[1,2]- and [1,4]-Wittig rearrangements of α-alkoxysilanes: Effect of substitutions at both the migrating benzylic carbon and the terminal sp2 carbon of the allyl moiety

Article abstract of DOI:10.1016/j.tet.2012.10.091

Substituted a-alkoxysilanes can be deprotonated by alkyllithium bases and made to undergo Wittig rearrangements to afford the [1,4]- and [1,2]-rearranged products in varying ratios. Substitution at the benzylic migrating carbon and/or at the allylic carbon of the allyl moiety impacts the rearrangement reaction, influencing the reactivity as well as the [1,4]-/[1,2]-selectivity. Diastereomeric α-alkoxysilanes show different reactivities with the syn diastereomer being the more reactive isomer.

Full text of DOI:10.1016/j.tet.2012.10.091

Tetrahedron 69 (2013) 849e860
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
[1,2]- and [1,4]-Wittig rearrangements of
a-alkoxysilanes: effect of
substitutions at both the migrating benzylic carbon and the terminal
sp2 carbon of the allyl moiety
,
Edith N. Onyeozili a, Luis M. Mori-Quiroz b, Robert E. Maleczka, Jr. b
*
a Department of Chemistry, Florida A&M University, Tallahassee, FL 32307, USA
b Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, MI 48824, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 June 2012
Received in revised form 8 October 2012
Accepted 10 October 2012
Available online 8 November 2012
Substituted
a-alkoxysilanes can be deprotonated by alkyllithium bases and made to undergo Wittig
rearrangements to afford the [1,4]- and [1,2]-rearranged products in varying ratios. Substitution at the
benzylic migrating carbon and/or at the allylic carbon of the allyl moiety impacts the rearrangement
reaction, influencing the reactivity as well as the [1,4]-/[1,2]-selectivity. Diastereomeric
show different reactivities with the syn diastereomer being the more reactive isomer.
a-alkoxysilanes
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Wittig rearrangement
Alkoxysilanes
Acylsilanes
1,4-Shift
1,2-Shift
1. Introduction
The isomerizations of ethers under basic conditions to the cor-
responding alcohols are known as Wittig rearrangements and can
proceed via two main pathways: a stepwise [1,2]-migration in-
volving
a a concerted
radical/radical-anion species1 or via
symmetry-allowed [2,3]-shift.2 In addition, during the re-
organization of allylic ethers [1,4]-Wittig rearrangements can
compete with the [1,2]-migration and give rise to carbonyl com-
pounds.3 Despite its potential to construct adjacent stereocenters,
transfer chirality, or obtain stereodefined enolates that could be
used in subsequent transformations, very few examples where
[1,4]-Wittig rearrangements predominate over [1,2]-pathways exist
in the literature.4 Furthermore, although some experiments sup-
port a stepwise [1,4]-Wittig process, the involvement of a concerted
mechanism has not been discarded.5
Scheme 1. [1,4]-/[1,2]-Wittig rearrangements of a-alkoxysilanes.
In an earlier communication,6a we showed that unsubstituted
a-
alkoxysilane 1 (R1¼R2¼H) rearranged exclusively via the [1,4]-
pathway at low temperatures to give acylsilane 2 in 80% yield
(Scheme 1). We observed that the [1,2]-pathway became compet-
itive with increasing temperature, leading to a gradual erosion in
[1,4]-selectivity and producing mixtures of 2 and the isomeric [1,2]-
Wittig product 4, with the [1,4]-/[1,2]-ratio reaching 2:1 at room
temperature.6,7 Following this report, we questioned whether
a high [1,4]-/[1,2]-selectivity could be retained if we made struc-
tural changes in our model substrate 1 (e.g., where R1 and/or
R2sH).
Nakai and co-workers previously showed that the scope and
limitations of the [1,2]-Wittig rearrangement are determined
principally by the migratory aptitude of the alkyl group
* Corresponding author. E-mail address: maleczka@chemistry.msu.edu
(R.E. Maleczka Jr.).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.091

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E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
(primary<secondary<tertiary¼allyl<benzyl) thus following in-
creasing radical stability.1 In cases of limited radical stability of the
migrating group, carbanion-stabilizing groups similarly facilitate
[1,2]-migrations.1 In contrast, the yield of [1,4]-Wittig products has
competitive benzylic deprotonation. In fact, 11 underwent in-
complete conversion in the same period of time that compounds 5
and 8 were completely consumed. In addition, increasing steric
hindrance increases the selectivity in favor of the [1,2]-Wittig
product. This could be interpreted as an increasingly prohibitive
[1,4]-recombination of the radical and radical-anion fragments, but
been reported to be relatively insensitive to substitution at the
a- or
g
-position of the allylic moiety,3 although Schlosser observed that
[1,4]-/[1,2]-selectivity is diminished with increasing alkyl sub-
stitution about the migrating carbon.8 In the context of these pre-
vious findings, we set out to systematically investigate the
introduction of alkyl substitution at the benzylic carbon and/or
also as the difficulty of the
adopt an optimum conformation for a concerted [1,4]-shift. Al-
though the inverse relationship between steric demand of the
alkyl group and the [1,4]-/[1,2]-selectivity is consistent with both
stepwise and concerted mechanisms for the [1,4]-migration, at this
point it is difficult to predict which mechanism would be more
susceptible to such steric effects.
a-(benzyloxy)allyllithium species to
g
-
terminal allylic carbon of
a-alkoxysilanes so as to gain insight into
the steric and stereochemical factors that might control the course
of Wittig rearrangements of
a
-alkoxysilanes.9
Based on our earlier observations 6,7 in which only the isomeric
[1,2]-product was isolated (4 instead of 3, Scheme 1) we were sur-
prised to find that the rearrangement of 5, 8 and 11 gave the direct
[1,2]-Wittig producs (alcohols 7, 10 and 12 Scheme 2) and none of
the corresponding isomeric [1,2]-products. The isomerization of the
[1,2]-Wittig alkoxides (i, Scheme 3) is likely to take place via Brook
rearrangement to homoenolate ii followed by a [1,4]-Retro-Brook
migration to enolate iii. As pointed out elsewere 11 such net carbon-
to-carbon 1,3-silyl migrations are generally substrate-dependent,
sensitive to steric and electronic factors, and favored at higher
temperatures. We have evidence, however, that in our case this
isomerization may, in part, also be an artifact of work-up and in
certain cases can be minimized (vide infra).
2. Results and discussion
We initiallystudied the effect of alkyl substituents at the terminal
sp2 carbon of the allyl moiety (R1¼alkyl, R2¼H in 1, Scheme 1).
Compounds 5, 8, and 11, possessing a methyl, n-hexyl, and t-butyl at
the terminal olefin carbon, respectively, were prepared from the
corresponding
a-(trimethylsilyl)-g-alkyl allyl alcohols by acid-
catalyzed O-alkylation with benzyl trichloroacetimidate.10
Subjection of methyl-substituted compound 5 to our previously
developed conditions (sec-BuLi, THF, ꢀ78 ꢁC)6 afforded 74% overall
yield of a 4:1 ratio of acylsilane 6 and alcohol 7 resulting from [1,4]-
and [1,2]-Wittig rearrangements, respectively (Scheme 2). The ef-
fect on the rate of deprotonation/rearrangement was negligible,
consistent with the fact that the site of deprotonation is at a rela-
tively remote position with respect to the alkyl substituent. The
observed erosion of the [1,4]-/[1,2]-selectivity with substitution at
the terminal allylic position is in apparent contrast with literature
We continued our studies by analyzing the influence of sub-
stituents at the migrating (benzylic) carbon, a structural change
reports.3 A longer alkyl chain at the
g-position in compound 8 led to
a lower ratio (2:1) of [1,4]-/[1,2]-Wittig products 9 and 10 in 78%
overall yield. This trend reached a maximum point in the case of
compound 11 in which the bulky t-butyl group completely inhibi-
ted the [1,4]-Wittig shift (Scheme 2). Allylic deprotonation of 11
preceeded [1,2]-Wittig rearrangement to give alcohol 12, in addi-
tion, benzylic deprotonation was competitive and allowed a [2,3]-
sigmatropic shift to afford alcohol 13 as a single diastereomer.
Thus, bulkier alkyl groups at the
activity toward deprotonation at the allylic position, allowing
g-carbon appear to lower the re-
Scheme 3. Plausible mechanism for the isomerization of the [1,2]-Wittig alkoxide i to
enolate iii.
Scheme 2. Effect of alkyl substitution at the terminal sp2 carbon of the allyl moiety.

E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
851
recovered in 43%. The [1,4]- and isomeric [1,2]-products (15 and 16,
respectively) were obtained in a ratio of 1.5:1 and in a combined
35% yield. It was observed that allowing the reaction to proceed
overnight resulted in an increased overall yield of 15 and 16 (46%)
and basically the same [1,4]-/[1,2]-ratio (1.7:1) with a correspond-
ing decrease in the recovery of the ‘less reactive’ anti-14 (26%). The
near complete erosion of the [1,4]-/[1,2]-selectivity (>99:1 in
compound 1)6 is in agreement with the detrimental effect of sub-
stituents at the migrating carbon in the [1,4]-/[1,2]-selectivity ob-
served by Schlosser.8b
The marked difference in the reactivity of diastereomers syn-14
and anti-14 points to the determinant role of relative stereo-
chemistry, and more specifically the steric environment around the
allylic proton (a to silicon) in allowing the key deprotonation step
to take place prior to rearrangement.12 The relative ability of the syn
and anti diastereomers to adopt an optimum conformation for
deprotonation might be responsible for the observed difference in
reactivity. We propose that the allylic CeH bond should be per-
pendicular to the olefin and therefore aligned with the
p system. At
the same time, antiperiplanar alignment of the allylic CeH bond to
the cleaving CeO would allow weakening of the CeH bond. The
phenyl group would take the less crowded and furthest position,
maximizing conjugation by aligning with the CeO bond and thus
leading to the pseudo-eclipsed conformers shown in Fig. 1. These
proposed conformational requirements pose a more severe steric
interaction in anti-14, the less reactive diastereomer, in which the
pseudo-eclipsing methyl and TMS groups collide. On the other
hand, in syn-14 the TMS group is pseudo-eclipsed with Hb and
a less unfavorable steric interaction between the benzylic methyl
and vinyl groups is possible. Alternatively, positioning the benzylic
Hb proton in an ‘eclipsed’ alignment with the TMS groups in both
anti-14 and syn-14 would lead to a more unfavorable steric in-
teraction in anti-14 (Ph vs vinyl) than in syn-14 (Me vs vinyl).
Our conformational analysis is consistent with the fact that in-
creasing the steric demand of the substituent at the benzylic po-
sition (methyl in 14) dramatically reduced deprotonation rate. The
diastereomeric 2-propenyl (17) and the isopropyl (20) analogs were
unreactive under standard reaction conditions (sec-BuLi, THF,
ꢀ78 ꢁC, 24 h). In these two cases the use of a less bulky base (n-
BuLi) was necessary to effect a reaction. A mixture of syn-17/anti-17
(2.6:1) required 30 h for complete reaction at ꢀ30 ꢁC, yielding
acylsilane 18 and ketone 19 in a 4.3:1 ratio. The seemingly higher
[1,4]-/[1,2]-selectivity is clouded by the reaction also affording
a
complex mixture of alkylated and otherwise unidentified
byproducts. A temperature of 0 ꢁC was necessary for the isopropyl
substituted syn-20 to undergo deprotonation and rearrangement to
give the [1,4]- and isomeric [1,2]-products 21 and 22, in 23% yield
(1.8:1 ratio), along with 27% of unreacted syn-20.
Scheme 4. Wittig rearrangements of
a-alkoxysilanes 14, 17, and syn-20 bearing
a substituent (methyl, 2-propenyl, and iso-propyl, respectively) at the benzylic carbon.
that inherently led to diastereomeric substrates. Our simplest
We also studied the behavior of diastereomeric ethers 23,
containing a para methyl group on the aromatic ring (Scheme 5).9
This weakly electron-donating group barely influenced the
[1,4]-/[1,2]-selectivity, relative to the unsubstituted analogs 14
(2:1 vs 1.5:1, respectively), providing [1,4]-product 24 and [1,2]-
product 25 in 40% overall yield. However, a significant amount
of diastereomeric dibenzyl dimer 26 was isolated from the re-
action mixture, suggesting that (1) the stepwise mechanism is the
major pathway in the rearrangements of 23, and (2) that the
models,
a-(trimethylsilyl)allyl ethers syn-14 and anti-14 bearing
a methyl group at the benzylic position, were not separable by
column chromatograph on silica gel, thus a 1:1.4 mixture of syn-14/
anti-14 was employed (Scheme 4). Employing such a mixture did
not constitute a problem since it was possible to monitor the re-
action by 1H NMR. Under our standard reaction conditions we
found that the more reactive diastereomer (syn-14) was consumed
within 8 h whereas the ‘less reactive’ diastereomer anti-14 was
Fig. 1. Proposed relevant conformers for allylic deprotonation in syn-14 and anti-14.

