Stereoselective synthesis of (E)-β-tributylstannyl-α,β-unsaturated ketones: Construction of a key intermediate for the total synthesis of zoanthamine

Article abstract of DOI:10.1021/jo025902s

(E)-β-Trialkylstannyl-α,β-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology

Full text of DOI:10.1021/jo025902s

Ster eoselective Syn th esis of (E)-â-Tr ibu tylsta n n yl-r,â-u n sa tu r a ted
Keton es: Con str u ction of a Key In ter m ed ia te for th e Tota l
Syn th esis of Zoa n th a m in e
Thomas E. Nielsen and David Tanner*
Department of Chemistry, Technical University of Denmark, Building 201,
Kemitorvet, DK-2800 Kgs. Lyngby, Denmark
dt@kemi.dtu.dk
Received May 3, 2002
(E)-â-Trialkylstannyl-R,â-unsaturated ketones are readily available from secondary propargylic
alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed
hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the
synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of
zoanthamine, a structurally complex marine natural product.
SCHEME 1
In tr od u ction
Previously,1 we described the highly stereoselective
synthesis of (Z)-â-tributylstannyl-R,â-unsaturated ke-
tones 2 via addition of stannylcuprates to alkynones 1
(Scheme 1).
Our work thus complements that of Takeda2 who has
described an alternative route to these useful intermedi-
ates and has demonstrated their use in Pd(0)-catalyzed
cross-coupling reactions. Piers has published yet another
route which leads to the Z isomers of the corresponding
trimethylstannyl enones.3 A drawback with all three
approaches is that (E)-â-trialkylstannyl-R,â-unsaturated
ketones are not directly available. For example, in
contrast to earlier work by Piers on the addition reactions
of stannylcuprates to alkynoates4 we were unable to find
reaction conditions which would allow access to the E
isomers of the corresponding ketones. This was of major
concern for a project dealing with the total synthesis of
the natural product zoanthamine 3, a simplified ret-
rosynthetic analysis of which5 is shown in Figure 1.
The proposed convergent route calls for stereoselective
synthesis of (E)-â-trialkylstannyl species C prior to cross-
coupling with B. Since the stannylcupration route proved
untenable, we turned our attention to the work of
Greeves6 who has described the regio- and stereoselective
hydrostannation7 of certain secondary propargylic alco-
hols 5 (Scheme 2).
SCHEME 2
the â-stannylated product always dominated.6 We deemed
this reaction worthy of further investigation, and we now
wish to report (i) an extension of the Greeves work which
demonstrates uniformly excellent â-regioselectivity; (ii)
that â-stannyl allylic alcohols such as 7a -j can be
smoothly oxidized in high yields to the desired (E)-â-
trialkylstannyl-R,â-unsaturated ketones 8a -j; (iii) an
application of this methodology to the synthesis of an
advanced key intermediate 12 for the total synthesis of
zoanthamine (cf. structure C in Figure 1).
Resu lts a n d Discu ssion
We first prepared a series of propargylic secondary
alcohols 5a -l (Table 1) by reaction of aldehydes with
lithiated acetylenes. These were then subjected to Pd-
catalyzed hydrostannation according to the method of
Greeves,6 and the results are collected in Table 1.
Greeves reported regioselectivities which varied widely
(from 0 to 100%), but in cases of nonzero regioselectivity,
(1) Nielsen, T. E.; Cubillo de Dios, M. A.; Tanner, D. Submitted for
publication.
With the exception of the reactions of the two terminal
alkyne substrates (entries 11 and 12), isolated yields of
product were generally very satisfactory. Furthermore,
in most cases, the desired â-regioisomer was the exclusive
product; in those cases (entries 5, 8-10) for which the R
isomer could be detected in the crude product, it was
present to the extent of <10% according to 1H NMR
(2) Takeda, T.; Kabasawa, Y.; Fujiwara, T. Tetrahedron 1995, 51,
2515.
(3) Piers, E.; Tillyer, R. D. Can. J . Chem. 1996, 74, 2048.
(4) Piers, E.; Chong, J . M.; Morton, H. E. Tetrahedron 1989, 45, 363.
(5) Tanner, D.; Tedenborg, L.; Somfai, P. Acta Chem. Scand. 1997,
51, 1217.
(6) Greeves, N.; Torode, J . S. Synlett. 1994, 537.
(7) Review: Smith, N. D.; Mancuso, J .; Lautens, M. Chem. Rev.
2000, 100, 3257.
10.1021/jo025902s CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/03/2002
6366
J . Org. Chem. 2002, 67, 6366-6371

Synthesis of Intermediate for Zoanthamine
F IGURE 1. Simplified retrosynthesis of zoanthamine 3.
TABLE 1. Hyd r osta n n a tion of P r op a r gylic Alcoh ols
TABLE 2. Oxid a tion of â-Sta n n yl Allylic Alcoh ols
propargylic
alcohol
product
entry
â-stannyl allylic alcohol
product (yield %)a
entry
R1, R2
(yield %)a
1
2
3
4
5
6
7
8
9
7a
7b
7c
7d
7e
7f
7g
7h
7i
8a (79)
8b (89)
8c (92)
8d (76)
8e (90)
8f (94)
8g (74)
8h (92)
8i (91)
8j (88)
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
5f
5g
5h
5i
Cyb, CH2(OTBDMS)
Cy, (CH2)2(OTBDMS)
Cy, (CH2)3(OTBDMS)
Cy, Bu
i-Pr, (CH2)2(OTBDMS)
i-Pent, (CH2)2(OTBDMS)
t-Bu, (CH2)2(OTBDMS)
Ph, (CH2)2(OTBDMS)
Mes, (CH2)2(OTBDMS)
1-naphthyl, (CH2)2(OTBDMS)
t-Bu, H
7a (75)
7b (71)
7c (73)
7d (82)
7e (70)c
7f (76)
7g (86)
7h (82)c
7i (74)c
7j (71)c
7k (54)
7l (40)
10
7j
10
11
12
5j
5k
5l
a
Isolated yield after flash chromatography.
Cy, H
a
Isolated yield of the pure E-â isomer after flash chromatog-
raphy. Cy ) cyclohexyl. c Minor amounts of the R isomers 6e,
h -j (<10%) were also isolated.
b
spectroscopy. Pure regioisomers were obtained after flash
chromatography in all cases.
The next task was to oxidize the â-stannyl allylic
alcohols 7a -j to the desired (E)-â-trialkylstannyl-R,â-
unsaturated ketones 8a -j, without isomerization to the
Z isomers.8 We found that this could be accomplished in
excellent yield by TPAP9 and the results are shown in
Table 2.
F IGURE 2. Spectroscopic data for (Z)- and (E)-â-(tributyl-
stannyl)-R,â-unsaturated ketones.
