Total synthesis of a hemiacetal polypropionate from Siphonaria australis

Article abstract of DOI:10.1071/CH04039

A highly stereocontrolled synthesis of (2S,3R,5R,6S)-6-[(1E,3R)-1,3- dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one has been achieved in 13 steps and an overall yield of 7.6% from (A)-(+)-4- benzyloxazolidin-2-one. This substrate-controlled asymmetric synthesis utilized Paterson's lactate-derived chiral ketone (2S)-2-(benzoyloxy) pentan-3-one to generate the 5R and 6S stereocentres and alkylation of an Evans' auxiliary to generate the remote side-chain 3R stereocentre. Furthermore, a novel, highly efficient, and selective strategy was used to generate an enol trimethylsilyl ether whose subsequent Mukaiyama aldol condensation gave the acyclic precursor to the final product. A thermodynamically controlled cyclization then gave (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3, 5-dimethyltetrahydro-4H-pyran-4-one with control of the 2S and 3R stereocentres. The NMR spectroscopic data and optical rotation obtained for synthetic (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3, 5-dimethyltetrahydro-4H-pyran-4-one were consistent with those reported forthe hemiacetal isolated from Siphonaria australis, and thus, prove the absolute and relative configuration of the natural product.

Full text of DOI:10.1071/CH04039

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2004, 57, 787–797
Total Synthesis of a Hemiacetal Polypropionate from
Siphonaria australis
Troy ListerA and Michael V. PerkinsA,B
A School of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide SA 2001, Australia.
B Author to whom correspondence should be addressed (e-mail: mike.perkins@flinders.edu.au).
A highly stereocontrolled synthesis of (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-
dimethyltetrahydro-4H-pyran-4-one has been achieved in 13 steps and an overall yield of 7.6% from (R)-(+)-4-
benzyloxazolidin-2-one. This substrate-controlled asymmetric synthesis utilized Paterson’s lactate-derived chiral
ketone (2S)-2-(benzoyloxy) pentan-3-one to generate the 5R and 6S stereocentres and alkylation of an Evans’auxil-
iary to generate the remote side-chain 3R stereocentre. Furthermore, a novel, highly efficient, and selective strategy
was used to generate an enol trimethylsilyl ether whose subsequent Mukaiyama aldol condensation gave the acyclic
precursor to the final product. A thermodynamically controlled cyclization then gave (2S,3R,5R,6S)-6-[(1E,3R)-
1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one with control of the 2S and 3R
stereocentres. The NMR spectroscopic data and optical rotation obtained for synthetic (2S,3R,5R,6S)-6-[(1E,3R)-
1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one were consistent with those
reported for the hemiacetal isolated from Siphonaria australis, and thus, prove the absolute and relative configuration
of the natural product.
Manuscript received: 15 February 2004.
Final version: 20 April 2004.
Introduction
equilibration of C8 (in compound 5 or 6) to give the thermo-
dynamically favoured hemiacetals 7 and 8. Unfortunately,
this equilibration was found to be a slower process than
acid catalyzed dehydration, which gave only dihydropyrones
9–11, while treatment with base only gave a retro-Claisen
product.
Marine pulmonates of the genus Siphonaria are a rich source
of diverse polyketide-derived natural products.[1] Nearly all
species examined have contained metabolites of polypro-
pionate origin that appear to share a common biosynthesis
with macrolide and polyether antibiotics.[2] The potential for
secondary metabolites of Siphonariids to display biological
activity drives current efforts to prepare them synthetically.
In 1984, Faulkner reported[3] the isolation of two new
polypropionate natural products from the marine pulmonate
Siphonaria australis collected near Auckland, New Zealand.
The structures of hemiacetal 1 and associated ester 2
(Scheme 1) were established by NMR analysis. The absolute
stereochemistry was not assigned, but NMR data allowed the
relative stereochemistry of the tetrahydro-γ-pyrone ring to be
defined. Moreover, base induced retro-Claisen fragmentation
of hemiacetal 1 gave the ester 2, in which an analogous rel-
ative stereochemistry of the C7–C8 segment was indicated.
The relative stereochemistry at C4 could not be assigned for
either structure.
