
These conditions were applied to a range of aliphatic and aro-
matic aldehydes and to several unhindered benzoates to explore
the generality and selectivity of the reaction (Table 2). In
general, the anti β-hydroxy E-allylsilanes 12 were formed in
excellent yield and high diastereoselectivity (via TS2, Scheme 3)
Landais18 has accounted for the stereochemical outcome of
this type of reaction by invoking a chair-like transition-state,
1798 | Org. Biomol. Chem., 2012, 10, 1795–1801
This journal is © The Royal Society of Chemistry 2012

View Article Online
with the bulky silyl group adopting a pseudoequatorial position
to minimize A1,3 strain (Scheme 5). With mCPBA there is little
steric interaction between R1 and mCPBA, so the reaction goes
through the hydrogen bonded TS3 leading to epoxide 20 as the
major product. However, with Ti(OiPr)4 and tBuOOH there is
significant steric repulsion between R1 and the bulky oxidizing
reagent in TS4 which is alleviated by placing the olefin in a
pseudoaxial position (TS5), resulting in epoxidation on the
opposite face and leading to 21 as the major product.
Completion of the synthesis of solandelactone F
Finally, we turned our attention to the application of this method-
ology to the synthesis of solandelactone F. Disconnection of the
syn-E-2-ene-1,4-diol according to the methodology described
above gives aldehyde 3 (as used in the synthesis of solandelac-
tone E5), vinyl boronic ester 6 and stannane 22 (Scheme 6).
Scheme 8 Synthesis of the required stannane for the synthesis of
solandelactone F.
achieved by a sequence of acetal deprotection, oxidative clea-
vage and Wittig olefination to give stannane 22 (Scheme 8).
Application of our optimized conditions for lithiation–boryla-
tion–allylation with stannane 22, aldehyde 3 and β-silyl vinyl-
boronic ester 6, gave our desired E-allylsilane 8 in 50% yield
and with the same d.r. as the e.r. of the stannane. It should be
noted that stannane 22 was required in this process to ensure
specific lithiation α to the benzoate. Direct deprotonation of the
corresponding carbamate or benzoate with s-BuLi/sparteine
resulted in substantial deprotonation at the allylic position fol-
lowed by elimination. Epoxidation with one equivalent of
mCPBA effected chemoselective epoxidation and, following
acid catalyzed elimination, gave solandelactone F as the major
stereoisomer (Scheme 9). Although the epoxidation/rearrange-
ment only occurred in 34% yield, the yield based on recovered
SM was 64% as we found it best to ensure that the reaction did
not go to completion as otherwise side-products were formed.
Synthetic solandelactone F was identical in all respects to the
data reported in the literature.1,3,4
Scheme 6 Retrosynthesis of solandelactone F.
Aldehyde 3 was synthesized in ten steps from propargylic
alcohol as previously described (Scheme 7).5 The key steps
included a Sharpless epoxidation,37 Taber cyclopropanation,38
Yamaguchi lactonization and chemoselective RANEY® nickel
reduction of the nitrile in the presence of the lactone.39
Scheme 7 Synthesis of aldehyde 3.5
Scheme 9 Completion of the synthesis of solandelactone F.
Stannane 22 was prepared as shown in Scheme 8. Following
conversion of the commercially available alcohol 23 into benzo-
ate 24, substrate-directed lithiation and trapping with Bu3SnCl
(as described by Hoppe40) furnished stannane 25 with 11 : 1 d.r.
(inseparable). Installation of the required aliphatic chain was
Conclusion
In conclusion, we have developed a selective method for the syn-
thesis of enantioenriched anti-β-hydroxy E-allylsilanes. The
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 1795–1801 | 1799

View Article Online
8 (a) Y. Takemoto, Y. Baba, G. Saha, S. Nakao, C. Iwata, T. Tanaka and
T. Ibuka, Tetrahedron Lett., 2000, 41, 3653–3656; (b) Y. Baba, G. Saha,
S. Nakao, C. Iwata, T. Tanaka, T. Ibuka, H. Ohishi and Y. Takemoto,
J. Org. Chem., 2001, 66, 81–88.
9 (a) M. Binanzer, G. Y. Fang and V. K. Aggarwal, Angew. Chem., Int. Ed.,
2010, 49, 4264–4268; . For other related work on lithiated carbamates
see: (b) J. L. Stymiest, G. Dutheuil, A. Mahmood and V. K. Aggarwal,
Angew. Chem., Int. Ed., 2007, 46, 7491–7494; (c) G. Dutheuil,
M. P. Webster, P. A. Worthington and V. K. Aggarwal, Angew. Chem., Int.
Ed., 2009, 48, 6317–6319; (d) M. Althaus, A. Mahmood, J. Ramón
Suárez, S. P. Thomas and V. K. Aggarwal, J. Am. Chem. Soc., 2010, 132,
4025–4028.
