Remote allylic silyloxy groups as stereocontrol elements in intramolecular oxymercurations of γ-hydroxyalkenes

Article abstract of DOI:10.1021/jo951853q

The diastereoselectivity in intramolecular oxymercurations of γ-hydroxyalkenes bearing a remote allylic oxy substituent has been investigated. It was found that the best selectivity was obtained by employing a combination of (Z)-alkene geometry and a tert-butyldiphenylsilyl protecting group attached to the remote allylic oxygen as in 4a-g. Cyclization, using mercuric acetate in dichloromethane, of all the (Z)-alkenols gave the syn diastereomer, 5a-g, as the major product. For example, cyclization of 4b gave syn diastereomer 5b and anti diastereomer 6b in a ratio of 7:1. It was found that this ratio could be improved by replacing dichloromethane with acetonitrile. Under these conditions the ratio of 5b to 6b increased to 19:1. Cyclization of (E)-alkene 9 gave very poor diastereoselection. These syn-selective intramolecular oxymercurations were exploited in enantioselective syntheses of two diastereomers of methyl nonactate.

Full text of DOI:10.1021/jo951853q

J . Org. Chem. 1996, 61, 2109-2117
2109
Rem ote Allylic Silyloxy Gr ou p s a s Ster eocon tr ol Elem en ts in
In tr a m olecu la r Oxym er cu r a tion s of γ-Hyd r oxya lk en es
Katharina Bratt,†,‡ Agatha Garavelas,† Patrick Perlmutter,*,† and Gunnar Westman†
Department of Chemistry, Monash University, Clayton, Victoria, 3168, Australia, and Department of
Organic Chemistry, University of Uppsala, 751 21 Uppsala, Sweden
Received October 16, 1995X
The diastereoselectivity in intramolecular oxymercurations of γ-hydroxyalkenes bearing a remote
allylic oxy substituent has been investigated. It was found that the best selectivity was obtained
by employing a combination of (Z)-alkene geometry and a tert-butyldiphenylsilyl protecting group
attached to the remote allylic oxygen as in 4a -g. Cyclization, using mercuric acetate in
dichloromethane, of all the (Z)-alkenols gave the syn diastereomer, 5a -g, as the major product.
For example, cyclization of 4b gave syn diastereomer 5b and anti diastereomer 6b in a ratio of 7:1.
It was found that this ratio could be improved by replacing dichloromethane with acetonitrile.
Under these conditions the ratio of 5b to 6b increased to 19:1. Cyclization of (E)-alkene 9 gave
very poor diastereoselection. These syn-selective intramolecular oxymercurations were exploited
in enantioselective syntheses of two diastereomers of methyl nonactate.
Sch em e 1
In tr od u ction
Stereoselective electrophilic ring closures have been the
subject of numerous articles and reviews over the past
decade.1 Several groups have identified the importance
of a “proximal” allylic oxygen-based substituent (i.e., a
substituent attached to the allylic carbon adjacent to the
alkene carbon undergoing ring closure) in the substrate
for controlling the stereochemistry of the closure (eq 1).
A few examples also exist of the use of a “remote” allylic
substituent as a stereocontrol element (eq 2).2 Recently
we reported our first results from a more systematic
study of the influence of the nature of the remote allylic
substituent on the diastereoselectivity of ring closures.3
In particular we examined intramolecular oxymercur-
ations of γ-hydroxyalkenes bearing a remote allylic
oxygen-based substituent. We have now extended the
range of substrates and have found that such closures
often proceed with high levels of diastereoselectivity.
Resu lts a n d Discu ssion
The alkenols used in this study were prepared by
Z-selective olefination of the appropriate aldehyde (1a -
e)4 with the ylide derived from (3-(ethoxycarbonyl)-
propyl)triphenylphosphonium bromide5 (2) (Scheme 1).
Reduction of alkenoates 3a -e with LiAlH4 gave the
primary alcohols 4b -f. Diol 4a was prepared by de-
† Monash University.
‡ University of Uppsala.
X Abstract published in Advance ACS Abstracts, February 15, 1996.
(1) (a) Harmange, J .-C.; Figadere, B. Tetrahedron: Asymmetry 1993,
4, 1711. (b) Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321. (c)
Boivin, T. L. B. Tetrahedron 1987, 43, 3309.
(2) (a) Hanessian, S.; Cooke, N. G.; DeHoff, B.; Sakito, Y. J . Am.
Chem. Soc. 1990, 112, 5276. (b) Evans, D. A.; Dow, R. L.; Shih, T. L.;
Takacs, J . M.; Zahler, R. J . Am. Chem. Soc. 1990, 112, 5290.
(3) Garavelas, A.; Mavropoulos, I.; Perlmutter, P.; Westman, G.
Tetrahedron Lett. 1995, 36, 463-466.
(4) The stereochemistry for the “c” series is enantiomeric to that
shown in Scheme 1 but has been left as shown for simplicity.
(5) Hellwinkel, D.; Kosack, T. Leibigs Ann. Chim. 1985, 226, 2.
0022-3263/96/1961-2109$12.00/0 © 1996 American Chemical Society

2110 J . Org. Chem., Vol. 61, No. 6, 1996
Bratt et al.
Ta ble 1. Resu lts fr om In tr a m olecu la r Oxym er cu r a tion sa
of Alk en ols 4a -g
yieldb ratio
entry alkenol
R
R′
R′′
solvent
(%)
5:6
1
2
3
4
5
6
7
8
9
10
11
12
13
14
4a
4b
H
H
H
Me
Me
CH2Cl2
CH2Cl2
CHCl3
85
93
92
90
76
92
84
86
89
92
99
80
90
89
2.5:1
7:1
10:1
19:1
7:1
10:1
6:1
10:1
6:1
TBDPS
CH3CN
4c
4d
4e
4f
H
H
H
H
TBDPS
TBDPS
n-Pr CH2Cl2
CHCl3
Ph
CH2Cl2
CH3CN
CH2Cl2
CH3CN
CH2Cl2
CHCl3
TBDMS Me
8:1
BOM
Me
Me
4.5:1
7.5:1
3:1
4g
Me TBDPS
CH2Cl2
CH3CN
10:1
a
b
Hg(OAc)2, solvent, rt; aqueous NaCl. Total isolated yield.
silylation of 4b. Alkenol 4g was prepared by addition of
excess methylmagnesium bromide to 3a .
From Table 1 it can be seen that good to excellent
diastereoselectivity may be obtained in these intramo-
lecular oxymercurations. The ether protecting group
which conferred the greatest selectivity was the tert-
butyldiphenylsilyl (TBDPS) group (entries 2-8 and 14).
The use of benzyloxymethyl (BOM, entries 11 and 12),
tert-butyldimethylsilyl (TBDMS, entries 9 and 10), or no
protecting group at all (entry 1) gave poorer, although
in some cases still useful, results. We also found that in
some cases increasing the polarity of the solvent signifi-
cantly improved diastereoselectivity. This was found to
be especially so when acetonitrile was used as solvent
(entries 4, 8, 10, and 14). This effect was also observed
where a tertiary alcohol was the internal nucleophile
(compare entries 13 and 14).
1
(within the usual limits of detection by high-field H NMR
spectroscopy). This observation is currently being ex-
ploited in a new synthesis of mono- and bicyclic alk-
aloids.7
We briefly examined the influence of alkene geometry
on the ring closure. Photoisomerization of (Z)-alkene 4b
gave (E)-alkene 9 in an E:Z isomer ratio of 83:17. The
mixture of geometrical isomers could not be separated
and was used as such in the ring closure. Intramolecular
oxymercuration of this mixture gave a similar ratio
(compared to that of the starting materials) of two pairs
of products. The minor pair of isomers was identical to
that obtained from the ring closure of pure Z-4b. The
major products, i.e., those obtained from ring closure of
9, were formed with little selectivity. This result is not
surprising as (E)-olefins suffer from little allylic strain
and probably react through several significantly popu-
lated conformers.6 It is worth noting here that the
isolation of the two pairs of oxymercuration products in
similar ratios to the starting E/Z alkenes suggests that
a stereochemically clean inversion process occurs during
ring closure. This in turn points to the involvement of a
mercuronium intermediate or a very tightly-bound π-com-
plex. If this were not the case, i.e., there were a
competing SN1-like process occurring, then it is unlikely
that these ratios would have been maintained.
Proof of the stereochemistry of these cyclizations was
first obtained by chemical means. Hence the major
product from the ring closure of 4b, i.e., 5b, was trans-
formed into the known acetate 178 following reductive
demercuration to 7b. This involved a sequence of de-
silylation, Swern oxidation, and Baeyer-Villiger oxida-
tion. Comparison of our synthetic sample with an
authentic sample prepared by Kenyon’s method8 provided
unambiguous proof that the stereochemistry at C1 was
R. Subsequently we confirmed these results by obtaining
an X-ray crystal structure of 5b.
We found that, compared to a cyclic acetonide, the use
of a TBDPS ether also had a remarkable effect on the
stereoselectivity of ring closure (eqs 3 and 4). Closure of
acetonide 14 proceeded with little diastereoselectivity. In
contrast, ring closure of 12 gave only one diastereomer
We were also interested in examining intramolecular
oxymercurations with stereochemically-defined second-
ary alcohols as internal nucleophiles. This also provided
(6) (a) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93,
1307. (b) Hoffmann, R. W. Chem. Rev. 1989, 89, 1841. (c) Chamberlin,
A. R.; Mulholland, R. L., J r.; Kahn, S. D.; Hehre, W. J . J . Am. Chem.
Soc. 1987, 109, 672.
(7) Bratt, K.; Enierga, G.; Perlmutter, P.; Pruis, J . Unpublished
results.
(8) Kenyon, J .; Balfe, M. P.; Irwin, M. J . Chem. Soc. 1941, 312.

Allylic Ethers in Oxymercurations of γ-Hydroxyalkenes
J . Org. Chem., Vol. 61, No. 6, 1996 2111
us with an opportunity to prepare two diastereomers of
nonactic acid which had previously been identified, but
not isolated pure, as byproducts in Bartlett’s total
synthesis of nonactin.9
Thus ester 3a was reduced to aldehyde 18. The
aldehyde proved to be surprisingly robust. It was quite
stable to chromatography on silica gel and could be stored
for several weeks under nitrogen without decomposition.
Syn aldol reaction of 18 with the N-propionylsultam
alkene or mercuronium intermediate in order to enable
ring closure to occur.)