Albizati reported[4] a similar aldol condensation between
diethyl ketone and aldehyde 4 (Scheme 3); this gave the C7–
C8-anti adducts 12 and 13 along with a C7–C8-syn adduct 14.
Compounds 12 and 13 could be separated chromatographi-
cally and their structures were assigned by the excitation chi-
rality method using the derived p-bromobenzoates.Acylation
of 12 and 13 gave esters 15 and 16, respectively. Compound
1
15 was reported to have an identical H NMR spectrum in
C6D6 to 2, and was found to have a similar optical rota-
tion. On this basis,Albizati assigned the relative and absolute
stereochemistry of ester 2 as being that shown for ester 15.
Consequently, the stereochemistry of the natural hemiacetal
1 was assigned to be the same as in hemiacetal 7,[4] as it was
reported[3] that hemiacetal 1 can be converted into ester 2.
When we began our synthesis of hemiacetal 1, Albizati’s
assignment[4] of the absolute and relative stereochemistry
based on a set of non-empirical rules was treated with some
trepidation. Therefore, we wished to design a synthesis that
could selectively produce both isomers (7 and 8) as well as
In 1992, Albizati reported[4] an attempted synthesis of
the natural products 1 and 2. The strategy employed[4]
(Scheme 2) involved an aldol coupling of the kinetic eno-
late of diketone 3 with aldehyde 4 to give stereochemically
undefined product 5.This approach relied on thermodynamic
© CSIRO 2004
10.1071/CH04039
0004-9425/04/080787

788
T. Lister and M. V. Perkins
their enantiomers. However, these fears were unfounded as
Albizati’s assignment[4] proved to be correct.
We now report the first stereocontrolled synthesis of hemi-
acetal 1 isolated from Siphonaria australis and a conclusive
assignment of the absolute stereochemistry of both 1 and 2.
Results and Discussion
The initial target for our retrosynthetic analysis was isomer
7, which was proposed by Albizati[4] to be the natural prod-
uct. Our synthetic approach was based on the cyclization of
a linear precursor 17, which has the desired configuration
at C4, C7, and C8 (Scheme 4). It was proposed that forma-
tion of the C10 stereocentre (which is between two carbonyl
groups in the linear precursor) would be under thermo-
dynamic control during the cyclization, and thus, that the
C10 methyl group would have an equatorial orientation in
hemiacetal 7. The hemiacetal centre (C11), which contains
an anomerically favoured axial oxygen, was also proposed to
arise under thermodynamic control. In turn, diketone 17 was
thought to be available from an aldol-type chain extension of
ketone 18, which itself could be formed by a highly stereo-
controlled aldol condensation[5,6] of lactate derived ketone
19 with aldehyde 4 to generate the desired stereochemistry
at C7 and C8.
Prior to commencing the synthesis of the natural products,
we wished to test our cyclization–epimerization strategy for
the hemiacetal ring found in compound 1 by using a racemic
modelcompoundthatlackstheC4stereocentre. Oursubstrate
controlled synthetic route to racemic model 20 is shown in
Scheme 5.
Reaction of 2-methylpenten-2-al with the E-enol dicyclo-
hexyl borinate of pentan-3-one gave the required anti aldol
product 21 in satisfactory yield and good diastereoselectivity,
and TBS protection then gave ketone 22. However, the chain
extension through aldol coupling of this ketone with propanal
proved difficult.[7] Attempted formation and reaction of the
dicyclohexyl or dibutyl borinates of ketone 22 gave none of
the desired product, while formation of the Tiiv enolate gave
only a low yield of an aldol product.[7] Fortunately, it was
found that a single isomer of the trimethylsilyl enol ether 23,
as detected by 1H and 13C NMR spectroscopy, could be read-
ily formed using trimethylsilyl trifluoromethanesulfonate
and2,6-lutidine. Onthebasisofliteratureprecedent[8] andthe
H
OH
7
O
O
4
4
8
7
8
O
O
O
1
2
Scheme 1.
(a) 2.2 equiv. LDA, THF,
Ϫ78 → 0ºC
Hϩ
OH
O
O
O
(b)
O
O
3
4
5
H
OH
O
H
OH
7
8
O
O
7
8
O
O
H
OH
6
O
O
ϩ
H
11
O
ϩ
H
H
O
O
ϩ
O
O
H
OH
9 (C7, C8-cis)
10
7
O
4
8
10
4
7
Scheme 2.