The desired products were isolated after flash chro-
matography and were shown to be stereoisomerically
pure by 1H NMR spectroscopy. Some typical data are
shown in Figure 2, which allows comparison with the
The enantiomerically pure aldehyde 9 was transformed
to the previously reported5 propargylic alcohol 10 in
standard fashion, affording a 2:1 mixture of diastereo-
mers. Since the newly formed stereogenic center is later
destroyed, the mixture of alcohols was used in the
hydrostannation reaction which proceeded in excellent
yield and with complete â-regioselectivity. The hydrostan-
nylated products could be separated chromatographically
and fully characterized (see Experimental Section). The
mixture of vinylstannanes 11 was oxidized cleanly by
TPAP to a single ketone 12 in good yield, thus completing
the synthesis of a substantial portion of the target
molecule. With intermediates corresponding to all three
spectroscopic characteristics of the earlier prepared1
isomers.
Z
Having secured an efficient route to the desired E
isomers, we applied the methodology to compound 12, a
projected intermediate for the zoanthamine total syn-
thesis (Scheme 3).
(8) The Z isomers may well be the thermodynamically more stable,
due to a stabilizing interaction between the lone pair of the carbonyl
oxygen and the tin (cf. ref 3).
(9) Review: Ley, S. V.; Norman, J .; Griffith, W. P.; Marsden, S. P.
Synthesis 1994, 639.
J . Org. Chem, Vol. 67, No. 18, 2002 6367

Nielsen and Tanner
SCHEME 3
Gen er a l P r oced u r e for P r ep a r a tion of P r op a r gylic
Alcoh ols 5a -l. To a solution of the freshly distilled alkyne,
or acetylene gas, (30.0 mmol) in THF (100 mL) was added
dropwise n-butyllithium (1.6 M in hexanes, 18.75 mL, 30.0
mmol) at -78 °C. The reaction mixture was stirred at -78 °C
for 30 min and then at -30 °C for 30 min, before recooling to
-78 °C and dropwise addition of the aldehyde (30.0 mmol).
After being stirred for 1 h at -78 °C, the reaction mixture was
allowed to reach rt. A mixture of ether (125 mL) and sat.
sodium bicarbonate (200 mL) was added, and the organic layer
was separated, washed with brine (2 × 100 mL), dried over
magnesium sulfate, filtered, and rotary evaporated. The
residue was purified by flash column chromatography on silica
gel (hexane:ethyl acetate, 15:1-5:1) to give the propargylic
alcohols 5a -l as colorless oils.
major fragments in Scheme 1 now at hand, the zoan-
thamine end-game can commence and details will be
reported separately.
Con clu sion s
We have described a convenient route to (E)-â-trialkyl-
stannyl-R,â-unsaturated ketones 8a -j, which relies on
regio- and stereoselective Pd(0)-catalyzed hydrostanna-
tion of secondary propargylic alcohols 6a -j followed by
TPAP oxidation. In conjunction with our earlier work,1
the present study means that both the E and Z isomers
of these versatile building blocks are now readily avail-
able in regio- and stereoisomerically pure form. The
present methodology has been applied to the preparation
of an advanced key intermediate 12 for the total synthe-
sis of the marine alkaloid zoanthamine 3.
Analytical data for compounds 5a -l:
4-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exylb u t -2-
yn -1-ol (5a ).10 Yield: 83%; 1H NMR (300 MHz, CDCl3) δ 4.36
(dd, J ) 1 Hz, J ) 2 Hz, 2H), 4.22-4.15 (m, 1H), 1.91-1.47
(m, 7H), 1.35-0.82 (m, 4H), 0.92 (s, 9H), 0.13 (s, 6H); 13C NMR
(75 MHz, CDCl3) δ 84.8, 84.3, 67.2, 51.7, 44.1, 28.5, 28.1, 26.4,
25.9 (two signals), 25.8, 18.3, -5.1.
Exp er im en ta l Section
1
Gen er a l Meth od s. H (300 MHz) and 13C (75 MHz) NMR
5-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exylp en t -2-
yn -1-ol (5b). Yield: 87%; IR (CDCl3): 2939, 1472, 1378, 1252,
spectra were recorded using CDCl3 as the solvent, and signal
positions (δ-values) were measured relative to the signals for
CHCl3 (7.27) and CDCl3 (77.0), respectively. Tin-hydrogen
coupling constants, J (Sn-H), are given as the average of the
117Sn and 119Sn values, due to overlap of the satellite peaks.
IR spectra were obtained for thin films on AgCl plates, and
1
1102, 1004; H NMR (300 MHz, CDCl3) δ 4.13 (m, 1H), 3.73
(t, J ) 7 Hz, 2H), 2.45 (dt, J ) 2 Hz, J ) 7 Hz, 2H), 1.91-0.80
(m, 11H), 0.91 (s, 9H), 0.09 (s, 6H); 13C NMR (75 MHz, CDCl3)
δ 83.0, 81.3, 67.3, 61.9, 44.3, 28.6, 28.2, 26.4, 25.9 (three
signals), 23.2, 18.3, -5.3; Anal. Calcd for C17H32O2Si: C, 68.86;
H, 10.88. Found: C, 68.62; H, 10.64.
only the strongest/structurally most important peaks (νmax
/
cm-1) are listed. Optical rotations were measured at ambient
temperature. Microanalyses were performed by the Microanal-
ysis Laboratory, Department of Physical Chemistry, Univer-
sity of Vienna, Austria, and at the Department of Chemistry,
University of Bath, England. HRMS was performed at the
Department of Chemistry, University of Copenhagen, Den-
mark, and the Department of Chemistry, University of Bath,
England. Molecular mass determinations (high-resolution
mass spectrometry) for substances containing a Bu3Sn group
are based on 120Sn and typically made on the [M - Bu]+, unless
otherwise stated. All compounds on which HRMS was per-
formed exhibited clean 1H NMR spectra and showed one spot
on TLC analysis. TLC analyses were performed on Merck
aluminum-backed F254 silica gel plates, using UV light, and
a solution of 5-10% phosphomolybdic acid in ethanol for
visualization. Column chromatography was performed using
Amicon Matrex silica gel (35-70 µm). All solvents were
distilled prior to use. THF was distilled under nitrogen from
Na-benzophenone. Dichloromethane was dried over calcium
hydride and distilled under nitrogen. Commercially available
compounds were used as received unless otherwise indicated
(important: the quality of the tributyltin hydride batch was
essential for the outcome of the hydrostannation reactions).
All reactions were carried out under an atmosphere of dry
argon using carefully flame-dried glassware. Argon gas was
dried by passage through phosphorus pentoxide and silica gel.
6-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exylh ex-2-
yn -1-ol (5c).11 Yield: 81%; 1H NMR (300 MHz, CDCl3) δ 4.17-
4.09 (m, 1H), 3.70 (t, J ) 6 Hz, 2H), 2.31 (dt, J ) 2 Hz, J ) 7
Hz, 2H), 1.72-1.45 (m, 9H), 1.40-0.82 (m, 4H), 0.90 (s, 9H),
0.07 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 85.7, 80.3, 67.4, 61.6,
44.4, 31.7, 28.6, 28.1, 26.4, 25.9 (two signals), 18.3, 15.1, -5.3.
1
1-Cycloh exylh ep t-2-yn -1-ol (5d ).12 Yield: 91%; H NMR
(300 MHz, CDCl3) δ 4.15-4.09 (m, 1H), 2.20 (dt, J ) 2 Hz, J
) 7 Hz, 2H), 1.95-0.85 (m, 15H), 0.90 (t, J ) 7 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 86.2, 80.1, 67.4, 44.4, 30.8, 28.6, 28.1,
26.5, 25.9 (two signals), 21.9, 18.4, 13.5.
