1,4-Pentenyne as a five-carbon synthon for efficient and selective syntheses of natural products containing 2,4-dimethyl-1-penten-1,5-ylidene and related moieties by means of Zr-catalyzed carboalumination of alkynes and alkenes

Article abstract of DOI:10.1002/chem.200701512

Two highly efficient protocols for enantioselective synthesis of 2,4-dimethyl-1-penten-1,5-ylidene derivatives involve the combined use of the Zr-catalyzed methylalumination of alkynes (ZMA) and the Zr-catalyzed asymmetric carboalumination of alkenes (ZAC

Full text of DOI:10.1002/chem.200701512

FULL PAPER
DOI: 10.1002/chem.200701512
1,4-Pentenyne as a Five-Carbon Synthon for Efficient and Selective Syntheses
of Natural Products Containing 2,4-Dimethyl-1-penten-1,5-ylidene and
Related Moieties by Means of Zr-Catalyzed Carboalumination of Alkynes
and Alkenes
Gangguo Zhu and Ei-ichi Negishi*[a]
Abstract: Two highly efficient protocols for enantioselective synthesis of 2,4-di-
methyl-1-penten-1,5-ylidene derivatives involve the combined use of the Zr-cata-
lyzed methylalumination of alkynes (ZMA) and the Zr-catalyzed asymmetric car-
boalumination of alkenes (ZACA). The ZMA/ZACA protocol has been applied
to the synthesis of a nafuredin intermediate 14 and a potential intermediate 18 for
milbemycin b3, while the ZACA/ZMA protocol has been applied to the synthesis
of a (À)-bafilomycin A1 intermediate 25.
Keywords:
asymmetric synthesis · catalysis ·
natural products · zirconium
pentenyne
·
Introduction
tide, contain a disubstituted (E)-alkene, while both di- and
trisubstituted alkenes are seen in delactonmycin (11).[11]
With the goal of developing widely applicable, efficient,
and stereo- and regioselective synthetic protocols, 1,4-pente-
nyne (12) and its silyl derivatives readily preparable by Cu-
A large number of natural products and related compounds
of biological and medicinal interest contain 2,4-dimethyl-1-
penten-1,5-ylidene moieties and derivatives thereof. Nafure-
din (1),[1] a selective NADH-fumarate reductase inhibitor
(NADH=nicotinamide adenine dinucleotide), scyphostatin
(2),[2] an inhibitor of neutral sphingomyelinase, (+)-ratja-
done (3),[3] an antifungal metabolite from Sorangium cellulo-
sum, milbemycin b3 (4),[4] a macrolide antibiotic, lacrimin A
[12]
or Pd-catalyzed[13] reactions of ethynyl- and silyl-protect-
ed ethynylmetals containing Li or Zn, respectively, were
considered as five-carbon synthons for the two-directional
construction of 2,4-dimethyl-1-penten-1,5-ylidene derivatives
by means of Zr-catalyzed methylalumination of alkynes
(ZMA reaction)[14] and Zr-catalyzed asymmetric carboalu-
mination of alkenes (ZACA reaction).[15] Our recent study
has indicated that, whilst conjugated dienes have not so far
satisfactorily undergone the ZACA reaction, 1,4-dienes
have.[15g] Thus, the 1,4-diene products obtained by means of
the ZMA reaction of 1,4-pentenyne (12) should undergo the
ZACA reaction, as depicted by protocol I (or the ZMA/
ZACA protocol; Scheme 1). In contrast, silylated 1,4-pente-
nynes might selectively undergo the ZACA reaction. If so,
the ZMA reaction can be performed at any later stage (pro-
tocol II or the ZACA/ZMA protocol). Thus, the main goal
of the work described below is to explore the feasibility of
both protocols I and II through the preparation of some key
intermediates used previously in the synthesis of a few
select natural products. For examining the practical synthetic
value of protocol I, nafuredin (1)[1] and milbemycin b3 (4)[4]
were chosen. In cases for which an early execution of the
ZMA reaction must be avoided, the ZACA/ZMA order of
execution would be desirable. We encountered this situation
(5),[5] an antihypotensive agent, (À)-bafilomycin A1 (6),[6]
a
potent vacuolar H+-APTase (APTase=adenosine triphos-
phatase) inhibitor, concanamycin F (7),[7] another specific
H+-APTase inhibitor, and FK-506 (8),[8] an active immuno-
suppressive agent, are some of the representative examples
containing an (E)-trisubstituted alkene moiety, whilst disco-
dermolide (9),[9] an anticancer marine natural product, for
example, contains a (Z)-trisubstituted alkene. Others includ-
ing (À)-callystatin A (10),[10] a potential antitumor polyke-
[a] Dr. G. Zhu, Prof. Dr. E.-i. Negishi
Herbert C. Brown Laboratories of Chemistry
Purdue University, 560 Oval Drive
West Lafayette, IN 47907–2084 (USA)
Fax : (+1)765-494-0239
E-mail: negishi@purdue.edu
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2008, 14, 311 – 318
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311

in an attempt to synthesize
known key intermediates of
(À)-bafilomycin A1 (6),[6] which
was thus chosen for exploring
the feasibility of protocol II.
Results and Discussion
Nafuredin (1) was isolated,
identified, and synthesized in
2001.[1] A key intermediate 14
was prepared from commercial-
ly available (S)-2-methyl-1-bu-
tanol (15) (TCI, 98% S) in 14
steps in 16% overall yield.[1c]
This intermediate 14 can be
synthesized according to proc-
tocol I in 21% yield in just six
steps from 15 (or three steps
from 12), as shown in
Scheme 2, featuring the Zr-cat-
alyzed alkyne carboalumina-
tion,[14] a controlled and syner-
gistic use of ZACA and lipase-
catalyzed acetylation,[16] and the
Pd–Zn cocatalyzed alkenyl–al-
kenyl coupling.[17] Both the Zr-
catalyzed methylalumination of
alkynes (ZMA) and the alkyne
Scheme 1. Two protocols for the conversion of 12 or 13 into 2,4-dimethyl-1-pentene and 2,4-dimethyl-1,5-hexa-
diene derivatives. ZACA=Me3Al, cat., [ZrCl2(nmi)2]; ZMA=Me3Al, cat., [ZrCl2Cp2].