Alternatively, the silyl ether is behaving, effectively,
as a sterically “smaller” group than methyl (a conse-
quence of the long carbon-silicon bond) or some favorable
interaction occurs between the silyl ether and the mer-
curonium. Such interactions might be coordination to
the silyl ether oxygen or mercury-phenyl complexation.
Coordination to silyl ethers by metal cations is generally
regarded as unlikely; however little work has so far been
carried out on mercuronium coordination.13
The greater selectivity associated with the cyclization
of 20 (93:7) compared to that of 27 (84:16) may be the
result of the difference in stereochemistry at C3 for each
compound. For 27 an unfavorable pseudodiaxial interac-
tion leads to a slightly higher energy transition state (D)
than that for 20 where no such interaction operates (E).
boron enolate 1910 gave adduct 20 as a single dia-
stereomer (Scheme 2) whose structure was confirmed by
single-crystal X-ray diffraction17 (see Figure 1). Intramo-
lecular oxymercuration of 20 gave a 93:7 mixture of
diastereomers in favor of 21a in excellent yield. Consis-
tent with all our previous observations the major isomer
was the product of a syn-selective ring closure. Reductive
demercuration,11 followed sequentially by amide hydroly-
sis, esterification, and desilylation, gave the methyl
nonactate isomer 25. Similarly, 32 was synthesized in
six steps using N-propionylsultam boron enolate 26.
Interestingly, the ring closure of 27 was slightly less
diastereoselective (84:16) than that for 20, although still
in favor of the syn diastereomer 28a .12
The syn stereochemistry observed in all the cyclizations
described in this work arises from intramolecular attack
(by the hydroxyl group) of the Re face of each alkene. In
turn, this is a consequence of preferential formation of
the mercuronium intermediate from the (opposite) Si face
of the alkene. What factors control this? First, assuming
With pure samples of 25 and 32 in hand, it was now
possible to compare the chemical shifts of these nonactate
isomers with those used earlier in Bartlett’s study to
assign the relative stereochemistry of ent-25 and ent-32.
The relevant data are collected in Table 2. All four
compounds in Table 2 possess the unnatural relative
configuration between C2 and C3 and between C6 and
C8. Bartlett9a noted that the C10 hydrogens resonate
at δ < 1.14 for the natural C2/C3 nonactate configuration
but at δ > 1.22 for the unnatural configuration. They
also observed that the C9 hydrogens resonate at δ > 1.20
for the natural nonactate C6/C8 configuration but at δ
< 1.18 for the unnatural configuration. Also the coupling
constants for the C9 and C10 hydrogens were consistently
6.2 and 7.0 Hz, respectively. All these trends are
apparent in Table 2 and fully support the assignment of
relative stereochemistry in this and earlier work.
that the hydrogen-eclipsed conformation (A, lower in
energy than B or C) most resembles the reacting con-
former in these reactions, then the role of the allylic
substituents is of critical importance. (Conformers which
involve the allylic C-O bond aligning itself orthogonal
to the plane of the double bond can be excluded on
stereoelectronic grounds).
In fact, the crystal structure of one of the alkenols, 20,
clearly shows that the allylic methyl group, C9, is
essentially perpendicular to the plane of the double bond
(Figure 1). Thus if one considers the possibility that, in
solution, the eclipsing allylic hydrogen (cf. H8 in Figure
1) is not quite in plane6b but rotated by an amount similar
to that found in the crystal structure, then the methyl
group blocks approach to the Si face of the alkene.
(Naturally, the phenyl group, as depicted in Figure 1,
would need to swing away from its position “above” the
The intramolecular oxymercurations carried out in this
study are noteworthy for several reasons. First, the
(12) We have also briefly examined the use of Evans’ valine-derived
auxiliary in this chemistry. We were rewarded with a crystalline
material for the major diastereomer ii of the ring closure (see below).
This clearly confirmed the syn relative stereochemistry between C6
and C8 (Garavelas, A. Ph.D. Thesis, Monash University, 1995).
(9) (a) Bartlett, P. A.; Meadows, J . D.; Ottow, E. J . Am. Chem. Soc.
1984, 106, 5304. (b) For a comprehensive list of nonactic acid and
nonactin syntheses, see: Fleming, I.; Ghosh, S. K. J . Chem. Soc., Chem.
Commun. 1994, 2285.
(10) Oppolzer, W.; Blagg, J .; Rodriguez, I.; Walther, E. J . Am. Chem.
Soc. 1990, 112, 2767.
(11) Evans, D. A.; Bender, S. L.; Morris, J . J . Am. Chem. Soc. 1988,
110, 2506.
(13) Kitching, W.; Drew, G. M.; Alberts, V. Organometallics 1982,
1, 331.

2112 J . Org. Chem., Vol. 61, No. 6, 1996
Bratt et al.
Sch em e 2
Ta ble 2.a Selected 1H NMR Ch em ica l Sh ifts a n d
Cou p lin g Con sta n ts for Meth yl Non a cta te Dia ster eom er s
25, 32, en t-25, a n d en t-32
CH3O
C(9)H3
C(9)H3
C(10)H3
C(10)H3
compd
δ
δ
J (Hz)
δ
J (Hz)
32
ent-32
25
3.679
3.678
3.682
3.681
1.176
1.178
1.178
1.177
6.2
6.2
6.2
6.2
1.228
1.226
1.221
1.221
7.0
7.0
7.0
7.0
ent-25
a
Chemical shifts are given for solutions in CDCl3 and were
recorded at 200 MHz. Spectra for compounds ent-25 and ent-32
were recorded at 250 MHz.8a
Exp er im en ta l Section
F igu r e 1. X-ray crystal structure of aldol adduct (20).
Gen er a l. Melting points were recorded on a hotstage
melting point apparatus and are uncorrected. 1H and 13C
NMR spectra were run in CDCl3 at 200 or 300 and 50 MHz,
respectively. Chemical shifts are downfield from tetrameth-
ylsilane as the internal reference for 1H NMR spectra while
the central peak of CDCl3 was used as the internal reference
for 13C NMR spectra. All solvents were dried and distilled
according to standard procedures. Ether refers to diethyl
ether. Microanalyses were conducted by the Commonwealth
and Microanalytical Service or National Analytical Laborato-
ries, Melbourne, Australia.
Eth yl (4Z,6S)-6-[(ter t-Bu tyld ip h en ylsilyl)oxy]-4-h ep -
ten oa te (3a ). To a stirred suspension of the phosphonium
salt 2 (13.16 g, 0.029 mol) in THF (150 mL) at 0 °C was added
NaN(SiMe3)2 (1 M in THF, 31.7 mL, 0.032 mol) dropwise. The
resulting egg yolk colored mixture was stirred for 20 min at 0
°C, and a solution of the aldehyde 1a 15 (3.00 g, 0.010 mol) in
THF (20 mL plus 10 mL rinse) was added dropwise. The pale
yellow mixture was stirred for 30 min and then poured into
ether (200 mL). The organic layer was washed with brine (2
× 100 mL), dried (MgSO4), and filtered and the solvent
removed under reduced pressure. The viscous oil was sub-
jected to flash column chromatography (silica, 5% ether/light
petroleum ether) to give 3a as a colorless oil (3.43 g, 87%).
cyclizations of these and other systems bearing a remote
allylic TBDPS ether show good to excellent syn selectiv-
ity. Second, the reaction conditions are very mild. Third,
the method described in this study provides access to both
cis- and trans-2,5-disubstituted tetrahydrofurans selec-
tively.
In summary, the use of remote allylic ethers, especially
TBDPS ethers of (Z)-alkenes, in intramolecular oxy-
mercurations of alkenols leads to a highly 1,3-syn-
diastereoselective process. This syn diastereoselectivity
is often enhanced when polar solvents, such as chloroform
or acetonitrile, are employed. This process, coupled to
an aldol reaction, has provided a stereoselective route to
nonactate isomers 32 and 25. Variation of this sequence,
for example anti aldol/anti cyclization, should lead to a
flexible approach to the synthesis of the other nonactate
isomers as well as the structurally-related pamamycins.14
The development of these alternative sequences is un-
derway in our laboratories.
(14) A related approach employing intramolecular oxymercurations
of allenes has been reported. See: (a) Walkup, R. D.; Kim, S. W. J .
Org. Chem. 1994, 59, 3433. (b) Walkup, R. D.; Park, G. J . Am. Chem.
Soc. 1990, 112, 1597.
(15) Massad. S. K.; Hawkins, L. D.; Baker, D. C. J . Org. Chem. 1983,
48, 5180.

Allylic Ethers in Oxymercurations of γ-Hydroxyalkenes
J . Org. Chem., Vol. 61, No. 6, 1996 2113
GLC analysis of the crude product indicated the Z:E ratio to
be 94:6 respectively: [R]19D +9.9° (c 1.01, CHCl3); IR (film) 3407
m, 1736 s, 1730 sh cm-1; 1H NMR (200 MHz, CDCl3) δ 1.04 (s,
9H), 1.17 (d, J ) 7.4 Hz, 3H), 1.22 (t, J ) 7.1 Hz, 3H), 1.80-
2.01 (m, 2H), 2.04-2.26 (m, 2H), 4.07 (q, J ) 7.1 Hz, 1H), 4.58
(dqd, J ) 8.5, 7.4, 1.1 Hz, 1H), 5.53 (ddt, J ) 10.9, 8.5, 1.6 Hz,
1H), 7.30-7.72 (m, 10H); MS (EI) m/ z 410 (M+, 0.1%), 199
(100). Anal. Calcd for C25H34O2Si: C, 73.1; H, 8.4. Found:
C, 72.7; H, 8.4.
additional brine (5 mL) and dried (MgSO4). Removal of the
solvent under reduced pressure gave the crude product as a
foam. Purification of the diastereomeric organomercury chlo-
rides was usually carried out by preparative TLC (silica).