7-(ter t-Bu tyld im eth yl-3sila n yloxy)-2-m eth ylh ep t-4-yn -
3-ol (5e).3 Yield: 83%; 1H NMR (300 MHz, CDCl3) δ 4.18-
4.11 (m, 1H), 3.72 (t, J ) 7 Hz, 2H), 2.44 (dt, J ) 2 Hz, J ) 7
Hz, 2H), 1.92-1.74 (m, 1H), 0.99 (d, J ) 7 Hz, 3H), 0.98 (d, J
) 7 Hz, 3H), 0.92 (s, 9H), 0.07 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 82.9, 81.0, 68.0, 61.9, 34.6, 25.9, 23.1, 18.1, 17.5, -5.3.
7-(ter t-Bu t yld im et h ylsila n yloxy)-2,2-d im et h ylh ep t -4-
yn -3-ol (5f). Yield: 96%; IR (CDCl3): 3406, 2960, 1464, 1382,
1256, 1105, 1006, 912, 836, 776, 735; 1H NMR (300 MHz,
(10) Frantz, D. E.; Faessler, R.; Carreira, E. M. J . Am. Chem. Soc.
2000, 122, 1806.
(11) Fournier-Nguefack, C.; Lhoste, P.; Sinou, D. J . Chem. Res.
Miniprint 1998, 3, 614.
6368 J . Org. Chem., Vol. 67, No. 18, 2002

Synthesis of Intermediate for Zoanthamine
CDCl3) δ 4.42-4.36 (m, 1H), 3.71 (t, J ) 7 Hz, 2H), 2.43 (dt,
J ) 2 Hz, J ) 7 Hz, 2H), 1.67-1.25 (m, 5H), 0.98-0.88 (m,
6H), 0.07 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 82.9, 81.4, 64.9,
61.9, 47.5, 25.9, 23.2, 22.0, 21.8, 18.3, 11.6, 11,5, -5.3; Anal.
Calcd for C16H32O2Si: C, 67.54; H, 11.34. Found: C, 67.65; H,
11.26.
7-(ter t-Bu t yld im et h ylsila n yloxy)-2,2-d im et h ylh ep t -4-
yn -3-ol (5g).13 Yield: 94%; 1H NMR (300 MHz, CDCl3) δ 3.98
(bs, 1H), 3.71 (t, J ) 7 Hz, 2H), 2.43 (dt, J ) 2 Hz, J ) 7 Hz,
2H), 0.98 (s, 9H), 0.90 (s, 9H), 0.07 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 83.0, 80.9, 71.5, 61.9, 35.7, 25.9, 25.3, 23.1, 18.3, -5.3.
5-(ter t-Bu tyld im eth ylsila n yloxy)-1-p h en ylp en t-2-yn -1-
ol (5h ).14 Yield: 84%; 1H NMR (300 MHz, CDCl3) δ 7.58-7.51
(m, 2H), 7.41-7.28 (m, 3H), 5.45 (bs, 1H), 3.76 (t, J ) 7 Hz,
2H), 2.50 (dt, J ) 2 Hz, J ) 7 Hz, 2H), 0.90 (s, 9H), 0.07 (s,
6H); 13C NMR (75 MHz, CDCl3) δ 141.0, 128.4, 128.1, 126.6,
84.3, 81.1, 64.6, 61.7, 25.8, 23.2, 18.3, -5.3.
5-(ter t-Bu t yld im et h ylsila n yloxy)-1-(2,4,6-t r im et h yl-
p h en yl)p en t-2-yn -1-ol (5i). Yield: 82%; IR (CDCl3): 3414,
2928, 1611, 1472, 1256, 1106, 1006; 1H NMR (300 MHz, CDCl3)
δ 6.84 (s, 2H), 5.90-5.85 (m, 1H), 3.71 (t, J ) 7 Hz, 2H), 2.49
(s, 6H), 2.43 (dt, J ) 2 Hz, J ) 7 Hz, 2H), 2.25 (s, 3H), 0.88 (s,
9H), 0.04 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 137.5, 136.3,
133.9, 129.9, 83.2, 80.8, 61.7, 60.4, 25.8, 23.3, 20.8, 20.2, 18.3,
-5.3; Anal. Calcd for C20H32O2Si: C, 72.23; H, 9.70. Found:
72.13, 9.75.
Analytical data for compounds 5a -l:
(E)-4-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exyl-3-
(tr ibu tylsta n n yl)bu t-2-en -1-ol (7a ). Yield: 75%; IR (neat):
1
3381, 2926, 1462, 1254, 1073; H NMR (300 MHz, CDCl3) δ
5.48 (d, J ) 8 Hz, J (Sn-H) ) 71 Hz, 1H), 4.48 (dd, J ) 2 Hz,
J ) 13 Hz, J (Sn-H) ) 53 Hz, 1H), 4.26 (dd, J ) 1 Hz, J ) 13
Hz, J (Sn-H) ) 43 Hz, 1H), 4.10-3.97 (m, 1H), 1.94-1.04 (m,
22H), 1.04-0.75 (m, 15H), 0.91 (s, 9H), 0.07 (s, 6H); 13C NMR
(75 MHz, CDCl3) δ 150.2, 138.9, 72.9, 64.6, 44.0, 29.2, 28.8,
28.4, 27.4, 26.5, 26.1, 26.0, 18.5, 13.7, 10.2, -5.3 (two signals);
Anal. Calcd for C28H58O2SiSn: C, 58.63; H, 10.19. Found: C,
59.05; H, 10.24; HRMS (FAB) calcd for C24H49O2SiSn [M -
C4H9]+ 517.2524, found 517.2515.
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exyl-3-
tr ibu tylsta n n ylp en t-2-en -1-ol (7b). Yield: 71%; IR
(CDCl3): 3461, 2926, 1464, 1256, 1088, 1004; H NMR (300
1
MHz, CDCl3) δ 5.70 (d, J ) 8 Hz, J (Sn-H) ) 70 Hz, 1H), 4.18-
4.06 (m, 1H), 3.71-3.58 (m, 1H), 3.58-3.44 (m, 1H), 2.93-
2.54 (m, 1H), 2.52-2.33 (m, 1H), 2.26 (bs, 1H), 2.01-1.90 (m,
1H), 1.81-1.09 (m, 22H), 1.04-0.76 (m, 15H), 0.91 (s, 9H), 0.08
(s, 6H); 13C NMR (75 MHz, CDCl3) δ 145.1, 143.6, 70.9, 62.7,
43.5, 36.9, 29.2, 29.0, 28.8, 27.4, 26.7, 26.2, 26.1 (two signals),
18.6, 13.7, 9.8, -5.3 (two signals); Anal. Calcd for C29H60O2-
SiSn: C, 59.28; H, 10.29. Found: C, 59.38; H, 10.08; HRMS
(FAB) calcd for C25H51O2SiSn [M - C4H9]+ 529.2680, found
529.2682.