8 10
TBSO
O
O
17
O
ϩ 14 (C7, C8-syn)
7
(a) 1.1 equiv. LDA
THF, Ϫ78ºC
ϩ
7
7
8
8
O
OH
O
OH O
12
13
(b)
4
TBSO
O
TBSO
O
OH
EtCOCl,
pyridine,
CH2Cl2
EtCOCl,
pyridine,
CH2Cl2
18
O
O
O
O
ϩ
OBz
O
O
O
O
15
16
4
19
Scheme 3.
Scheme 4.

Total Synthesis of a Hemiacetal Polypropionate
789
stereochemistry of subsequent products,[9] compound 23 was
assigned as the Z-isomer.A BF3 · OEt2 catalyzed Mukaiyama
aldol coupling of 23 with propionaldehyde gave adduct 24
in 68% yield and 79% diastereoselectivity. The major isomer
was tentatively assigned[10] the configuration shown at C10
and C11 (numbering based on hemiacetal 1), although this is
inconsequential as neither stereocentre remains intact in the
final product. The configuration at C11 is lost upon subse-
quent Swern oxidation to the diketone 25, which contains a
β-dicarbonyl system that then undergoes epimerization of the
C10 centre during silica gel purification. Attempted removal
of the t-butylsilyl protecting group to initiate cyclization and
give hemiacetal 20 using tetrabutyl ammonium fluoride gave
only ester 26. This product presumably arises under the basic
conditions by a retro-Claisen fragmentation of hemiacetal 20.
However, treatment of diketone 25 with HF/pyridine in pyri-
dine and a catalytic amount of water[11] for 6 days resulted
in the formation of hemiacetal 20 in 46% yield. The product
was accompanied by a small amount of the dehydrated prod-
uct 27. Thus, we had established a viable synthetic route to
the required hemiacetal ring system and were in a position to
embark on the synthesis of the natural product.
Although the configuration at the remote C4 centre of alde-
hyde 4 was not expected to influence the asymmetric control
of the initial aldol condensation, it was imperative to generate
this fragment with high enantiopurity to avoid a diastere-
omeric mixture of aldol adducts. A literature preparation of
highly enantiomerically pure 4 has been reported.[12] This
procedure was modified using oxazolidinone 28, which was
acylated and selectively alkylated to give product 29 as an
inseparable mixture of diastereomers in greater than 90% d.s.
(diastereomer selectivity; Scheme 6). Despite the inability to
separate the small amount of diastereomeric product, the high
diastereoselectivity of the alkylation step ensured that a high
enantiomeric excess of aldehyde 4 was obtained. Lithium
borohydride mediated reductive cleavage of the chiral auxil-
iary gave alcohol 30 in excellent yield and regenerated pure
free auxiliary that could be recycled. Swern oxidation to the
aldehyde followed by an in situ Wittig reaction with commer-
cially available stabilized yield 31 afforded the geometrically
pure E-ester 32 in high yield. Reduction to the alcohol with
lithium aluminium hydride and subsequent Swern oxida-
tion gave the volatile aldehyde 4 in 86% overall yield from
ester 32.
Synthesis of hemiacetal 7 using our proposed strategy
required the formation of a single enantiomer of aldehyde 4.
Aldehyde 4 (>80% e.e. based on the d.s. of compound
29) was immediately used in an aldol coupling reaction with
ketone (S)-19.[5] Selective formation of the E-enolate of (S)-
19 was readily achieved using dicyclohexylboron chloride
(c-Hex2BCl) in conjunction with N,N-dimethylethylamine.
The in situ generated E-enolate was treated with aldehyde 4 at
−78◦C and allowed to warm to −20◦C, at which temperature
the reaction mixture was stirred for 16 hours. After standard
oxidative product isolation and purification by column chro-
matography, adduct 33 was obtained as a single observable
diastereomer in moderate yield. Notably, the diastereomeric
adduct from condensation of ketone (S)-19 with the enan-
tiomer of aldehyde 4 does not form in detectable quantities
or is separated from 33 by column chromatography (see later
discussion of the reaction of aldehyde 4 with the enantiomer
of ketone 19). The C5 hydroxyl group of adduct 33 was
protected as the t-butyldimethylsilyl ether and subsequent
(a), (b)
(c)
70%
73%
Ͼ95% d.s.
