Highly (≥98%) stereo- and regioselective trisubstituted alkene synthesis of wide applicability via 1-Halo-1-alkyne hydro- boration-tandem Negishi-Suzuki coupling or organoborate migratory insertion

Article abstract of DOI:10.1002/adsc.201100420

(Z)-1-Halo-1-alkenylboranes (7), preparable in 80-90% yields as ≥98% isomerically pure compounds via hydroboration of 1-halo-1-alkynes, have been converted to a wide range of trisubstituted alkenes via three different routes in the tail-to-head (T-to-H) direction, i.e., (i) palladium-catalyzed Negishi-Suzuki tandem alkenylation, (ii) treatment with organolithium or Grignard reagents to generate α-bromo-1-alkenylboronate complexes that can undergo migratory insertion of a carbon group (R²) to form (E)-alkenylboranes with inversion of alkene configuration (≥98% inversion), followed by fluoride-promoted Suzuki alkenylation, and (iii) Negishi coupling to generate (Z)-alkenylboranes in ≥98% retention of configuration, followed by treatment with organolithium or Grignard reagents to produce trisubstituted alkenes with reversed stereo configurations. The synthetic utility of the present methodology has been demonstrated in the highly selective synthesis of the side chain of scyphostatin in 28% yield over nine steps in the longest linear sequence from allyl alcohol. Thus, this new tandem protocol has been emerged as the most widely applicable and highly selective route to trisubstituted alkenes including those that are otherwise difficult to prepare. Copyright

Full text of DOI:10.1002/adsc.201100420

FULL PAPERS
DOI: 10.1002/adsc.201100420
Highly (ꢀ98%) Stereo- and Regioselective Trisubstituted Alkene
Synthesis of Wide Applicability via 1-Halo-1-alkyne Hydro-
boration–Tandem Negishi–Suzuki Coupling or Organoborate
Migratory Insertion
Shiqing Xu,a Ching-Tien Lee,a Honghua Rao,a and Ei-ichi Negishia,*
a
Herbert C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Dr., West Lafayette, IN 47907-2084, USA
Fax : (+1)-765-494-0239; e-mail: negishi@purdue.edu or negishi@purdue.edu
Received: May 23, 2011; Published online: October 20, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100420.
Abstract: (Z)-1-Halo-1-alkenylboranes (7), prepara- with organolithium or Grignard reagents to produce
ble in 80–90% yields as ꢀ98% isomerically pure trisubstituted alkenes with reversed stereo configura-
compounds via hydroboration of 1-halo-1-alkynes, tions. The synthetic utility of the present methodolo-
have been converted to a wide range of trisubstituted gy has been demonstrated in the highly selective syn-
alkenes via three different routes in the tail-to-head thesis of the side chain of scyphostatin in 28% yield
(T-to-H) direction, i.e., (i) palladium-catalyzed Ne- over nine steps in the longest linear sequence from
gishi–Suzuki tandem alkenylation, (ii) treatment with allyl alcohol. Thus, this new tandem protocol has
organolithium or Grignard reagents to generate a- been emerged as the most widely applicable and
bromo-1-alkenylboronate complexes that can under- highly selective route to trisubstituted alkenes in-
go migratory insertion of a carbon group (R2) to cluding those that are otherwise difficult to prepare.
form (E)-alkenylboranes with inversion of alkene
configuration (ꢀ98% inversion), followed by fluo-
ride-promoted Suzuki alkenylation, and (iii) Negishi Keywords: alkene synthesis; alkenylation; (Z)-1-
coupling to generate (Z)-alkenylboranes in ꢀ98% halo-1-alkenylboranes; hydroboration; palladium-
retention of configuration, followed by treatment catalyzed cross-coupling
Introduction
tion of the single-most important case of propyne to
ꢀ98% syn-selectivity, (ii) minimization of undesirable
Sequential alkyne elementometalation[1], such as hy-
drometalation and carbometalation, and Pd-catalyzed
alkenylation constitute a powerful route that provides
various types of acyclic alkenes in a high level (ꢀ
98%) of stereoselectivity which is often difficult to
achieve with carbonyl olefination reactions [e.g., Wit-
tig,[2a] Horner–Wadsworth–Emmons (HWE),[2b,c] Still–
Gennari,[2d] Peterson,[2e] Julia[2f] olefination, etc.], be-
cause these conventional methods must involve car-
bonyl addition and b-elimination that often lack high
stereoselectivity (Scheme 1).