5-(ter t-Bu t yld im et h ylsila n yloxy)-1-n a p h t h a len -1-yl-
p en t-2-yn -1-ol (5j). Yield: 74%; IR (CDCl3): 3398, 2928, 2856,
(E)-6-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exyl-3-
(tr ibu tylsta n n yl)h ex-2-en -1-ol (7c). Yield: 73%; IR
(CDCl3): 3454, 2930, 1464, 1377, 1256, 1096, 1005; H NMR
1
1472, 1388, 1256, 1105, 1057; H NMR (300 MHz, CDCl3) δ
1
8.34-8.27 (m, 1H), 7.92-7.81 (m, 3H), 7.60-7.44 (m, 3H), 6.12
(s, 1H), 3.77 (t, J ) 7 Hz, 2H,), 2.52 (dt, J ) 1 Hz, J ) 7 Hz,
2H), 2.25 (bs, 1H), 0.89 (s, 9H), 0.06 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 136.0, 134.0, 130.5, 129.1, 128.6, 126.2, 125.7, 125.2,
124.4, 124.0, 85.1, 80.8, 62.9, 61.7, 25.9, 23.3, 18.3, -5.3; Anal.
Calcd for C21H28O2Si: C, 74.07; H, 8.29. Found: 73.82, 8.21.
(300 MHz, CDCl3) δ 5.56 (d, J ) 9 Hz, J (Sn-H) ) 72 Hz, 1H),
4.25-4.12 (m, 1H), 3.61 (t, J ) 7 Hz, 2H), 2.68-2.36 (m, 1H),
2.3 6-2.12 (m, 1H), 2.01-1.91 (m, 1H), 1.88 (d, J ) 3 Hz, 1H),
1.81-1.05 (m, 24H), 1.00-0.76 (m, 15H), 0.90 (s, 9H), 0.06
(2×s, 6H); 13C NMR (75 MHz, CDCl3) δ 146.9, 142.9, 70.9, 62.3,
43.8, 33.3 29.7, 29.2, 29.0, 28.9, 27.4, 26.2, 26.1, 25.9, 18.3,
13.7, 9.8, -5.2, -5.3.; Anal. Calcd for C30H62O2SiSn: C, 59.89;
H, 10.39. Found: C, 60.13; H, 10.48; HRMS (FAB) calcd for
1
4,4-Dim eth ylp en t-1-yn -3-ol (5k ).15 Yield: 68%; H NMR
(300 MHz, CDCl3) δ 4.04 (d, J ) 2 Hz, 1H), 2.48 (d, J ) 2 Hz,
1H), 1.03 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 83.6, 73.6, 70.9,
35.4, 25.0.
C
26H53O2SiSn [M - C4H9]+ 543.2837, found 543.2884.
(E)-Cycloh exyl-3-(tr ibu tylsta n n yl)h ep t-2-en -1-ol (7d ).
1
1-Cycloh exylp r op -2-yn -1-ol (5l).16 Yield: 69%; H NMR
Yield: 82%; IR (CDCl3): 3386, 2924, 1451, 1376, 1079, 1012;
1H NMR (300 MHz, CDCl3) δ 5.49 (d, J ) 9 Hz, J (Sn-H) ) 71
Hz, 1H), 4.26-4.14 (m, 1H), 2.43-2.12 (m, 2H), 1.99-1.88 (m,
1H), 1.82-1.07 (m, 26H), 1.03-0.76 (m, 18H); 13C NMR (75
MHz, CDCl3) δ 148.4, 141.6, 71.5, 44.1, 33.5, 32.9, 29.2, 28.9,
28.8, 27.4, 26.7, 26.3, 26.1, 22.8, 14.0, 13.7, 9.9; Anal. Calcd
for C25H50OSn: C, 61.86; H, 10.38. Found: C, 61.86; H, 10.56
(FAB) calcd for C21H41OSn [M - C4H9]+ 427.2179, found
427.2192.
(300 MHz, CDCl3) δ 4.23-4.10 (m, 1H), 2.48 (d, J ) 2 Hz, 1H),
1.85-0.90 (m, 11H); 13C NMR (75 MHz, CDCl3) δ 83.9, 73.6,
67.0, 43.9, 28.3, 27.9, 26.4, 25.8 (two signals).
P r ep a r a tion of P d Cl2(P (o-Tol)3)2. To a solution of PdCl2-
(MeCN)2 (426 mg, 1.64 mmol) in benzene (25 mL) was added
in one portion solid tri-o-tolylphosphine (1.00 g, 3.29 mmol).
The reaction mixture was stirred overnight at room temper-
ature to afford a suspension of a yellow solid, which was
cautiously filtered, and washed with several portions of
benzene. The product was dried under high vacuum, affording
the title compound (1.25 g, 97%) as a yellow powder.
Gen er a l P r oced u r e for Hyd r osta n n a tion of P r op a r g-
ylic Alcoh ols 7a -l. To a solution of PdCl2(P(o-Tol)3)2 (8 mg,
0.01 mmol) and the propargylic alcohol (1.0 mmol) in THF (2.0
mL) was added dropwise tributyltin hydride (364 mg, 1.25
mmol) during 0.5 h. The reaction mixture was stirred at room
temperature for 1 h, and another amount of tributyltin hydride
(364 mg, 1.25 mmol) was dropwise added during 0.5 h, followed
by stirring overnight. The reaction mixture was added to ether
(50 mL) and filtered through a pad of Celite. The volatiles were
removed in vacuo, and the residue was purified by flash
column chromatography on silica gel (hexane:ethyl acetate, 25:
1-15:1) giving the â-stannyl allylic alcohols 7a -l as colorless
oils.
(E)-7-(ter t-Bu t yld im et h ylsila n yloxy)-2-m et h yl-5-(t r i-
bu tylsta n n yl)h ep t-4-en -3-ol (7e). Yield: 70%; IR (CDCl3):
3449, 2957, 1464, 1377, 1256, 1081, 1006; 1H NMR (300 MHz,
CDCl3) δ 5.73 (d, J ) 8 Hz, J (Sn-H) ) 71 Hz, 1H), 4.20-4.05
(m, 1H), 3.80-3.62 (m, 1H), 3.60-3.46 (m, 1H), 2.98-2.60 (m,
1H), 2.52-2.27 (m, 1H), 2.45 (d, J ) 4 Hz, 1H), 1.80-1.62 (m,
1H), 1.61-1.22 (m, 12H), 0.97 (d, J ) 7 Hz, 6H), 0.97-0.76
(m, 15H), 0.08 (s, 3H), 0.07 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 144.9, 143.9, 71.6, 62.6, 36.9, 33.6, 29.1, 27.4, 26.1, 18.6, 18.4,
18.3, 13.7, 9.8, -5.3 (two signals); Anal. Calcd for C26H56O2-
SiSn: C, 57.04; H, 10.31. Found: C, 57.33; H, 10.37; HRMS
(FAB) calcd for C22H47O2SiSn [M - C4H9]+ 489.2367, found
489.2349.