(2R)-2-[(1R,2S)-1-(Ch lor om er cu r io)-2-h ydr oxy-1-pr opyl]-
tetr a h yd r ofu r a n (5a ) a n d (2S)-2-[(1S,2S)-1-(Ch lor om er -
cu r io)-2-h yd r oxy-1-p r op yl]tetr a h yd r ofu r a n (6a ). Using
the general procedure described above diol 4a was cyclized to
yield 5a and 6a as an inseparable 2.5:1 mixture in 85% yield:
[R]23D -25.6° (c 3.11, EtOH); IR (CHCl3) 3331 bs cm-1; 1H NMR
(200 MHz) δ 1.26 (d, J ) 6.1 Hz, 3H 5a ), 1.37 (d, J ) 6.2 Hz,
3H, 6a ), 1.36-1.59 (m, 2H), 1.84-2.25 (m, 2H), 3.07 (t
obscured, 1H, 6a ), 3.10 (t, J ) 1.9 Hz, 1H, 5a ), 3.65 (bs, 1H),
3.71-3.83 (m, 1H), 3.91-4.07 (m, 1H), 4.27 (dddd, J ) 383.0
(J 3H,Hg), 8.5, 6.1, 2.3 Hz, 1H, 5a ), 4.40 (dqd, J ) 380.0 (J 3H,Hg),
6.1, 1.9 Hz, 1H, 5a ); 13C NMR (50 MHz) δ 25.0, 25.1, 25.6,
25.7, 34.1, 34.2, 67.9, 68.2, 69.9, 70.4, 71.6, 72.7, 78.7, 83.3;
MS (CI) m/ z 367 (M+ , 0.3%), (100). Anal. Calcd for
C7H13ClHgO2: C, 23.02; H, 3.59. Found: C, 23.05; H, 3.60.
(2R)-2-[(1R,2S)-1-(Ch lor om er cu r io)-2-((ter t -b u t yld i-
p h en ylsilyl)oxy)-1-p r op yl]tetr a h yd r ofu r a n (5b) a n d (2S)-
2-[(1S ,2S )-1-(Ch lor om e r cu r io)-2-((t er t -b u t yld ip h e n yl-
silyl)oxy)-1-p r op yl]tetr a h yd r ofu r a n (6b). Using the gen-
eral intramolecular oxymercuration procedure, alkenol 4b gave
5b and 6b in a 19:1 ratio, respectively and an overall yield of
90%. 5b: mp 69-71 °C; [R]20D -31.2° (c 2.80, CHCl3); 1H NMR
(200 MHz) δ 1.07 (s, 9H), 1.15 (d, J ) 6.0 Hz, 3H), 1.57-1.96
(m, 4H), 2.68 (ddd, J ) 221.0, 7.6, 3.0 Hz, 1H), 3.56-3.67 (m,
1H), 3.78-3.89 (m, 1H), 3.94-4.04 (m, 1H), 4.20 (qd, J ) 6.0,
3.0 Hz, 1H), 7.28-7.75 (m, 10H); 13C NMR (50 MHz) δ 19.1,
25.9, 26.5, 27.1, 32.9, 67.3, 70.7, 73.0, 79.5, 12.5, 127.8, 129.7,
129.9, 133.3, 134.0, 136.0; MS (CI) m/ z no M+ at 603 observed,
367 (100%). Anal. Calcd for C23H31ClHgO2Si: C, 45.77; H,
(4Z,6S)-6-[(ter t-Bu tyld ip h en yl)silyloxy]-4-h ep ten -1-ol
(4b). A solution of 3a (6.00 g, 14.6 mmol) in ether (20 mL)
was added dropwise to a stirred suspension of lithium alumi-
num hydride (1.11 g, 29.3 mmol) in ether (30 mL) at room
temperature. The mixture was heated under reflux for 1 h
and then left to cool to room temperature. Ice was added
carefully and the mixture stirred until white granules formed.
The solid was removed by filtration and the organic layer dried
(MgSO4) and filtered. The solvent was removed under reduced
pressure and the remaining oil subjected to flash column
chromatography (10% ether/light petroleum ether) to give 4b
(>95% Z) as a colorless liquid (5.01 g, 93%): [R]19 +13.3° (c
D
2.29, CHCl3); IR (film) 3342 bs cm-1
;
1H NMR (200 MHz,
CDCl3) δ 1.04 (s, 9H), 1.17 (d, J ) 6.4 Hz, 3H), 1.30-1.45 (m,
3H, one exch), 1.63-1.76 (m, 2H), 3.41 (t, J ) 6.4 Hz, 2H),
4.57 (dqd, J ) 8.4, 6.4, 1.0 Hz, 1H), 5.17 (dtd, J ) 11.0, 8.4,
1.5 Hz, 1H), 5.53 (ddt, J ) 11.0, 8.4, 1.5 Hz, 1H), 7.30-7.74
+
(m, 10H); MS (EI) m/ z no M at 368 observed, 311 (M+
-
C(CH3)3, 8%), 199 (100); TLC Rf 0.11 (10% ether/light petro-
leum ether). Anal. Calcd for C23H32O2Si: C, 74.95; H, 8.75.
Found: C, 74.77; H, 9.01.
(4Z,6S)-4-Hep ten e-1,6-d iol (4a ). A mixture of 4b (150 mg,
0.41 mmol) and TBAF (1 M in THF, 1.3 mL, 1.3 mmol) was
stirred at room temperature for 18 h. The reaction mixture
was diluted with ether (20 mL), dried (MgSO4), and filtered
and the mixture concentrated. Purification of the oil by
preparative TLC (silica, 50% ether/light petroleum ether) gave
the diol 4a (48 mg, 91%) as a colorless viscous oil: [R]21D +3.7°
5.18. Found: C, 45.56; H, 4.94. 6b: [R]22 -26.2° (c 1.08,
D
1
CHCl3); H NMR (200 MHz) δ 1.07 (s, 9H), 1.25 (d, J ) 5.8
Hz, 3H), 1.68-1.87 (m, 4H), 2.87 (t, J ) 4.9 Hz, 1H), 3.41-
3.63 (m, 1H), 3.70-3.68 (m, 2H), 4.19 (qd, J ) 5.8, 4.9 Hz,
1H), 7.32-7.75 (m, 10H); 13C NMR (50 MHz) δ 19.0, 25.6, 26.5,
27.0, 33.1, 67.3, 71.0, 72.7, 78.4, 127.7, 127.8, 129.7, 129.8,
129.9, 133.7, 133.8, 134.8, 135.8, 136.0; MS (CI) m/ z no M+
at 603 observed, 233 (100%). Anal. Calcd for C23H31ClHgO2-
Si: C, 45.77; H, 5.18. Found: C, 45.63; H, 4.96.
1
(c 1.82, CHCl3); IR (film) 3332 bs cm-1; H NMR (200 MHz,
CDCl3) δ 1.25 (d, J ) 6.3 Hz, 3H), 1.46-1.82 (m, 2H), 2.02-
2.17 (m, 1H), 2.33-2.52 (m, 1H), 2.82 (bs, 2H), 3.63 (dd, J )
6.9, 5.1 Hz, 1H), 4.26 (dq J ) 6.3, 6.3 Hz, 1H), 4.66 (dq, J )
7.4, 6.9 Hz, 1H), 5.35-5.73 (m, 1H); 13C NMR (50 MHz, CDCl3)
δ 23.4, 23.5, 31.4, 60.9, 63.2, 130.8, 134.6; MS (CI) 261 (2M+
+ 1, 13%), 95 (100).
(2R)-2-[(1R,2R)-1-(Ch lor om er cu r io)-2-((ter t-b u t yld i-
p h en ylsilyl)oxy)-1-p en tyl]tetr a h yd r ofu r a n (5c) a n d (2S)-
2-[(1S,2R)-1-(Ch lor om er cu r io)-2-((ter t -b u t yld ip h en yl-
silyl)oxy)-1-p en tyl]tetr a h yd r ofu r a n (6c). Using the gen-
eral intramolecular oxymercuration procedure, alkenol 4c was
cyclized to yield 5c and 6c as an inseparable 10:1 mixture in
(4E,6S)-[(ter t-Bu tyldiph en ylsilyl)oxy]-4-h epten -1-ol (9).
A solution of 4b (600 mg, 1.63 mmol) and diphenyl disulfide
(107 mg, 30 mol%) in benzene (7 mL) was placed in a quartz
vessel and exposed to sunlight for 6 h. Benzene was removed
under reduced pressure and analysis of the crude product
indicated the ratio of esters 4b and 9 to be 27:73, respectively.
A further portion of diphenyl disulfide (107 mg) was added to
the crude material in benzene (7 mL), and the mixture was
exposed to sunlight for 4 h. After the solvent was evaporated,
analysis of the crude material indicated no change in the
isomer ratio. The crude product was purified using flash
column chromatography (silica, 20% ether/light petroleum
ether) giving the isomeric mixture of products as a colorless
liquid (591 mg). This material was cycled twice more through
the above procedure, yielding an 83:17 mixture of 9 and 4b,
respectively. This mixture of products was used for the
subsequent cyclization reactions: [R]22D -36.0° (c 1.81, EtOH);
IR (film) 3424 bs cm-1; 1H NMR (200 MHz) δ 1.06 (s, 9H), 1.15
(d, J ) 6.3 Hz, 3H), 1.46-1.60 (m, 2H), 1.64 (bs, 1H), 1.94-
2.04 (m, 2H), 3.40 (t, J ) 6.5 Hz, 2H, 4b), 3.54 (t, J ) 6.5 Hz,
2H, 9), 4.26 (dq, J ) 6.3 Hz, 1H, 4b), 5.17 (dtd, J ) 11.0, 7.3,
0.9 Hz, 1H, 4b), 5.28-5.58 (m, 2H), 7.28-7.75 (m, 10H); MS
(EI) m/ z 368 (M+, 0.1%), 95 (100). Anal. Calcd for C23H32O2-
Si: C, 74.95; H, 8.75. Found: C, 74.97; H, 8.85.
92% yield: [R]20 13.8° (c 0.22, CHCl3); 1H NMR (200 MHz) δ
D
0.67 (t, J ) 7.3 Hz, 3H), 1.07 (s, 9H), 1.15-1.56 (m, 6H), 1.70-
1.85 (m, 2H), 2.72 (dd, J ) 1.7, 8.5, 1H), 3.56-3.65 (m, 1H),
3.76-3.97 (m, 3H), 7.35-7.45 (m, 4H), 7.62-7.72 (m, 6H); 13
C
NMR (50 MHz, CDCl3) δ 18.8, 27.1, 32.7, 42.1, 67.3, 69.9, 74.4,
77.6, 79.8, 127.5, 127.7, 129.7, 129.9, 133.4, 136.0, 136.1.
(2R)-2-[(1R,2S)-1-(Ch lor om er cu r io)-2-((ter t -b u t yld i-
p h en ylsilyl)oxy)-2-p h en yl-1-eth yl]tetr a h yd r ofu r a n (5d )
a n d (2S)-2-[(1R,2S)-1-(Ch lor om er cu r io)-2-((ter t-b u t yl-
diph en ylsilyl)oxy)-2-ph en yl-1-eth yl]tetr ah ydr ofu r an (6d).