Recently, we reported highly selective and widely
applicable procedures for synthesizing trisubstituted
alkenes via alkyne haloboration–fluoride-promoted
Pd-catalyzed tandem alkenylation.[3] Crucial to the
development were the following three breakthroughs:
Scheme 1. Carbonyl olefination and alkyne elementometala-
(i) improvement of the stereoselectivity of halobora- tion–Pd-catalyzed alkenylation.
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debromoboration in the Pd-catalyzed Negishi cou- scyphostatin[6] may demonstrate the importance of the
pling of b-bromoalkenylboranes by using highly direction of building trisubstituted alkenes
active catalysts, such as Pd
[(t-Bu)3P]2 or PEPPSITM (Scheme 3). In the H-to-T construction,[7a] 1 (Z=
A
-
IPr, where PEPPSI stands for pyridine enhanced pre- TBDPS) was sequentially tosylated, ethynylated,
catalyst preparation stabilization and initiation,[4] and methylaluminated, and subjected to an “SN2” reaction
(iii) improvement of the yields in the generally slug- with (S)-EtO2CCH(Me)OTf to provide 3 in 34%
gish Suzuki alkenylation by using fluoride bases.
yield in 3 steps, which was then converted to 4 in 54%
Notably, the approach described in Scheme 2 repre- yield in three steps or in 18% yield in six linear steps
sents a head-to-tail (H-to-T) construction route to from 1. In the T-to-H construction,[7b,c] 1 (Z=TBS)
stereodefined trisubstituted alkenes. Additionally, a was iodinated and cross-coupled with 6a to give 4 just
complementary tail-to-head (T-to-H) route[5] is also in two steps in 82% yield after desilylation, while the
desirable. As an example, the following pair of syn- key intermediate 6a was prepared from allyl alcohol
theses of the C-7/C-16 fragment 4 of the side-chain of in 30% yield over 7 steps.
Scheme 2. H-to-T construction route to stereodefined trisubstituted alkenes.
Scheme 3. Syntheses of the C7/C16 fragment 4 of the side-chain of scyphostatin.
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Highly (ꢀ98%) Stereo- and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability
Table 1.
Herein, we report the development of a few addi-
tional T-to-H procedures, via (Z)-1-halo-1-alkenylbor-
anes 7 as key intermediates, prepared via hydrobora-
tion of 1-halo-1-alkynes, providing widely applicable
and highly selective routes to trisubstituted alkenes.
Results and Discussion
Whereas hydroboration of internal alkynes often suf-
fers from low regioselectivity levels, that of 1-halo-1-
alkynes is nearly 100% regioselective to give ꢀ98%
isomerically pure (Z)-1-halo-1-alkenylboranes (7).[9] If
both halogen (X) and boryl groups (BY2) can selec-
tively and sequentially be substituted with a wide
range of carbon groups by Pd-catalyzed alkenylation,
(Z)-1-halo-1-alkenylboranes (7) would serve as useful
intermediates for preparing various types of trisubsti-
tuted alkenes as shown in Scheme 4.[10]
1-Halo-1-alkynes, prepared by iodination of the cor-
responding lithium acetylides or by bromination of
the corresponding terminal alkynes catalyzed by
silver nitrate,[11] can be converted regioselectively and
stereoselectively (ꢀ98%) to (Z)-1-halo-1-alkenyl-
ACHTUNGTRENNUNG(pinacol)boranes (7) by hydroboration with HBBr2
followed by quenching with pinacol.[9] During the
course of this investigation, we also noticed that the
hydroboration of 1-iodo-1-alkynes with diisopinocam-
pheylborane,[12] followed by treatment with acetalde-
hyde and subsequent esterification with pinacol, pro-
vided the desired 1-iodo-1-alkenylboranes in similarly
high regioselectivity and stereoselectivity (ꢀ98%),
but in higher yields (83–90%).