AHCTREUNG
Scheme 2. Synthesis of 14 as a key intermediate of nafuredin (1) by means of Zr-catalyzed alkyne carboalumi-
nation and ZACA-lipase-catalyzed acetylation. Swern oxidation=(COCl)2 (1.2 equiv), DMSO (2.0 equiv),
Et3N (2.2 equiv); Bestmann=(MeO)2POC(N2)COMe, K2CO3, MeOH; (À)-ZACA=Me3Al (2.5 equiv), 5%
[ZrCl2{(À)-(nmi)2}], CH2Cl2, 08C; then O2; lipase cat. acetylation=vinyl acetate (5 equiv), Amano PS lipase
hydrozirconation
proceeded (30 mgmmolÀ1) CH2Cl2; Dess–Martin=1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)one.
312
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Natural Products
FULL PAPER
with 98% stereoselectivity. The conjugated diene 16 ob-
tained by means of Pd-catalyzed cross-coupling was ach-
ieved to give 98% of the E,E isomer without any stereoiso-
meric purification. Its ZACA reaction with 5.0 mol% of
[ZrCl2{(À)-(nmi)2}][18] (nmi=1-neomenthylindenyl) as a cat-
alyst followed by oxidation with O2 gave 17 with 72% ee in
79% yield. Although this compound contains two asymmet-
ric carbon centers with a relatively rigid (E,E)-diene moiety
between them, attempts to purify 17 by column chromatog-
raphy proved to be difficult. On the other hand, its purifica-
tion by lipase-catalyzed acetylation by using Amano PS
lipase (30 mgmmolÀ1) provided 17 with 98% ee in 52%
overall yield from 16. Oxidation of 17 with Dess–Martin pe-
riodinane furnished 14 with 98% isomeric purity, as deter-
nBuLi (1.3 equiv), and addition of ethylene oxide
(3.0 equiv) all in one pot produced 21 in 74% yield, after
protection with tert-butyldiphenylsilyl chloride (TBDPSCl)
and imidazole. The ZACA reaction of 21 with Me3Al
(2.5 equiv) and 1.0% of [ZrCl2{(À)-(nmi)2}] gave crude 22
with 75% ee in 78% yield, which was purified by treatment
with vinyl acetate (5.0 equiv) and Amano PS lipase
(30 mgmmolÀ1) to give 22 with 98% ee in 53% yield from
21. After conversion of 22 into 23 in 69% yield over three
steps, hydrozirconation–Pd–Zn cocatalyzed alkenyl–alkenyl
coupling with 20 permitted the crucial synthesis of 24, which
was converted to 98% isomerically pure 18 in 81% yield
over three steps. It should be noted that 23 in Scheme 3 may
be expected to serve as a useful intermediate for the synthe-
sis of other related compounds, such as lacrimin A (5).[5]
As is widely known, the Zr-catalyzed methylalumina-
tion[14] is generally incompatible with various carbonyl com-
pounds and some of those hydroxyl groups protected with
commonly used silyl and other protecting groups. Thus,
timing of its execution in synthesis is often critically impor-
tant. It is generally advisable to carry out the Zr-catalyzed
alkyne methylalumination before the ZACA reaction
(Scheme 1, protocol I) and incorporation of carbonyl
groups. In some cases, however, it is desirable to reverse the
order of their execution (protocol II). Synthesis of the vari-
ously protected preferred intermediate 25[6e–j] for the synthe-
sis of (À)-bafilomycin A1 is a case in point. Conversion of
12 into 26 proceeded in 72% yield. Disappointing, however,
the ZACA reaction of 26 produced, after oxidation with O2,
the desired product 27 in only 53% yield. The results point-
1
mined by 13C and H NMR spectroscopy, in 91% yield.
For an efficient and selective synthesis of 18, a potential
key intermediate for the synthesis of milbemycin b3 (4),[4]
a
10-step scheme converting 12 into 18 in 18% overall yield
has been developed (Scheme 3). A five-step conversion of
commercially available (Aldrich) 3-methyl-4-methoxybenz-
aldehyde (19) into the requisite alkenyl iodide 20 in 36%
overall yield is also shown in Scheme 3. Selective iodination
of 19 (63% yield after reduction with NaBH4) through the
use of 1.05 equivalents of LiMeN
(CH2)2NMe2,[19] Pd-cata-
G
lyzed direct ethynylation[20] (77%), Zr-catalyzed alkyne car-
boalumination–iodinolysis,[14] and protection with tert-butyl-
dimethylsilyl chloride (TBSCl) afforded 20 with 98% iso-
meric purity in 74% yield. In the longer linear sequence
starting with 12, its Zr-catalyzed methylalumination, evapo-
ration of the volatiles, ate complexation of the alane with
Scheme 3. Synthesis of 18 as a potential intermediate for the synthesis of milbemycin b3 by means of Zr-catalyzed alkyne carboalumination and ZACA–
lipase-catalyzed acetylation. TBS=tBuMe2Si, TBDPS=tBuPhSi, (À)-ZACA=Me3Al (2.0 equiv), 1% [ZrCl2{(À)-(nmi)2}], IBAO (1.0 equiv), CH2Cl2,
238C.
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313

E. Negishi and G. Zhu
Scheme 4. Synthesis of a key intermediate 25 for (À)-bafilomycin A1 by means of a ZACA/ZMA protocol. ZMA=i) [ZrCl2Cp2] (0.2 equiv), Me3Al
(3.0 equiv), H2O (0.2 equiv), CH2Cl2; ii) I2, CH2Cl2/THF. (+)-crotylboration=trans-2-butene, tBuOK, nBuLi, (+)-(Ipc)2BOMe, BF3·Et2O, ether/THF.
ed to the desirability of deferring the Zr-catalyzed alkyne
carboalumination until after execution of the ZACA reac-
tion. And yet, it should nevertheless be performed before
incorporation of the carbonyl-containing C1–C5 moiety.
With this in mind, the trimethylsilyl- (TMS) and triisoprop-
yl- (TIPS) protected 1,4-pentenynes 13a and 13b were pre-
pared by CuBr-catalyzed allylation of lithio derivatives of
TMS- and TIPS-protected ethynes with allyl bromide in
THF at 508C in 81 and 95% yields, respectively.[12] Their
ZACA reaction proceeded cleanly without competition
coming from the silyl-protected alkynyl group and produced
28a and 28b in 76 and 85% yields, respectively. Whereas
the ZACA reaction of TMS-protected pentenyne 13a was
slower and required 4.0 mol% of [ZrCl2{(+)-(nmi)2}] and 0.5
equivalents of water for generation of MAO (methylalumi-
noxane) as a promoter,[21] the corresponding reaction of
TIPS-protected pentenyne 13b required only 0.5 mol% of
[ZrCl2{(+)-(nmi)2}] and 0.2 equivalents of H2O for full con-
sumption of the starting pentenyne 13b within 5 h at 238C.