Using the general intramolecular oxymercuration procedure,
alkenol 4d was cyclized to yield 5d and 6d . Syn:anti ratio:
6:1 (CH2Cl2), 84%, 10:1 (CH3CN), 86%. 5d : [R]19D 2.81° (c 0.92,
1
CHCl3); H NMR (200 MHz, CDCl3) δ 1.06 (s, 9H), 1.20 (d, J
) 6.1 Hz, 3H), 1.39-1.52 (m, 2H), 1.62-1.1.82 (m, 2H), 2.78
(dd, J ) 3.9,7.5 Hz, 1H), 3.49 (ddd, J ) 8.0, 8.0, 7.9 Hz, 1H),
3.59-3.80 (m, 2H), 5.06 (d, J ) 3.9 Hz, 6H), 7.16-7.46 (m,
11H), 7.69-7.74 (m, 4H); 13C NMR (50 MHz, CDCl3) δ 19.9,
26.6, 27.9, 33.5, 67.9, 76.1, 77.4, 79.8, 126.2, 128.0, 128.3, 128.5,
129.2, 130.3, 130.6, 136.5, 136.7; MS (EI) m/ z no M+ at 665
observed, 295 (66%), 71 (100).
Gen er a l Meth od for In tr a m olecu la r Oxym er cu r a tion
Rea ction s. Mercuric acetate (0.12 g, 0.38 mmol) was added
in one portion to a solution of the appropriate alkenol (0.32
mmol) in a solvent (5 mL, see Table 1). After stirring (usually
for 20 h) at room temperature, brine (2 mL) was added and
the mixture stirred for a further 15 min. The mixture was
partitioned between hexanes (10 mL) and brine (10 mL), and
the layers were separated. The organic layer was washed with
(2R)-2-[(1R,2S)-1-(Ch lor om er cu r io)-2-((ter t -b u t yld i-
m eth ylsilyl)oxy)-1-pr opyl]tetr ah ydr ofu r an (5e) an d (2R)-
2-[(1R,2S)-1-(Ch lor om er cu r io)-2-((ter t-b u t yld im et h yl-
silyl)oxy)-1-p r op yl]tetr a h yd r ofu r a n (6e). Using the gen-
eral intramolecular oxymercuration procedure, alkenol 4e was
cyclized to yield 5e and 6e; [R]20 -22.83° (c 0.60, CHCl3, 6:1
D
1
mixture of 5e and 6e); H NMR (200 MHz, CDCl3) δ 0.08 (s,

2114 J . Org. Chem., Vol. 61, No. 6, 1996
Bratt et al.
3H), 0.09 (s, 3H), 0.88 (s, 9H, 6e), 0.90 (s, 9H), 1.22 (d, J ) 6.0
Hz, 3H), 1.27 (d, J ) 6.0 Hz, 3H, 6e), 1.30-1.48 (m, 1H), 1.85-
2.14 (m, 3H), 2.76 (dd, J ) 4.0, 6.7 Hz, 1H), 3.05 (t, J ) 4.6
Hz, 1H, 6e), 3.67 (ddd, J ) 1.0, 7.4, 14.3 Hz, 1H), 3.84-3.97
(m, 1H), 4.06 (dd, J ) 6.9, 13.7 Hz, 1H), 4.18 (m, 1H); 13C NMR
(50 MHz, CDCl3) δ -4.7, -3.9, 17.7, 25.9, 26.4, 33.1, 67.4, 69.5,
72.9, 73.6, 79.7; MS (EI) m/ z M+ 479 (0.2%), 75 (100).
136.3, 136.5, 136.7; MS (EI) m/ z no M+ observed at 858.03,
199 (100%). Anal. Calcd for C39H49ClHgO3Si2: C, 54.59; H,
5.76. Found: C, 54.47; H, 5.93.
4-[(4S)-[(1R)-1-(Ch lor om er cu r io)((2S)-tetr ah ydr ofu r an -
2-yl)m eth yl]-2,2-d im eth yl-1,3-d ioxola n e a n d 4-[(4S)-[(1S)-
1-(Ch lor om er cu r io)((2R)-tetr a h yd r ofu r a n -2-yl)m eth yl]-
2,2-d im eth yl-1,3-d ioxola n e (15). Mercuric acetate (1.438 g,
4.51 mmol) was added in one portion to a stirred solution of
the alcohol (0.420 g, 2.28 mmol) in CH2Cl2 (30 mL) at room
temperature. The mixture was stirred for 18 h and then brine
(12 mL) was added and the reaction left to stir for a further
15 min. The aqueous phase was extracted with CH2Cl2, and
the combined organic extracts were washed with brine and
dried (MgSO4) to give a solid (0.835 g, 87%). Separation by
flash column chromatography (50% ether/light petroleum
ether) gave the diastereomers as colorless crystals. Dia-
stereomer 1: [R]D +11.9° (c 0.68, CHCl3); 1H NMR (200 MHz,
CDCl3) δ 1.35 (s, 3H), 1.43 (s, 3H), 1.93 (m, 2H), 2.13 (m, 2H),
3.12 (m, 1H), 3.71 (m, 2H), 3.93 (m, 2H), 4.15 (m, 1H), 4.50 (q,
J ) 6.1Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 25.6, 25.7, 27.4,
34.0, 65.1, 67.7, 71.1, 77.4, 78.7, 109.3; MS (EI) m / z 421 (M+,
0.8%), 111 (100). Anal. Calcd for C10H17ClHgO3: C, 28.51;
H, 4.07. Found: C, 28.29; H, 4.07. Diastereomer 2: [R]D +0.6°
(c 0.64, CHCl3); 1H NMR (200 MHz, CDCl3) δ 1.33 (s, 3H), 1.41
(s, 3H), 2.02 (m, 4H), 2.86 (t, J ) 5.2 Hz, 1H), 3.53 (m, 2H),
3.74 (m, 2H), 3.93 (m, 1H), 4.48 (q, J ) 6.1 Hz, 1H); 13C NMR
(50 MHz, CDCl3) δ 25.3, 25.8, 27.4, 33.5, 65.1, 67.9, 70.5 , 76.8,
79.8, 109.6; MS (EI) m/ z 421 (M+, 0.2%), 71 (100). Anal.
Calcd for C10H17ClHgO3: C, 28.51; H, 4.07. Found: C, 28.25;
H, 4.10.
(2R )-2-[(1R ,2S )-1-(C h lo r o m e r c u r io )-2-(b e n zy lo x y -
m et h oxy)-1-p r op yl]t et r a h yd r ofu r a n (5f) a n d (2R)-2-
[(1R,2S)-1-(Ch lor om er cu r io)-2-(b en zyloxym et h oxy)-1-
p r op yl]tetr a h yd r ofu r a n (6f). Using the general intramo-
lecular oxymercuration procedure, alkenol 4f was cyclized to
yield an inseparable mixture of 5f and 6f: [R]18 -13.58° (c
D
1
1.06, CHCl3, 7.5:1 mixture of 5f and 6f); H NMR (200 MHz,
CDCl3) δ 1.27 (d, J ) 6.0 Hz, 3 H, 5f), 1.33 (d, J ) 6.1 Hz, 3
H, 6f), 1.27-1.48 (m, 1H), 1.85-2.08 (m, 3 H), 2.75 (dd, J )
4.0, 7.0 Hz, 1H, 5f), 3.06 (t, J ) 4.0 Hz, 1H, 6f), 3.68 (dd, J )
6.8, 16 Hz, 1 H), 3.90 (dd, J ) 5.6, 6.0 Hz, 1 H), 4.09-4.21 (m,
2H), 4.59 (d, J ) 12.0 Hz, 1 H, 5f), 4.69 (d, J ) 12.0 Hz, 1 H,
5f), 4.75 (d, J ) 7.2 Hz, 1 H, 5f), 4.77 (d, J ) 7.2 Hz, 1 H, 6f),
4.84 (d, J ) 7.2 Hz, 1 H, 6f), 4.86 (d, J ) 7.2 Hz, 1 H, 5f),
7.28-7.38 (m, 5 H); 13C NMR (50 MHz, CDCl3) δ 12.9, 22.5,
25.7, 25.9, 33.4, 33.7, 67.6, 69.8, 69.9, 70.0, 74.2, 74.7, 79.8,
92.6, 127.8, 127.8, 127.9, 128.5, 128.5; MS m/ z M+ 485 (4%),
97 (100). Anal. Calcd for C15H21ClHgO3: C, 37.12; H, 4.36.
Found: C, 37.14, H, 4.29.
(2R)-2-[(1R,2S)-1-(Ch lor om er cu r io)-2-((ter t -b u t yld i-
p h e n y ls ily l)o x y )-1-p r o p y l]-5,5-d im e t h y lt e t r a h y d r o -
fu r a n (5g) a n d (2R)-2-[(1R,2S)-1-(Ch lor om er cu r io)-2-
((ter t-bu tyld ip h en ylsilyl)oxy)-1-p r op yl]-5,5-d im eth yltet-
r a h yd r ofu r a n (6g). Using the general intramolecular oxy-
mercuration procedure, alkenol 4g was cyclized to yield 5g and
(2R)-2-[(2S)-2-((ter t-Bu tyld ip h en ylsilyl)oxy)-1-p r op yl]-
tetr a h yd r ofu r a n (7b). Tributylstannane (0.17 mL, 0.63
mmol) was added in one portion to a stirred solution of the
chloromercurial 5b (0.154 g, 0.26 mmol) and azobis(isobutyro-
nitrile) (AIBN) (3.4 mg, 0.021 mmol) in toluene (2.5 mL) under
an atmosphere of argon at room temperature. Mercury began
to precipitate almost immediately, and the reaction mixture
was stirred at room temperature for 1 h and then at 50 °C for
6g: [R]18 +2.69° (c 0.26, CHCl3, 10:1 mixture of 5g and 6g).
D
5g: 1H NMR (200 MHz, CDCl3) δ 1.07 (s, 9 H), 1.12 (d, J )
6.0 Hz, 3 H), 1.16 (s, 3H), 1.20 (s, 3H), 1.24-1.29 (m, 1H),
1.56-1.72 (m, 3 H), 2.69 (dd, J ) 2.6, 7.0 Hz, 1 H), 4.07-4.22
(m, 2 H), 7.35-7.46 (m, 6 H), 7.64-7.75 (m, 4 H); 13C NMR
(50 MHz, CDCl3) δ 19.1, 26.5, 27.08, 33.7, 38.9, 70.9, 74.5, 78.8,
80.9, 127.5, 127.7, 129.7, 129.8, 134.2, 136.0, 136.1; MS (EI)
m/ z no M+ observed at 631, 199 (100%). Anal. Calcd for
C25H35ClHgO2Si: C, 47.54; H, 5.59. Found: C, 47.31; H, 5.32.