(E )-8-(t er t -Bu t yld im e t h ylsila n yloxy)-3-e t h yl-6-(t r i-
bu tylsta n n yl)oct-5-en -4-ol (7f). Yield: 76%; IR (CDCl3):
3448, 2958, 2927, 1465, 1377, 1256, 1089, 1005; 1H NMR (300
MHz, CDCl3) δ 5.75 (d, J ) 8 Hz, J (Sn-H) ) 70 Hz, 1H), 4.45-
4.28 (m, 1H), 3.80-3.59 (m, 1H), 3.58-3.46 (m, 1H), 2.95-
2.62 (m, 1H), 2.50-2.26 (m, 1H), 2.40 (d, J ) 2 Hz, 1H,), 1.63-
1.12 (m, 16H), 1.02-0.77 (m, 15H), 0.90 (s, 9H), 0.08 (s, 3H),
0.07 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 144.1, 142.9, 128.3,
74.0, 62.6, 36.9, 34.5, 29.1, 27.4, 26.0, 25.6, 18.5, 13.7, 9.8, -5.3;
Anal. Calcd for C28H60O2SiSn: C, 58.43; H, 10.51. Found: C,
(12) Tzalis, D.; Knochel, P. Angew. Chem., Int. Ed. 1999, 38, 1463.
(13) Maynard, D. F.; Okamura, W. H. J . Org. Chem. 1995, 60, 1763.
(14) Edwards, N.; Macritchie, J . A.; Parsons, P. J .; Drew, M. G. B.;
J ahans, A. W. Tetrahedron 1997, 53, 12651.
(15) Henderson, M. A.; Heathcock, C. H. J . Org. Chem. 1988, 53,
4736.
(16) Feldman, K. S.; Bruendl, M. M.; Schildknegt, K.; Bohnstedt,
A. C. J . Org. Chem. 1996, 61, 5440.
J . Org. Chem, Vol. 67, No. 18, 2002 6369

Nielsen and Tanner
58.63; H, 10.68; HRMS (FAB) calcd for C24H51O2SiSn [M -
C4H9]+ 517.2680, found 517.2685.
pulverized 4 Å molecular sieves (1 g) in dichloromethane (2
mL) were added 4-methylmorpholine N-oxide (22 mg, 0.19
mmol) and a solution of the â-stannyl allylic alcohol (0.105
mmol) in dichloromethane (1 mL). The reaction mixture was
stirred for 10 min, before the addition of tetrapropylammonium
perruthenate (2.1 mg, 0.006 mmol). The reaction mixture was
stirred overnight and diluted with dichloromethane (50 mL)
before filtering off the molecular sieves, which were washed
with further amounts of dichloromethane (3 × 25 mL). The
combined organic phases were concentrated, and then was
added the minimum amount of dichloromethane to redissolve
the thick, dark oil, which was purified by flash column
chromatography on silica gel (petroleum ether:ethyl acetate,
50:1-35:1) to give the oxidation products 8a -j as colorless oils.
(E)-7-(ter t-Bu t yld im et h ylsila n yloxy)-2,2-d im et h yl-5-
(tr ibu tylsta n n yl)h ep t-4-en -3-ol (7g). Yield: 86%; IR
(neat): 3468, 1463, 1254, 1089, 1002; 1H NMR (300 MHz,
CDCl3) δ 5.78 (d, J ) 8 Hz, J (Sn-H) ) 71 Hz, 1H), 4.13-4.05
(m, 1H), 3.72-3.60 (m, 1H), 3.59-3.46 (m, 1H), 2.92-2.61 (m,
1H), 2.55-2.26 (m, 1H), 2.19 (d, J ) 3 Hz, 1H), 1.63-1.20 (m,
12H), 1.01-0.77 (m, 15H), 0.92 (s, 9H), 0.90 (s, 9H), 0.08 (s,
3H), 0.07 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 144.1, 142.9,
128.3, 74.0, 62.6, 34.5, 29.1, 27.4, 26.0, 25.6, 18.5, 13.7, 9.8,
-5.3; Anal. Calcd for C27H58O2SiSn: C, 57.75; H, 10.41.
Found: C, 57.80; H, 10.25; HRMS (FAB) calcd for C23H49O2-
SiSn [M - C4H9]+ 503.2524, found 503.2534.
(E)-4-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exyl-3-
(tr ibu tylsta n n yl)bu t-2-en -1-on e (8a ). Yield: 79%; IR (CH2-
Cl2): 2928, 1677, 1574, 1463, 1254, 1070; 1H NMR (300 MHz,
CDCl3) δ 6.35 (m, J (Sn-H) ) 66 Hz, 1H), 4.82 (d, J ) 3 Hz,
J (Sn-H) ) 28 Hz, 2H), 2.50-2.33 (m, 1H), 1.97-1.10 (m, 25H),
1.10-0.80 (m, 12H), 0.92 (s, 9H), 0.08 (s, 6H); 13C NMR (75
MHz, CDCl3) δ 201.8, 179.9, 130.1, 68.9, 50.8, 29.1, 28.5, 27.4,
26.3, 25.9, 25.8, 18.7, 13.7, 11.0, -5.2; Anal. Calcd for C28H56O2-
SiSn: C, 58.84; H, 9.88. Found: C, 58.49; H, 10.10; HRMS
(FAB) calcd for C24H47O2SiSn [M - C4H9]+ 513.2367, found
513.2401.
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-1-p h en yl-3-(t r i-
bu tylsta n n yl)p en t-2-en -1-ol (7h ). Yield: 82%; IR (neat):
3421, 2926, 1461, 1254, 1086, 1013; 1H NMR (300 MHz, CDCl3)
δ 7.45-7.19 (m, 5H), 5.92 (d, J ) 8 Hz, J (Sn-H) ) 67 Hz,
1H), 5.53 (dd, J ) 2 Hz, J ) 8 Hz, 1H), 3.80-3.67 (m, 1H),
3.65-3.51 (m, 1H), 3.14 (d, J ) 2 Hz, 1H), 3.06-2.76 (m, 1H),
2.64-2.31 (m, 1H), 1.54-1.18 (m, 12H), 0.99-0.76 (m, 15H),
0.91 (s, 9H), 0.09 (2 × s, 6H); 13C NMR (75 MHz, CDCl3) δ
145.8, 144.2, 144.1, 128.3, 126.9, 126.1, 68.5, 62.3, 36.8, 29.0,
27.4, 26.1, 18.6, 13.7, 9.7, -5.4 (two signals); Anal. Calcd for
C
29H54O2SiSn: C, 59.90; H, 9.36. Found: C, 59.55; H, 9.37;
HRMS (FAB) calcd for C25H45O2SiSn [M - C4H9]+ 523.2211,
found 523.2204.
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exyl-3-
(t r ib u t ylst a n n yl)p en t -2-en -1-on e (8b ). Yield: 89%; IR
1
(CDCl3): 2929, 1684, 1569, 1464, 1255, 1087; H NMR (300
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-3-(t r ib u t ylst a n -
n yl)1-(2,4,6-t r im et h ylp h en yl)-p en t -2-en -1-ol (7i). Yield:
74%; IR (CDCl3): 3420, 2957, 2928, 1464, 1376, 1256, 1004;
1H NMR (300 MHz, CDCl3) δ 6.82 (s, 2H), 6.13 (d, J ) 6 Hz,
J (Sn-H) ) 68 Hz, 1H), 5.85 (dd, J ) 1 Hz, J ) 6 Hz, 1H),
3.81-3.71 (m, 1H), 3.63-3.52 (ddd [app. dt], J ) 4 Hz, J ) 10
Hz, 1H), 3.43 (d, J ) 2 Hz, 1H), 3.06-2.92 (m, 1H), 2.46-2.35
(m, 1H), 2.40 (s, 6H), 2.25 (s, 3H), 1.60-1.21 (m, 12H), 1.00-
0.75 (m, 15H), 0.91 (s, 9H), 0.09 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 145.6, 145.0, 136.7, 136.5, 136.3, 129.8, 66.1, 62.2,
37.0, 29.1, 27.4, 26.1, 20.8, 18.5, 13.7, 9.8, -5.4 (two signals);
Anal. Calcd for C32H60O2SiSn: C, 61.63; H, 9.70. Found: C,
61.85; H, 9.71; HRMS (FAB) calcd for C28H51O2SiSn [M -
C4H9]+ 565.2680, found 565.2669.