852
E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
Scheme 5. Wittig rearrangements of diastereomeric 23 having an electron-rich migrating (benzylic) group.
expected benzyl radical stabilization by the para methyl group
prevents radical/radical-anion recombination within the solvent
cage,13 allowing benzyl radicals to escape and dimerize.
products from [1,4]- and [1,2]-migrations were obtained in low di-
astereomeric ratios (ranging from 1:1 to w3:1). Isolation of the [2,3]-
Wittig product is diagnostic of competitive deprotonation at the
It is important to mention that we have consistently observed
that syn diastereomers (general structure 1, R2sH, Scheme 1) are
more reactive than the corresponding anti isomers in all cases. The
relative stereochemistry of diastereomers syn-14/anti-14 and syn-
17/anti-17 was determined as shown in Scheme 5.14 Derivatization
of syn-14/anti-14 to the 3,5-dinitrobenzoyl esters syn-28/anti-28
and crystallization of syn-28 allowed the determination of its
crystal structure.15 On the other hand, ring-closing metathesis of
syn-17 and anti-17 followed by NOE studies of the corresponding
products trans-29 and cis-29 led to the assignment of relative ste-
reochemistry in syn-17 and anti-17 (Scheme 6).
Finally, we studied the behavior of substrates bearing sub-
stitution at both the migrating carbon and the terminal allylic
carbon. These experiments gave us the opportunity to evaluate the
effect of olefin geometry not only on the reactivity and selectivity of
the rearrangements, but also on the stereochemistry of the bond
reorganization.
Compounds 30 were synthesized as geometrically pure Z or E
isomers, however, while the Z diastereomers (syn Z-30 and anti Z-
30)16 could be largely separated by column chromatography
(dr>19:1), the E diastereomers proved very difficult to separate and
therefore were used as a diastereomeric mixture (E-30).
In theory, clean deprotonation of 30 (E or Z) followed by rear-
rangement should afford pairs of diastereomeric [1,4]- and [1,2]-
products (31 and 32, respectively). As described above, further
isomerization of the [1,2]-products via silyl migration could also
lead to another pair of diastereomeric ketones (33). In practice, syn
and anti Z-30 were very unreactive when treated with n-BuLi or
other bases17 at low temperature, and even at room temperature
these diastereomers reacted sluggishly. Reaction of syn Z-30
(Scheme 7) with n-BuLi led to almost 50% conversion and w20%
yield of a complex mixture of products. Careful examination and
separation of these mixtures revealed that compound 33 was ac-
companied by [2,3]-Wittig (34),18 diastereomeric [1,2]- and [1,4]-
Wittig products lacking the trimethylsilyl group (35 and 36, re-
spectively) and alkylated products (not shown). The actual [1,2]-
Wittig product (32, Scheme 8) was not observed.
Although it was not possible to obtain exact ratios of products or
diastereomers from either 1H NMR or HPLC of crude reaction mix-
tures, the products could be partially purified allowing their ap-
proximate ratios to be determined.19 The [2,3]-Wittig rearrangement
of syn Z-30 proceeded through a standard transition structure2a to
give syn-34 as a single diastereomer,18 on the other hand all other
Scheme 6. Determination of relative stereochemistry of syn-14/anti-14 and syn-17/
anti-17.

E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
853
Scheme 7. Substitution at the migrating carbon and terminal sp2 carbon, Z isomers.
52 h and quenched at ꢀ78 ꢁC, which gave the [1,4]- and [1,2]-Wittig
products 31 and 32 in 30% yield (1:1 ratio) with only traces of the
isomeric [1,2]-product 33. Thus, in certain cases, quenching the re-
action at low temperature significantly reduces silyl migration.
The relative stereochemistry of diastereomeric acylsilane 31 was
determined by oxidation to the corresponding carboxylic acid.22,23
The relative stereochemistry of diastereomeric alcohol 32 was not
determined. Attempts to derivatize 32 to the corresponding 3,5-
dinitrobenzoyl ester failed presumably due to the congested na-
ture of the tertiary alcohol. The relative stereochemistry in isomeric
[1,2]-Wittig product (33) was determined as shown in Scheme 9.
Compound 33 (dr¼1.4:1) was reduced to the corresponding alcohol
39 as a mixture of only three diastereomers. Partial separation of
the diastereomers of 39 led to a mixture with a ratio 10:2:1. Ben-
zoylation of this mixture with 3,5-dinitrobenzoyl chloride in pyri-
dine gave 40 as a mixture of diastereomers. Recrystallization from
CH2Cl2/hexanes gave a single diastereomer and its relative stereo-
chemistry was determined by X-ray. Hydrolysis (NaOH) and oxi-
dation (DMP) of this single isomer (40) gave anti-33, which
matched spectroscopically with the major diastereomer in the
initial diastereomeric mixture of 33.
Scheme 8. Substitution at the migrating carbon and terminal sp2 carbon, E isomers.
benzylic position, rather than
a to silicon, likely as a consequence of
the relatively high temperature required for the desired reaction to
occur. The elevated temperature may allow these substrates to
overcome an unfavorable conformation for deprotonation of the al-
lylic hydrogen due to the minimization of A(1,3)-strain.20
3. Conclusions
As expected, anti Z-30 was less reactive under the same reaction
conditions. Here, the starting material was recovered in 77% and
only a total w10% yield of products 34e36 was obtained (Scheme 7).
In conclusion, we have shown that substitution at the migrating
carbon impacts the Wittig rearrangement of a-alkoxysilanes, de-
The absence of compounds 31e33 suggests that deprotonation
a to
creasing reactivity toward deprotonation and eroding the [1,4]-/
[1,2]-selectivity. Similarly, substitutions at the terminal carbon of
the allyl moiety alone or in combination with substitution at the
migrating carbon also lowers the [1,4]-/[1,2]-selectivity, especially
where substitution comes in the form of Z-olefins. Increasingly
bulkier substituents at the terminal allylic position gradually de-
crease the [1,4]-/[1,2]-selectivity, leading to complete inhibition of
the [1,4]-pathway in the bulkier case (t-butyl). The reactivity in
these diastereomeric substrates heavily depends on their relative
stereochemistry, syn or anti, the former being more reactive in all
cases. Taken together these results show the beneficial effect of silyl
groups on reactivity (by lowering the acidity of allylic hydrogens) is
countered by the steric congestion afforded upon substitution at the
benzylic or allylic (or both) positions, which presumably prevents
the access of optimal conformation for the key deprotonation step.
silicon is inhibited due to severe steric crowding. [2,3]-Wittig rear-
rangement of anti Z-30 proceeded stereospecifically2a to give only
anti-34.21 Compounds 35 and 36, likely to be formed via a silicon/
lithium exchange7 followed by [1,2]- and [1,4]-Wittig rearrange-
ment, respectively, were obtained again in low diastereomeric ra-
tios. Interestingly, the [1,2]-product 35 showed an inverse
diastereoselection in comparison to that observed in the rear-
rangement of syn Z-30.
Changing the geometry of the olefin had a pronounced effect
(Scheme 8). Inlinewith our previousdiscussion, thereactivitytoward
initial deprotonation was dominated by the relative configuration at
the
a
and a0 positions of the ethers, as illustrated by the rearrange-
ment of E-30 (syn/anti¼1:1.5). For example, syn E-30 was completely
consumed by n-BuLi at low temperature, while its diastereomer anti
E-30 was mostly recovered (Scheme 8). Quenching the reaction at
ꢀ30ꢁC led tothe isolation of the [1,4]-Wittig product (31) in 23% yield
and with low diastereoselectivity,22 accompanied by the isomeric
[1,2]-product (33) also in low yield. Interestingly, quenching the re-
action at lower temperature allowed the isolation of the direct [1,2]-
Wittig product 32,23 which in our previous room temperature ex-
periments (Scheme 7) had undergone silicon migration and rear-
rangement to 33. This was evidenced in an experiment run at 0 ꢁC for
4. Experimental section
4.1. General considerations
All reactions were run under nitrogen in previously flame-dried
flasks or disposable vials. THF was freshly distilled from sodium