After removal of the TMS or TIPS group by treatment with
K2CO3 or TBAF, 29 was obtained in 91 and 90% yields, re-
spectively. The Zr-catalyzed methylalumination of 29 with
3.0 molar equivalents of Me3Al, 0.2 equivalents of
[ZrCl2Cp2] (Cp=cyclopentadienyl), and 0.2 equivalents of
H2O followed by treatment with 2.5 equivalents of I2 cleanly
produced 27 (>98% E) in 88% yield. Oxidation of 27 with
tetramethylpiperdinyloxy free radical (TEMPO) and PhI-
The aldehyde 30 was subjected to the Brown crotylbora-
tion[22] by using trans-2-butene and (+)-(Ipc)2BOMe, but the
crotylboration reaction was not clean, producing an unat-
tractive mixture, which contained the desired compound 31
in <10% yield, as determined by GC analysis. These unsat-
isfactory results are summarized in the top part of
Scheme 4.
Yet another modification of the synthetic scheme was
made here. Thus, the ZACA–lipase-catalyzed acetylation
product 28b was oxidized with PhI(OAc)2 (1.1 equiv) in the
A
presence of 1.0 mol% of TEMPO to afford aldehyde 32 in
79% yield, which was then subjected to the same Brown
crotylboration as above. This reaction proceeded cleanly to
give 33 in 75% yield, and the product consisted of two dia-
stereoisomers (dr 92:8) detectable by 13C NMR spectrosco-
py, while its enantiomeric purity may safely be estimated to
be well over 98%. After deprotection with TBAF, the Zr-
catalyzed carboalumination–iodinolysis cleanly produced 31
in 86% yield over two steps. After protection of the hydrox-
yl group with TBSOTf (98% yield), oxidation first with N-
methylmorpholine-N-oxide (NMO) in the presence of
1.0 mol% of OsO4 and then with NaIO4 produced 35 in
71% yield. The same compound was also used by the
Roush[6e,f] and Marshall[6g,h] groups in the synthesis of 25 and
eventually of (À)-bafilomycin A1.[6] A similar route to the
TES-protected analogue of 25 and (À)-bafilomycin A1 was
also reported by Hanessian.[6i] Our conversion of 35 to 25
followed closely the route employed by Roush[6e,f] and Mar-
(OAc)2 in CH2Cl2/H2O at 238C afforded 30 in 75% yield.
314
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Chem. Eur. J. 2008, 14, 311 – 318

Natural Products
FULL PAPER
shall,[6g,h] as shown in Scheme 4. Thus, 25 with 98% isomeric
Clearly, it is very desirable to improve the 72–75% ee
range observed in the ZACA reaction used in this study,
which is limiting the yields of pure products. Such efforts
are currently in progress in our laboratories.
ꢀ
purity was prepared in 11 steps from TIPSC CH in 16%
overall yield. Besides being efficient, in part by virtue of the
use of 1,4-pentenyne and its derivatives permitting the com-
bined use of the ZMA and ZACA reactions, this appears to
be the only catalytic and fully enantioselective synthesis of
25 or its analogues with different protective groups.[6e–j]
Experimental Section
General methods: Unless otherwise stated, all starting materials were ob-
tained from commercial suppliers and used without further purification.
THF and ether were distilled from sodium and benzophenone. CH2Cl2
was distilled from CaH2. Flash chromatographic separation was carried
out on 230–400 mesh silica gel 60. Gas chromatography was performed
on an HP 6890 gas chromatograph by using an HP-5 capillary column
(30 m”0.32 mm, 0.5 mm film) with appropriate hydrocarbons as internal
standards. 1H and 13C NMR spectra were recorded in CDCl3 on a Varian
Inova-300 spectrometer. Optical rotations were measured on an Autopol
III automatic polarimeter. ZnBr2 was flame-dried under vacuum prior to
use. [ZrCl2{(+)-(nmi)2}] and [ZrCl2{(À)-(nmi)2}][18] were prepared as re-
ported in the literature. Further intermediates and 1H and 13C NMR
spectra are given in the Supporting Information.
Conclusion
The ZMA reaction of 1,4-pentenyne (12) followed by the
ZACA reaction at an appropriate stage (Scheme 1, protoco-
l I) promises to provide a highly efficient, catalytic, and
asymmetric route to a wide range of natural products con-
taining one or more 2,4-dimethyl-1-penten-1,5-ylidene moi-
eties. The ZMA reaction is usually 98% E selective. Al-
though the ZACA reaction with Me3Al has thus far typically
provided a 70–80% ee, the crude products of either R or S
configuration can be readily and satisfactorily purified by
lipase-catalyzed acetylation with vinyl acetate. By using pro-
tocol I, the known advanced intermediate 14 for nafuredin
(1) has been efficiently and selectively synthesized in 21%
yield in six steps from 15 or in 37% yield in mere three
steps from 12. Although not an actual intermediate in any
of the previous syntheses of milbemycin b3,[4] 18, which ap-
pears to be imminently applicable as an advanced inter-
mediate for the synthesis of 4, was also prepared as a 98%
pure compound in 18% yield over 10 steps from 12. In this
synthesis, a five-step procedure for converting commercially
available 19 was devised to produce 98% pure 20 in 36%
yield over five steps by means of 1) regioselective lithiation–
5-Triisopropylsilyl-1-penten-4-yne (13b): nBuLi in hexanes (2.5m, 21 mL,
52.5 mmol) was added to a solution of triisopropylsilylacetlyne (11.5 mL,
50 mmol) in THF (30 mL) at À788C. After stirring for 30 min at À788C,
CuBr[12] (360 mg, 2.5 mmol) and allyl bromide (4.5 mL, 55 mmol) were
added. After stirring for 5 h at 508C, the reaction mixture was quenched
with saturated aqueous NH4Cl, extracted with ether, washed with brine,
dried over MgSO4, and concentrated. Column chromatography (silica
gel, hexanes/Et2O 98:2) afforded 13b (10.1 g, 95%) as a colorless oil.