O
OH
O
TBSO
O
21
22
(d) 91%
(e)
68%, 79% d.s.
11
10
TBSO
O
OH
TBSO
OTMS
100% Z
24
23
(f) 95%
(g)
H
OH
O
O
Bn
HN
Bn
TBSO
O
O
(a) 88%
(c)
46%
O
N
O
25
(b) 65%, Ͼ 90% d.s.
85%
OH
O
O
O
20
(h) 20%
28
29
30
ϩ
86%
Ͼ98% E
H
(d), (e)
O
O
O
(f), (g)
20%
H
OEt
86%
O
O
O
O
26
27
4
32
Scheme 5. Reagents and conditions: (a) (c-C6H11)2BCl, Et3N, Et2O,
0◦C; (b) 2-methylpent-2-enal, Et2O, −78◦C to 0◦C; (c) 2,6-lutidine,
TBSOTf, CH2Cl2, −78◦C; (d) 2,6-lutidine, TMSOTf, CH2Cl2, −78◦C
to room temp.; (e) propanal, CH2Cl2 then add BF3·OEt2, −78◦C;
( f ) (COCl)2, DMSO, CH2Cl2, −78◦C, 43 min, Et3N, warmed to 0◦C,
1 h; (g) HF/pyridine, H2O, room temp., 6 days; (h) Bu4N+F−, THF,
room temp.
Scheme 6. Reagents and conditions: (a) BuLi, THF, −78◦C then
BuCOCl, warmed to 0◦C; (b) LDA, −78◦C then MeI, warmed to
room temp.; (c) LiBH4, EtOH, −10◦C; (d) (COCl)2, DMSO, CH2Cl2,
−78◦C, 45 min, Et3N, warmed to 0◦C, 1 h; (e) Ph3P=C(CH3)CO2Et
31, CH2Cl2, reflux; ( f ) DIBALH, CH2Cl2, −78◦C, 1.5 h; (g) (COCl)2,
DMSO, CH2Cl2, −78◦C, 45 min, Et3N, warmed to 0◦C, 1 h.

790
T. Lister and M. V. Perkins
Table 1. Comparison of the 1H and 13C NMR data for synthetic hemiacetal 7, the epimeric hemiacetal 8, and the 13C NMR data previously
reported[3] for natural hemiacetal 1
1
17
16
1
17
16
H
OH
H
OH
O
9
O
9
13
13
3
5
7
11
3
5
7
11
15
14
15
14
O
O
7
8
C
Hemiacetal 1A
Hemiacetal 7B
Hemiacetal 8B
C
C
C
δC
δC
14.4
δH, mult., no. H, J [Hz]C
δC
14.3
δH, mult., no. H, J [Hz]C
1
2,3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
14.4
0.85, d, 3H, 7.2
1.34–1.15, m, 4H
2.38–2.31, m, 1H
5.12, dd, 1H, 9.3, 0.9
–
4.15, d, 1H, 10.8
2.18, dqd, 1H, 10.8, 6.6, 1.2
–
0.86, t, 3H, 7.2
1.29–1.12, m, 4H
2.38–2.30, m, 1H
5.12, dd, 1H, 9.6, 1.2
–
4.15, d, 1H, 10.2
2.19, dqd, 1H, 10.2, 6.6, 1.2
–
21.0, 40.0
32.2
21.0, 39.9
32.2
21.0, 40.0
32.1
136.5
131.7
81.5
46.6
207.3
49.9
102.8
33.2
8.2
9.0
10.2
136.6
131.7
82.8
46.6
207.2
49.9
102.8
33.2
8.1
9.0
10.1
136.7
131.7
82.9
46.4
207.3
49.8
102.8
33.2
8.2
8.9
10.1
2.26, br q, 1H, 6.6
–
2.27, br q, 1H, 6.6
–
1.54–1.45, 1.32–1.23, m (2 × 1H)
0.79, t, 3H, 7.5
1.13, d, 3H, 6.6
1.01, d, 3H, 6.6
1.65, d, 3H, 1.2
0.87, d, 3H, 6.6
1.38, br s, 1H (OH)
1.53–1.47, 1.34–1.28, m (2 × 1H)
0.80, t, 3H, 7.5
1.13, d, 3H, 6.6
1.02, d, 3H, 6.6
1.66, t, 3H, 1.8
0.93, d, 3H, 7.2
1.47, br s, 1H (OH)
11.0
21.0
11.0
21.0
11.0
21.0
A From S. australis. Chemical shifts and coupling constants as reported in ref. [3] (90 MHz).