(2S )-2-[(1R ,2S )-1-(Ch lor om e r cu r io)-2-((t er t -b u t yld i-
p h en ylsilyl)oxy)-1-p r op yl]tetr a h yd r ofu r a n (10) a n d (2R)-
2-[(1S ,2S )-1-(Ch lor om e r cu r io)-2-((t er t -b u t yld ip h e n yl-
silyl)oxy)-1-p r op yl]tetr a h yd r ofu r a n (11). Using the gen-
eral procedure described above, alkenol 9 (200 mg, 0.51 mmol,
containing 20% 4b) was cyclized to yield two pairs of diaster-
eomers in 76% overall yield and a ratio of 3.3:1. The minor
pair of isomers was shown, by comparison of their 1H NMR
spectra with authentic samples, to consist of 5b and 6b in a
7:1 ratio. The major pair of isomers, 10 and 11, was obtained
in a ratio of 1.6:1, respectively. Purification by preparative
TLC (silica, ether/light petroleum ether) gave an inseparable
mixture of 10 and 11 (190 mg) as a colorless gum. 10 and 11
a
further 1 h. The oil bath was removed, and carbon
tetrachloride (0.5 mL) was added to consume the excess
tributylstannane. After 1 h, the solution was decanted from
mercury, diluted with 25% dichloromethane/light petroleum
ether and washed with a 5% aqueous potassium fluoride
solution (3 × 5 mL). The organic layer was dried (MgSO4)
and filtered and the solvent removed under reduced pressure.
Purification of the crude product using preparative TLC (silica)
gave 7b as a colorless oil (94 mg, 100%): [R]19D -10.9° (c 0.52,
1
CHCl3); H NMR (200 MHz, CDCl3) δ 1.05 (s, 9H), 1.12 (d, J
) 2.9 Hz, 3H), 1.21-1.40 (m, 1H), 1.43-1.56 (m, 1H), 1.68-
1.93 (m, 4H), 3.56-3.76 (m, 2H), 3.85-4.07 (m, 2H), 7.31-
7.74 (m, 10H); 13C NMR (50 MHz, CDCl3) δ 19.2, 23.4, 25.5,
27.0, 45.2, 67.3, 67.6, 76.2, 127.4, 127.5, 129.4, 128.5, 134.4,
134.7, 135.9; MS (EI) m/ z no M+ at 368 observed, 367 (M+
-
1, 15%), 311 (100), 291 (100); TLC Rf 0.24 (silica, 20% ether/
light petroleum ether). Anal. Calcd for C23H32O2Si: C, 74.95;
H, 8.75. Found: C, 74.68; H, 8.54.
(2:1 ratio): [R]21 -21.6° (c 1.35, CHCl3); 1H NMR (200 MHz)
D
δ 1.07 (s, 9H, 10), 1.09 (s, 9H, 11), 1.25 (d, J ) 5.9 Hz, 3H),
1.29-1.42 (m, 1H), 1.73-1.95 (m, 2H), 1.97-2.14 (m, 1H), 2.89
(dd, J ) 8.7, 3.3 1H, 10), 3.03 (dd, J ) 9.3, 5.0 Hz, 1H, 11),
3.60-3.71 (m, 1H), 3.77-3.88 (m, 1H), 3.98-4.15 (m, 1H),
4.43-4.54 (m, 1H), 7.34-7.74 (m, 10H); 13C NMR (50 MHz) δ
19.1, 11; 19.2, 10; 25.7, 11; 25.8, 10; 25.9, 11; 26.8, 10; 27.2,
10; 34.7, 34.8, 10; 67.9, 70.2, 11; 70.5, 10; 72.0 11; 73.0, 10;
78.8, 11; 79.6, 10; 127.7, 127.8, 127.9, 127.9, 129.8, 129.9,
130.0, 133.5, 133.8, 134.2, 135.9, 136.0 136.0, CH; MS (CI) m/ z
(2S)-2-[(2S)-2-((ter t-Bu tyld ip h en ylsilyl)oxy)-1-p r op yl]-
tetr a h yd r ofu r a n (8b). Using the procedure described above
for 5b, demercuration of the chloromercurial 6b (210 mg, 0.35
mmol) gave 8b as a colorless oil (120 mg, 94%); [R]22 -7.6° (c
D
1
1.54, CHCl3); H NMR (200 MHz) δ 1.05 (s, 9H), 1.12 (d, J )
6.1 Hz, 3H), 1.28-1.56 (m, 2H), 1.68-1.93 (m, 2H), 3.56-3.76
(m, 2H), 3.85-4.07 (m, 2H), 7.32-7.71 (m, 10H); 13C NMR (50
MHz) δ 19.3, 23.5, 25.6, 27.1, 31.7, 127.5, 127.6, 129.5, 129.6,
134.5, 134.9, 135.99, 136.01; MS (CI) m/ z 367 (M+ - 1, 8%),
311 (100). Anal. Calcd for C23H32O2Si: C, 74.95; H, 8.75.
Found: C, 75.05; H, 8.90.
no M+ at 603 observed, 79 (100). Anal. Calcd for C23H31
ClHgO2Si: C, 45.77; H, 5.18. Found: C, 45.81; H, 5.17.
-
2-(1′-(Ch lor om er cu r io)-2′,3′-b is[(ter t-b u t yld ip h en yl-
silyl)oxy]-2-p r op yl)tetr a h yd r ofu r a n (13). Using the gen-
eral intramolecular oxymercuration procedure, alkenol 12 was
cyclized to yield 13 as a single diastereomer in 95% yield:
[R]18D 1.81° (c 0.55, CHCl3); 1H NMR (200 MHz, CDCl3) δ 1.00
(s, 18H), 1.36-1.57 (m, 2H), 1.61-1.90 (m, 2H), 2.83 (dd, J )
1.8, 7.8 Hz, 1H), 3.39 (d, J ) 7.8 Hz, 1H), 3.56-3.68 (m, 2H),
3.73-4.01 (m, 3H), 7.22-7.66 (m, 10H); 13C NMR (50 MHz,
CDCl3) δ 19.7, 19.8, 26.4, 27.7, 33.5, 66.5, 68.0, 68.4, 75.1, 79.9,
128.2, 128.4, 128.5, 130.4, 130.5, 130.6, 133.6, 134.2, 136.2,
1-((2R)-2-Tetr ah ydr ofu r an yl)-(2S)-2-pr opan ol (7a). Tet-
rabutylammonium fluoride (1 M, 17 mL, 17 mmol) was added
dropwise to a stirred solution of 7b (2.081 g, 5.65 mmol) in
THF (30 mL). The reaction mixture was stirred at room
temperature for 42 h, then diluted with ether (150 mL), dried
(MgSO4), and filtered and the solvent removed under reduced
pressure. The oily residue was purified using flash column
chromatography (silica, 50% ether/light petroleum ether) to
give the alcohol as a colorless oil (723 mg, 99%): [R]22D +14.5°

Allylic Ethers in Oxymercurations of γ-Hydroxyalkenes
J . Org. Chem., Vol. 61, No. 6, 1996 2115
(c 0.42, EtOH), [R]20 +3.7° (c 1.36 CHCl3); IR (film) 3418 bs
(10 mL) was added to the cooled (room temperature) solution,
and the layers were separated. The aqueous layer was
extracted with dichloromethane (3 × 5 mL), the organic layers
were combined and dried (MgSO4), and the solvent was
removed in vacuo. Purification of the residue by preparative
TLC (silica, 50% ether/light petroleum ether) gave the ester
D
cm-1; H NMR (200 MHz, CDCl3) δ 1.18 (d, J ) 6.2 Hz, 3H),
1
1.40-1.71 (m, 2H), 1.79-2.10 (m, 2H), 3.71-3.88 (m, 3H),
3.91-4.10 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 23.5, 25.3,
32.3, 44.1, 68.0, 68.1, 79.9; MS (CI) m/ z 131 (M+ + 1, 2%), 71
(100). Satisfactory elemental analysis proved to be unobtain-
able with this compound. Therefore it was fully characterized
as its 3,5-dinitrobenzoate. 3,5-Dinitrobenzoyl chloride (21 mg,
0.91 mmol) was added to a stirred solution of 7a (11 mg, 0.085
mmol) in dry pyridine (1 mL) at room temperature. After
stirring for 18 h, dichloromethane (5 mL) was added, the
mixture washed successively with 5% aqueous sulfuric acid
(2 × 5 mL) and saturated aqueous sodium bicarbonate solution
(2 × 5 mL) and dried (MgSO4), and the solvent was removed
in vacuo. The residue was purified by preparative TLC (silica,
20% ether/light petroleum ether) giving colorless needles: mp
17 as a colorless oil (40 mg, 71%): [R]20D -25.2° (c 0.82, CHCl3),
1
lit.16 [R]20 -17.9° (neat, l ) 0.5): H NMR (200 MHz, CDCl3)
D
δ 1.52-1.70 (m, 1H), 1.84-2.08 (m, 3H), 2.10 (s, 3H), 3.75-
4.21 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 20.9, 25.6, 27.9,
66.6, 68.4, 76.5, 171.1; TLC Rf 0.35 (50% ether/light petroleum
ether).
(4Z,6S)-[(ter t-Bu tyld ip h en ylsilyl)oxy]-4-h ep ten a l (18).
DIBAL-H (1 M in toluene, 1.28 mL, 1.28 mmol) was added
dropwise to a stirred solution of the ester (S)-(+)-3a (95% Z,
0.500 g, 1.22 mmol) in toluene (5 mL) at -78 °C. The reaction
mixture was stirred for 1 h, the reaction was quenched with
water (1 mL), and then the mixture was allowed to warm to
room temperature. The insoluble material was removed by
filtration and rinsed with ether (3 × 10 mL). The filtrate was
separated and the aqueous phase extracted with ether (3 ×
10 mL). The combined organic phases were dried (MgSO4) and
filtered, and the solvent was removed in vacuo. Purification
of the residue by preparative TLC (silica, 20% ether/light
petroleum ether) gave aldehyde (S)-(+)-18 (>95% Z) as a
75-77 °C; [R]24D +29.7° (c 0.94, CHCl3); IR (Nujol) 1718 s cm-1
;
1H NMR (200 MHz, CDCl3) δ 1.43-1.61 (m, 1H), 1.48 (d, J )
6.3 Hz, 3H), 1.78-2.18 (m, 3H), 3.64-4.00 (m, 3H), 5.42 (ddq,
J ) 6.1, 1.9, 1.9 Hz, 1H), 9.17-9.21 (m, 2H), 9.22-9.23 (m,
1H); 13C NMR (50 MHz, CDCl3) δ 20.3, 25.5, 32.0, 41.8, 67.9,
72.9, 76.3; mass spectrum (CI) m/ z 325 (M+, 1%), 71 (100).