1H NMR (300 MHz, CDCl3): d=1.00–1.20 (m, 21H), 3.05–3.10 (m, 2H),
5.15 (dt, J=10.2, 1.5 Hz, 1H), 5.41 (dd, J=17.1, 1.8 Hz, 1H), 5.75–
5.9 ppm (m, 1H); 13C NMR (75 MHz, CDCl3): d=11.28 (3C), 18.61
(6C), 24.11, 83.01, 104.79, 115.97, 132.42 ppm.
(4E,8S)-4,8-Dimethyl-1,4,6-decatriene (16): A solution of 12 (132 mg,
2.0 mmol) in CH2Cl2 (3 mL) was added to a solution of [ZrCl2Cp2]
(117 mg, 0.4 mmol) and Me3Al (0.6 mL, 6.0 mmol) in CH2Cl2 (2 mL) at
08C. After stirring overnight at 08C, the solvent and excess Me3Al were
evaporated. The residue was dissolved in THF (2 mL), followed by addi-
tion of a solution of ZnBr2 (473 mg, 2.1 mmol) in THF (1 mL) at À788C.
After stirring for 30 min at 08C, (1E,3S)-1-iodo-3-methyl-1-pentene
iodinolysis of 19 by using LiMeN(CH2)2NMe2, 2) Pd-cata-
G
ꢀ
lyzed direct ethynylation with HC CZnBr, and 3) ZMA re-
action followed by iodinolysis.
Difficulties encountered in the ZACA reaction and the
crotylboration of iodoalkenyl-containing intermediates in an
attempted synthesis of advanced intermediate 25 for the
synthesis of (À)-bafilomycin A1 pointed to the need to defer
the ZMA reaction followed by iodinolysis until both ZACA
and crotylboration reactions have been executed. This was
feasible if the TIPS-protected 1,4-pentenyne 13b was used
in place of the parent 1,4-pentenyne (12). Crucial to this de-
velopment was the finding that 13b would undergo the de-
sired ZACA reaction without a competition coming from
the alkynyl group. It was also important to find that little or
no cleavage of the TIPS group occurred, whereas partial
cleavage of the TMS protecting group was detected in cases
in which 1,4-pentenyne was protected with this silyl group.
Besides being one of the most efficient synthesis of 25 and
related derivatives with different protecting groups, the syn-
thesis herein reported appears to provide the only catalytic
and fully enantioselective route to 25. Even at the current
stage of development, this novel, efficient, and catalytic
asymmetric method promises to provide alternative routes
to a wide range of chiral natural products.
(650 mg, 3.0 mmol) and [Pd(PPh3)4] (115 mg, 0.1 mmol) in THF (2 mL)
G
were added. After stirring overnight at 238C, the reaction mixture was
quenched with saturated aqueous NH4Cl, extracted with ether, washed
with brine, dried over MgSO4, and concentrated. Column chromatogra-
phy (silica gel, hexanes/Et2O 95:5) afforded 16 (256 mg, 78%) as a color-
less oil. 1H NMR (300 MHz, CDCl3): d=0.86 (t, J=7.2 Hz, 3H), 0.99 (d,
J=6.9 Hz, 3H), 1.15–1.40 (m, 2H), 1.73 (d, J=1.2 Hz, 3H), 2.0–2.15 (m,
1H), 2.76 (d, J=6.9 Hz, 2H), 5.00–5.10 (m, 2H), 5.46 (dd, J=15.0,
7.8 Hz, 1H), 5.70–5.90 (m, 2H), 6.19 ppm (ddd, J=15.0, 10.5, 0.9 Hz,
1H); 13C NMR (75 MHz, CDCl3): d=11.78, 16.52, 20.26, 29.89, 38.73,
44.21, 115.94, 124.84, 125.77, 134.22, 136.41, 138.86 ppm; MS (70 eV, EI):
m/z (%): 164 (52) [M+], 135 (26), 93 (100); HRMS (EI): m/z: calcd for
C12H20: 164.1565 [M+]; found: 164.1563.
(2R,4E,6E,8S)-2,4,8-Trimethyl-4,6-decadien-1-ol (17)
Representative procedure A: Compound 16 (164 mg, 1.0 mmol) in CH2Cl2
(3 mL) was added to
a solution of Me3Al (0.3 mL, 3.0 mmol) and
[ZrCl2{(À)-(nmi)2}] (33 mg, 0.05 mmol) in CH2Cl2 (2 mL) at 238C. After
total consumption of starting material (determined by GC analysis), the
reaction mixture was treated with a vigorous stream of oxygen bubbled
through it for 1 h at 08C, and was then stirred for further 5 h under an
oxygen atmosphere at 238C. After this time, it was quenched with NaOH
(2n), extracted with CH2Cl2, washed with saturated aqueous NH4Cl,
brine, dried over MgSO4, and concentrated. After passing it through a
short path column of silica gel by using EtOAc as an eluent to remove
metal-containing impurities, evaporation provided the crude product 17
(155 mg, 79%). The optical purity was determined by Mosher ester anal-
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315

E. Negishi and G. Zhu
ysis to be 72% ee. Amano PS lipase (23 mg, 30 mgmmolÀ1) and vinyl ace-
tate (0.39 mL, 3.9 mmol) were added to a solution of crude 17 (151 mg,
0.77 mmol) in CH2Cl2 (2.3 mL) at 238C. After stirring for 5 h (conver-
sion=30%, as determined by GC analysis), the reaction mixture was fil-
tered, concentrated, and purified by column chromatography (silica gel,
hexanes/EtOAc 70:30) to give 17[1c] (102 mg, 52% from 16). The optical
(70 eV, EI): m/z (%): 432 (2) [M+], 375 (80), 305 (32); 174 (100); HRMS
(EI): m/z: calcd for C18H29SiIO2: 432.0981 [M+]; found: 432.0986.