MHz, CDCl3) δ 6.41 (m, J (Sn-H) ) 67 Hz, 1H), 3.66 (t, J ) 7
Hz, 2H), 2.99 (t, J ) 7 Hz, J (Sn-H) ) 55 Hz, 2H), 2.40-2.25
(m, 1H), 1.90-1.12 (m, 22H), 1.00-0.82 (m, 15H), 0.88 (s, 9H),
0.06 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 202.3, 167.1, 137.2,
63.1, 51.2, 39.4, 29.1, 28.6, 27.4, 26.1, 26.0, 25.8, 18.5, 13.7,
10.2, -5.2; Anal. Calcd for C29H58O2SiSn: C, 59.48; H, 9.98.
Found: C, 59.24; H, 9.78; HRMS (FAB) calcd for C25H49O2-
SiSn [M - C4H9]+ 527.2524, found 527.2527.
(E)-6-(ter t-Bu t yld im et h ylsila n yloxy)-1-cycloh exyl-3-
(tr ibu tylsta n n yl)h ex-2-en -1-on e (8c). Yield: 92%; IR (CH2-
Cl2): 2928, 1681, 1568, 1457, 1377, 1252, 1096; 1H NMR (300
MHz, CDCl3) δ 6.34 (bs, J (Sn-H) ) 67 Hz, 1H), 3.62 (t, J ) 7
Hz, 2H), 2.77 (m, J (Sn-H) ) 58 Hz, 2H), 2.33 (m, 1H), 1.90-
1.11 (m, 24H), 1.09-0.83 (m, 15H), 0.88 (s, 9H), 0.05 (s, 6H);
13C NMR (75 MHz, CDCl3) δ 202.5, 171.5, 135.5, 63.2, 51.1,
32.9, 32.4, 28.9, 28.5, 27.3, 25.9, 25.8, 18.3, 13.7, 10.0, -5.3;
Anal. Calcd for C30H60O2SiSn: C, 60.09; H, 10.09. Found: C,
59.68; H, 9.81; HRMS (FAB) calcd for C26H51O2SiSn [M -
C4H9]+ 541.2680, found 541.2688.
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-1-n a p h t h a len -1-
yl-3-t r ibu t ylst a n n ylp en t -2-en -1-ol (7j). Yield: 71%; IR
1
(CDCl3): 3423, 2925, 1464, 1376, 1256, 1081, 1005; H NMR
(300 MHz, CDCl3) δ 8.07-7.98 (m, 1H), 7.90-7.73 (m, 3H),
7.54-7.39 (m, 3H), 6.19-6.07 (m, 1H), 6.06 (d, J ) 7 Hz, J (Sn-
H) ) 66 Hz, 1H), 3.95-3.82 (m, 1H), 3.83 (d, J ) 2 Hz, 1H),
3.71-3.58 (m, 1H), 3.42-3.05 (m, 1H), 2.65-2.42 (m, 1H),
1.58-1.34 (m, 12H), 0.96 (s, 9H), 0.96-0.74 (m, 15H), 0.14 (s,
6H); 13C NMR (75 MHz, CDCl3) δ 146.4, 145.2, 139.6, 133.9,
130.6, 128.6, 127.5, 125.5, 125.4, 125.2, 124.2, 123.2, 66.4, 62.2,
36.9, 29.1, 27.4, 26.1, 18.7, 13.6, 9.8, -5.3 (two signals); Anal.
Calcd for C33H56O2SiSn: C, 62.75; H, 8.94. Found: C, 62.80;
H, 8.83; HRMS (FAB) calcd for C29H47O2SiSn [M - C4H9]+
573.2367, found 573.2382.
(E)-1-Cycloh exyl-3-(tr ibu tylstan n yl)h ept-2-en -1-on e (8d).
Yield: 76%; IR (CH2Cl2): 2927, 1682, 1568, 1455, 1374, 1145,
1
1070; H NMR (300 MHz, CDCl3) δ 6.33 (bs, J (Sn-H) ) 68
Hz, 1H), 2.76 (m, J (Sn-H) ) 59 Hz, 2H), 2.34 (m, 1H), 1.91-
1.10 (m, 26H), 1.06-0.83 (m, 18H); 13C NMR (75 MHz,
CDCl3): δ 202.6, 172.0, 135.3, 51.2, 35.5, 32.0, 29.0, 28.5, 27.3,
26.0, 25.8, 22.9, 14.0, 13.7, 10.0; Anal. Calcd for C25H48OSn:
C, 62.12; H, 10.01. Found: C, 62.01; H, 9.99; HRMS (FAB)
calcd for C21H39OSn [M - C4H9]+ 425.2023, found 425.2024.
(E)-4,4-Dim eth yl-1-(tr ibu tylsta n n yl)p en t-1-en -3-ol (7k ).
Yield: 54%; IR (neat): 3423, 2956, 2926, 1594, 1461, 1376,
(E)-7-(ter t-Bu t yld im et h ylsila n yloxy)-2-m et h yl-5-(t r i-
bu tylsta n n yl)h ep t-4-en -3-on e (8e). Yield: 90%; IR (CH2-
Cl2): 2927, 1686, 1569, 1463, 1380, 1254, 1088; 1H NMR (300
MHz, CDCl3): δ 6.42 (bs, J (Sn-H) ) 66 Hz, 1H), 3.66 (t, J )
7 Hz, 2H), 3.01 (dt, J ) 7 Hz, J ) 1 Hz, J (Sn-H) ) 55 Hz,
2H), 2.62 (hept, J ) 7 Hz, 1H), 1.64-1.19 (m, 12H), 1.02-
0.83 (m, 15H), 0.88 (s, 9H), 0.05 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 202.9, 167.8, 136.7, 63.0, 41.2, 39.3, 29.0, 27.4, 26.0,
18.4, 18.2, 13.7, 10.1, -5.2; Anal. Calcd for C26H54O2SiSn: C,
57.25; H, 9.98. Found: C, 57.21; H, 9.96; HRMS (FAB) calcd
for C22H45O2SiSn [M - C4H9]+ 487.2211, found 487.2218.