854
E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
Scheme 9. Determination of the relative stereochemistry of 33 by derivatization to the crystalline ester 40 (major diastereomer) followed by the reverse transformations to anti-33.
benzophenone ketyl. Dichloromethane was distilled from calcium
hydride. Cyclohexane and hexane were used without further pu-
rification. Ultrapure silica gel 60 (230e400 mesh ASTM) from Sili-
cycle was used for flash column chromatography. Melting points
are not corrected.
Nuclear Magnetic Resonance spectra were recorded on 300 MHz,
500 MHz, and 600 MHz Varian instruments using CDCl3 as solvent
and referenced to 7.24 ppm (residual proton). IR was recorded on
a PerkineElmer instrument. High Resolution Mass Spectrometry
spectra were recorded at the Michigan State University Mass Spec-
trometry Facility using a Waters Qtof Ultima (ESI) and JEOL AX 505H
(EI/CI) instruments.
(70.29 mmol) of trichloroacetimidate of benzyl alcohol, and
BF3$OEt2 (0.65 mL, 5.15 mmol) in cyclohexane afforded 2.11 g (34%)
of 5 as a colorless oil. 1H NMR (300 MHz, CDCl3)
d 7.35 (m, 5H),
5.55e5.39 (m, 2H), 4.69e4.65 (d, J¼12.4 Hz, 1H), 4.37e4.28 (d,
J¼12.4 Hz, 1H), 3.52e3.50 (d, J¼7.1 Hz, 1H), 1.74e1.72 (d, J¼4.7 Hz,
3H), 0.01 (s, 9H). 13C NMR (75 MHz, CDCl3)
d 139.4, 129.7, 128.0 (2C),
127.5 (2C),127.0,125.1, 75.1, 71.3,18.0, ꢀ3.7. HRMS (CI) m/z 252.1775
[(MþNH4)þ; calcd for C14H22OSi, 252.1784].
4.2.2. Preparation of compound 8. Compound 8 was prepared by
alkylation of (E)-1-(trimethylsilyl)non-2-en-1-ol. Preparation of
(E)-1-(trimethylsilyl)non-2-en-1-ol: To a solution of (E)-2-nonen-
1-ol (800 mg, 5.62 mmol, 1 equiv) in THF (15 mL) at ꢀ78 ꢁC was
added n-BuLi (1.6 M in hexanes, 3.9 mL, 6.19 mmol, 1.1 equiv)
slowly. After 30 min, TMSCl (0.79 mL, 6.19 mmol, 1.1 equiv) was
added and the mixture stirred at room temperature for 1 h. The
reaction mixture was cooled down to ꢀ78 ꢁC and t-BuLi (3.97 mL,
6.74 mmol, 1.2 equiv) was added dropwise (within 15 min). The
reaction was monitored by 1H NMR. After 8 h the reaction was
quenched by quickly adding NH4Cl(sat) (7 mL). The mixture was
diluted with Et2O (20 mL) and the aqueous phase was extracted
with Et2O (3ꢂ10 mL). Combined organic extracts were washed with
brine, dried over MgSO4 and concentrated to give 1.1 (91%, crude
yield) of almost pure (E)-1-(trimethylsilyl)non-2-en-1-ol as a yel-
4.2. Preparation of a-alkoxysilanesdgeneral procedure A
Trichloroacetimidate of the appropriate alcohol (prepared
according to literature procedure)10 (2.0 equiv) was added to
a stirred solution of the requisite a
-(trimethylsilyl)allyl alcohol11d
(1.0 equiv) in cyclohexane or hexane (0.2 M) at room tempera-
ture. A solution of TMSOTf (0.055 equiv) in cyclohexane or hexane
(usually 0.1 mL/1.0 mL cyclohexane) or, alternatively, BF3$OEt2 in
dry diethyl ether, was then added dropwise. White precipitate
formed upon addition of the Lewis acid. The reaction mixture was
stirred at room temperature until completion as judged by 1H NMR
(typically overnight) and filtered through a plug of Celite. The
precipitate was then washed with pentane or hexane (precipitate is
soluble in ether) and the filtrate diluted with ether. The diluted
filtrate was subsequently washed with NaHCO3 (aq satd) (twice),
1 M HCl (twice), and lastly with brine (twice). The organic phase
was dried over anhydrous MgSO4, filtered, and concentrated to
furnish the crude product. Purification by column chromatography
on silica gel (0e2% EtOAc in hexane gradient) afforded the pure
product.
lowish oil. 1H NMR (500 MHz, CDCl3)
d
5.56 (ddt, J¼1.0, 6.5, 15.0 Hz,
1H), 5.46 (m, 1H), 3.88 (dt, J¼1.5, 7.0 Hz, 1H), 2.01 (q, J¼7.0 Hz, 2H),
1.35e1.25 (m, 8H), 0.86 (t, J¼7.0 Hz, 3H), 0.02 (s, 9H). 13C NMR
(126 MHz, CDCl3) d 131.2, 127.8, 68.4, 32.5, 31.7, 29.7, 28.8, 22.7, 14.1,
1.3, ꢀ4.2. IR (neat) 3416, 2928, 1248, 841 cmꢀ1. HRMS (EI) m/z
196.1647 [(MꢀH2O)þ; calcd for C12H24Si, 196.1647].
Alkylation of (E)-1-(trimethylsilyl)non-2-en-1-ol: Applying
general procedure
A
to (E)-1-(trimethylsilyl)non-2-en-1-ol
(300 mg, 1.4 mmol, 1 equiv) and trichloroacetimidate of benzyl
alcohol (671 mg, 2.5 mmol, 1.8 equiv) in 10:1 hexane/CH2Cl2 (8 mL)
4.2.1. Preparation of 5. Applying general procedure A to 6.75 g
with TMSOTf (38
m
L, 0.21 mmol, 0.15 equiv) for 2.5 h afforded
(46.86 mmol) of (E)-1-(trimethylsilyl)but-2-en-1-ol, 17.75
g
134 mg (31%) of 8 as a colorless oil. 1H NMR (500 MHz, CDCl3)
d
7.30

E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
855
(m, 4H), 7.24 (m, 1H), 5.43 (m, 2H), 4.66 (d, J¼12.5 Hz, 1H), 4.30 (d,
J¼12.0 Hz, 1H), 3.50 (d, J¼8.0 Hz, 1H), 2.04 (q, J¼7.0 Hz, 2H),
1.38e1.24 (m, 8H), 0.88 (t, J¼8.0 Hz, 3H). 13C NMR (126 MHz, CDCl3)
afforded 1.32 g of 20 (75%) as a 1:1 mixture of diastereomers after
column chromatography (0e2% EtOAc gradient). IR (neat)
1628 cmꢀ1
.
d
139.5, 130.9, 128.6, 128.1, 127.6, 127.1, 75.1, 71.3, 32.5, 31.7, 29.6,
anti-20: 1H NMR (300 MHz, CDCl3)
d 7.31e7.19 (m, 5H),
28.8, 22.7,14.1, ꢀ3.9. IR (film) 3030, 2957,1246, 841 cmꢀ1. HRMS (EI)
5.77e5.70 (m, 1H), 5.03e4.92 (dd, J¼10.6, 17.2 Hz, 2H), 4.07e4.06
(d, J¼7.5 Hz, 1H), 3.39e3.37 (d, J¼8.0 Hz, 1H), 1.91e1.85 (m, 1H),
1.01e1.00 (d, J¼6.6 Hz, 3H), 0.72e0.70 (d, J¼7.1 Hz, 3H), ꢀ0.01 (s,
m/z 289.1985 [(MꢀCH3)þ; calcd for C18H29OSi, 289.1988].
4.2.3. Preparation of compound 11. Compound 11 was prepared by
alkylation of (E)-4,4-dimethyl-1-(trimethylsilyl)pent-2-en-1-ol.
Preparation of (E)-4,4-dimethyl-1-(trimethylsilyl)pent-2-en-1-ol:
9H). 13C NMR (75 MHz, CDCl3)
d 141.8, 138.0, 128.1 (2C), 127.8, 127.1
(2C), 113.1, 84.7, 72.6, 35.0, 19.2, 19.0, ꢀ4.0. HRMS (APCI) m/z
263.1821 [(MþH)þ; calcd for C16H27OSi, 263.1831].
To
a
solution of (E)-4,4-dimethyl-2-penten-1-ol (700 mg,
syn-20: 1H NMR (300 MHz, CDCl3)
d 7.35e7.17 (m, 5H),
6.13 mmol, 1 equiv) in THF (17.5 mL) at ꢀ78 ꢁC was added n-BuLi
(1.6 M in hexanes, 2.7 mL, 6.74 mmol, 1.1 equiv) slowly. After
30 min, TMSCl (0.86 mL, 6.74 mmol, 1.1 equiv) was added and the
mixture stirred at room temperature for 1 h. The reaction mixture
was cooled down at ꢀ78 ꢁC and t-BuLi (9 mL, 15.3 mmol, 2.5 equiv)
was added dropwise (within 25 min). The reaction was transferred
to a cold bath at ꢀ30 ꢁC and monitored by 1H NMR. After 6 h the
reaction was quenched by quickly adding NH4Cl(sat) (10 mL). The
mixture was diluted with Et2O (20 mL) and the aqueous phase was
extracted with Et2O (3ꢂ10 mL). Combined organic extracts were
washed with brine, dried over MgSO4, and concentrated. The crude
product was purified by column chromatography (5% EtOAc in
hexanes) to give 790 (69%) of 11 as a yellowish oil. 1H NMR
5.64e5.53 (m, 1H), 4.89e4.72 (dd, J¼10.7, 16.7 Hz, 2H), 4.01e3.99
(d, J¼6.9 Hz, 1H), 3.72e3.68 (d, J¼7.4 Hz, 1H), 1.99e1.89 (m, 1H),
0.93e0.91 (d, J¼6.9 Hz, 3H), 0.77e0.74 (d, J¼6.9 Hz, 3H), 0.05 (s,
9H), 0.08 (s, 9H). 13C NMR (75 MHz, CDCl3)
d 142.6, 138.2, 127.4 (2C),
127.3 (2C), 126.5, 111.4, 87.5, 76.6, 34.5, 18.7 (2C), ꢀ3.5. HRMS (APCI)
m/z 263.1821 [(M)þ; calcd for C16H27OSi, 263.1831].
4.2.6. Preparation of 23. Applying general procedure A to 1 g
(7.68 mmol) of 1-(trimethylsilyl)-prop-2-en-1-ol, 3 g (10.75 mmol)
of the trichloroacetimidate of 4-methylbenzyl alcohol and TMSOTf
(35
23 as a colorless oil. Mixture of syn-23/anti-23 (1:1)
(500 MHz, CDCl3)
m
L, 0.19 mmol) in hexane afforded 1.7 g (95%) of diastereomeric
d
1H NMR
d
7.20 (d, J¼8.5 Hz, 2H), 7.15e7.09 (m, 6H), 5.73
(500 MHz, CDCl3)
d
5.49 (m, 2H), 3.90 (dd, J¼1.0, 3.5 Hz, 1H), 1.0 (s,
(m, 2H), 5.01e4.94 (m, 3H), 4.88 (dt, J¼11.0 Hz, 1H), 4.48 (q,
J¼6.5 Hz, 1H), 4.45 (d, J¼6.5 Hz, 1H), 3.78 (dt, J¼1.5, 6.5 Hz, 1H), 3.40
(dt, J¼1.5, 7.0 Hz,1H), 2.33 (s, 3H), 2.31 (s, 3H),1.35 (d, J¼6.5 Hz, 3H),
1.32 (d, J¼6.5 Hz, 3H), 0.03 (s, 9H), ꢀ0.05 (s, 9H). 13C NMR (151 MHz,
9H), 0.01 (s, 9H). 13C NMR (126 MHz, CDCl3)
d 138.6, 125.9, 68.4,
32.8, 29.8, ꢀ4.2. IR (film) 3406, 2959, 1248, 843 cmꢀ1. HRMS (EI) m/
z 168.1334 [(MꢀH2O)þ; calcd for C10H20Si, 168.1334].
Alkylation of (E)-4,4-dimethyl-1-(trimethylsilyl)pent-2-en-1-ol:
CDCl3) d 142.5, 141.3, 137.84, 137.81, 136.7, 136.3, 128.8 (2C), 128.7
Applying general procedure
thylsilyl)pent-2-en-1-ol (350 mg, 1.88 mmol, 1 equiv) and tri-
chloroacetimidate of benzyl alcohol (900 mg, 3.38 mmol, 1.8 equiv)
A
to (E)-4,4-dimethyl-1-(trime-
(2C), 126.7 (2C), 125.9 (2C), 112.1, 111.6, 75.9, 75.4, 74.1, 73.1, 24.7,
22.2, 21.13, 21.09, ꢀ3.0, ꢀ4.0. IR (film) 3050, 2972, 1248, 841 cmꢀ1
.
HRMS (EI) m/z 248.1597 [(Mþ); calcd for C15H24OSi, 248.1596].
in 10:1 hexane/CH2Cl2 (10 mL) with TMSOTf (51
0.15 equiv) for 2.5 h afforded 245 mg (49%) of 11 as a colorless oil. 1H
NMR (500 MHz, CDCl3)
mL, 0.282 mmol,
4.2.7. Preparation of compound E-30. Applying general procedure A
to 3.6 g of (E)-1-(trimethylsilyl)but-2-en-1-ol (24.98 mmol),11d
13.32 g of the trichloroacetimidate of phenethyl alcohol
d
7.30 (m, 4H), 7.24 (m, 1H), 5.49 (dd, J¼1.0,
15.5 Hz, 1H), 5.31 (dd, J¼6.5, 16.0 Hz, 1H), 4.64 (d, J¼12.5 Hz, 1H),
4.30 (d, J¼12.5 Hz, 1H), 3.51 (dd, J¼1.0, 8.5 Hz, 1H), 1.01 (s, 9H), 0.00
(49.5 mmol, 2 equiv)and 0.47 mL of BF3$OEt2 (3.74 mmol, 0.15 equiv)
afforded 3.07 g of E-30 (39%).
(s, 9H). 13C NMR (126 MHz, CDCl3)
d 141.7, 139.5, 128.1, 127.7, 127.1,
123.2, 75.2, 71.3, 29.8, ꢀ3.9. IR (film) 3026, 2959, 1246, 841 cmꢀ1
.
E-30 (mixture of diastereomers anti/syn 0.58:0.42): 1H NMR
HRMS (EI) m/z 185.1353 [(MþBn)þ; calcd for C10H21OSi, 185.1362].
(500 MHz, CDCl3) d 7.33e7.19 (m, 5H), 5.42e5.31 (m, 2H), 4.52 (q,
J¼6.5 Hz, 0.58H), 4.49 (q, J¼6.0 Hz, 0.42H), 3.69 (d, J¼7.0 Hz, 0.42H),
3.29 (d, J¼7.0 Hz, 0.58H), 1.71 (d, J¼5.5 Hz, 1.74H), 1.61 (d, J¼6.0 Hz,
1.26H), 1.35 (d, J¼6.5 Hz, 1.74H), 1.32 (d, J¼6.0 Hz, 1.26H), 0.03 (s,
3.78H), ꢀ0.05 (s, 5.22H). 13C NMR (125 MHz, CDCl3) anti E-30:
4.2.4. Preparation of compounds 14. Applying general procedure A
to 4.01 g (30.82 mmol) of a-hydroxysilane 1-(trimethylsilyl)-prop-
2-en-1-ol, 17.25 g (58.57 mmol) of the trichloroacetimidate of 2-
methyl-1-phenylpropan-1-ol, and 0.38 g (1.70 mmol) of TMSOTf,
and stirring the reaction overnight afforded 5.7 g (79%) of 14 as
a 1:1 mixture of diastereomers. IR (neat) 2972, 2928, 2899, 1628,
d
144.6, 130.2, 128.1 (2C), 127.0, 126.8 (2C), 124.6, 75.0, 72.4, 24.7,
17.9, ꢀ3.9. syn E-30:
d 145.8, 130.4, 127.9 (2C), 126.6, 125.9 (2C),
124.0, 75.2, 73.2, 22.0, 17.8, ꢀ3.8. HRMS (CI) m/z 248.1591 [(M)þ;
1493, 1452, 1248 cmꢀ1
.
Mixture of syn-14/anti-14: 1H NMR
7.36e7.10 (m, 10H), 5.83e5.68 (m, 2H),
calcd for C15H24OSi, 248.1596].
(300 MHz, CDCl3)
d
5.06e4.87 (m, 4H), 4.56e4.46 (m, 2H), 3.82e3.80 (dt, J¼6.9, 1.4 Hz,
1H), 3.43e3.41 (dt, J¼6.9, 1.4 Hz, 1H), 1.39 (d, J¼6.6 Hz, 3H), 1.35 (d,
J¼6.6 Hz, 3H), 0.06 (s, 9H), 0.02 (s, 9H). 13C NMR (75 MHz, CDCl3)
4.2.8. Preparation of compound Z-30. Following the general pro-
cedure A to 3.49 g of 1-(trimethylsilyl)but-2-yn-1-ol (24.53 mmol)
and 13.1 g of the trichloroacetimidate of sec-phenethyl alcohol
(49.06 mmol, 2 equiv) in cyclohexane (140 mL) at 0 ꢁC was added
0.46 mL of BF3$OEt2 (3.68 mmol, 0.15 equiv). After 1 h the reaction
was stopped, worked up according to the general procedure A
followed by column chromatography (8% DCM in hexanes) to afford
5 g (83%) of diastereomeric alkyne 37 as a colorless oil (di-
astereomers partially separated). Alkyne reduction: To a solution of
1.435 g of 37 (5.82 mmol, dr¼1:1) in hexanes (210 mL) was added
Et3N (2.6 mL, 2.5 mL/mmol 37) and Lindlar’s catalyst (38.8 mg,
37.5 mg/mmol 37). The flask was flushed with hydrogen and a hy-
drogen balloon attached. The mixture was vigorously stirred and
the reaction monitored by NMR (about 4 h). The reaction mixture
was partially concentrated, filtered through a plug of Celite, and
fully concentrated. Column chromatography (10% DCM in hexanes)
afforded 900 mg (62%) of Z-30. Note: Pure alkyne 37 decomposes
d
145.3, 144.2, 137.6, 128.4, 128.0, 127.9, 127.1, 126.7, 126.6, 125.8,
112.1, 111.7, 76.0, 75.6, 74.1, 73.2, 24.8, 22.3, ꢀ3.7, ꢀ3.8. HRMS (EI) m/
z 234.1434 [(M)þ; calcd for C14H22OSi, 234.1440]. anti-14: 1H NMR
(500 MHz, CDCl3)
d 7.35e7.21 (m, 5H), 5.82e5.70 (m, 1H),
5.05e4.95 (m, 2H), 4.56e4.49 (q, J¼6.6, Hz, 1H), 3.43e3.40 (dt,
J¼7.1, 1.3 Hz, 1H), 1.39 (d, J¼6.6 Hz, 3H), 0.00 (s, 9H). 13C NMR
(125 MHz, CDCl3) d 144.4, 137.8, 128.2, 127.2, 126.8, 112.2, 75.7, 73.3,
24.6, ꢀ3.9. HRMS (EI) m/z 234.1428 [(M)þ; calcd for C14H22OSi,
234.1440].
4.2.5. Preparation of compound 20. Applying general procedure A
to 0.88 g of 1-(trimethylsilyl)-prop-2-en-1-ol (6.73 mmol), 3.96 g of
the trichloroacetimidate of 1-phenylbutan-1-ol (13.45 mmol,
2 equiv), and 0.07 mL of TMSOTf (0.4 mmol, 0.055 equiv) overnight