10 (a) S. E. Denmark and N. G. Almstead, in Modern Carbonyl Chemistry;
J. Otera,ed.; Wiley-VCH: Weinheim, Germany, 2000; Chapter 10, p 299;
(b) S. R. Chemler and W. R. Roush, in Modern Carbonyl Chemistry;
J. Otera, ed.; Wiley-VCH: Weinheim, Germany, 2000; Chapter 11, p 403;
(c) H. Lachance and D. G. Hall, in Organic Reactions; S. E. Denmark,
ed.; John Wiley & Sons: New York, 2008, Vol. 73; (d) S. E. Denmark
and J. Fu, Chem. Rev., 2003, 103, 2763; (e) W. R. Roush, in Stereo-
selective Synthesis, 4th ed.; G. Helmchen, R. W. Hoffman, J. Muler,
E. Schaumann, ed.; Thieme Verlag: Stuttgart, 1996; Vol. 3, p 1410.
11 (a) R. W. Hoffmann and H.-J. Zeiss, Angew. Chem., Int. Ed. Engl., 1979,
18, 306; (b) R. W. Hoffmann and H.-J. Zeiss, J. Org. Chem., 1981, 46,
1309; (c) R. W. Hoffmann, Pure Appl. Chem., 1988, 60, 123;
(d) R. W. Hoffmann, G. Niel and A. Schlapbach, Pure Appl. Chem.,
1990, 62, 1993.
components used to assemble such motifs comprise an α-alkyl
lithiated hindered benzoate, β-silyl vinyl ethylene glycol boronic
ester, and an aldehyde. Thus, reaction of the lithiated benzoate
with the boronic ester gave an intermediate allyl boronic ester
which was trapped with an aldehyde in the presence of the
Lewis acid, MgBr2 to give the anti β-hydroxy E-allylsilane in
high yield and high d.r. Key to the success of this one pot trans-
formation is the use of the alkyl 2,4,6-triisopropylbenzoate
which enables the 1,2-metallate rearrangement to proceed under
milder conditions and leads to the formation of the intermediate
allyl boronic ester without interference from side reactions.
Through complex-induced proximity effects it also directs the
initial lithiation. The use of a small group on boron (ethylene
glycol) is key to controlling the relative stereochemistry in the
aldehyde-allylboration step. The optimized conditions and
reagents employed have now considerably increased the range of
both the alkyl benzoates and the aldehydes that can participate in
the reaction.
The methodology has enabled us to complete a short, highly
selective route to solandelactone F. Previously this compound
and the series in general had been isolated as minor components
from a mixture. However, now we can target either solandelac-
tones A, C, E & G using our previously described methodology
comprising a lithiated carbamate, β-silyl vinyl-9BBN 2 and an
aldehyde, or the remaining solandelactones B, D, F, & H using
the methodology described herein.
12 The synthesis of anti-β-hydroxy E-allylsilanes via allylboration has been
reported, however products were not isolated but eliminated on work-up
to give dienes: K. K. Wang, Y.-G. Gu and C. Liu, J. Am. Chem. Soc.,
1990, 112, 4424–4431.
13 (a) W. R. Roush and P. T. Grover, Tetrahedron Lett., 1990, 52, 7567–
7570; (b) W. R. Roush and P. T. Grover, Tetrahedron, 1992, 48, 1981–
1998; (c) W. R. Roush, A. N. Pinchuk and G. C. Micalizio, Tetrahedron
Lett., 2000, 41, 9413–9417; (d) A. G. M. Barrett and J. W. Malecha, J.
Org. Chem., 1991, 56, 5243–5254; (e) M. A. Sparks and J. S. Panek,
J. Org. Chem., 1991, 56, 3431–3438; (f) D. Hodgson and M. C. Wells,
Tetrahedron Lett., 1992, 33, 4761–4762; (g) A. Alexakis and D. Jachiet,
Tetrahedron, 1989, 45, 381–389; (h) N. Kishi, T. Maeda, K. Mikami and
T. Nakai, Tetrahedron, 1992, 48, 4087–4098; For impressive recent appli-
cations see: (i) J. Wu, Y. Chen and J. S. Panek, Org. Lett., 2010, 12,
2112–2115; ( j) J. Lee and J. S. Panek, Org. Lett., 2011, 13, 502–505;
(k) M. Chen and W. R. Roush, Org. Lett., 2011, 13, 1992–1995.