B Varian Unity Inova 600 MHz NMR spectrometer (C6D6). Assigments assisted by 1H–13C HMBC, HSQC, 1H–1H COSY.
C Chemical shifts in ppm referenced to C6D5H at 7.15 ppm and to C6D6 at 128.0 ppm.
samarium iodide mediated reductive removal of the benzy-
loxy group gave ketone 34. Highly selective formation of the
Z-trimethylsilylenol ether 35 was achieved under the mild
conditions developed in the model system and in near quan-
titative yield using trimethylsilyl trifluoromethanesulfonate
and 2,6-lutidine (−78◦C to room temperature).
for hemiacetal 1, but apparent inconsistencies in the 1H
NMR spectra[13] initially led us to question the structural
assignment of hemiacetal 1 as being that of compound 7.
Hemiacetal 7 was then almost completely converted into
ester 15 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
The resultant mixture of products could not be separated,
but the spectroscopic data for ester 15 were obtained by
subtracting the minor peaks due to hemiacetal 7 (Scheme 7).
To confirm the stereochemical assignment of the natural
product we needed to determine the effect that the configu-
A BF3 · OEt2 catalyzed Mukaiyama aldol coupling of 35
with propionaldehyde gave adduct 36 in good yield and
high diastereoselectivity. Purification of the crude product
by column chromatography led to the isolation of a sin-
gle diastereomer whose stereochemistry could be assigned
from the observations made in the model system. Sub-
sequent Swern oxidation followed by purification (SiO2) led
to 37 as a mixture of dione and enol forms. As suspected,
the C10 methyl group was readily epimerized under acidic
conditions. This was a critical factor as the C10 substituent
is initially incorrectly orientated for thermodynamic cycliza-
tion to occur. Employing conditions originally devised by
Hoffman[11] for the TBS deprotection of precursors to give
acetalfunctionalities, compound 37 wastreatedwithbuffered
pyridinium hydrofluoride and a catalytic amount of water
for six days at room temperature. This facilitated epimeriza-
tion of the C10 methyl centre and subsequent formation of
a single diastereomeric hemiacetal 7 in satisfactory yield,
along with a small amount of the dehydrated dihydropy-
rone 10. The 13C NMR spectral shifts (see Table 1) for
compound 7 showed excellent agreement with those reported
1
ration of the remote C4 stereocentre would have on the H
and 13C NMR spectroscopic data for hemiacetal 1. Thus, we
set out to synthesize the isomer of hemiacetal 7, in which
this stereocentre was epimeric. For convenience, we chose
to use aldehyde 4 and the enantiomeric ketone (R)-38; this
should give hemiacetal 8 (the enantiomer of the C4 epimer
of 7; Scheme 8). Reaction of the E-enol dicylohexyl bori-
nate of ketone (R)-38 with aldehyde 4 gave aldol product 39
in good yield and selectivity. Small differences observed in
the 13C NMR spectra between compound 39 and 33 enabled
identification of the minor diastereomer in the crude reaction
products. The amount of this minor isomer decreased after
each purification process as product 39 was taken through the
subsequent reaction sequence. The same six-step sequence
as previously applied to compound 33 gave hemiacetal 8
as a single diastereomer (6.2% overall yield, 13 steps from
oxazolidone 28). The unprotected adduct 39 was also treated

Total Synthesis of a Hemiacetal Polypropionate
791
(a), (b)
(a), (b)
ϩ
OBz
OBz
OBz
OBz
60%, Ͼ 99% d.s.
(73%,
Ͼ 99% d.s.)
O
O
OH
O
O
OH
O
19
33
4
38
39
(c), (d) 89%
(c), (d)
2 steps
(18%)
6 steps
(e)
99%
100% cis
TBSO
OTMS
TBSO
O
H
OH
O
O
35
34
O
O
(f ) 75%, 87% d.s.