Anal. Calcd for C14H16N2O7: C, 51.85; H, 4.97; N, 8.64.
Found: C, 51.74; H, 4.95; N, 8.51.
Desilyla tion of 5b. A 1 M solution of tetrabutylammonium
fluoride (0.19 mL, 0.19 mmol) was added dropwise to a solution
of the chloromercurial 5b (37 mg, 0.06 mmol) in THF (1 mL)
at room temperature. After stirring for 24 h, the reaction
mixture was worked up as described above. Purification by
preparative TLC (silica, ether/light petroleum ether) gave 5a
colorless oil (0.360 g, 81%): [R]19 +12.1° (c 4.43, CHCl3); IR
D
(film) 1726 cm-1; H NMR (200 MHz, CDCl3) δ 1.04 (s, 9H),
1
1.18 (d, J ) 6.3 Hz, 3H), 1.83-2.06 (m, 2H), 2.12-2.23 (m,
2H), 4.57 (dqd, J ) 8.5, 6.3, 1.0 Hz, 1H), 5.11 (dtd, J ) 10.9,
7.2, 1.0 Hz, 1H), 5.54 (ddt, J ) 10.9, 8.5, 1.6 Hz, 1H), 7.30-
as a colorless gum (21 mg, 94%); [R]23 -25.6° (c 3.11, EtOH);
D
7.47 (m, 6H), 7.64-7.73 (m, 4H), 9.56 (t, J ) 1.5 Hz, 1H); 13
C
IR (CHCl3) 3406 bs, cm-1; H NMR (200 MHz, CDCl3) δ 1.26
1
NMR (50 MHz, CDCl3) δ 19.1, 19.2, 20.0, 24.5, 26.9, 43.3, 65.7,
125.6, 127.3, 127.5, 129.46, 129.53, 134.1, 134.3, 135.6, 135.8,
135.9, 136.0, 201.6; MS (CI) m/ z 369 (M+ + 1, 10%), 291 (100).
Anal. Calcd for C23H30O2Si: C, 75.36; H, 8.25. Found: C,
75.01, H, 8.49.
(d, J ) 6.1 Hz, 3H), 1.29-1.50 (m, 1H), 1.86-2.01 (m, 2H),
2.10-2.25 (m, 1H), 3.10 (dt, J ) 115.8, 2.2 Hz, 1H), 3.65 (bs,
1H), 3.71-3.83 (m, 1H), 3.96-4.07 (m, 1H), 4.28 (ddd, J ) 8.6,
6.1, 2.2 Hz, 1H), 4.40 (bqd, J ) 6.1, 1.6 Hz, 1H); 13C NMR (50
MHz, CDCl3) δ 25.1, 34.4, 68.3, 71.6, 83.3; MS (CI) m/ z 351
(M+ + CH4, 4%), 85 (100). Anal. Calcd for C7H13ClHgO2: C,
23.02; H, 3.59. Found: C, 23.15; H, 3.58.
1-((2R)-2-Tet r a h yd r ofu r a n yl)-2-p r op a n on e (16). Di-
methyl sulfoxide (0.360 g, 4.61 mmol) in dichloromethane (2.5
mL) was added dropwise to a stirred solution of oxalyl chloride
(0.268 g, 2.11 mmol) in dichloromethane (5 mL) at -78 °C.
Stirring was continued at this temperature for 10 min followed
by dropwise addition of a solution of 5b (0.250 g, 1.92 mmol)
in dichloromethane (2 mL). The reaction mixture was stirred
for a further 15 min and then NEt3 (0.973 g, 9.62 mmol) was
added over a period of 5 min. The cooling bath was removed,
water (6 mL) was added at room temperature, and stirring
was continued for 10 min. The organic phase was separated
and the aqueous layer extracted with dichloromethane (3 ×
10 mL). The organic layers were combined and dried (MgSO4),
and the solvent was removed in vacuo. Purification of the
yellow oil by flash column chromatography (silica, 40% ether/
Ald ol Ad d u ct (-)-(2R,3S,6Z,8S)-20. Trifluoromethane-
sulfonic acid (89 µL, 152 mg, 1.01 mmol) was added dropwise
to a stirred solution of triethylborane (1 M in hexanes, 1.01
mL, 1.01 mmol) at room temperature. Bubbles of gas were
observed to evolve. The mixture was heated at 40 °C until it
became homogeneous (ca. 40 min) and then cooled to -5 °C.
N-Propionylsultam (137 mg, 0.51 mmol) dissolved in dichlo-
romethane (2 mL) was added dropwise to the cooled solution
i
followed by Pr2EtN (137 mg, 1.06 mmol) in dichloromethane
(1 mL). The reaction mixture was stirred for 30 min at this
temperature and then cooled to -78 °C. A solution of aldehyde
18 (200 mg, 0.55 mmol) in dichloromethane (1.0 mL) was then
added dropwise, and the reaction mixture was stirred for a
further 75 min. Phosphate buffer (pH 7, 1 mL) was added
and the reaction mixture left to warm to room temperature.
The layers were separated, and the aqueous phase was
extracted with ether (3 × 10 mL). The combined organic layers
were washed with saturated aqueous NH4Cl (20 mL), dried
(MgSO4), and filtered and the solvent removed in vacuo.
Purification of the residue using flash column chromatography
(silica, 30% ether/light petroleum ether) followed by prepara-
tive TLC (silica, 30% ether/light petroleum ether, Rf 0.23) to
remove traces of 18 gave 20 as a colorless gum (170 mg, 53%):
light petroleum ether) gave 16 as a colorless oil (0.210 g,
1
85%): [R]20 +1.9° (c 0.85, CHCl3); IR (film) 1714 s cm-1; H
D
NMR (200 MHz, CDCl3) δ 1.38-1.56 (m, 1H), 1.83-1.97 (m,
2H), 2.03-2.18 (m, 1H), 2.20 (s, 3H), 2.56 (dd, J ) 15.9, 5.6
Hz, 1H), 2.76 (dd, J ) 15.9, 7.2 Hz, 1H), 3.68-3.92 (m, 2H),
4.23 (dq, J ) 7.4, 6.0 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ
25.6, 30.8, 31.6, 49.7, 67.9, 75.1, 207.4; MS (EI) m/ z 128 (M+,
4%), 71 (100); TLC Rf 0.25 (40% ether/light petroleum ether);
HRMS (EI) 128.083 ( 0.001 (M+ calcd for C7H12O2 128.084).
((2R)-2-Tetr a h yd r ofu r a n yl)m eth yl Aceta te (17). Tri-
fluoroacetic anhydride (0.51 mL) was added dropwise to an
unstirred solution of hydrogen peroxide (82%, 0.12 mL) in
dichloromethane (0.5 mL) at 0 °C. Stirring was begun, and
the reaction mixture was stirred for 10 min at 0 °C, warmed
to room temperature, and then stirred for a further 30 min.
Trifluoroperacetic acid solution prepared as just described (1.4
mL) was added dropwise to a stirred suspension of the ketone
16 (50 mg, 0.40 mmol) and dipotassium hydrogen phosphate
(400 mg, 2.3 mmol) in dichloromethane (2.5 mL) at 0 °C. The
cooling bath was removed, and the mixture was heated at
reflux for 2 h when all starting material had been consumed
as indicated by analytical TLC. Saturated NaHCO3 solution
[R]21 -93.3° (c 0.12, CHCl3); IR (CHCl3) 3531, 1677, 1336
D
1
cm-1; H NMR (200 MHz, CDCl3) δ 0.97 (s, 3H), 1.04 (s, 9H),
1.14 (s, 3H), 1.16 (d, J ) 7.0 Hz, 3H), 1.19 (d, J ) 7.2 Hz, 3H),
1.39-1.45 (m, 2H), 1.72-1.92 (m, 7 H), 2.03 (bd, J ) 6.2 Hz,
2H), 2.84 (bs, 1H), 2.93 (qd, J ) 7.2, 3.0 Hz, 1H), 3.43 (d, J )
13.8 Hz, 1H), 3.50 (d, J ) 13.8 Hz, 1H), 3.69-3.80 (m, 1H),
3.86 (bt, J ) 6.2 Hz, 1H), 4.62 (dqd, J ) 8.4, 7.1, 0.9 Hz, 1H),
5.16 (dtd, J ) 11.0, 8.6, 0.9 Hz, 1H), 5.50 (ddt, J ) 11.0, 8.4,
1.2 Hz, 1H), 7.31-7.72 (m, 10 H); 13C NMR (50 MHz, CDCl3)
δ 11.7, 19.2, 19.9, 20.9, 23.8, 24.8, 26.5, 27.0, 32.9, 33.6, 38.4,
44.4, 44.6, 47.8, 48.4, 53.1, 65.0, 66.0, 69.8, 127.47, 127.54,
(16) Gagnaire, D.; Butt, A. Bull. Soc. Chem. Fr. 1961, 312.
(17) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.

2116 J . Org. Chem., Vol. 61, No. 6, 1996
Bratt et al.
129.5, 134.4, 134.8, 135.3, 135.9, 136.0, 177.1; MS (EI) m/ z
637 (M+, 0.2%), 199 (100). Anal. Calcd for C36H51NO5SSi: C,
67.78; H, 8.06; N, 2.20. Found: C, 68.07; H, 8.37, N, 2.06.
Ald ol Ad d u ct (+)-(2S,3R,6Z,8S)-27. The aldol adduct (+)-
27 was prepared from aldehyde 18 according to the procedure
described above using N-propionylsultam 11 in place of 16.