856
E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
relatively quickly after isolation and its decomposition products
appear to poison the catalyst and hamper reduction thus requiring
addition of more catalyst. Samples of 37 stored at ꢀ20 ꢁC slowly
decomposed turning yellow, such samples in hexanes were filtered
through a short silica gel plug and rinsed with more hexanes. After
concentration clean 37 was immediately submitted to the re-
duction reaction. IR (neat) 2963, 2203, 1248, 1082, 843 cmꢀ1. HRMS
(EI) m/z 246.1444 [(M)þ; calcd for C15H22OSi, 246.1440].
nitrogen. The required amount of s-BuLi (1.5e4.0 equiv, 1.3 M in
cyclohexane) or n-BuLi (1.6 M in hexanes) was added dropwise via
syringe. The reaction mixture was stirred at the reaction temper-
ature for the desired length of time, then quenched with saturated
aqueous NH4Cl and diluted with ether. Phases separated and the
organic phase was washed with water and brine. The organic phase
was dried over anhydrous MgSO4 and concentrated. Silica gel
chromatography (0e2% EtOAc in hexane gradient) afforded the
rearranged products usually as light oils.
anti-37: 1H NMR (500 MHz, CDCl3)
d 7.37e7.23 (m, 5H), 4.79 (q,
J¼6.5 Hz, 1H), 3.43 (q, J¼2.5 Hz, 1H), 1.88 (d, J¼2.5 Hz, 3H), 1.40 (d,
J¼7.0 Hz, 3H), 0.06 (s, 9H). 13C NMR (126 MHz, CDCl3)
d
143.8, 128.3
4.3.1. Wittig rearrangements of compound 5. Applying the general
procedure B to 141 mg (0.60 mmol) of 5 and 0.69 mL (0.90 mmol) of
s-BuLi (1.3 M in cyclohexane) at ꢀ78 ꢁC for 30 min, after purifica-
tion by column chromatography on silica gel, afforded 106 mg
(75%) of a 4:1 mixture of both [1,4]- and [1,2]-rearrangement
products 6 (a light yellow oil) and 7 as a colorless oil.
(2C), 127.3, 126.8 (2C), 82.7, 77.6, 76.3, 60.5, 24.4, 3.9, ꢀ4.0.
syn-37: 1H NMR (500 MHz, CDCl3)
d
7.35 (d, J¼7.5 Hz, 2H), 7.30
(m, 2H), 7.21 (tt, J¼1.5, 7.5 Hz, 1H), 4.71 (q, J¼6.5 Hz, 1H), 3.88 (q,
J¼2.5 Hz, 1H), 1.78 (d, J¼2.5 Hz, 3H), 1.36 (d, J¼6.5 Hz, 3H), 0.12 (s,
9H). 13C NMR (126 MHz, CDCl3)
d 145.0, 128.0 (2C), 126.8, 126.1 (2C),
83.1, 77.6, 76.1, 61.0, 21.4, 3.8, ꢀ3.8.
Compound 6: 1H NMR (300 MHz, CDCl3)
d 7.32e7.17 (m, 5H),
anti Z-30: 1H NMR (500 MHz, CDCl3)
d
7.29 (t, J¼7.0 Hz, 2H), 7.23
2.61e2.50 (m, 2H), 2.47e2.30 (m, 3H), 0.84e0.81 (d, J¼6.6 Hz, 3H),
(m, 3H), 5.50 (ddq, J¼1.0, 7.0, 11.0 Hz, 1H), 5.39 (ddq, J¼1.5, 10.5,
11.0 Hz,1H), 4.44 (q, J¼6.5 Hz,1H), 3.67 (d, J¼10.5 Hz,1H),1.35 (ddd,
J¼0.5, 2.0, 7.0 Hz, 3H), 1.34 (d, J¼6.5 Hz, 3H), ꢀ0.03 (s, 9H). 13C NMR
ꢀ0.13 (s, 9H). 13C NMR (125 MHz, CDCl3)
d 248.6, 140.6, 129.2 (2C),
128.2 (2C), 125.9, 54.9, 43.3, 29.6, 19.9, ꢀ3.3. IR (neat) 1709 cmꢀ1
.
HRMS (EI) m/z 233.1355 [(MꢀH)þ; calcd for C14H21OSi, 233.1362].
(126 MHz, CDCl3)
d
144.6, 130.5, 128.1 (2C), 127.1, 126.9 (2C), 124.4,
Compound 7: 1H NMR (500 MHz, CDCl3)
d 7.26e7.10 (m, 5H),
75.6, 67.4, 24.6,13.4, ꢀ3.9. HRMS (ESI) m/z 249.1663 [(MþH)þ; calcd
5.60e5.56 (dq, J¼15.4, 1.6 Hz, 1H), 5.19e5.12 (apparent dq, J¼15.4,
6.6 Hz, 1H), 2.86 (d, J¼7.7 Hz, 1H), 2.81 (d, J¼7.7 Hz, 1H), 1.64e1.62
(dd, J¼6.6, 1.6 Hz, 3H), 0.05 (s, 9H). 13C NMR (125 MHz, CDCl3)
for C15H25OSi, 249.1675].
syn Z-30: 1H NMR (500 MHz, CDCl3)
d 7.32e7.26 (m, 4H), 7.20
(m, 1H), 5.43e5.32 (m, 2H), 4.45 (q, J¼6.5 Hz, 1H), 4.13 (d, J¼9.5 Hz,
d 136.2, 135.4, 130.6 (2C), 127.9 (2C), 126.3, 121.62, 70.4, 43.1, 17.8,
1H), 1.51 (m, 3H), 1.34 (d, J¼6.5 Hz, 3H), 0.04 (s, 9H). 13C NMR
ꢀ4.2. IR (neat) 3432 cmꢀ1. HRMS (EI) m/z 234.1435 [(M)þ; calcd for
(126 MHz, CDCl3)
d
145.6, 130.9, 127.9 (2C), 126.7, 126.0 (2C), 123.2,
C14H22OSi, 234.1440].
75.8, 68.4, 22.0, 13.5, ꢀ3.8. HRMS (ESI) m/z 249.1675 [(MþH)þ;
calcd for C15H25OSi, 249.1675].
4.3.2. Wittig rearrangements of compound 8. Applying the general
procedure B to compound 8 (62 mg, 0.204 mmol, 1 equiv) and sec-
BuLi (1.4 M in cyclohexane, 0.22 mL, 1.5 equiv) at ꢀ78 ꢁC for 40 min,
after purification by silica gel column chromatography (3% EtOAc in
hexanes), afforded 48.4 mg (78%) of a 2:1 mixture of both [1,4]- and
[1,2]-rearrangement products 9 and 10 as colorless oils. An ana-
lytically pure sample of 9 could be obtained by subsequent silica gel
column chromatography (3% EtOAc in hexanes).
4.2.9. Preparation of compound 17. Compound 17 was prepared
following a procedure reported in literature.24 Allyltrimethylsilane
1-(trimethylsilyl)prop-2-en-1-ol (1.26 g, 11.0 mmol, 1.75 mL),
benzaldehyde (1.67 g, 11.0 mmol, 1.12 mL), and TMSOTf (0.36 mL,
2.0 mmol, 0.44 g) were successively added to a stirred cold (ꢀ78 ꢁC)
solution of
a-(trimethylsilyl)allyl trimethysilyl ether (2.0 g,
10.0 mmol) in CH2Cl2 (100 mL). The reaction was stirred for 70 min
and then quenched with NaHCO3 (aq satd). The aqueous phase was
extracted with CH2Cl2 (100 mLꢂ4), and the combined organic
layers were washed with NaHCO3 (100 mLꢂ2), brine (100 mLꢂ2),
and then dried (MgSO4). Filtration and concentration afforded the
crude product as a 1:2.56 mixture of diastereomers. After silica gel
chromatography 1.96 g (7.58 mmol) of the pure products were
obtained in a combined yield of 77%. The pair of diastereomers is
separable by column chromatography on silica gel (5% and 10%
CH2Cl2 in hexanes).
Compound 9: 1H NMR (500 MHz, CDCl3)
d 7.24 (m, 2H), 7.15 (m,
1H), 7.11 (m, 2H), 2.58 (dd, A of ABX system, J¼6.5, 13.5 Hz, 1H), 2.49
(d, J¼6.5 Hz, 2H), 2.42 (dd, B of ABX system, J¼7.0, 13.5 Hz, 1H), 2.29
(m, 1H), 1.23 (m, 10H), 0.85 (t, J¼7.5 Hz, 3H), 0.12 (s, 9H). 13C NMR
(125 MHz, CDCl3)
d 248.7, 140.7, 129.3 (2C), 128.2 (2C), 125.8, 52.5,
40.5, 34.1, 33.9, 31.8, 29.5, 26.8, 22.6, 14.1, ꢀ3.2. IR (film) 3026, 2926,
1643, 1456, 1250, 844 cmꢀ1. HRMS (EE) m/z 304.2242 [(M)þ; calcd
for C19H32OSi, 304.2222].
Mixture of 9 and 10 (1.8:1): 1H NMR (500 MHz, CDCl3)
d
7.23e7.11 (m, 14H), 5.55 (dt, J¼1.0, 15.5 Hz, 1H), 5.13 (dt, J¼7.0,
anti-17: 1H NMR (300 MHz, CDCl3)
d
7.35e7.22 (m, 5H),
15.5 Hz, 1H), 2.87 (d, J¼13.0 Hz, 1H), 2.81 (d, J¼13.5 Hz, 1H), 2.58
(dd, J¼7.0, 13.5 Hz, 1.8H), 2.49 (d, J¼6.5 Hz, 3.6H), 2.42 (dd, J¼7.0,
13.5 Hz, 1.8H), 2.29 (m, 1.8H), 1.97 (m, 2H), 1.21 (m, 26H), 0.85 (m,
8.4H), 0.12 (s, 16.2H), 0.06 (s, 9H). 13C NMR (126 MHz, CDCl3) signals
5.88e5.69 (m, 2H), 5.05e4.95 (m, 4H), 4.46e4.42 (dd, J¼7.7, 5.8 Hz,
1H), 3.44e3.42 (d, J¼7.4 Hz, 1H), 2.59e2.49 (quint, J¼7.7 Hz, 1H),
2.39e2.30 (quint, J¼6.86, 1H), ꢀ0.01 (s, 9H). 13C NMR (126 MHz,
CDCl3)
d
142.5, 137.7, 135.4, 128.1 (2C), 127.4 (3C), 116.3, 112.9, 79.3,
corresponding to 9
40.5, 34.1, 33.9, 31.8, 29.5, 26.8, 22.6, 14.1, ꢀ3.2. Signals corre-
sponding to 10 136.2, 134.3, 130.6 (2C), 127.8 (2C), 127.3, 126.3,
d 248.7, 140.7, 129.3 (2C), 128.2 (2C), 125.8, 52.5,
73.0, 43.03, ꢀ4.0. HRMS (CI) m/z 261.1664 [(MþH)þ; calcd for
C
16H24OSi, 261.1675.
d
syn-17: 1H NMR (300 MHz, CDCl3)
d
7.30e7.20 (m, 5H),
70.3, 43.1, 32.5, 31.7, 29.7, 28.7, 22.6, 14.0, ꢀ4.2. IR (film) 3534, 3028,
2957, 1745, 1643, 1248, 843 cmꢀ1. HRMS for 10 (EI) m/z 286.2150
[(MꢀH2O)þ; calcd for C19H30Si, 286.2117].
5.79e5.60 (m, 2H), 5.01e4.80 (m, 4H), 4.39e4.35 (t, J¼6.2 Hz, 1H),
3.82e3.78 (dt, J¼7.1, 1.3 Hz, 1H), 2.54e2.40 (m, 2H), 0.05 (s, 9H). 13
C
NMR (500 MHz, CDCl3) d 143.6, 137.9, 134.9, 127.8 (2C), 126.9, 126.6
(2C), 116.8, 111.9, 81.1, 75.8, 41.5, ꢀ3.7. HRMS (CI) m/z 261.1681
4.3.3. Wittig rearrangements of compound 11. Applying the general
procedure B to compound 11 (91 mg, 0.329 mmol, 1 equiv) and sec-
BuLi (1.4 M in cyclohexane, 0.35 mL, 1.5 equiv) at ꢀ78 ꢁC for 40 min,
after purification by silica gel column chromatography (3% EtOAc in
hexanes), afforded 56.2 mg (62%) of [1,2]-product 12, 3.7 mg (4%) of
[2,3]-product 13, and 14 mg of unreacted 11 (15%) as colorless oils.
[(MþH)þ; calcd for C16H24OSi, 261.1675].
4.3. Wittig rearrangements of
cedure B
a-alkoxysilanesdgeneral pro-
A solution of
a-alkoxysilane (1.0 equiv) in freshly distilled THF
Compound 12: 1H NMR (500 MHz, CDCl3)
1H), 7.10 (m, 2H), 5.46 (d, J¼16.0 Hz, 1H), 5.14 (d, J¼16.0 Hz, 1H),
d 7.23 (m, 2H), 7.17 (m,
(0.06e0.07 M) was cooled to the desired temperature under