(4E)-7-(tert-Butyldiphenylsilyloxy)-4-methyl-1,4-heptadiene (21): A solu-
tion of 12 (1.3 g, 20 mmol) in CH2Cl2 (10 mL) was added to a solution of
[ZrCl2Cp2] (1.2 g, 4.0 mmol) and Me3Al (4.0 mL, 40 mmol) in CH2Cl2
(20 mL) at 08C. After stirring overnight at 08C, the solvent and excess
Me3Al were evaporated. To the residue thus formed in dry THF (30 mL)
was added nBuLi in hexanes (2.5m, 10.4 mL, 26 mmol) at À788C. After
stirring for 30 min at À788C, ethylene oxide (2.0 mL, 40 mmol) was
added, and the reaction mixture was warmed to 238C overnight. It was
quenched with saturated aqueous NH4Cl, extracted with ether, washed
with brine, and then dried over MgSO4. Concentration afforded the de-
sired alcohol, which was directly used in the following step. Protection
with TBDPSCl according to the procedure used above afforded 21 (5.3 g,
74%, two steps) as a colorless oil. 1H NMR (300 MHz, CDCl3): d=1.14
(s, 9H), 1.64 (s, 3H), 2.35–2.45 (m, 2H), 2.77 (d, J=6.0 Hz, 2H), 3.70–
3.80 (m, 2H), 5.05–5.15 (m, 2H), 5.26 (t, J=1.2 Hz, 1H), 5.80–5.90 (m,
1H), 7.40–7.50 (m, 6H), 7.70–7.80 ppm (m, 4H); 13C NMR (75 MHz,
CDCl3): d=16.11, 19.20, 26.83 (3C), 31.61, 44.15, 63.69, 115.66, 121.50,
127.59 (4C), 129.50 (2C), 134.05 (2C), 135.45, 135.59 (4C), 136.89 ppm.
purity was determined by Mosher ester analysis to be 99% ee. [a]D23
=
+41.3 (c=1.2 in CHCl3); 1H NMR (300 MHz, CDCl3): d=0.87 (t, J=
6.9 Hz, 3H), 0.89 (d, J=6.6 Hz, 3H), 0.99 (d, J=7.2 Hz, 3H), 1.05–1.20
(m, 2H), 1.74 (d, J=1.2 Hz, 3H), 1.80–1.90 (m, 2H), 2.05–2.20 (m, 2H),
3.40–3.55 (m, 2H), 5.46 (dd, J=15.3, 8.1 Hz, 1H), 5.81 (d, J=11.1 Hz,
1H), 6.18 ppm (dd, J=15.3, 11.4 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d=11.79, 16.47, 16.73, 20.18, 29.84, 33.88, 38.62, 44.29, 68.35, 124.61,
126.61, 134.55, 138.73 ppm; MS (70 eV, EI): m/z (%): 197 (41) [M++H],
196 (46) [M+], 179 (57), 109 (100).
(2R,4E,6E,8S)-2,4,8-Trimethyl-4,6-decadienal (14)
Representative procedure B: Dess–Martin periodinane (509 mg,
0.6 mmol) was added to a solution of 17 (98 mg, 0.5 mmol) in CH2Cl2
(3 mL) at 08C. After stirring for 2 h at 238C, the reaction mixture was
quenched with saturated aqueous Na2S2O3, extracted with ether, washed
with brine, dried over MgSO4, and concentrated. Column chromatogra-
phy (silica gel, hexanes/Et2O 95:5) afforded 14[1c] (88 mg, 91%) as a col-
orless oil. [a]2D3 =+28.3 (c=1.0 in CHCl3); 1H NMR (300 MHz, CDCl3):
d=0.86 (t, J=7.2 Hz, 3H), 0.99 (d, J=6.6 Hz, 3H), 1.06 (d, J=6.3 Hz,
3H), 1.20–1.40 (m, 2H), 1.74 (d, J=1.2 Hz, 3H), 2.00–2.15 (m, 2H),
2.45–2.60 (m, 2H), 5.49 (dd, J=15.3, 7.8 Hz, 1H), 5.82 (d, J=10.5 Hz,
1H), 6.17 (ddd, J=15.3, 10.5, 1.5 Hz, 1H), 9.64 ppm (d, J=1.5 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=11.79, 13.22, 16.39, 20.12, 29.75, 38.63,
40.87, 44.52, 124.36, 127.62, 131.94, 139.60, 204.99 ppm; HRMS (EI): m/z:
calcd for C13H22O: 194.1671 [M+]; found: 194.1675.
A
(22):
Compound 22 was prepared according to representative procedure A,
with the exception that one equivalent of isobutylaluminoxane (IBAO)
and 1.0 mol% of [ZrCl2{(À)-(nmi)2}] were used to provide 22 in 78%
yield. The optical purity was determined by Mosher ester analysis to be
75% ee. Lipase-catalyzed acetylation gave 22 (2.1 g, 53%). The optical
purity was determined by Mosher ester analysis to be >98% ee. [a]D23
=
+22.4 (c=2.0 in CHCl3); 1H NMR (300 MHz, CDCl3): d=0.87 (d, J=
6.6 Hz, 3H), 1.05–1.1 (m, 10H), 1.57 (s, 3H), 1.75–1.85 (m, 2H), 2.05–
2.15 (m, 1H), 2.28 (q, J=6.9 Hz, 2H), 3.40–3.55 (m, 2H), 3.66 (t, J=
6.9 Hz, 2H), 5.18 (t, J=1.2 Hz, 1H), 7.15–7.25 (m, 6H), 7.70–7.75 ppm
(m, 4H); 13C NMR (75 MHz, CDCl3): d=15.94, 16.56, 19.11, 26.78 (3C),
31.52, 33.46, 44.15, 63.67, 68.24, 122.25, 127.53 (4C), 129.47 (2C), 133.93
(2C), 134.78, 135.51 ppm (4C); HRMS (EI): m/z: calcd for C25H37SiO2:
397.2557 [M++H]; found: 397.2562.