The title compound (+)-27 (220 mg, 62%) was obtained as a
colorless gum which crystallized on standing following puri-
fication by flash chromatography and preparative TLC (silica,
20% ether/light petroleum ether, Rf 0.10). A sample for X-ray
crystallographic analysis was obtained by recrystallization
from ether/light petroleum ether to give colorless rhomboid
crystals (mp 95-97°) [R]22D +54.7° (c 1.75, CHCl3); IR (CHCl3)
product indicated the two diastereomers to be in a ratio of 84:
16. 28a : Rf 0.17 [R]22D +10.9° (c 1.94, CHCl3); IR (CHCl3) 1687
1
cm-1; H NMR (200 MHz, CDCl3) δ 0.98 (s, 3H), 1.08 (s, 9H),
1.14 (d, J ) 6.5 Hz, 3H), 1.15 (s, 3H), 1.26-1.59 (m, 7H), 1.31
(d, J ) 6.9 Hz, 3H), 1.88-2.05 (m, 4H), 2.65 (dd, J ) 8.1, 2.6
Hz, 1H), 3.04 (dq, J ) 9.2, 6.9 Hz, 1H), 3.46 (d J ) 13.6 Hz,
1H), 3.54 (d J ) 13.6 Hz, 1H), 3.87 (bt, J ) 6.3 Hz, 1H), 4.08-
4.19 (m, 3H), 7.35-7.73 (m, 10 H); 13C NMR (50 MHz, CDCl3)
δ 17.1, 19.1, 20.0, 20.8, 26.6, 26.7, 27.2, 31.3, 32.9, 33.4, 38.4,
44.6, 46.1, 47.9, 48.4, 53.3, 64.9, 70.5, 74.2, 79.0, 79.4, 127.6,
128.0, 129.8, 130.1, 134.3, 136.1, 136.06, 136.14, 174.6; MS
(EI) m/ z no M+ 202Hg35Cl) at 873 observed, 199 (100%). Anal.
(
Calcd for C36H50ClHgNO5SSi: C, 49.53; H, 5.77; N, 1.60.
Found: C, 49.79; H, 6.01; N, 1.43. 28b: Rf 0.23; [R]22D +18.1°
1
3530, 1677 cm-1; H NMR (300 MHz, CDCl3) δ 0.98 (s, 3H),
(c 1.40, CHCl3); IR (CHCl3) 1688, 1333 cm-1 1H NMR (200
;
1.03 (s, 9H), 1.15 (s, 3H), 1.17 (d, J ) 6.8 Hz, 3H), 1.18 (d, J
) 7.0 Hz, 3H), 1.26-1.46 (m, 4H), 1.59-1.70 (m, 1H), 1.80-
1.95 (m, 4H), 2.04 (bd, J ) 6.3 Hz, 2H), 2.90 (bd, J ) 2.7 Hz,
1H), 2.92 (qd, J ) 7.0, 2.7 Hz, 1H), 3.40 (d, J ) 13.8 Hz, 1H),
3.46 (d, J ) 13.8 Hz, 1H), 3.73 (bdq, J ) 9.2, 2.7 Hz, 1H), 3.88
(bt, J ) 6.3 Hz, 1H), 4.59 (dqd, J ) 8.6, 6.8,1.1 Hz, 1H), 5.14
(dtd, J ) 10.2, 8.1, 1.1 Hz, 1H), 5.49 (ddt, J ) 10.2, 8.6, 1.8
Hz, 1H), 7.31-7.71 (m, 10 H); 13C NMR (50 MHz, CDCl3) δ
11.7, 19.2, 19.9, 20.9, 24.0, 24.7, 26.5, 27.0, 32.9, 33.7, 38.4,
44.3, 44.6, 47.8, 48.4, 53.2, 65.0, 66.1, 70.1, 127.47, 127.56,
127.61, 129.5, 134.4, 134.7, 135.2, 135.9, 136.0, 177.1; MS (EI)
m/ z 637 (M+, 0.1%), 199 (100). Anal. Calcd for C36H51NO5-
SSi: C, 67.78; H, 8.06. Found: C, 67.64; H, 8.07.
MHz, CDCl3) δ 0.97 (s, 3H), 1.07 (s, 9H), 1.15 (s, 3H), 1.16-
1.76 (m, 5H), 1.23 (d, J ) 5.8 Hz, 3H), 1.26 (d, J ) 7.2 Hz,
3H), 1.79-2.03 (m, 6H), 2.87 (bt, J ) 5.1 Hz, 1H), 3.19, (dq J
) 7.2, 7.2 Hz, 1H), 3.51 (m, 2H), 3.70-3.79 (m, 1H), 3.86-
3.93 (m, 1H), 4.02 (bt, J ) 6.3 Hz, 1H), 4.17 (qd, J ) 5.8, 5.1
Hz, 1H), 7.34-7.69 (m, 10 H); 13C NMR (50 MHz, CDCl3) δ
16.2, 19.0, 19.9, 20.9, 26.4, 26.7, 27.0, 28.7, 32.6, 38.3, 44.7,
45.0, 47.7, 48.2, 53.2, 64.8, 71.0, 72.3, 78.8, 79.8, 127.6, 127.8,
129.8, 129.9, 133.7, 133.8, 135.8, 135.8, 174.4; MS (EI) m/ z
no M+ 202Hg35Cl) at 873 observed, 199 (100%). Anal. Calcd
(
for C36H50ClHgNO5SSi: C, 49.53; H, 5.77; N, 1.60. Found: C,
49.52; H, 5.64; N, 1.41.
Red u ctive Dem er cu r a tion of 21a . Tributylstannane
(0.148 g, 0.509 mmol) was added in one portion to a solution
of the chloromercurial 21a (177 mg, 0.203 mmol) and AIBN
(2.7 mg, 0.016 mmol) in toluene (4 mL). Mercury began to
precipitate almost immediately, and the mixture was left to
stir at room temperature for 1 h and then at 55 °C for 1 h.
The heating bath was removed, carbon tetrachloride (0.5 mL)
was added, and the mixture was stirred for a further 1 h. The
reaction mixture was decanted from mercury, diluted with 25%
dichloromethane/light petroleum ether (20 mL), and washed
with aqueous potassium fluoride (5% 4 × 10 mL). The organic
layer was dried (MgSO4) and filtered and the solvent removed
in vacuo. Purification of the crude product by preparative TLC
(silica, 20% ether/light petroleum ether, Rf 0.20) gave the
In tr a m olecu la r Oxym er cu r a tion of 20. Mercuric ace-
tate (234 mg, 0.734 mmol) was added in one portion to a stirred
solution of 20 (237 mg, 0.372 mmol) in dichloromethane (5 mL)
at room temperature. After stirring for 20 h, brine was added
(2 mL) and the reaction left to stir for a further 15 min. The
mixture was diluted with light petroleum ether (25 mL), and
the layers were separated. The organic phase was washed
with a further portion of brine (10 mL), dried (MgSO4), and
filtered. The solvent was removed under reduced pressure to
give the crude product as a highly viscous oil. The 1H NMR
spectrum (200 MHz) of the crude mixture indicated that the
chloromercurials 21a and 21b were in a 93:7 ratio. The
products were purified and separated using preparative TLC
(silica, 20%, ether/light petroleum ether) to give each of the
diastereomers as colorless gums. 21a : Rf 0.12 (294 mg, 90%);
reduced product 22 as a viscous oil (130 mg, 100%); [R]22
D
-62.0° (c 2.83, CHCl3); IR (CHCl3) 1687, 1334 cm-1; 1H NMR
(200 MHz, CDCl3) δ 0.97 (s, 3H) 1.04 (s, 9H), 1.09 (d, J ) 6.1
Hz, 3H), 1.16 (s, 3H), 1.28 (d, J ) 6.9 Hz, 3H), 1.33-1.61 (m,
6H), 1.67-1.99 (m, 5H), 2.03 (bd, J ) 6.2 Hz, 2H), 3.01 (dq, J
) 9.2, 6.9 Hz, 1H), 3.43 (d, J ) 13.8 Hz, 1H), 3.50 (d, J ) 13.8
Hz, 1H), 3.83-4.12 (m, 4H), 7.26-7.73 (m, 10 H); MS (elec-
trospray) 638 (M+ + 1, 100%); HRMS (FAB) m/ z 638.335 (
0.006 (M+ calcd for C36H52NO5SSi 638.334).
[R]21 -44.5° (c 1.09, CHCl3); IR (CHCl3) 1689, 1332 cm-1; 1H
D
NMR (200 MHz, CDCl3) δ 0.97 (s, 3H), 1.07 (s, 9H), 1.14 (s,
3H), 1.27 (d, J ) 6.3 Hz, 3H), 1.30 (d, J ) 7.0 Hz, 3H), 1.33-
1.64 (m, 2H), 1.72-1.91 (m, 7 H), 2.03 (bd, J ) 6.1 Hz, 2H),
2.64 (dd, J ) 8.5, 2.4 Hz, 1H), 3.12 (dq, J ) 8.5, 7.0 Hz, 1H),
3.42-3.53 (m, 2H), 3.84-4.04 (m, 3H), 4.15 (qd, J ) 6.3, 2.4
Hz, 1H), 7.33-7.72 (m, 10 H); 13C NMR (50 MHz, CDCl3) δ
16.6, 19.1, 19.8, 20.8, 26.4, 26.5, 27.1, 29.7, 32.6, 38.3, 44.6,
45.8, 47.7, 48.3, 53.2, 64.8, 70.4, 73.0, 79.6, 79.8, 127.5, 127.7,
127.8, 129.7, 133.3, 134.0, 134.8, 135.8, 136.0, 174.4; MS (EI)
Red u ctive Dem er cu r a tion of 28a . Using the procedure
described above, reductive demercuration of the chloromer-
curial 28a (176 mg, 0.202 mmol) and purification by prepara-
tive TLC (silica, 20% ether/light petroleum ether, Rf 0.20) gave
m/ z no M+ 202Hg35Cl) at 873 observed, 199 (100%). Anal.
(
Calcd for C36H50ClHgNO5SSi: C, 49.53; H, 5.77; N, 1.60.
Found: C, 49.67; H, 5.52; N, 1.33. 17b: Rf 0.06 (22 mg, 7%);
the reduced product 29 as a viscous oil (128 mg, 99%); [R]22
D
[R]19 -67.7° (c 0.07, CHCl3); IR (CHCl3) 1686, 1334 cm-1; 1H
+36.9° (c 1.80, CHCl3); IR (CHCl3) 1689, 1334s cm-1; 1H NMR
(200 MHz, CDCl3) δ 0.97 (s, 3H), 1.04 (s, 9H), 1.10 (d, J ) 6.2
Hz, 3H), 1.15 (s, 3H), 1.29 (d, J ) 6.9 Hz, 3H), 1.31-1.61 (m,
6H), 1.82-1.92 (m, 5H), 2.03 (bd, J ) 6.0 Hz, 2H), 3.02 (dq, J
) 9.2, 6.9 Hz, 1H), 3.44 (d, J ) 13.8 Hz, 1H), 3.50 (d, J ) 13.8
Hz, 1H), 3.87-4.01 (m, 4H), 7.32-7.70 (m, 10 H); 13C NMR
(50 MHz, CDCl3) δ 17.0, 19.3, 19.9, 20.8, 23.5, 26.5, 27.1, 30.7,
31.9, 32.9, 38.4, 44.6, 45.3, 46.2, 47.8, 48.3, 53.3, 64.9, 67.6,
75.8, 79.1, 127.4, 129.5, 129.6, 134.4, 135.0, 136.0, 174.9; MS
(EI) m/ z no M+ at 637 observed, 199 (100%). Anal. Calcd for
C36H51NO5SSi: C, 67.78; H, 8.06; N, 2.20. Found: C, 67.88;
H, 7.99; N, 2.06.