6.2% overall
O
(g)
16
8
99%
Scheme 8. Reagents and conditions: (a) (c-C6H11)2BCl, Me2EtN,
Et2O, 0◦C; (b) aldehyde 4, Et2O, −78◦C to 0◦C; (c) SmI2, THF, MeOH,
0◦C; (d) propionyl chloride, pyridine.
TBSO
O
OH
TBSO
O
O
36
37
(h)
compound 7. The optical rotation measured for hemiacetal 8
was [α]2D0 −65.9 (c 2.0 in CHCl3), which is notably of the
opposite sign.
(i)
H
OH
O
O
63%
Inspection of the authentic 1H NMR (C6D6) spectrum[15]
of ester 2 clearly indicates that it is identical to that of
synthetic ester 15, but different from ester 16. The notable
difference between the spectra of esters 15 and 16, as reported
by Albizati,[4] is the presence of two discrete multiplets at δ
1.30 (1H) and 1.20 (3H) for ester 15, while for ester 16 these
protons appear as a 4H multiplet centered around δ 1.10.
Minor differences were also observed in the methyl region
(δ 0.91–0.75) of the two compounds. The optical rotation of
ester 16 [α]2D0 −6.0 (c 0.5 in CHCl3) was consistent with that
reported[4] ([α]2D0 −10.3).
O
O
54%
O
15
7
ϩ
H
O
O
21%
10
Scheme 7. Reagents and conditions: (a) (c-C6H11)2BCl, Me2EtN,
Et2O, 0◦C; (b) aldehyde 4, Et2O, −78◦C to 0◦C; (c) 2,6-lutidine,
TBSOTf, CH2Cl2, −78◦C; (d) SmI2,THF, MeOH, 0◦C; (e) 2,6-lutidine,
TMSOTf, CH2Cl2, −78◦C to room temp.; ( f ) propanal, CH2Cl2 then
add BF3·OEt2, −78◦C; (g) (COCl)2, DMSO, CH2Cl2, −78◦C, 45 min,
Et3N, warmed to 0◦C, 1 h; (h) HF/pyridine, pyridine, H2O, room temp.,
6 days; (i) DBU, benzene, room temp.
Conclusion
A highly stereocontrolled synthesis of hemiacetal 7 has been
achieved in 13 steps and an overall yield of 7.6% from oxa-
zolidone 28. This synthesis utilized Paterson’s lactate derived
chiral ketone 19 in a substrate controlled aldol reaction to
generate the C7 and C8 stereocentres and alkylation of an
Evans’auxiliary to generate the remote C4 stereocentre. This
total synthesis has also used a novel, highly efficient, and
selective strategy to generate an enol trimethylsilyl ether
whose subsequent Mukaiyama aldol condensation gave the
required acyclic precursor. A thermodynamically controlled
cyclization then gave hemiacetal 7, in which the requisite
stereocentres at C10 and C11 were set. A comparison of the
NMR spectroscopic data and optical rotation obtained for
hemiacetal 7 with that reported[13–15] for the natural product
1 proves that the absolute and relative configuration of the
natural product is as shown in compound 7.
with samarium iodide to give the free alcohol in low yield,
which was subsequently acylated with propionyl chloride to
give ester 16.