14 For a review of Hoppe’s seminal contributions see: (a) D. Hoppe and
T. Hense, Angew. Chem., 1997, 109, 2376–2410; D. Hoppe and T. Hense,
Angew. Chem., Int. Ed. Engl., 1997, 36, 2282–2316; (b) E. Beckmann,
V. Desai and D. Hoppe, Synlett, 2004, 2275–2280.
Acknowledgements
We thank the EPSRC for support of this work. VKA thanks the
Royal Society for a Wolfson Research Merit Award and the
EPSRC for a Senior Research Fellowship. We thank Professor
Hisashi Yamamoto for a generous gift of bishydroxamic acid
ligands to test reagent controlled epoxidations.
15 (a) D. S. Matteson and D. Majumdar, J. Am. Chem. Soc., 1980, 102,
7588–7590; (b) D. S. Matterson, Chem. Rev., 1989, 89, 1535–1551.
16 G. Besong, K Jarowicki, P. J. Kocienski, E. Sliwinski and F. T. Boyle,
Org. Biomol. Chem., 2006, 4, 2193–2207.
17 P. R. Blakemore and M. S. Burge, J. Am. Chem. Soc., 2007, 129, 3068–
3069.
18 Y. Landais and L. Parra-Rapado, Tetrahedron Lett., 1996, 37, 1205–1208.
19 (a) I. Fleming, A. K. Sarkar and A. P. Thomas, J. Chem. Soc., Chem.
Commun., 1987, 157–159; I. Fleming, N. J. Lawrence, A. K. Sarkar and
A. P. Thomas, J. Chem. Soc., Perkin Trans. 1, 1992, 3303–3308.
20 For examples, see: (a) J. M. Stoddard and K. J. Shea, Chem. Commun.,
2004, 830; (b) A. Bottoni, M. Lombardo, A. Neri and C. Trombini,
J. Org. Chem., 2003, 68, 3397; (c) G. Y. Fang and V. K. Aggarwal,
Angew. Chem., Int. Ed., 2007, 46, 359.
Notes and references
1 Y. Seo, K. W. Cho, J.-R. Rho and J. Shin, Tetrahedron, 1996, 52, 10583–
10596.
2 (a) J. E. Davoren and S. F. Martin, J. Am. Chem. Soc., 2007, 129, 510–
511; (b) J. E. Davoren, C. Harcken and S. F. Martin, J. Org. Chem.,
2008, 73, 391–402.
3 (a) J. D. White, W. H. C. Martin, C. Lincoln and J. Yang, Org. Lett.,
2007, 9, 3481–3483; (b) J. D. White, C. Lincoln, J. Yang,
W. H. C. Martin and D. B. Chan, J. Org. Chem., 2008, 73, 4139–4150.
4 J. Pietruszka and A. C. Rieche, Adv. Synth. Catal., 2008, 350, 1407–
1412.
5 A. Robinson and V. K. Aggarwal, Angew. Chem., Int. Ed., 2010, 49,
6673–6675.
21 Allylboranes react readily with aldehydes at −78 °C (a), whereas allyl-
boronic esters require room temperature or above (b). For examples see:
(a) H. C. Brown and P. K. Jadhav, J. Am. Chem. Soc., 1983, 105, 2092;
(b) R. W. Hoffmann and B. Landmann, Angew. Chem., Int. Ed. Engl.,
1984, 23, 437–438.
6 For syntheses of halicholactone featuring
a NHK coupling see:
(a) D. J. Critcher, S. Connolly and M. Wills, J. Org. Chem., 1997, 62,
6638–6657; (b) D. J. Critcher, S. Connolly and M. Wills, Tetrahedron
Lett., 1995, 36, 3763–3766; (c) T. Takahashi, H. Watanabe and
T. Kitahara, Heterocycles, 2002, 58, 99–104; (d) C.-Y. Zhu, X.-Y. Cao,
B.-H. Zhu, C. Deng, X.-L. Sun, B.-Q. Wang, Q. Shen and Y. Tang,
Chem.–Eur. J., 2009, 15, 11465–11468; (e) M. Bischop, V. Doum,
A. C. M. Nordschild (née Rieche), J. Pietruszka and D. Sandkuhl,
Synthesis, 2010, 3, 527–537.
22 (a) D. J. S. Tsai, P. K. Jesthi and D. S. Matteson, J. Am. Chem. Soc.,
1983, 105, 2077–2078.