For substitution of iodine or bromine with a carbon
group, Pd-catalyzed cross-coupling of 7 with organo-
zincs is by far the most satisfactory method that has
uniformly provided satisfactory results based on our
recent studies,[3,13] although organoindium and organo-
zirconium reagents were also satisfactory in some
cases, as reported in our brief survey.[13c] As shown in
[a]
(i) HBBr2 (1.1 equiv.), CH2Cl2; (ii) pinacol (1.1 equiv.).
(i) (Ipc)2BH (1.2 equiv.), THF; (ii) acetaldehyde
(10 equiv.); (iii) pinacol (1.1 equiv.).
(i) HBBr2 (1.1 equiv.), CH2Cl2; (ii) 1,3-propanediol
(1.1 equiv.).
5% PdACHTNUTGRNEUGN(PPh3)4 was used.
[b]
[c]
[d]
[e]
NMR yield. The product decomposed during chromatog-
raphy.
[f]
Isolated yields.
Yield in parentheses is overall yield from R C CX in
three steps.
[g]
1
ꢁ
Table 1, PdACHTUNGTRENNUNG(PPh3)4 is an effective catalyst in some
cases (entries 3, 4, and 12). However, when alkyl- or
alkenylzincs were used as coupling partners,
Pd
regenerated the original terminal alkynes as major
side products as a result of unwanted deiodoboration. and aryl groups, leading to the formation of (Z)-alke-
Pd[(t-Bu)3P]2 facilitated the cross-coupling reaction of nylboranes (8) in good yields and, most importantly,
ACHTUNGTRENNUNG(PPh3)4 led to the formation of 8 in low yields and
ACHTUNGTRENNUNG
(Z)-1-halo-1-alkenylboranes (7) with a variety of or- with full (ꢀ98%) retention of configuration. The sub-
ganozincs, including those with alkyl, benzyl, alkenyl, sequent Pd-catalyzed cross-coupling of a,b-disubsti-
Scheme 4. T-to-H construction route to stereodefined trisubstituted alkenes.
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tuted alkenylboranes 8 with aryl or alkenyl iodides, isomerically pure trisubstituted alkenes 12 in good
proceeded smoothly by using PdCl2A(DPEphos) as a yields.
CTHUNGTRENNUNG
catalyst and TBAF as a promoter.[3] Trisubstituted al-
Alternatively, treatment of 8 with an organometal
kenes 9 were thus obtained in high yields and high (R3M) containing Li or Mg to generate the corre-
isomeric purities. The geometrical configurations and sponding borate complex, followed by addition of I2
isomeric purities of all products, i.e., 7, 8, and 9, were to induce migratory insertion of R3, and then treat-
1
confirmed by H and 13C NMR spectroscopy including ment with aqueous NaOH to induce deiodoboration
NOE measurements. It should be clearly noted that, produces 14 of ꢀ98% isomeric purity in good yields
even in cases where R1 and R2 groups were similar (72–84%) as shown in Table 3.[15] It should be noted
(entries 1, 2, 5, 9, and 12 in Table 1), the desired tri- that the protocol in Table 3 offers some advantageous
substituted alkenes can be obtained in ꢀ98% stereo-
selectivity.
Table 3.