D
NMR (200 MHz, CDCl3) δ 0.98 (s, 3H), 1.07 (s, 9H), 1.17 (s,
3H), 1.23 (d, J ) 7.1 Hz, 3H), 1.25 (d, J ) 6.8 Hz, 3H), 1.28-
1.63 (m, 2H), 1.88-2.01 (m, 7 H), 2.05 (bd, J ) 6.4 Hz, 2H),
2.81 (dd, J ) 9.2, 2.8 Hz, 1H), 3.02 (dq, J ) 8.9, 7.1 Hz, 1H),
3.40-3.57 (m, 2H), 3.87 (bt, J ) 6.4 Hz, 1H), 4.05-4.12 (m,
1H), 4.13-4.30 (m, 1H), 4.48-4.53 (m, 1H), 7.35-7.74 (m, 10
H); 13C NMR (50 MHz, CDCl3) δ 17.1, 19.2, 19.9, 20.8, 26.4,
27.1, 29.7, 31.1, 32.8, 38.3, 44.6, 46.4, 47.8, 48.3, 53.2, 64.8,
70.2, 73.3, 77.9, 80.0, 127.5, 127.9, 129.7, 130.0, 135.9, 175.5;
MS (CI) m/ z no M+ 202Hg35Cl) at 873 observed, 199 (100%);
(
HRMS (EI) m/ z 579.246 ( 0.006 ((M - C(CH3)3HgCl)+ calcd
for C32H41NO5SSi 579.247). Anal. Calcd for C36H50ClHg-
NO5SSi: C, 49.5; H, 5.8; N, 1.6. Found: C, 49.8; H, 5.6; N,
1.4.
Meth yl (2R,3S,6R,8S)-O-(ter t-Bu tyld ip h en ylsilyl)n on -
a cta te (24). Hydrogen peroxide (30%, w/v, 0.030 mL, 0.265
mmol) was added dropwise to a stirred solution of tetrahy-
drofuran 22 (47 mg, 0.074 mmol) and LiOH‚H2O (6.0 mg, 0.143
mmol) in 80% THF/H2O (1.5 mL) at 0 °C. The solution was
stirred at this temperature for 30 min and then allowed to
warm to room temperature. No starting material remained
after 7 h as indicated by analytical TLC. A saturated aqueous
sodium sulfite solution (1 mL) was added, and the mixture
In tr a m olecu la r Oxym er cu r a tion of 27. Oxymercuration
of aldol adduct 27 (288 mg, 0.452 mmol) according to the
procedure described above afforded the chloromercurials 28a
(329 mg, 82%) and 28b (55 mg, 14%) as colorless gums after
purification by preparative TLC (silica, 20% ether/light petro-
leum ether). The 1H NMR spectrum (200 MHz) of the crude

Allylic Ethers in Oxymercurations of γ-Hydroxyalkenes
J . Org. Chem., Vol. 61, No. 6, 1996 2117
was acidified with hydrochloric acid (1 M) and then saturated
with sodium chloride. The mixture was separated, and the
aqueous phase was extracted with ether (3 × 10 mL). The
organic phases were combined, dried (MgSO4), and filtered and
the solvent removed under reduced pressure. Crude carboxylic
acid 23 was dissolved in ether (10 mL) and treated with excess
diazomethane at 0 °C using the method described by Lom-
bardi.12 After allowing the excess diazomethane to dissipate,
the solution was dried (MgSO4) and filtered and the solvent
removed in vacuo. Purification of the residue by preparative
TLC (silica, 20% ether/light petroleum ether, Rf 0.50) gave 24
as a colorless gum (22 mg, 66%): [R]21D -20.7° (c 0.83, CHCl3);
TLC indicated that no starting material remained (24 h). The
solution was diluted with ether (20 mL), dried (MgSO4), and
filtered and the solvent removed under reduced pressure. The
residue was purified by preparative TLC (silica, 50% ether/
light petroleum ether, Rf 0.37) to give nonactate 25 as a
colorless viscous oil (6.5 mg, 88%): [R]20 -16.9° (c 0.33,
D
CHCl3); IR (CHCl3) 1730 cm-1; H NMR (200 MHz, CDCl3) δ
1
1.178 (d, J ) 6.2 Hz, 3H), 1.221 (d, J ) 7.0 Hz, 3H), 1.36-
1.79 (m, 4H), 1.88-2.07 (m, 2H), 2.579, (dq, J ) 7.0 Hz, 1H),
3.65 (bs, 1H), 3.682 (s, 3H), 3.94-4.11 (m, 3H); 13C NMR (50
MHz, CDCl3) δ 13.9, 23.4, 28.5, 31.9, 44.4, 44.8, 51.7, 68.0,
80.2, 80.9, 174.9; MS (CI) m/ z 217 (M+ + 1, 44), 157 (100%);
HRMS (CI) m/ z 217.145 ( 0.002 (M+ + H calcd for C11H21O4
217.144).
Meth yl (2S,3R,6R,8S)-Non a cta te (32). Treatment of silyl
ether 31 (18.0 mg, 0.396 mmol) with TBAF (120 µL, 0.120
mmol) in THF (0.5 mL) according to the procedure described
above gave nonactate 32 as a colorless viscous oil: Rf 0.35 (7.9
1
IR (CHCl3) 1729 cm-1; H NMR (200 MHz, CDCl3) δ 1.04 (s,
9H), 1.09 (d, J ) 6.2 Hz, 3H), 1.18 (d, J ) 7.1 Hz, 3H), 1.19-
1.62 (m, 3H), 1.83-1.93 (m, 3H), 2.44 (dq, J ) 7.1 Hz, 1H),
3.65 (s, 3H), 3.86-4.04 (m, 3H), 7.32-7.71 (m, 10 H); 13C NMR
(50 MHz, CDCl3) δ 14.1, 19.3, 23.4, 27.0, 29.2, 31.2, 45.3, 45.7,
51.5, 67.5, 76.5, 79.4, 127.4, 127.5, 129.6, 129.6, 134.4, 134.8,
135.9, 136.0, 175.2; MS (EI) m/ z no M+ at 454 observed, 199
(100%); HRMS (EI) m/ z 397.186 ( 0.004 (M+ - (CH3)3C calcd
for C23H29O4Si 397.184).
Meth yl (2S,3R,6R,8S)-O-(ter t-Bu tyld ip h en ylsilyl)n on -
a cta te (31). Using a procedure similar to that described
above, tetrahydrofuran 29 (47 mg, 0.074 mmol) gave 30 as a
colorless gum after reaction with hydrogen peroxide (30% w/v,
0.020 mL, 0.176 mmol) and LiOH‚H2O (4.0 mg, 0.095 mmol)
for 10 h. The residue was treated with excess diazomethane
and then purified by preparative TLC (silica, 20% ether/light
mg, 92%); [R]19D +13.3° (c 0.34, CHCl3); IR (CHCl3) 1731 cm-1
;
1H NMR (200 MHz, CDCl3) δ 1.176 (d, J ) 6.2 Hz, 3H), 1.228
(d, J ) 7.0 Hz, 3H), 1.43-1.77 (m, 4H), 1.98-2.14 (m, 2H),
2.506 (dq, J ) 7.0 Hz, 1H), 3.679 (s, 3H), 3.69 (bs, 1H), 3.92-
4.03 (m, 1H), 4.04-4.21 (m, 2H); 13C NMR (50 MHz, CDCl3) δ
14.0, 23.3, 29.4, 32.7, 44.0, 44.7, 51.7, 68.1, 79.96, 79.99, 174.9;
MS m/ z no M+ at 216 observed, 71 (100%); HRMS (CI) m/ z
217.145 ( 0.002 (M+ + H calcd for C11H21O4 217.144).
Ack n ow led gm en t. We thank Ms. I. Mavropoulos
and Mr. J . Pruis for assistance in the preparation of
some synthetic intermediates. A.G. is grateful to the
Australian Government for an Australian Postgraduate
Research Award. P.P. is grateful to BIOTA Holdings
for financial support. G.W. is grateful to the Wenner-
Gren Foundation for financial support and BIOTA
Holdings for the award of a BIOTA Postdoctoral Re-
search Fellowship.
petroleum ether, Rf 0.51) as above to give 31 (33 mg, 100%);
1
[R]21 -2.0° (c 0.46, CHCl3); IR (CHCl3) 1729 cm-1; H NMR
D
(200 MHz, CDCl3) δ 1.04 (s, 9H), 1.11 (d, J ) 6.1 Hz, 3H),
1.17 (d, J ) 7.0 Hz, 3H), 1.22-1.65 (m, 2H), 1.74-1.95 (m,
4H), 2.45 (dq, J ) 7.0 Hz, 1H), 3.65 (s, 3H), 3.84-4.04 (m,
3H), 7.32-7.70 (m, 10 H); 13C NMR (50 MHz, CDCl3) δ 14.4,
19.3, 23.5, 27.1, 29.9, 32.1, 45.0, 45.2, 51.6, 67.6, 76.1, 79.4,
127.5, 127.6, 129.5, 129.6, 134.5, 134.8, 135.9, 136.0, 177.3;
MS m/ z no M+ at 454 observed, 199 (100%); HRMS (EI) m/ z
397.185 ( 0.004 (M+ - C(CH3)3 calcd for C23H29O4Si 397.184).
Met h yl (2R,3S,6R,8S)-Non a ct a t e (25). Tetrabutyl-
ammonium fluoride (TBAF) (1 M in THF, 130 µL, 0.130 mmol)
was added to a solution of silyl ether 24 (15.5 mg, 0.034 mmol)
in THF (0.5 mL) at room temperature. After the reaction
mixture was stirred for 24 h, analytical TLC indicated that
starting material was still present. A further portion of TBAF
(100 µL) was added and the solution stirred until analytical
Su p p or tin g In for m a tion Ava ila ble: Full experimental
details for the preparation of compounds 4c-g, 12, and 14 (9
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O951853Q