2-Ethynyl-4-methoxy-5-methyl-benzyl alcohol: A solution of dry ZnBr2
(5.4 g, 24 mmol) in THF (10 mL) was treated with 0.5m ethynylmagnesi-
um bromide in THF (48 mL, 24 mmol) at 08C. After stirring for 30 min,
a solution of [Pd(PPh3)4] (462 mg, 0.4 mmol) and 2-iodo-4-methoxy-5-
R
methyl-benzyl alcohol in THF (10 mL) were added. After stirring for 3 h
at 238C, the reaction mixture was quenched with saturated aqueous
NH4Cl, extracted with ether, washed with brine, dried over MgSO4, and
concentrated. Column chromatography (silica gel, hexanes/EtOAc 70:30)
Compound 24: To a solution of [ZrCl2Cp2] (190 mg, 0.65 mmol) in THF
(2 mL) was added DIBAL-H (DIBAL-H=diisobutylaluminium hydride)
(0.11 mL, 0.65 mmol) at 08C. After stirring for 30 min at 08C, a solution
of 23 (234 mg, 0.6 mmol) in THF (1 mL) was added. After stirring for 2 h
at 238C, a solution of dry ZnBr2 (146 mg, 0.65 mmol) in THF (1 mL) was
gave the desired product (1.35 g, 77%) as
a
white solid. 1H NMR
(300 MHz, CDCl3): d=2.21 (s, 3H), 2.20–2.30 (m, 1H), 3.28 (s, 1H), 3.81
(s, 3H), 4.71 (s, 2H), 6.92 (s, 1H), 7.16 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3): d=16.19, 55.38, 63.27, 80.73, 81.66, 113.69, 118.44, 128.52,
130.37, 135.28, 156.70 ppm.
added. After stirring for 30 min at 08C, a solution of [Pd(PPh3)4] (29 mg,
N
0.025 mmol) and 20 (216 mg, 0.5 mmol) in THF (2 mL) were added.
After stirring for 3 h at 238C, the reaction mixture was quenched with sa-
turated aqueous NH4Cl, extracted with ether, washed with brine, dried
over MgSO4, and concentrated. Column chromatography (silica gel, hex-
Compound 20
Representative procedure C:[14d] H2O (27 mL, 1.5 mmol) was added to a
solution of Me3Al (1.0 mL, 10 mmol) and [ZrCl2Cp2] (176 mg, 0.6 mmol)
in CH2Cl2 (5 mL) at À788C. After stirring for 30 min at À788C, the reac-
tion mixture was warmed to 238C over 30 min. To this was added 2-eth-
ynyl-4-methoxy-5-methyl-benzyl alcohol (528 mg, 3.0 mmol) in CH2Cl2
(5 mL) at À788C. After stirring for 3 h at 238C, the reaction mixture was
treated with a solution of I2 (1.5 g, 6. 0 mmol) in THF (10 mL) at À788C.
After stirring for 30 min at À788C, the reaction mixture was stirred for a
further 30 min at 08C, which was followed by addition of saturated aque-
ous Na2S2O3 and extraction with ether. The resulting solution was
washed with brine, dried over MgSO4, and concentrated. Column chro-
matography (silica gel, hexanes/EtOAc 70:30) afforded the desired com-
pound (715 mg, 75%) as a colorless oil. To a solution of the alcohol
(636 mg, 2. 0 mmol) obtained above and imidazole (204 mg, 3.0 mmol) in
DMF (6 mL) was added TBSCl (320 mg, 2.1 mmol) at 08C. After stirring
for 2 h at 238C, the reaction mixture was quenched with water, extracted
with ether, washed with water, brine, dried over MgSO4, and concentrat-
ed. Column chromatography (silica gel, hexanes/EtOAc 97:3) afforded 20
1
anes/EtOAc 95:5) afforded 24 (282 mg, 81%) as a colorless oil. H NMR
(300 MHz, CDCl3): d=0.09 (s, 6H), 0.95 (s, 9H), 1.00 (d, J=6.9 Hz, 3H),
1.08 (s, 9H), 1.58 (s, 3H), 1.93 (dd, J=13.2, 8.7 Hz, 1H), 2.08 (s, 3H),
2.24 (s, 3H), 2.25–2.5 (m, 4H), 3.68 (t, J=7.2 Hz, 2H), 3.82 (s, 3H), 4.59
(s, 2H), 5.17 (t, J=7.8 Hz, 1H), 5.65 (dd, J=15.3, 7.2 Hz, 1H), 5.96 (d,
J=10.8 Hz, 1H), 6.34 (dd, J=15.0, 10.5 Hz, 1H), 6.60 (s, 1H), 7.22 (s,
1H), 7.40–7.50 (m, 6H), 7.65–7.75 ppm (m, 4H); 13C NMR (75 MHz,
CDCl3): d=À5.20 (2C), 15.97, 16.08, 18.47, 18.89, 19.17, 19.59, 26.05
(3C), 26.83 (3C), 31.63, 34.81, 47.52, 55.36, 62.71, 63.75, 109.65, 122.42,
124.19, 124.81, 127.56 (4C), 129.36, 129.50 (2C), 130.73, 134.07 (2C),
134.69, 135.25, 135.59 (4C), 140.89, 142.78, 156.45 (2C); HRMS (EI):
m/z: calcd for C44H64Si2O3: 696.4394 [M+]; found: 696.4398.
Compound 18: 2-Methyl-2-butene (1 mL), followed by NaH2PO4 (83 mg,
0.6 mmol) and NaClO2 (54 mg, 0.6 mmol) were added to an aldehyde
(105 mg, 0.18 mmol), which was deprotected by removal of TBS with
HCl (1n) from 24 and then oxidized by Dess–Martin periodinane, in
tBuOH (2 mL) and H2O (1 mL). After stirring overnight at 238C, the re-
action mixture was extracted with ether, washed with brine, dried over
MgSO4, and concentrated. Purification by column chromatography (silica
1
(847 mg, 98%) as a colorless oil. H NMR (300 MHz, CDCl3): d=0.10 (s,
gel, hexanes/EtOAc 70:30) gave 18 (96 mg, 89%) as a white solid. [a]D23
=
6H), 0.93 (s, 9H), 2.18 (d, J=1.2 Hz, 3H), 2.22 (s, 3H), 3.82 (s, 3H), 4.51
(s, 2H), 6.20 (s, 1H), 6.54 (s, 1H), 7.18 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3): d=À5.20 (2C), 15.97, 18.36, 25.99 (3C), 26.61, 55.30, 62.60,
79.81, 109.12, 125.85, 129.13, 131.10, 139.88, 147.35, 156.56 ppm; MS
+2.7 (c=2.0 in CHCl3); 1H NMR (300 MHz, CDCl3): d=1.03 (d, J=
6.6 Hz, 3H), 1.10 (s, 9H), 1.61 (s, 3H), 1.95 (dd, J=13.5, 8.7 Hz, 1H),
2.14 (s, 3H), 2.26 (s, 3H), 2.30–2.50 (m, 4H), 3.71 (t, J=6.6 Hz, 2H), 3.89
316
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 311 – 318

Natural Products
FULL PAPER
(s, 3H), 5.21 (t, J=7.2 Hz, 1H), 5.72 (dd, J=15.0, 6.9 Hz, 1H), 6.00 (d,
J=10.5 Hz, 1H), 6.39 (dd, J=15.0, 10.5 Hz, 1H), 6.67 (s, 1H), 7.20–7.30
(m, 6H), 7.70–7.80 (m, 4H), 7.87 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3): d=15.69, 16.03, 19.00, 19.14, 19.39, 26.83 (3C), 31.61, 34.64,
47.47, 55.47, 63.75, 111.33, 119.14, 122.45, 124.39, 124.95, 127.39, 127.56
(3C), 129.47 (2C), 133.74, 134.02 (2C), 135.22, 135.56 (4C), 137.53,
140.90, 148.39, 160.97, 172.56 ppm; MS (70 eV, EI): m/z (%): 596 (11)
[M+], 539 (34), 461 (22), 259 (100); HRMS (EI): m/z: calcd for
C38H48Si2O4: 596.3322 [M+]; found: 596.3325.