E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
857
2.88 (d, J¼13.5 Hz, 1H), 2.83 (d, J¼13.0 Hz, 1H), 0.92 (s, 9H), 0.05 (s,
9H). 13C NMR (125 MHz, CDCl3)
137.9,136.1,130.6 (2C),129.2,127.7
Compound 22: 1H NMR (500 MHz, CDCl3)
d
7.29e7.20 (m, 5H),
d
3.30 (d, J¼10.2 Hz, 1H), 2.42e2.25 (m, 3H), 0.94 (d, J¼6.3 Hz, 3H),
(2C), 126.3, 70.0, 43.1, 32.8, 29.9, ꢀ4.2. IR (film) 3534, 3028, 2959,
0.74e0.67 (m, 1H), 0.63 (d, J¼6.8 Hz, 3H), 0.61e0.54 (m, 1H), ꢀ0.11
1248, 843 cmꢀ1. HRMS (EI) m/z 258.1820 [(MꢀH2O)þ; calcd for
(s, 9H). 13C NMR (126 MHz, CDCl3)
d 211.7, 138.4, 128.7 (2C), 128.6
C
17H26Si, 258.1804].
(2C), 127.0, 66.4, 37.8, 30.7, 21.7, 20.4, 9.9, ꢀ1.9. IR (neat) 1715 cmꢀ1
.
Compound 13: 1H NMR (500 MHz, CDCl3)
d
7.25 (m, 2H), 7.19 (m,
HRMS (CI) m/z 262.1755 [(M)þ; calcd for C16H26OSi, 262.1753].
3H), 6.11 (dd, J¼10.0, 18.5 Hz, 1H), 5.25 (dd, J¼0.5, 18.0 Hz, 1H), 5.03
(t, J¼3.0 Hz, 1H), 1.93 (dd, J¼2.5, 9.0 Hz, 1H), 1.70 (d, J¼3.5 Hz, 1H),
4.3.7. Wittig rearrangements of compound 23. Applying the general
procedure B to compound 23 (anti/syn¼1:1) (66 mg, 0.282 mmol,
1 equiv) and n-BuLi (1.6 M in cyclohexane, 0.53 mL, 3 equiv) at
ꢀ78 ꢁC and then at ꢀ30 ꢁC for 3 h, after purification by silica gel
column chromatography (3% EtOAc in hexanes), afforded 16.3 mg
(26%) of 24, 10.2 mg (14%) of 25 as colorless oils, and 7.5 mg of
a mixture of anti-23 and 26 (1:9 ratio). An analytical sample of 26
was obtained by column chromatography eluting with hexanes.
0.97 (s, 9H), 0.00 (s, 9H). 13C NMR (125 MHz, CDCl3)
d 145.3, 142.1,
136.3, 127.8 (2C), 126.9 (2C), 126.2, 73.6, 65.0, 33.0, 28.9, ꢀ1.2. IR
(film) 3422, 2955, 1246, 837 cmꢀ1. HRMS (EI) m/z 258.1791
[(MꢀH2O)þ; calcd for C17H26Si, 258.1804].
4.3.4. Wittig rearrangements of compound 14. Applying general
procedure B to 360 mg (1.53 mmol) of 14 and 1.8 mL (2.30 mmol) of
s-BuLi (1.3 M in cyclohexane) at ꢀ78 ꢁC overnight, afforded 162 mg
(46%) of a 1.68:1 mixture of 15 and 16 as a colorless oil.
Compound 24: 1H NMR (600 MHz, CDCl3)
d
7.08 (d, J¼7.8 Hz,
2H), 7.02 (d, J¼8.4 Hz, 2H), 2.59 (m, 1H), 2.51 (ddd, A of ABX system,
J¼6.0, 9.0, 16.8 Hz, 1H), 2.41 (ddd, B of ABX system, J¼6.0, 9.0,
17.4 Hz, 1H), 2.30 (s, 3H), 1.80 (m, 1H), 1.72 (m, 1H), 1.20 (d, J¼6.6 Hz,
Compound 15: 1H NMR (300 MHz, CDCl3)
d 7.33e7.12 (m, 5H),
2.67e2.57 (m, 1H), 2.54e2.41 (m, 1H), 1.89e1.67 (m, 2H), 1.24e1.21
(d, J¼7.1 Hz, 3H), 0.11 (s, 9H). 13C NMR (125 MHz, CDCl3)
d
248.2,
3H), 0.12 (s, 9H). 13C NMR (151 MHz, CDCl3)
d 248.2, 143.6, 135.5,
146.6, 128.4, 127.0, 126.0, 46.4, 39.3, 30.2, 22.4, ꢀ3.2. IR (neat)
1643 cmꢀ1. HRMS (EI) m/z 233.1358 [(MꢀH)þ; calcd for C14H21OSi,
233.1362].
129.1 (2C), 126.9 (2C), 46.5, 38.9, 30.3, 22.5, 21.0, ꢀ3.2. IR (film)
2959, 1643, 1250, 844 cmꢀ1. HRMS (EI) m/z 248.1595 [(M)þ; calcd
for C15H24OSi, 248.1596].
Compound 16: 1H NMR (300 MHz, CDCl3)
d
7.33e7.19 (m, 5H),
Compound 25: 1H NMR (500 MHz, CDCl3)
d
7.11 (d, J¼8.0 Hz,
3.82e3.75 (q, J¼6.9 Hz, 1H), 2.34e2.28 (m, 2H), 1.38 (d, J¼6.9 Hz,
2H), 7.08 (d, J¼8.5 Hz, 2H), 3.74 (q, J¼7.0 Hz, 1H), 2.30 (m, 6H), 1.35
(d, J¼7.0 Hz, 3H), 0.71 (ddd, A of ABX system, J¼6.5, 10.0, 15.0 Hz,
1H), 0.60 (ddd, B of ABX system, J¼6.5, 9.0, 14.0 Hz, 1H), 0.11 (s, 9H).
3H), 0.77e0.55 (m, 2H), ꢀ0.11 (s, 9H). 13C NMR (126 MHz, CDCl3)
d
211.8, 140.8, 128.8 (2C), 127.8 (2C), 127.0, 52.3, 35.6, 17.7, 10.3, ꢀ1.9.
IR (neat) 1717, 1601 cmꢀ1. HRMS (CI) m/z 234.1466 [(M)þ; calcd for
14H22OSi, 234.1440].
13C NMR (126 MHz, CDCl3)
d 212.0, 137.9, 136.7, 129.5 (2C), 127.7
C
(2C), 51.9, 35.5, 21.0, 17.7, 10.4, ꢀ1.9. IR (film) 2955, 1716, 1456, 1250,
837 cmꢀ1. HRMS (EI) m/z 233.1363 [(MꢀCH3)þ; calcd for C14H21OSi,
233.1362].
4.3.5. Wittig rearrangements of compound 17. Applying general
procedure B to 165 mg (0.638 mmol) of 17 and 1.6 mL of n-BuLi
(2.55 mmol, 4 equiv, 1.6 M in hexanes) at ꢀ78 ꢁC, allowing the re-
action to warm to ꢀ30 ꢁC and stirring at this temperature for about
48 h, after purification by column chromatography on silica gel
afforded 45 mg (32%) of a 4.53:1 mixture of 18 and 19 as light
yellow oils. Note: the reported yield is based on 2.64:1 di-
astereomeric ratio of anti/syn 17.
Compound 26: (1:0.7 mixture of diastereomers) 1H NMR
(500 MHz, CDCl3)
d
7.09 (m, 8H), 6.97 (d, J¼8.0 Hz, 2.8H), 6.91 (d,
J¼8.5 Hz, 2.8H), 2.90 (m, 1.4H), 2.72 (m, 2H), 2.32 (s, 6H), 2.25 (s,
4.2H), 1.20 (m, 4.2H), 0.98 (m, 6H). 13C NMR (126 MHz, CDCl3)
d
143.6, 142.8, 135.4, 135.0, 128.9, 128.5, 127.7, 127.5, 46.8, 45.8, 21.2,
21.0, 20.9, 17.8. IR (film) 3021, 2961, 1514, 1452, 817 cmꢀ1. HRMS (EI)
m/z 238.1724 [(M)þ; calcd for C18H22, 238.1722].
Compound 18: 1H NMR (500 MHz, CDCl3)
d 7.34e7.16 (m, 5H),
5.78e5.60 (m, 1H), 5.00e4.89 (m, 2H), 2.58e2.52 (m, 1H),
2.50e2.45 (m, 1H), 2.39e2.31 (m, 3H), 2.00e1.93 (m, 1H), 1.72e1.64
4.3.8. Wittig rearrangements of anti/syn E-30. Applying represen-
tative procedure B to 235 mg (0.946 mmol) of E-30 (anti/syn¼1.5:1)
and 2.36 mL of n-BuLi (3.78 mmol, 4 equiv, 1.6 M in hexanes) in THF
(12 mL) at ꢀ30 ꢁC for 44 h. After purification by column chroma-
tography on silica gel (30% CH2Cl2 in hexanes) 101 mg of anti E-30
(43%), 10.1 mg of 32 (16%), and 72 mg of a mixture of 31 (23%, anti/
syn¼1.9:1) and 33 (6%, anti/syn¼1.44:1) were obtained. Analytical
samples of 31 and 33 were obtained by subsequent column chro-
matography of the mixture (30% CH2Cl2 in hexanes).
(m, 1H), 0.09 (s, 9H). 13C NMR (126 MHz, CDCl3)
d 248.1,144.4,136.8,
128.4 (2C), 127.7 (2C), 126.2, 116.0, 46.1, 45.1, 41.4, 27.9, ꢀ3.2. IR
(neat) 1717, 1643 cmꢀ1. HRMS (EI) m/z 260.1595 [(M)þ; calcd for
C16H24OSi, 260.1596].
Compound 19: 1H NMR (500 MHz, CDCl3)
d 7.31e7.08 (m, 5H),
5.68e5.60 (m, 1H), 5.00e4.91 (m, 2H), 3.72 (t, J¼7.4 Hz, 1H),
2.81e2.75 (m, 1H), 2.45e2.39 (m, 1H), 2.31 (m, 2H), 0.74e0.68 (m,
1H), 0.62e0.56 (m, 1H), ꢀ0.11 (s, 9H). 13C NMR (126 MHz, CDCl3)
Compound 31 (mixture of diastereomers anti-31/syn-31,
d
210.6, 138.6, 135.9, 128.8 (2C), 128.2 (2C), 127.2, 116.6, 58.1, 36.7,
0.65:0.35 ratio): 1H NMR (600 MHz, CDCl3)
d 7.28e7.24 (m, 2H),
36.5, 10.1, ꢀ1.9. IR (neat) 1716, 1643 cmꢀ1. HRMS (EI) m/z 260.1593
7.18e7.12 (m, 3H), 2.64 (m, 0.65H), 2.61 (m, 0.65H), 2.52 (m, 0.35H),
2.46 (m, 0.35H), 2.38e2.26 (m, 2H), 1.21 (d, J¼6.6 Hz, 1.05H), 1.20 (d,
J¼7.2 Hz, 1.95H), 0.84 (d, J¼6.6 Hz, 1.05H), 0.70 (d, J¼6.6 Hz, 1.95H),
0.14 (s, 5.85H), 0.08 (s, 3.15H). 13C NMR (151 MHz, CDCl3) major
[(M)þ; calcd for C16H24OSi, 260.1596].
4.3.6. Wittig rearrangements of compound 20. Applying general
procedure B to 69.5 mg of syn-20 (0.265 mmol) and 0.33 mL of n-
BuLi (0.5296 mmol, 2 equiv) in THF (3.3 mL) at ꢀ78 ꢁC and then at
0 ꢁC for 17 h afforded a mixture (15.8 mg) of 21 and 22 in a combined
23% yield as colorless oil along with 18.6 mg of unreacted syn-20.
Column chromatography was performed with 3% EtOAc in hexanes.
diastereomer (anti-31):
d 248.6, 145.4, 128.1 (2C), 127.9 (2C), 126.0,
53.0, 44.6, 33.5, 18.2, 18.04, ꢀ3.16. Minor diastereomer (syn-31):
d
248.7, 146.3, 128.2 (2C), 127.6 (2C), 126.0, 54.0, 45.0, 33.8, 18.05,
17.4, ꢀ3.25. IR (neat) 1643 cmꢀ1. HRMS (ESI) m/z 249.1665
[(MþHþ); calcd for C15H25OSi, 249.1675].
Compound 21: 1H NMR (500 MHz, CDCl3)
d
7.26e7.03 (m, 5H),
Compound 32 (mixture of diastereomers, 0.88:0.12 ratio, rela-
tive stereochemistry not assigned): 1H NMR (600 MHz, CDCl3)
2.39e2.35 (m,1H), 2.30e2.24 (m, 1H), 2.20e2.15 (m,1H), 2.08e2.02
(m, 1H), 1.80e1.73 (m, 1H), 1.71e1.63 (m, 1H), 0.94 (d, J¼6.8 Hz, 3H),
0.68 (d, J¼6.8 Hz, 3H), 0.06 (s, 9H). 13C NMR (126 MHz, CDCl3)
d
7.26e7.14 (m, 5H), 5.72 (dd, J¼1.2, 15.6 Hz, 0.12H), 5.59 (dd, J¼1.2,
15.6 Hz, 0.88H), 5.28 (dq, J¼6.6, 15.6 Hz, 0.12H), 5.12 (dq, J¼6.6,
15.6 Hz, 0.88H), 3.04 (q, J¼7.2 Hz, 0.88H), 3.00 (q, J¼7.2 Hz, 0.12H),
1.71 (dd, J¼1.8, 6.6 Hz, 0.36H), 1.61 (dd, J¼1.2, 6.6 Hz, 2.64H), 1.32 (d,
J¼7.2 Hz, 2.64H), 1.27 (d, J¼7.2 Hz, 0.36H), 1.03 (s, 0.12H), 1.02 (s,
d
248.6, 143.8, 128.4 (2C), 128.1 (2C), 126.0, 52.4, 33.7, 25.2, 20.9,
15.3, ꢀ3.3. IR (neat) 1719, 1643 cmꢀ1. HRMS (APCI) m/z 263.1840
[(MþH)þ; calcd for C16H27OSi, 263.1831].