As previously reported,[14] treatment of (Z)-1-halo-
1-alkenylboranes (7) with organolithium or Grignard
reagents would form a-bromo-1-alkenylboronate
complexes (10) which would then undergo migratory
insertion of R2 to give (E)-alkenylboranes (11) via
ꢀ98% stereoinversion. As shown in Table 2, use of
the OACHTUNGTRENNUNG(CH2)3O group (entries 1–3) led to satisfactory
yields of substitution product 11 (72–87%), whereas
use of O[C(CH3)2]2O group (entries 4–6) led to disap-
ACHTUNGTRENNUNG
pointingly low yields (40–64%) due to a competitive
pathway for formation of a mixture of 11 and the dis-
sociation product 13. The subsequent fluoride-pro-
moted Suzuki alkenylation of 11 led to ꢀ98% stereo-
Table 2.
[a]
[b]
Isolated yields from ref.[8]
Yield in parentheses is overall yield from R C CX in
three steps.
1
ꢁ
features that are not readily available in those shown
in Table 1 and Table 2, involving Suzuki coupling of
alkenylboranes for introduction of the R3 group. In
these protocols, it would not be readily feasible to
prepare trisubstituted alkenes containing an alkyl
group as R3. As exemplified by entry 3 in Table 3, no
difficulty was encountered in the introduction of Me
as R3. To further demonstrate this potentially signifi-
cant advantage, an all-alkyl-substituted trisubstituted
alkene 4, used as the C-7/C-16 side chain fragment of
(+)-scyphostatin, was performed and achieved as
shown in Scheme 5. Although the overall yield of 4 in
28% over 9 steps in this longest linear sequence is
roughly comparable to that reported recently by us
(25% yield in 9 steps),[7c] the previous route involved
generation of a 85/15 regioisomeric mixtures of 6a
and 6b, which were purified by chromatographic sepa-
ration. Even though further comparisons are needed,
the highly (ꢀ98%) selective synthesis without the
need for isomeric separation (Scheme 5) promises to
[a]
NMR yield is 90% from 1-bromooct-1-yne.
NMR yield.
Isolated yields.
Yield in parentheses is overall yield from R C CX in
three steps.
[b]
[c]
[d]
1
ꢁ
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Highly (ꢀ98%) Stereo- and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability
Scheme 5. An enantioselective T-to-H route to the C7/C16 fragment 4 of the side-chain of (+)-scyphostatin.
distillation under argon from sodium/benzophenone. CH2Cl2
reveal advantages in cases where the formation of iso-
meric mixtures should prove to be more cumbersome.
was dried by distillation under argon from CaH2. Other
commercially available solvents and reagents were of re-
agent grade and used without further purification, unless
otherwise indicated.
Conclusions
Representative Procedure I for the Hydroboration of
1-Bromo-1-alkynes with HBBr2·SMe2: (Z)-2-(1-Bro-
mooct-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(7; entry 4 in Table 1)
A highly stereo- and regioselective and widely appli-
cable route to trisubstituted alkenes in the T-to-H di-
rection has been developed. Its synthetic utility has
been demonstrated in a highly selective synthesis of
scyphostatin side chain (4) by using one of these pro-
tocols shown in Scheme 5. In two other protocols, hy-
To a solution of 1-bromo-1-octyne (1.9 g, 10 mmol) in
CH2Cl2 (10 mL) was added HBBr2·SMe2 (1M in CH2Cl2,
droboration of 1-halo-1-alkynes followed by either 11 mL, 11 mmol) at 08C. The solution was allowed to stir at
238C for overnight and then quenched with ice/water. The
aqueous layer was extracted with ether (3ꢁ15 mL). The
combined organic layers were dried over anhydrous MgSO4
and concentrated to give the crude alkenylboronic acid. The
resulting boronic acid was dissolved in CH2Cl2 and pinacol
(1.3 g, 11 mmol) was added, the mixture was then stirred for
1 h, dried over MgSO4, filtered and concentrated. The crude
product was purified via flash chromatograghy (Rf =0.28;
20% ethyl acetate/hexane) to give a clear oil; yield: 2.76 g
Pd-catalyzed Negishi–Suzuki tandem alkenylation or
nucleophilic substitutions of alkenylboranes with or-
ganometallic reagents containing Li or Mg to induce
migratory induction of R2 with configurational inver-
sion. A wide range of trisubstituted alkenes was ob-
tained in ꢀ98% isomeric purity and in synthetically
useful yields (45–73%) in three steps starting from 1-
halo-1-alkynes. This practical and satisfactory ap-
proach also nicely complements their H-to-T con-
struction reported by us recently.[3]
1
(87%). H NMR (300 MHz, CDCl3): d=6.79 (t, J=6.9 Hz,
1H), 2.24 (m, 2H), 1.2–1.4 (m, 20H), 0.83 (t, J=6.9 Hz,
3H); 13C NMR (75 MHz, CDCl3): d=149.3, 84.4, 32.3, 31.5,
28.9, 27.6, 24.6, 22.4, 13.9.