(E )-8-(t er t -Bu t yld im e t h ylsila n yloxy)-3-e t h yl-6-(t r i-
bu tylsta n n yl)oct-5-en -4-on e (8f). Yield: 94%; IR (CH2Cl2):
2927, 1681, 1567, 1462, 1380, 1254, 1089. 1H NMR (300 MHz,
CDCl3) δ 6.41 (bs, J (Sn-H) ) 66 Hz, 1H), 3.67 (t, J ) 7 Hz,
2H), 3.03 (dt, J ) 7 Hz, J ) 1 Hz, J (Sn-H) ) 55 Hz, 2H), 2.30
1
1075; H NMR (300 MHz, CDCl3) δ 6.32-5.95 (m, 2H), 3.73
(t, J ) 5 Hz, 1H), 1.67-1.05 (m, 12H), 1.03-0.77 (m, 15H),
0.92 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 148.0, 129.6, 83.5,
34.8, 29.1, 27.2, 25.7, 13.7, 9.6; HRMS (FAB) calcd for C15H31
-
OSn [M - C4H9]+ 347.1397, found 347.1432.
(E)-Cycloh exyl-3-(tr ibu tylsta n n yl)p r op -2-en -1-ol (7l).
Yield: 40%; IR (neat): 3428, 2923, 1642, 1451, 1376, 1260,
1
1072, 1017; H NMR (300 MHz, CDCl3) δ 6.29-5.84 (2H, m),
3.83 (1H, dd, J ) 5 Hz, J ) 10 Hz), 3.28-3.15 (1H, m), 1.90-
0.65 (37H, m); 13C NMR (75 MHz, CDCl3) δ 149.7, 128.7, 80.1,
43.5, 29.2, 28.9, 28.4, 27.3, 26.6, 26.2 (two signals), 13.7, 9.6;
HRMS (FAB) calcd for C17H33OSn [M - C4H9]+ 373.1553, found
373.1611.
Gen er a l P r oced u r e for Oxid a tion of â-Sta n n yl Allylic
Alcoh ols 7a -j. To a slurry of freshly activated and finely
6370 J . Org. Chem., Vol. 67, No. 18, 2002

Synthesis of Intermediate for Zoanthamine
(m, 1H), 1.71-1.22 (m, 16H), 1.10-0.80 (m, 21H), 0.88 (s, 9H),
0.05 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 202.8, 167.8, 137.5,
63.1, 55.9, 39.4, 29.0, 27.4, 26.0, 24.4, 18.5, 13.7, 11.9, 10.1,
-5.2; Anal. Calcd for C28H58O2SiSn: C, 58.63; H, 10.19.
Found: C, 58.26; H, 9.84; HRMS (FAB) calcd for C24H49O2-
SiSn [M - C4H9]+ 515.2524, found 515.2539.
(E)-7-(ter t-Bu t yld im et h ylsila n yloxy)-2,2-d im et h yl-5-
(tr ibu tylsta n n yl)h ep t-4-en -3-on e (8g). Yield: 74%; IR (CH2-
Cl2): 2942, 1680, 1568, 1465, 1370, 1255, 1077, 1004; 1H NMR
(300 MHz, CDCl3) δ 6.62 (m, J (Sn-H) ) 68 Hz, 1H), 3.66 (t,
J ) 7 Hz, 2H), 2.94 (dt, J ) 1 Hz, J ) 7 Hz, J (Sn-H) ) 56
Hz, 2H), 1.60-1.24 (m, 15H), 1.15 (s, 9H), 1.07-0.84 (m, 12H),
0.05 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 204.6, 166.4, 134.4,
63.1, 43.5, 39.3, 29.1, 27.4, 26.5, 26.0, 18.5, 13.7, 10.2, -5.2;
Anal. Calcd for C27H56O2SiSn: C, 57.96; H, 10.09. Found: C,
57.99; H, 10.12; HRMS (FAB) calcd for C23H47O2SiSn [M -
C4H9]+ 501.2367, found 501.2355.
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-1-p h en yl-3-(t r i-
bu tylsta n n yl)p en t-2-en -1-on e (8h ). Yield: 92%; IR (CH2-
Cl2): 2927, 1660, 1571, 1462, 1252, 1229, 1087; 1H NMR (300
MHz, CDCl3) δ 7.98-7.88 (m, 2H), 7.58-7.41 (m, 3H), 6.97
(m, J (Sn-H) ) 66, 1H), 3.71 (t, J ) 7 Hz, 2H), 2.98 (dt, J ) 7
Hz, J ) 1 Hz, J (Sn-H) ) 54 Hz, 2H), 1.69-1.22 (m, 15H),
1.15-0.82 (m, 12H), 0.85 (s, 9H), 0.02 (s, 6H); 13C NMR (75
MHz, CDCl3) δ 190.6, 167.1, 138.6, 136.2, 132.5, 128.6, 128.5,
63.0, 39.6, 29.1, 27.4, 26.0, 18.4, 13.7, 10.2, -5.2; Anal. Calcd
for C29H52O2SiSn: C, 60.10; H, 9.04. Found: C, 59.99; H, 9.10;
HRMS (FAB) calcd for C25H43O2SiSn [M - C4H9]+ 521.2054,
found 521.2077.
colorless oils: Minor diastereomer; [R]25 -28.6 (c 1.8, CH2-
D
Cl2); IR (CDCl3): 2927, 1464, 1255, 1149, 1094, 1041; 1H NMR
(300 MHz, CDCl3) δ 5.66 (s, 1H), 5.62 (d, J ) 9 Hz, J (Sn-H)
) 69 Hz, 1H), 4.89 (s, 1H). 4.88 (s, 1H), 4.79 (d, J ) 7 Hz, 1H),
4.67 (d, J ) 7 Hz, 1H), 4.40-4.28 (m, 1H), 4.12 (m, 1H), 3.71-
3.60 (m, 1H), 3.57-3.45 (m, 1H), 3.41 (s, 3H), 2.95 (d, J ) 2
Hz, 1H), 2.89-2.65 (m, 2H), 2.44-2.30 (m, 1H), 2.21-2.14 (m,
1H), 2.07-1.98 (m, 2H), 1.89-1.78 (m, 1H), 1.79 (s, 3H), 1.71
(s, 3H), 1.60-1.41 (m, 6H), 1.40-1.24 (m, 6H), 0.96 (d, J ) 7
Hz, 3H), 1.00-0.78 (m, 15H), 0.91 (s, 9H), 0.07 (s, 6H); 13C
NMR (75 MHz, CDCl3) δ 148.5, 146.6, 142.6, 138.2, 121.6,
112.8, 95.4, 74.3, 68.9, 62.8, 55.7, 40.9, 40.6, 40.5, 37.3, 37.1,
29.2, 27.5, 26.1, 23.2, 19.6, 18.6, 14.6, 13.7, 9.8, -5.2; HRMS
(FAB) calcd for C33H63O4SiSn [M - C4H9]+ 669.3518, found
669.3519. Major diastereomer: [R]25D -40.9 (c 2.8, CH2Cl2); IR
1
(CDCl3): 2926, 1464, 1253, 1151, 1092, 1028; H NMR (300
MHz, CDCl3) δ 5.69 (d, J ) 7 Hz, J (Sn-H) ) 72 Hz, 1H), 5.68
(s, 1H), 4.95-4.89 (m, 2H), 4.88 (d, J ) 7 Hz, 1H), 4.72 (m,
1H), 4.63 (d, J ) 7 Hz, 1H), 4.55 (s, 1H), 4.25 (m, 1H), 3.59-
3.49 (m, 2H), 3.43 (s, 3H), 2.90-2.74 (m, 1H), 2.74-2.60 (m,
1H), 2.50-2.37 (m, 1H), 2.19-1.76 (m, 4H), 1.74 (s, 3H), 1.72
(s, 3H), 1.50-1.42 (m, 6H), 1.38-1.24 (m, 6H), 1.07 (d, J ) 7
Hz, 3H), 0.94-0.76 (m, 15H), 0.92 (s, 9H), 0.08 (s, 6H); 13C
NMR (75 MHz, CDCl3) δ 146.9, 145.8, 140.3, 139.6, 120.3,
113.7, 94.2, 69.3, 66.1, 63.4, 56.3, 45.0, 40.2, 39.8, 37.6, 37.4,
30.9, 29.2, 27.5, 26.1, 23.1, 19.2, 18.4, 13.7, 11.8, 9.9, -5.2;
HRMS (FAB) calcd for C33H63O4SiSn [M - C4H9]+ 669.3518,
found 669.3536.