858
E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
0.88H), ꢀ0.03 (s, 7.92H), ꢀ0.09 (s, 1.08H). 13C NMR (151 MHz, CDCl3)
product. Purification by silica gel (EtOAc 0e10% in hexanes) gave
702 mg of pure syn-27/anti-27 in 97% yield. IR (neat) 3370 cmꢀ1
anti-27: 1H NMR (500 MHz, CDCl3)
7.40e7.23 (m, 5H), 4.56 (q,
major diastereomer:
d
142.8, 135.1, 128.9 (2C), 127.8 (2C), 126.3,
.
120.8, 73.6, 46.8,17.8,16.4, ꢀ2.5. Minor diastereomer:
d
143.0,133.5,
d
129.2 (2C), 127.9 (2C), 126.6, 122.0, 73.4, 46.9, 18.0, 16.5, ꢀ3.0. HRMS
(CI) m/z 249.1666 [(MþH)þ; calcd for C15H24OSi, 249.1675].
Compound 33 (mixture of diastereomers, anti-33/syn-33,
J¼6.5 Hz, 1H), 3.86 (m, 1H), 3.78 (m, 1H), 3.23 (t, J¼5.0 Hz, 1H), 2.75
(m, 1H), 2.20e2.13 (m, 1H), 1.63 (m, 1H), 1.42 (d, J¼6.5 Hz, 3H),
ꢀ0.06 (s, 9H). 13C NMR (126 MHz, CDCl3)
d 143.5, 128.2 (2C), 127.5,
126.8 (2C), 76.4, 70.1, 62.4, 31.7, 23.7, ꢀ2.8. HRMS (EI) m/z 253.1618
0.55:0.45) 1H NMR (600 MHz, CDCl3)
d
7.30 (m, 2H), 7.24e7.20 (m,
3H), 3.78 (q, J¼7.2 Hz, 0.55H), 3.71 (q, J¼7.2 Hz, 0.45H), 2.36 (m,
0.45H), 2.33 (m, 0.55H), 2.14 (dd, J¼10.2, 16.8 Hz, 0.45H), 2.08 (dd,
J¼10.8, 16.2 Hz, 0.55H), 1.38 (d, J¼6.6 Hz, 1.35H), 1.37 (d, J¼7.2 Hz,
1.65H), 1.18 (m, 0.55H), 1.13 (m, 0.45H), 0.82 (d, J¼7.8 Hz, 1.35H),
0.69 (d, J¼7.2 Hz, 1.65H), ꢀ0.118 (s, 4.95H), ꢀ0.160 (s, 4.05H). 13C
[(MþH)þ; calcd for C14H25O2Si, 253.1624].
syn-27: 1H NMR (500 MHz, CDCl3)
d 7.34 (m, 4H), 7.29 (m, 1H),
4.36 (q, J¼6.5 Hz, 1H), 3.54e3.45 (m, 2H), 3.26 (dd, J¼4.5, 9.5 Hz,
1H), 1.81 (m, 1H), 1.67e1.60 (m, 2H), 1.42 (d, J¼6.5 Hz, 3H), 0.09 (s,
9H). 13C NMR (126 MHz, CDCl3)
d 143.6, 128.5 (2C), 127.8, 126.8 (2C),
NMR (151 MHz, CDCl3) major diastereomer (anti-33):
d
210.8, 140.6,
77.9, 69.1, 61.3, 33.8, 23.6, ꢀ2.5. HRMS (EI) m/z 253.1627 [(MþH)þ;
128.8 (2C), 127.91 (2C), 127.05, 52.2, 43.3, 17.6, 15.3, 14.1, ꢀ3.55.
calcd for C14H25O2Si, 253.1624].
Minor diastereomer (syn-33):
d 211.4, 128.7 (2C), 127.89 (2C),
127.03, 53.6, 43.5, 17.4, 15.5, 14.7, ꢀ3.54. IR (neat) 1718 cmꢀ1. HRMS
4.5. Preparation of ester syn-28
(ESI) m/z 249.1667 [(MþHþ); calcd for C15H25OSi, 249.1675].
A mixture of the substrate alcohol obtained by 9-BBN oxidation
of reactive syn-27 (201 mg, 0.80 mmol) and 3,5-dinitrobenzoyl
chloride (366 mg, 1.59 mmol) in pyridine as solvent, was heated
to reflux for 52e55 h. Then the solvent was removed under reduced
pressure and the crude product purified by chromatography on
silica gel (hexanes/EtOAc 0e10%) to afford 194 mg, 55% of the ex-
pected ester syn-28 as a solid. Recrystallization from a 1:1 EtOH/
hexane mixed solvent afforded product as colorless crystals mp
74.5e75.5 ꢁC. IR (neat) 1728, 1630 cmꢀ1. 1H NMR (300 MHz, CDCl3)
4.3.9. Wittig rearrangement of compound syn Z-30. Following the
general procedure B to 253.8 mg of syn Z-30 (1.02 mmol) in 10.5 mL
of THF at ꢀ78 ꢁC was added 2.56 mL of n-BuLi (4.086 mmol, 4 equiv,
1.6 M in hexanes), the cold bath was removed and the reaction
stirred at room temperature for 48 h. After work up and column
chromatography (gradient of 2e10% EtOAc in hexanes, then 50%
EtOAc in hexanes) afforded 142.1 mg of syn Z-30 (56%, dr¼18:1),
11.1 mg of a 1:1 mixture of 31 (syn/anti¼1.1:1) and 33 (syn/
anti¼1:1.6), 15.6 mg of 34 (6%, single diastereomer), 13 mg of 35
(7%, dr¼3:1), and 5.4 mg of 36 (3%, syn/anti¼1.3:1).
d
9.17 (t, J¼2.2 Hz, 1H), 8.88 (d, J¼2.2 Hz, 2H), 7.29e6.99 (m, 5H),
4.36e4.29 (m, 2H), 4.18e4.10 (m, 1H), 3.25e3.20 (dd, J¼8.0, 6.0 Hz,
Compound 34 (tentatively assigned as syn-34):17 1H NMR
1H), 1.90e1.83 (m, 2H), 1.41 (d, J¼6.3 Hz, 3H), 0.15 (s, 9H). 13C NMR
(500 MHz, CDCl3)
d
7.36 (m, 2H), 7.31 (m, 2H), 7.21 (tt, J¼1.5, 7.5 Hz,
(500 MHz, CDCl3) d 162.2, 148.4, 143.9, 134.0, 129.2, 128.2, 127.4,
1H), 5.97 (dd, J¼8.0, 19.0 Hz, 1H), 5.70 (dd, J¼1.0, 19.0 Hz, 1H), 2.52
126.7, 122.1, 78.1, 66.7, 64.4, 30.6, 23.6, ꢀ2.7. HRMS (ESI) m/z
(m, 1H), 1.85 (s, 1H), 1.50 (s, 3H), 0.84 (d, J¼6.5 Hz, 1H), 0.04 (s, 9H).
447.1599 [(MþH)þ; calcd for C21H27N2O7Si, 447.1587].
13C NMR (151 MHz, CDCl3)
d 147.8, 147.0, 132.4, 127.8 (2C), 126.4,
125.2 (2C), 75.9, 51.4, 28.3, 14.5, ꢀ1.2. IR (neat) 3474 cmꢀ1. HRMS
(ESI) m/z 249.1680 [(MþH)þ; calcd for C15H25OSi, 249.1675].
Compound 35 (mixture of diastereomers, 0.63:0.37 ratio): 1H
4.6. Preparation of cis-29 and trans-29
To a solution of unreactive (anti) 17 (167 mg, 0.641 mmol) in
CH2Cl2 (10 mL, w0.7 M) was added Grubbs second-generation
catalyst (4 mol %, 21.4 mg, 0.025 mmol) and the solution was stir-
red under nitrogen at room temperature for 3 h. The reaction
mixture was concentrated and purified by column chromatography
(10% CH2Cl2 in hexanes) to afford 144 mg of cis-29 (97%).
NMR (500 MHz, CDCl3)
d 7.34e7.26 (m, 3H), 7.19 (m, 2H), 5.68 (m,
0.37H), 5.49 (m, 0.63H), 5.40 (m, 0.37H), 5.31 (m, 0.63H), 4.51 (m,
1H), 1.66 (ddd, J¼0.5, 2.0, 7.0 Hz, 1.11H), 1.53 (ddd, J¼0.5, 1.5, 6.5 Hz,
1.89H), 1.43 (s, 1H), 1.33 (dd, J¼0.5, 7.0 Hz, 1.89H), 1.21 (dd, J¼0.5,
7.5 Hz, 1.11H). 13C NMR (151 MHz, CDCl3)
d 143.28, 143.26, 131.33,
131.30, 128.6, 128.2, 128.1, 128.1, 127.7, 126.9, 126.7, 126.4, 71.7, 71.5,
46.6, 45.9, 17.5, 16.0, 13.5, 13.2. IR (neat) 3397 cmꢀ1
Compound 36 (mixture of diastereomers 1:1 ratio): 1H NMR
(500 MHz, CDCl3) 9.70 (m, 1H) 9.57 (m, 1H), 7.28 (m, 4H), 7.18 (m,
cis-29: 1H NMR (500 MHz, CDCl3)
5.82e5.78 (m, 2H), 4.38 (dd, J¼3.5, 10 Hz, 1H), 4.17e4.15 (m, 1H),
2.26e2.12 (m, 2H), 0.08 (s, 9H); 13C NMR (126 MHz, CDCl3)
144.0,
d 7.34e7.22 (m, 5H),
.
d
d
128.10 (2C), 128.06, 126.9, 125.6 (2C), 121.1, 75.3, 71.6, 34.2, ꢀ4.0.
HRMS (CI) m/z 261.1681 [(MþHþ) calcd for C16H24OSi, 261.1675].
The relative stereochemistry of cis-29 was assigned based on pos-
itive NOESY signals between protons at 4.15 ppm and
2.26e2.12 ppm.
2H), 7.14 (m, 4H), 2.67 (m, 1H), 2.56 (m, 1H), 2.49 (ddd, J¼1.0, 4.5,
16.0 Hz, 1H), 2.33e2.26 (m, 3H), 2.17 (ddd, J¼3.0, 9.0, 16.0 Hz, 1H),
2.07 (ddd, J¼2.5, 8.5, 16.0 Hz, 1H), 1.26 (d, J¼2.5 Hz, 3H), 1.25 (d,
J¼2.5 Hz, 3H), 0.99 (d, J¼6.5 Hz, 3H), 0.85 (d, J¼6.5 Hz, 1H). 13C NMR
(151 MHz, CDCl3)
d
202.8, 202.5, 145.7, 144.8, 128.4, 128.2, 127.8,
Following the same procedure for the reactive (syn) 17 (184 mg,
0.707 mmol) and Grubbs second-generation catalyst (4 mol %,
24 mg, 0.028 mmol) in CH2Cl2 for 3 h, followed by column chro-
matography (30% CH2Cl2 in hexanes) afforded 151 mg (92%) of
trans-29.
127.5, 126.3, 126.2, 49.5, 48.3, 45.1, 44.5, 34.6, 34.4, 18.4, 18.03, 17.98,
17.6. IR (neat) 1724 cmꢀ1. Diastereomers 36 are known compounds
and have spectral data in accord with those previously reported.20b
4.4. Preparation of diastereomeric 27
trans-29: 1H NMR (500 MHz, CDCl3)
d
7.38e7.24 (m, 5H),
5.83e5.76 (m, 2H), 4.72 (t, J¼5.5 Hz, 1H), 4.01 (m, 1H), 2.41e2.38
(m, 2H), 0.09 (s, 9H); 13C NMR (126 MHz, CDCl3)
142.3, 128.5 (2C),
A 100 mL round-bottomed flask equipped with a magnetic stir
bar and a N2 line was charged with 9-BBN (0.5 M solution in THF,
2.04 mL,1.02 mmol) and substrate 14 (671 mg, 2.85 mmol) was then
added as a THF solution (0.57 M). The reaction was refluxed at an oil
bath temperature of 90 ꢁC, for 10 h. The reaction mixture was cooled
to 55e65 ꢁC and ethanol (2.0mL), NaOH (6 M, 0.5 mL), and H2O2 (30%
w/w,1.0mL)wereadded. Thereactionwas stirred at 55e 65ꢁC for1 h
and cooled to room temperature. The aqueous phase was saturated
withK2CO3, phaseswereseparated, theorganic phasewas driedover
anhydrous magnesium sulfate, and concentrated to afford the crude
d
128.4, 127.5, 126.9 (2C), 120.3, 72.6, 70.4, 30.4, ꢀ2.7. HRMS (CI) m/z
261.1664 [(MþHþ) calcd for C16H24OSi, 261.1675]. The relative ste-
reochemistry of trans-29 was confirmed based on negative NOESY
signals between protons at 4.72 ppm and 4.01 ppm.
4.7. Preparation of compound 38
The [1,4]-Wittig product 31 from the Wittig rearrangement of
a-
alkoxysilane of E-30 (217 mg, 0.87 mmol) was dissolved in THF