Experimental Section
Representative Procedure II for the Hydroboration
of 1-Iodo-1-alkynes with (Ipc)2BH: (Z)-2-(5-Chloro-1-
iodopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (7; entry 5 in Table 1)
General Remarks
All reactions were run under a dry argon atmosphere. Reac-
tions were monitored by thin layer chromatography (TLC)
carried out on 0.25 mm Merck silica gel plates (60F-254) or
by GC analysis of reaction aliquots. GC analysis was per-
formed on an HP 6890 Gas Chromatograph using an HP-5
capillary column (30 mꢁ0.32 mm, 0.5 mm film) packed with
SE-30 on Chromosorb W. Column chromatography was car-
AHCTUNGRTEG(NNUN Ipc)2BH was prepared by treating borane-methyl sulfide
complex (0.8 mL, 8.4 mmol) in THF (5 mL) at 08C, and fol-
lowed by addition of a-pinene (3.0 mL, 18.6 mmol). The re-
action mixture was stirred at 08C for 1 h, and 238C for 2 h.
The reaction mixture was then cooled to À358C, 5-chloro-1-
iodopent-1-yne (1.8 g, 7.9 mmol) was added slowly. The re-
sulting solution was allowed to stir for 1.5 h at À358C and
5 h at 238C, and then cooled down to 08C before acetalde-
ried out on 230–400 mesh silica gel. H and 13C NMR spec-
tra were recorded on a Varian-Inova-300 spectrometer.
ZnBr2 was flame-dried under vacuum. THF was dried by
1
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hyde (6.4 mL) was added. The solution was refluxed for 12 h
and then concentrated under vacuum (10 mmHg for 1 h) to
remove excess acetaldehyde and volatiles. Then, a solution
of pinacol (1.0 g, 8.7 mmol) in THF (2 mL) was added.
After 3 h stirring at 238C, the pure 1-iodo-1-alkenylboronic
ester was obtained via flash chromatography (Rf =0.32; 20%
ethyl acetate/hexane) to give a clear oil; yield: 2.45 g (87%).
1H NMR (300 MHz, CDCl3): d=6.77 (t, J=6.6 Hz, 1H),
3.55 (t, J=6.3 Hz, 2H), 2.40 (dd, J=7.8, 6.6 Hz, 2H), 1.94
(dt, J=7.5, 6.9 Hz, 2H), 1.28 (s, 12H); 13C NMR (75 MHz,
CDCl3): d=153.14, 84.8, 44.3, 35.7, 30.5, 24.7; HR-MS:
m/z=356.0212, calcd. for C11H19O2BICl [M]+: 356.0211.
(m, 12H), 0.92 (t, J=7.2 Hz, 3H), 0.85 (t, J=6.9 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=143.5, 140.1, 129.1, 128.1,
126.3, 32.2, 31.7, 29.7, 29.3, 28.7, 28.3, 24.8, 22.7, 22.5, 14.1;
HR-MS: m/z=244.2190, calcd. for C18H28 [M]+: 244.2191.