Compound 35: NMO (0.8 mL, 3.0 mmol) and OsO4 (80 mL, 0.01 mmol)
were added to a solution of 34 (409 mg, 1 mmol) in acetone (8 mL) and
H2O (2 mL). After stirring for 6 h at 238C, the reaction mixture was
quenched with aqueous Na2S2O3, extracted with EtOAc, washed with
brine, and dried over MgSO4. Concentration gave the crude diol. To a so-
lution of the crude diol obtained above in THF (4 mL) and H2O (1 mL)
was added NaIO4 (320 mg, 1.5 mmol). After stirring for 2 h at 238C, the
reaction was quenched with aqueous Na2S2O3, extracted with ether,
washed with brine, dried over MgSO4, and concentrated. Column chro-
matography (silica gel, hexanes/EtOAc 95:5) provided 35 (295 mg, 71%)
(1E)-1-Iodo-2-methyl-1,4-pentadiene (26): This Compound was prepared
according to representative procedure C in absence of H2O (MAO).[21]
Yield: 72%; 1H NMR (300 MHz, CDCl3): d=1.83 (s, 3H), 2.90–2.95 (m,
2H), 5.00–5.10 (m, 2H), 5.70–5.85 (m, 1H), 5.95 ppm (q, J=1.2 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=23.85, 43.59, 75.91, 117.07, 134.78,
146.04 ppm.
1
as a colorless oil. H NMR (300 MHz, CDCl3): d=0.065 (s, 3H), 0.071 (s,
3H), 0.82 (d, J=6.6 Hz, 3H), 0.89 (s, 9H), 1.11 (d, J=6.9 Hz, 3H), 1.80
(d, J=1.2 Hz, 3H), 1.85–2.05 (m, 2H), 2.35–2.60 (m, 2H), 3.70–3.75 (m,
1H), 5.88 (s, 1H), 9.77 ppm (d, J=2.4 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=À4.33, À4.19, 12.04, 15.32, 18.13, 23.58, 25.85 (3C), 36.10,
42.95, 49.54, 75.88, 77.90, 146.15, 204.59 ppm.
Compound 36: This compound was prepared by a literature method[6f,h]
to give 36 in 89% yield. [a]2D3 =+27.3 (c=1.1 in CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.038 (s, 3H), 0.043 (s, 3H), 0.76 (d, J=6.6 Hz,
3H), 0.90 (s, 9H), 0.98 (d, J=6.9 Hz, 3H), 1.27 (t, J=6.9 Hz, 3H), 1.75–
1.80 (m, 1H), 1.78 (d, J=1.2 Hz, 3H), 1.83 (d, J=1.5 Hz, 3H), 1.97 (dd,
J=13.8, 10.5 Hz, 1H), 2.36 (dd, J=13.5, 4.5 Hz, 1H), 2.60–2.70 (m, 1H),
3.44 (t, J=4.2 Hz, 1H), 4.10–4.25 (m, 2H), 5.84 (s, 1H), 6.87 ppm (dd,
J=9.9, 1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=À3.94, À3.77, 12.46,
14.17, 15.97, 18.13, 18.27, 23.55, 25.99 (3C), 35.93, 36.46, 42.58, 60.27,
75.37, 79.58, 126.21, 144.91, 146.59, 168.18 ppm.
(2S)-2-Methyl-5-triisopropylsilyl-4-pentyn-1-ol (28b): The title compound
was prepared according to representative procedure
A except that
0.5 mol% of [ZrCl2{(+)-(nmi)2}] and 20 mol% of MAO were used. The
product was formed in 85% yield with an optical purity, as determined
by Mosher ester analysis of the hydrogenated product, of 73% ee.
Lipase-catalyzed acetylation afforded pure 28b in 63% yield with an op-
tical purity, as determined by Mosher ester analysis of the hydrogenated
product, of 97% ee. [a]2D3 =+7.8 (c=1.5 in CHCl3); 1H NMR (300 MHz,
CDCl3): d=0.99 (d, J=6.9 Hz, 3H), 1.00–1.15 (m, 21H), 1.8–1.95 (m,
1H), 2.25–2.35 (m, 2H), 2.58 (brs, 1H), 3.53 ppm (brs, 2H); 13C NMR
(75 MHz, CDCl3): d=11.22 (3C), 16.02, 18.52 (6C), 23.69, 35.17, 66.89,
81.66, 106.87 ppm; MS (70 eV, EI): m/z (%): 255 (3) [M++H], 253 (6),
211 (100), 157 (37); HRMS (EI): m/z: calcd for C15H31SiO: 255.2139
[M++H]; found: 255.2143.