E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
859
(0.24 M, 3.6 mL), and 3 N NaOH (0.83 mL/mmol starting material,
0.72 mL) added. The mixture was heated to 35e40 ꢁC, and then
oxidized by dropwise addition of 30% H2O2 (0.42 mL/mmol starting
material, 0.36 mL), while maintaining the reaction temperature
below 50 ꢁC for 2 h. The aqueous phase was cooled to 0 ꢁC, and
acidified to pH of 1e2 with 6 M HCl. The resulting aqueous material
was extracted with ether (5ꢂ20 mL), and the ether solution dried
with anhydrous MgSO4. Filtration and concentration afforded
158 mg (94% yield) of diastereomeric 38 as a thick colorless oil.
Purification by column chromatography on silica gel (hexane/EtOAc
0e10%) afforded 38 as a 2.8:1 mixture of diastereomers (ratio by 1H
NMR). IR (neat) 3100e2500 (br), 2967, 1707, 1495, 1452, 1412,
127.0, 122.3, 79.4, 44.5, 34.2,17.7, 15.4, 13.5, ꢀ3.7. Mp 139e140 ꢁC. IR
(neat) 3107, 2957, 1726, 1545, 1348, 1278, 1170 cmꢀ1
.
4.8.3. Preparation of anti-33 from recrystallized 40. To a solution of
40 (4.4 mg, 0.010 mmol, dr>95:5) in THF (1 mL) was added 3 M
NaOH (0.5 mL) and the mixture stirred for 2 h in an oil bath at 45 ꢁC.
Then, the reaction mixture was diluted with diethyl ether (10 mL).
The aqueous phase was washed with diethyl ether (2 mLꢂ2).
Combined organic extracts were washed with H2O, brine, dried
over MgSO4, and concentrated. Pasteur pipette chromatography
(5% EtOAc in hexanes) gave 1.5 mg (61%) of 39 as a single di-
astereomer. This alcohol (1.5 mg) was dissolved in dry CH2Cl2
(0.5 mL) and DMP (0.3 M in CH2Cl2, 0.25 mL, excess) was added at
room temperature. After 1 h the reaction mixture was concen-
trated, suspended in 5% EtOAc in hexanes, and filtered through
a plug of silica to give w1.5 mg (ca. 100%) of anti-33.
1290 cmꢀ1
Major, anti-38: 1H NMR (500 MHz, CDCl3)
.
d
11.49 (br s, 1H),
7.31e7.18 (m, 5H), 2.72e2.65 (quint, J¼7.1 Hz, 1H), 2.53e2.48 (dd,
J¼14.8, 4.4 Hz, 1H), 2.28e2.18 (m, 1H), 2.14e2.09 (dd, J¼15.1, 9.1 Hz,
1H), 1.28e1.26 (d, J¼7.1 Hz, 3H), 0.88 (d, J¼6.6 Hz, 3H). 13C NMR
(125 MHz, CDCl3)
18.3, 17.5.
d 179.8, 144.8, 128.2, 127.6, 126.2, 44.4, 38.9, 36.2,
Acknowledgements
Minor, syn-38: 1H NMR (500 MHz, CDCl3)
d 11.49 (br s, 1H),
We acknowledge Dr. Richard J. Staples and Dr. Rui Huang for X-
ray crystallographic analysis. We thank the National Institutes of
Health, Astellas, and the Office of the Provost, Michigan State Uni-
versity for financial support.
7.33e7.18 (m, 5H), 2.63e2.56 (quint, J¼7.1 Hz, 1H), 2.35e2.31 (ap-
parent dd, J¼15.4, 4.4 Hz, 1H), 2.28e2.18 (m, 1H), 2.04e1.99 (dd,
J¼14.8, 9.3 Hz, 1H), 1.27e1.24 (d, J¼7.1 Hz, 3H), 1.04 (d, J¼6.6 Hz,
3H). 13C NMR (125 MHz, CDCl3)
d 179.8, 145.7, 128.2, 127.5, 126.1,
44.7, 39.8, 36.4, 18.3, 17.2. anti-38 and syn-38 are known com-
pounds and have spectral data in accord with those previously
reported.19
Supplementary data
Supplementary data: Copies of 1H and 13C NMR for compounds
5e40 and X-ray structural data of compounds syn-28 and 40. The
crystal structures of syn-28 and 40 were deposited in the Cam-
bridge Crystallographic Data Centre and allocated deposition
numbers CCDC 886782 and 886781, respectively. Supplementary
data associated with this article can be found in the online version,
at http://dx.doi.org/10.1016/j.tet.2012.10.091.
4.8. Assignment of relative stereochemistry for compound 33
4.8.1. Preparation of 39. To a cold (ꢀ78 ꢁC) solution of 33 (50 mg,
0.20 mmol, dr¼1.4:1) in 1:1 CH2Cl2/EtOH (3 mL) was added a sus-
pension of NaBH4 (15.2 mg, 2 equiv) in EtOH (0.8 mL). After 1 h the
temperature was slowly raised to rt and the reaction stirred over-
night. The reaction mixture was then treated with H2O (2 mL) and
diluted with diethyl ether. The aqueous phase was washed with
diethyl ether (ꢂ2). Combined organic extracts were washed with
brine, dried over MgSO4, and concentrated. Column chromatogra-
phy (5% EtOAc in hexanes) gave 28.5 mg (57%) of 39 in two fractions
of different diastereomeric ratio along with 5.2 mg (11%) of
unreacted 33.
References
1. Tomooka, K.; Yamamoto, H.; Nakai, T. Liebigs Ann. 1997, 1275e1281 and refer-
ences therein.
2. (a) Marshall, J. A. In Comprehensive Organic Synthesis; Pattenden, G., Ed.; Pergamon:
London, 1991; Vol. 3, pp 975e1014; (b) Nakai, T.; Mikami, K. Org. React. 1994, 46,
105e209.
3. Felkin, H.; Tambute, A. Tetrahedron Lett. 1969, 10, 821e822.
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4500e4502; (b) Rautenstrauch, V. Helv. Chim. Acta 1972, 55, 594e609.
5. Both concerted and a stepwise mechanisms might be operative. (a) Schollkopf,
U. Angew. Chem., Int. Ed. Engl. 1970, 9, 763e773; (b) Felkin, H.; Frajerman, C.
Tetrahedron Lett. 1977, 18, 3485e3488.
6. (a) Onyeozili, E. N.; Maleczka, R. E., Jr. Chem. Commun. 2006, 2466e2468; (b)
Onyeozili, E. N.; Maleczka, R. E., Jr. Tetrahedron Lett. 2006, 47, 6565e6568.
7. Maleczka, R. E., Jr.; Geng, F. Org. Lett. 1999, 1, 1115e1118.
8. (a) Hayakawa, K.; Hayashida, A.; Kanematsu, K. J. Chem. Soc., Chem. Commun.
1988, 1108e1110; (b) Schlosser, M.; Strunk, S. Tetrahedron 1989, 45, 2649e2664.
9. A report on the effect of electronic factors in the Wittig rearrangements of
Compounds 39 (major diastereomer): 1H NMR (600 MHz,
CDCl3)
d 7.29 (m, 2H), 7.20 (m, 3H), 3.80 (m, 1H), 2.72 (quint,
€
J¼6.6 Hz, 1H), 1.42 (m, 1H), 1.31 (d, J¼7.2 Hz, 3H), 1.29 (d, J¼4.8 Hz,
1H), 1.07 (m, 1H), 0.84 (s, 3H), 0.82 (m, 1H), ꢀ0.10 (m, 9H). 13C NMR
(151 MHz, CDCl3)
d 144.8, 128.4 (2C), 127.7 (2C), 126.3, 73.0, 46.4,
36.3, 15.9, 15.0, 13.1, ꢀ3.6. IR (neat) 3423, 2955, 1456, 1248,
839 cmꢀ1. HRMS (ESI) m/z 232.1651 [(MꢀOH)þ; calcd for C15H24Si,
232.1647].
a
-alkoxysilanes will be disclosed in due course.
a
4.8.2. Preparation of 40. One fraction of 39 (15.6 mg, 0.063 mmol,
dr¼10:2:1) was dissolved in pyridine (1 mL) and 3,5-dinitrobenzoyl
chloride (flakes were crushed prior to addition) was added in one
portion. After 48 h the mixture was diluted with diethyl ether
(15 mL) and washed with 1 M HCl (2 mLꢂ3), H2O, brine, dried over
MgSO4, and concentrated. Partial separation of the diastereomers
(two fractions) by column chromatography (4% EtOAc in hexanes)
gave 24.4 mg (56%) of 40 as a solid. Recrystallization of one fraction
from CH2Cl2/hexanes gave a single diastereomer of 40 whose rel-
ative stereochemistry was determined by X-ray crystallography.
Compound 40 (major diastereomer): 1H NMR (500 MHz, CDCl3)
10. All -alkoxysilanes involved in this study were prepared according to the
method described Maleczka, R. E., Jr.; Geng, F. Org. Lett. 1999, 1, 1111e1113.
11. For examples of the latter process see:: (a) Nakazaki, A.; Nakai, T.; Tomooka, K.
Angew. Chem., Int. Ed. 2006, 45, 2235e2238; (b) Still, W. C. J. Org. Chem. 1976, 41,
3063e3064; (c) Kuwajima, I. J. Organomet. Chem. 1985, 285, 137e148; (d)
Danheiser, R. L.; Fink, D. M.; Okano, K.; Tsai, Y.-M.; Szczepanski, S. W. J. Org.
Chem. 1985, 50, 5393e5396; (e) Oppolzer, W.; Snowden, R. L.; Simmons, D. P.
Helv. Chim. Acta 1981, 64, 2002e2021.
12. Attemptstotraptheinitiallyformedallylicanionfromsyn-14/anti-14 withD2Owere
unsuccessful suggesting it quickly rearranges (<5% D incorporation by 1H NMR).
13. Braden, D. A.; Parrack, E. E.; Tyler, D. R. Coord. Chem. Rev. 2001, 211, 279e294.
14. The stereochemistry of other diastereomeric substrates was then assigned by
comparison of their 1H NMR spectra with that of 14 or 17.
15. Notice that although crystalline syn-28 was obtained from a mixture of di-
astereomers syn-28/anti-28, independent derivatization of the ‘less reactive’
anti-14 following the sequence in Scheme 6 led to a clear oil spectroscopically
identical to the non-crystalline ester anti-28 obtained from the mixture of di-
astereomers syn-28/anti-28 depicted in Scheme 6.
d
9.22 (t, J¼2.0 Hz, 1H), 9.13 (d, J¼2.0 Hz, 2H), 7.30 (t, J¼7.5 Hz, 2H),
7.22 (m, 3H), 5.86 (m,1H), 3.09 (m,1H),1.75 (ddd, J¼2.5,10.0,13.0 Hz,
1H),1.32 (d, J¼7.0 Hz, 3H),1.26 (ddd, J¼2.5,12.0,14.5 Hz,1H), 0.87 (d,
J¼7.5 Hz, 3H), 0.47 (m, 1H), ꢀ0.14 (s, 9H). 13C NMR (126 MHz, CDCl3)
16. syn Z-30 and anti Z-30 were prepared by semihydrogenation of the corre-
sponding alkynes syn/anti-37. See Experimental section
d
162.4, 148.8 (2C), 142.7, 134.3, 129.4 (2C), 128.7 (2C), 127.7 (2C),