23 (a) J. W. J. Kennedy and D. G. Hall, J. Am. Chem. Soc., 2002, 124,
11586; (b) T. Ishiyama, T. Ahiko and N. Miyaura, J. Am. Chem. Soc.,
2002, 124, 12414–12415; . For reviews, see: (c) D. G. Hall, Synlett,
2007, 11, 1644; (d) J. W. J. Kennedy, D. G. Hall, in Boronic Acids;
D. G. Hall, ed.; Wiley-VCH: Weinheim, Gerandmany, 2005; Chapter 6,
p 241.
7 For syntheses of constanolactone featuring
a NHK coupling see:
(a) J. Pietruszka and T. Wilhelm, Synlett, 2003, 1698–1700;
(b) J. Pietruszka, A. C. M. Rieche and N. Schoene, Synlett, 2007, 2525–
2528; (c) C. B.-D. Silva, A. Benkouider and P. Pale, Tetrahedron Lett.,
2000, 41, 3077–3081; (d) J. D. White and M. S. Jensen, J. Am. Chem.
Soc., 1995, 117, 6224–6233.
24 The ethylene glycol boronic ester was chosen as this is what we had
found to work best with β-silylvinyl boronic esters (ref. 9a). The
1800 | Org. Biomol. Chem., 2012, 10, 1795–1801
This journal is © The Royal Society of Chemistry 2012

View Article Online
corresponding β-silylvinyl neopentyl glycol boronic esters gave consider-
ably lower diastereoselectivity (∼80 : 20). In contrast, β-alkylvinyl neo-
pentyl glycol boronic esters gave >95 : 5 d.r. (ref. 9d).
35 Z-Allylsilanes usually give high diastereoselectivity in epoxidation in
contrast to E-allylsilanes with either mCPBA or metal-mediated reactions.
This is because the conformation of Z-allylsilanes is far better controlled,
25 We had previously described a single example of the synthesis of an anti-
β-hydroxy E-allylsilane, but our only real success was with the aromatic
aldehyde, benzaldehyde. See ref. 9a.
26 (a) R. W. Hoffmann and H. J. Zeiss, J. Org. Chem., 1981, 46, 1309–
1314; (b) H. C. Brown, M. V. Rangaishenvi and S. Jayaraman, Organo-
metallics, 1992, 11, 1948–1954.
and thus epoxidation occurs almost exclusively through
conformer.
36 The substrate scope with mCPBA was briefly explored as this was most
relevant to our synthesis of solandelactone F. Indeed, this reaction worked
well on a range of substrates. See supporting information for further
details†.
a single
27 R. Larouche-Gauthier, C. J. Fletcher, I. Couto and V. K. Aggarwal,
Chem. Commun., 2011, 47, 12592–12594.
28 P. Beak, M. Baillargeon and L. G. Carter, J. Org. Chem., 1978, 43,
4255–4256.
29 F. Hammerschmidt, A. Hanninger, B. P. Simov, H. Völlenkle and
A. Werner, Eur. J. Org. Chem., 1999, 3511–3518.
30 J. A. Hunt and W. R. Roush, J. Org. Chem., 1997, 62, 1112–1124.
31 G. T. Giuffredi, S. Purser, M. Sawicki, A. L. Thompson and
V. Gouverneur, Tetrahedron: Asymmetry, 2009, 20, 910–920.
32 J. S. Panek and M. Yang, J. Am. Chem. Soc., 1991, 113, 6594–6600.
33 J. S. Panek and M. Yang, J. Am. Chem. Soc., 1991, 113, 9868–9870.
34 H. Huang and J. S. Panek, J. Am. Chem. Soc., 2000, 122, 9836–9837.
37 For Sharpless epoxidation of this substrate see: (a) Y. E. Raifeld, A.
A. Nikitenko, B. M. Arshava, I. E. Mikerin, L. L. Zilberg, G. Y. Vid,
S. A. Lang Jr. and V. J. Lee, Tetrahedron, 1994, 50, 8613–8616;
(b) X. Ginesta, M. A. Pericas and A. Riera, Tetrahedron Lett., 2002, 43,
779–782; For Sharpless’ seminal work on catalytic asymmetric epoxida-
tion see: (c) Y. Gao, J. M. Klunder, R. M. Hanson, H. Masamune,
S. Y. Ko and K. B. Sharpless, J. Am. Chem. Soc., 1987, 109, 5765–5780;
(d) H. C. Kolb, M. S. Van Nieuwenhze and K. B. Sharpless, Chem. Rev.,
1994, 94, 2483–2547.
38 D. F. Taber, G. Bui and B. Chen, J. Org. Chem., 2001, 66, 3423–3426.
39 O. G. Backeberg and B. Staskun, J. Chem. Soc., 1962, 3961–3963.
40 H. Helmke and D. Hoppe, Synlett, 1995, 978–980.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 1795–1801 | 1801