Oxid a tion of â-Sta n n yl Allylic Alcoh ol 11. A 2:1 dia-
stereomeric mixture of â-stannyl allylic alcohols 11 (20 mg,
0.027 mmol), 4 Å molecular sieves (0.5 g), and N-methylmor-
pholine N-oxide (5.2 mg. 0.044 mmol) were slurried in dichlo-
romethane (2 mL) and stirred for 15 min before the addition
of tetrapropylammonium peruthenate (0.4 mg, 0.0011 mmol).
After the reaction mixture was stirred for 1 h, another portion
of tetrapropylammonium perruthenate (0.4 mg, 0.0011 mmol)
was added, and the reaction mixture was stirred overnight.
The reaction mixture was diluted with dichloromethane (50
mL) and filtered through a pad of Celite. The organic phase
was concentrated by rotary evaporation, and the residue was
purified by flash column chromatography (hexane:ethyl ac-
etate, 15:1) to give the oxidation product 12 (14 mg, 70%) as
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-3-(t r ib u t ylst a n -
n yl)1-(2,4,6-t r im et h yl-p h en yl)-p en t -2-en -1-on e
(8i).
Yield: 91%; IR (CH2Cl2): 2927, 1660, 1571, 1462, 1379, 1252,
1
1229, 1087, 1004; H NMR (300 MHz, CDCl3) δ 6.84 (s, 2H),
6.56 (m, J (Sn-H) ) 64 Hz, 1H), 3.72 (t, J ) 7 Hz, 2H), 3.11
(dt, J ) 7 Hz, J ) 1 Hz, J (Sn-H) ) 55 Hz, 2H), 2.28 (s, 3H),
2.21 (s, 6H), 1.62-1.21 (m, 15H), 1.12-0.83 (m, 12H), 0.89 (s,
9H), 0.06 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 197.3, 170.8,
140.2, 139.2, 138.1, 133.4, 128.5, 62.9, 39.5, 29.0, 27.4, 26.0,
21.1, 19.3, 18.5, 13.7, 10.2, -5.2; Anal. Calcd for C32H58O2-
SiSn: C, 61.83; H, 9.40. Found: C, 61.77; H, 9.53; HRMS
(FAB) calcd for C28H49O2SiSn [M - C4H9]+ 563.2524, found
563.2511.
(E)-5-(ter t-Bu t yld im et h ylsila n yloxy)-1-n a p h t h a len -1-
yl-3-(tr ibu tylsta n n yl)p en t-2-en -1-on e (8j). Yield: 88%; IR
(CH2Cl2): 2926, 1658, 1565, 1462, 1253, 1231, 1093; 1H NMR
(300 MHz, CDCl3) δ 8.60-8.52 (m, 1H), 8.01-7.78 (m, 3H),
7.61-7.44 (m, 4H), 6.88 (m, J (Sn-H) ) 65 Hz, 1H), 3.77 (t, J
) 7 Hz, 2H), 3.09 (dt, J ) 7 Hz, J ) 1 Hz, J (Sn-H) ) 54 Hz,
2H), 1.68-1.62 (m, 15H), 1.13-0.82 (m, 12H), 0.87 (s, 9H), 0.04
(s, 6H); 13C NMR (75 MHz, CDCl3) δ 193.6, 168.4, 139.2, 137.5,
133.9, 132.0, 130.3, 128.4, 128.1, 127.5, 126.3, 125.8, 124.5,
63.0, 39.6, 29.1, 27.4, 26.0, 18.5, 13.7, 10.2, -5.2; Anal. Calcd
for C33H54O2SiSn: C, 62.96; H, 8.65. Found: C, 62.38; H, 8.63;
HRMS (FAB) calcd for C29H45O2SiSn [M - C4H9]+ 571.2211,
found 571.2216.
a colorless oil: [R]25 -23.4 (c 0.8, CH2Cl2); IR (CDCl3): 2927,
D
1
1684, 1459, 1256, 1097, 1040; H NMR (300 MHz, CDCl3) δ
6.38 (s, J (Sn-H) ) 68 Hz, 1H), 5.34 (bs, 1H), 4.82 (bs, 1H),
4.67 (bs, 1H), 4.41 (d, J ) 7 Hz, 1H), 4.32 (d, J ) 7 Hz, 1H),
4.04 (bs, 1H), 3.76-3.58 (m, 2H), 3.21 (s, 3H), 3.13-2.99 (m,
1H), 2.98-2.82 (m, 1H), 2.75-2.40 (m, 3H), 2.13-1.88 (m, 2H),
1.80 (s, 3H), 1.73 (s, 3H), 1.64-1.41 (m, 6H), 1.40-1.23 (m,
6H), 1.05 (d, J ) 7 Hz, 3H), 1.00-0.84 (m, 15H), 0.90 (s, 9H),
0.07 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 202.1, 163.9, 147.0,
139.5, 135.4, 122.2, 111.0, 95.1, 72.3, 63.3, 55.3, 31.9, 29.1, 27.4,
26.1, 23.0, 21.5, 18.5, 15.6, 13.7, 10.2, -5.1; HRMS (FAB) calcd
for C33H61O4SiSn [M - C4H9]+ 667.3361, found 667.3381.
Hyd r osta n n a tion of P r op a r gylic Alcoh ol 10. To the 2:1
diastereomeric mixture of propargylic alcohols 10 (44 mg, 0.10
mmol) and PdCl2(P(o-Tol)3)2 (4 mg, 0.005 mmol) in THF (1 mL)
was added dropwise tributyltin hydride (116 mg, 0.40 mmol)
during 3.5 h, at which time TLC showed a complete conversion.
The mixture was added 1 mL of eluent and subjected to flash
column chromatography on silica gel (hexane:ethyl acetate, 12:
1) to give the separated two diastereomers of the title
compound 11 (minor diastereomer: 19 mg, 26%, major dias-
tereomer: 42 mg, 58%; 84% total yield, dr ) 2:1), each as
Ack n ow led gm en t. We thank the Technical Uni-
versity of Denmark and the Danish Technical Research
Council for financial support.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 7a -l, 8a -j, 10, 11, and 12. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O025902S
J . Org. Chem, Vol. 67, No. 18, 2002 6371