860
E.N. Onyeozili et al. / Tetrahedron 69 (2013) 849e860
17. sec-BuLi led to lower conversion. No improvement was observed with n-BuLi/
TMEDA. The ‘super’ basic mixture of n-BuLi/potassium tert-butoxide led to
complete desilylation of Z-30 followed by rearrangement in low yields, sig-
nificant amounts of alkylated products were also observed.
18. The relative stereochemistry of this diastereomer was assigned tentatively as syn-
34 by comparison with the 1H NMR of the syn and anti desilylated analogs Wada,
R.; Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2004, 126, 8910e8911 At-
tempts to protodesilylate the [2,3]-Wittig product syn-34 with TBAF or TFA failed.
19. Approximated diastereomeric ratios from the crude reaction mixture were
obtained by 1H NMR (by integration of the TMS groups or vinylic protons) and
were in accord with the isolated diastereomeric ratios.
20. We thank a reviewer for suggesting A(1,3) strain in syn/anti Z-30 as a possible
explanation for the sluggishness with which these compounds undergo allylic
deprotonation.
21. The relative stereochemistry was tentatively assigned as anti-34 by comparison
with the 1H NMR of syn and anti desilylated analogues. See Ref. 18.
22. Relative stereochemistry was assigned by oxidizing diastereomeric 31 (1.9:1) to
the corresponding carboxylic acid 38: (a) Darcel, C.; Flachsmann, F.; Knochel, P.
Chem. Commun. 1998, 205e206; (b) Boudier, A.; Darcel, C.; Flachsmann, f;
Micouin, L.; Oestreich, M.; Knochel, P. Chem.dEur. J. 2000, 6, 2748e2760.
23. See Experimental section.
24. Cossrow, J.; Rychnovsky, S. D. Org. Lett. 2002, 4, 147e150.