Representative Procedure V for the Preparation of
(R,E)-2-(3-Methyl-1-phenylnon-1-enyl)-1,3,2-dioxa-
borinane (11; entry 1 in Table 2)
A flame-dried, 25-mL, round-bottomed flask, equipped a
magnetic stirring bar, a rubber septum, was charged with 7
(100 mg, 0.29 mmol), and ether (2 mL) in a dry ice-acetone
bath under an atmosphere of argon. Phenyllithium
(0.17 mL, 0.3 mmol) was added against the inside wall of the
flask. The solution was allowed to stir for 30 min at À788C,
another 30 min at 238C, and was then cooled down to
À788C before the addition of MeOH (0.6 mL) and KOH
(0.3 mL, 3M, 0.9 mmol). The reaction mixture was then
warmed up to 238C, stirred for overnight, and quenched
with aqueous NH4Cl. The aqueous layer was separated and
extracted with ether (3ꢁ10 mL). The combined organic
layers were washed with brine, dried over anhydrous magne-
sium sulfate, filtered, and concentrated by rotary evaporator
(308C, 20 mmHg) to give the boronic acid. The resulting
boronic acid was reesterified with 1,3-propanediol (23 mg,
0.3 mmol) in pentane (2 mL). The reaction mixture was then
stirred for 2 h at 238C, dried over anhydrous magnesium sul-
fate, filtered, and concentrated by rotary evaporator (408C,
20 mmHg) to give the crude product. The crude product
(NMR yield: 87%) was used without further purification for
the subsequent Suzuki coupling.
Representative Procedure III for the Negishi Cross-
Coupling: (Z)-2-(Dodec-5-en-6-yl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (8; entry 2 in Table 1)
A flame-dried, 25-mL, round-bottomed flask, equipped a
magnetic stirring bar, a rubber septum, and an argon inlet,
was charged with Pd
ACHTUGNRTEN[NUGN (t-Bu)3P]2 (15.6 mg, 0.03 mmol), 1-
bromo-1-hexenyl(pinacol)borane (864 mg, 3.0 mmol), and
ACHTUNGTRENNUNG
THF (6 mL). A solution of n-hexylzinc bromide (3.6 mmol),
[prepared by treating ZnBr2 (810 mg, 3.6 mmol) in THF
(6 mL) at À788C, followed by addition hexyllithium
(1.6 mL, 3.6 mmol) for 30 min at 08C] was added. The mix-
ture was allowed to stir at 238C and monitored by TLC.
The reaction mixture was then quenched with aqueous
NH4Cl. The aqueous layer was separated and extracted with
ether (3ꢁ10 mL). The combined organic layers were washed
with brine, dried over anhydrous magnesium sulfate, fil-
tered, and concentrated by rotary evaporator (308C,
20 mmHg). The crude product was purified via flash chro-
matography (Rf =0.35; 5% ethyl acetate/hexane) to give a
1
Representative Procedure VI for the Preparation of
(Z)-Dodec-5-en-6-ylbenzene (14; entry 2 in Table 3)
clear oil; yield: 776 mg (88%). H NMR (300 MHz, CDCl3):
d=6.27 (t, J=6.9 Hz, 1H), 2.15–2.08 (m, 4H), 1.25–1.38 (m,
24H), 0.85–0.91 (m, 6H); 13C NMR (75 MHz, CDCl3): d=
145.8, 132.1, 82.8, 31.8, 31.4, 30.1, 29.2, 28.4, 28.1, 24.6, 22.6,
22.5, 14.0, 13.9; HR-MS: m/z=294.2730, calcd. for
C18H35O2B [M]+: 294.2730.
A flame-dried, 25-mL, round-bottomed flask, equipped a
magnetic stirring bar, a rubber septum, and an argon inlet,
was charged with (Z)-2-(dodec-5-en-6-yl)-4,4,5,5-tetrameth-
yl-1,3,2-dioxaborolane (147 mg, 0.5 mmol), and ether (2 mL)
in a dry ice-acetone bath under an atmosphere of argon.