Compound 37: DIBAL-H in hexanes (1.0m, 1.0 mL, 1.0 mmol) was
added to a solution of 36 (248 mg, 0.50 mmol) in dry CH2Cl2 (3 mL) at
À788C. After stirring for 30 min at À788C, the reaction mixture was
quenched with MeOH (2 mL) at À788C, which was followed by the addi-
tion of saturated aqueous Rochelle salt and extraction with ether. This
solution was then washed with brine, dried over MgSO4, and concentrat-
ed. Column chromatography (silica gel, hexanes/EtOAc 70:30) afforded
37 (209 mg, 93%) as a colorless oil. [a]2D3 =+8.7 (c=1.0 in CHCl3);
1H NMR (300 MHz, CDCl3): d=0.070 (s, 3H), 0.073 (s, 3H), 0.75 (d, J=
7.2 Hz, 3H), 0.92 (s, 9H), 1.05 (d, J=7.2 Hz, 3H), 1.75 (d, J=1.2 Hz,
3H), 1.75–1.80 (m, 1H), 1.79 (s, 3H), 1.97 (dd, J=12.9, 9.9 Hz, 1H), 2.36
(dd, J=12.9, 4.8 Hz, 1H), 2.85–2.90 (m, 1H), 3.51 (dd, J=7.5, 2.7 Hz,
1H), 5.86 (s, 1H), 6.67 (dd, J=9.6, 1.2 Hz, 1H), 9.40 ppm (s, 1H);
13C NMR (75 MHz, CDCl3): d=À3.88 (2C), 9.32, 15.35, 18.21, 18.38,
23.46, 25.93 (3C), 36.15, 36.52, 43.11, 75.60, 79.16, 137.41, 146.15, 156.84,
195.27 ppm.
Compound 25: This compound was prepared by a literature method[6f,h]
to give 25 in 87% yield. [a]2D3 =+43.7 (c=1.1 in CHCl3), 1H NMR
(300 MHz, CDCl3): d=0.05 (s, 6H), 0.75 (d, J=6.9 Hz, 3H), 0.92 (s, 9H),
0.98 (d, J=6.6 Hz, 3H), 1.70–1.85 (m, 1H), 1.79 (s, 3H), 1.85–1.95 (m,
1H), 1.97 (d, J=1.2 Hz, 3H), 2.35–2.45 (m, 1H), 2.65–2.75 (m, 1H), 3.41
(dd, J=4.8, 2.7 Hz, 1H), 3.66 (s, 3H), 3.80 (s, 3H), 5.84 (s, 1H), 5.93 (d,
J=9.3 Hz, 1H), 6.60 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=À3.80,
À3.74, 14.76, 15.88, 18.36, 18.72, 23.58, 26.10 (3C), 35.96, 36.15, 43.12,
51.96, 60.27, 75.29, 79.78, 129.89, 130.00, 141.91, 142.66, 146.85,
165.49 ppm; HRMS (ESI): m/z: calcd for C23H41SiKO4: 575.1450
[M++K]; found: 575.1453.
(2S)-2-Methyl-4-pentyn-1-ol (29): K2CO3 (62 mg, 0.45 mmol) was added
to a solution of 27a (255 mg, 1.5 mmol) in MeOH (4 mL). After stirring
overnight at 238C, the reaction mixture was quenched with water, ex-
tracted with ether, washed with brine, dried over MgSO4, and concentrat-
ed. Column chromatography (silica gel, hexanes/Et2O 70:30) provided 29
(132 mg, 90%) as a colorless oil. 1H NMR (300 MHz, CDCl3): d=1.01
(d, J=7.2 Hz, 3H), 1.80–1.95 (m, 1H), 2.00 (t, J=3.0 Hz, 1H), 2.20–2.50
(m, 3H), 3.55 ppm (d, J=6.3 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=
15.94, 22.09, 34.75, 66.53, 69.48, 82.59 ppm.
(2S,4E)-2,4-Dimethyl-5-iodo-4-peten-1-ol (27): This compound was pre-
pared from 29 according to representative procedure C to provide 27 in
88% yield. 1H NMR (300 MHz, CDCl3): d=0.88 (d, J=6.6 Hz, 3H),
1.75–1.90 (m, 1H), 1.83 (s, 3H), 2.02 (dd, J=13.5, 8.4 Hz, 1H), 2.36 (dd,
J=13.5, 6.6 Hz, 1H), 3.40–3.50 (m, 2H), 5.90 ppm (q, J=1.2 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=16.27, 23.71, 33.70, 43.53, 67.51, 75.60,
146.49 ppm.
Compound 33: This compound was prepared according to Brownꢁs cro-
tylboration procedure[22] to give 33 in 75% yield (dr=92:8, as determined
by 13C NMR spectroscopy). 1H NMR (300 MHz, CDCl3): d=1.00–1.15
(m, 27H), 1.75–1.90 (m, 2H), 2.30–2.50 (m, 3H), 3.25–3.35 (m, 1H),
5.05–5.20 (m, 2H), 5.75–5.90 ppm (m, 1H); 13C NMR (75 MHz, CDCl3):
d=11.28 (3C), 16.53, 17.37, 18.58 (6C), 22.73, 35.73, 40.51, 78.18, 81.60,
107.66, 116.19, 139.24 ppm.
A
diene (34): Lutidine (0.8 mL, 7.0 mmol) and tert-butyldimethylsilyl tri-
flate (TBSOTf) (1.4 mL, 6.0 mmol) were added to a solution of 31
(1.23 g, 4.2 mmol) in CH2Cl2 (8 mL) at 08C. After stirring for 2 h at
238C, the reaction mixture was quenched with saturated aqueous NH4Cl,
extracted with ether, washed with brine, dried over MgSO4, and concen-
trated. Column chromatography (silica gel, hexanes/Et2O 95:5) provided
34 (1.68 g, 98%). 1H NMR (300 MHz, CDCl3): d=0.06 (s, 3H), 0.07 (s,
3H), 0.79 (d, J=6.9 Hz, 3H), 0.93 (s, 9H), 1.03 (d, J=6.9 Hz, 3H), 1.80
(s, 3H), 1.75–1.85 (m, 1H), 1.95 (dd, J=13.5, 10.5 Hz, 1H), 2.35–2.50 (m,
2H), 3.35 (dd, J=5.7, 3.3 Hz, 1H), 4.95–5.05 (m, 2H), 5.84 (s, 1H),
5.90 ppm (ddd, J=17.4, 10.2, 7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d=À3.80, À3.63, 16.31, 18.33, 23.57, 26.13 (3C), 35.37, 42.05, 43.00 (2C),
75.09, 79.92, 114.00, 141.43, 147.16 ppm; MS (70 eV, EI): m/z (%): 409
(3), 393 (5), 353 (9), 149 (100); HRMS (EI): m/z: calcd for C13H34SiIO:
409.1418 [M++H]; found: 409.1423.
Acknowledgements
We thank the National Institutes of Health (GM 36792), the National
Science Foundation (CHE-0309613), and Purdue University for their sup-
port of this research. Earlier related studies by Dr. S. Huo are gratefully
acknowledged.
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Received: September 24, 2007
Published online: October 30, 2007
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