Phenyllithium (0.32 mL, 0.55 mmol) was added against the
inside wall of the flask. The solution was allowed to stir for
30 min at À788C, and 1 h at 08C. The solvents were pumped
off and MeOH (1.0 mL) was added at 08C. Then the solu-
tion was cooled down to À788C before the addition of I2
(127 mg, 0.5 mmol) in MeOH (1 mL). After 3 h stirring at
À788C, it was allowed to warm up to 238C and NaOH
(0.5 mL, 3M, 1.5 mmol) was added. Stirred for 15 min, the
reaction was diluted with water and extracted with n-
hexane. The aqueous layer was separated and extracted with
n-hexane (3ꢁ10 mL). The combined organic layers were
washed with brine, dried over anhydrous magnesium sulfate,
filtered, and concentrated by rotary evaporator (308C,
20 mmHg) to give the crude product. The product was puri-
fied by flash chromatography (Rf =0.36; 1% ethyl acetate/
Representative Procedure IV for the Suzuki Cross-
Coupling: (E)-Dodec-5-en-6-ylbenzene (9; entry 2 in
Table 1)
A flame-dried, 25-mL, round-bottomed flask, equipped a
magnetic stirring bar, a rubber septum, and an argon inlet,
was charged with PdCl
(Z)-2-(dodec-5-en-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane (150 mg, 0.51 mmol), iodobenzene (124 mg,
2ACHTUNGTNER(NUNG DPEphos) (3.5 mg, 0.0051 mmol),
0.61 mmol), and THF (2 mL) under an atmosphere of
argon. TBAF (0.76 mL, 0.76 mmol) was added. The mixture
was heated to 658C and monitored by TLC. The reaction
mixture was then quenched with aqueous NH4Cl. The aque-
ous layer was separated and extracted with ether (3ꢁ
10 mL). The combined organic layers were washed with
brine, dried over anhydrous magnesium sulfate, filtered, and
concentrated by rotary evaporator (308C, 20 mmHg) to give
the crude product. The crude product was purified via flash
chromatography (Rf =0.38; 1% ethyl acetate/hexane) to
1
hexane) to give a clear oil; yield: 102 mg (84%). H NMR
(300 MHz, CDCl3): d=7.1–7.35 (m, 5H), 5.41 (t, J=7.5 Hz,
1H), 2.21–2.47 (m, 2H), 1.91 (dt, J=7.5, 6.6 Hz, 2H), 1.21–
1.37 (m, 12H), 0.73–0.87 (m, 6H); 13C NMR (75 MHz,
CDCl3): d=140.2, 140.1, 128.5, 127.9, 127.2, 126.2, 39.3, 32.4,
31.7, 28.9, 28.6, 28.1, 22.7, 22.3, 14.2, 14.1; HR-MS: m/z=
244.2190, calcd for C18H28 [M]+: 244.2191.
1
give a clear oil; yield: 114 mg (92%). H NMR (300 MHz,
CDCl3): d=7.20–7.35 (m, 5H), 5.63 (t, J=7.5 Hz, 1H), 2.47
(t, J=7.5 Hz, 2H), 2.18 (dd, J=7.5, 6.9 Hz, 2H), 1.20–1.44
2986
asc.wiley-vch.de
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2981 – 2987

Highly (ꢀ98%) Stereo- and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability
Chem. 2004, 116, 4303–4305; Angew. Chem. Int. Ed.
Acknowledgements
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This work was mainly supported by National Institutes of
Health (GM36792) and Purdue University. We also acknowl-
edge support of various forms by Aldrich Chemical Co. and
Johnson Matthey Catalysts Co.
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Adv. Synth. Catal. 2011, 353, 2981 – 2987
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2987