A comparison of the spectroscopic data for hemiacetals
7 and 8 is shown in Table 1. Notably, the 13C NMR data
for the two isomers in C6D6 are virtually identical and con-
sistent with those reported[3] for hemiacetal 1.[14] While the
13C NMR data are not able to distinguish between these two
isomers, the 1H NMR spectra (C6D6) display small but sig-
nificant differences. Most notably, the C17 methyl group in
hemiacetal 7 resonates at δ 0.87, while in hemiacetal 8, this
methyl group resonates at δ 0.93. Inspection of the authentic
1H NMR (C6D6) spectrum[15] of hemiacetal 1 clearly indi-
cates that it is identical to that of synthetic hemiacetal 7,
but different to hemiacetal 8. The optical rotation found for
hemiacetal 7 was [α]2D0 27.1 (c 0.6 in CHCl3); this was in
good agreement with that reported[3] for the natural product
1 {[α]2D0 22.3 (c 0.84 in CHCl3)} and allowed the assignment
of the absoluteconfiguration of 1 tobemadeasthatshown for
Experimental
1H NMR spectra were recorded at either 200, 300, or 600 MHz on a
Varian Mercury, Varian Gemini, or Varian Unity Inova spectrometer,
while 13C NMR spectra were recorded at either 50.3, 75.5 or 151 MHz
on a Varian Mercury, Varian Gemini, or Varian Unity Inova spectrome-
ter. All spectra were recorded in either CDCl3 as solvent and referenced
to CHCl3 (δ 7.26) for 1H NMR and CDCl3 (δ 77.0) for 13C NMR,
or in C6D6 as solvent and referenced to C6D5H (δ 7.15) for 1H NMR

792
T. Lister and M. V. Perkins
and C6D6 (δ 128.0) for 13C NMR. Electron-impact mass spectra were
recorded using a Bruker 4.7T FTMS Ultra High Resolution spectrom-
eter. All optical rotations were measured on a PolA AR 21 polarimeter
referenced to the sodium D line (589 nm) at 20◦C. All reactions were
performed under an atmosphere of nitrogen using anhydrous solvents
that were purified and dried according to recommended procedures.
d, J 9.2, CHOTBS), 2.24–2.09 (1H, dq, J 9.4 and 7.0, CH3CHC), 2.09–
1.92 (2H, m, CH3CHAHBCH), 1.51 (3H, m, (CH3)C=CH), 1.48 (3H,
d, J 6.6, (CH3)CH=C), 0.94 (3H, t, J 7.6, CH3CH2CH), 0.83 (9H, s,
(CH3)3C), 0.74 (3H, d, J 7.2, CH3CHC), 0.20 (9H, s, (CH3)3Si), −0.03
(3H, s, CH3Si), −0.06 (3H, s, CH3Si). δC (50 MHz, CDCl3) 153.2,
135.4, 129.3, 101.5, 80.8, 44.7, 25.8, 20.7, 18.2, 15.7, 13.9, 11.2, 10.4,
1.0, −4.8, −5.3.
5-Hydroxy-4,6-dimethylnon-6-en-3-one 21
7-(tert-Butyldimethylsilyloxy)-3-hydroxy-4,6,8-trimethylundec-
8-en-5-one 24
Dicyclohexylboron chloride (5.29 mL, 24.4 mmol) was added to a 0.2 M
solution of pentan-3-one (2.45 mL, 23.2 mmol) in Et2O (116 mL) at
0◦C, and then triethylamine (3.56 mL, 25.5 mmol) was added drop-
wise. The resultant white mixture was stirred at 0◦C for 1 h then cooled
to −78◦C. A solution of 2-methylpenten-2-al (3.98 mL, 34.5 mmol) in
Et2O (30 mL) was added dropwise and the resultant mixture was stirred
at −78◦C for 2 h. The mixture was quenched at −30◦C with an equiva-
lent volume of pH 7 buffer diluted with 2 : 1 v/v MeOH. After warming
to 0◦C, 30% aqueous H2O2 (24.4 mL) was added dropwise and the
mixture was stirred at room temperature for 1 h. The volatiles were
removed, the resultant residue was diluted with Et2O (100 mL), and the
organic phase was washed once with H2O, saturated aqueous NaHCO3,
and brine (100 mL each). The combined aqueous washings were further
extracted with Et2O (100 mL), and the combined organic extracts were
dried (MgSO4) and concentrated under vacuum. The crude product was
purified by column chromatography (30% EtOAc/hexanes) to give aldol
adduct 21 (2.98 g, 70%) as a clear oil, RF 0.37 (30% EtOAc/hexanes).
δH (300 MHz, CDCl3) 5.40 (1H, t, J 7.2, CH=C), 4.08 (1H, d, J 7.2,
CHOH), 2.82–2.72 (1H, dq, J 9.0 and 7.2, CH(CH3)C=O), 2.62–2.46
(2H, m, CH3CHAHBCH), 2.24 (1H, s, CHOH), 2.08–1.98 (2H, m,
C(=O)CHAHBCH3), 1.60–1.59 (3H, m, (CH3)C=CH), 1.04 (3H, t,
J 7.5, CH3CH2CH=C), 0.95 (3H, t, J 7.5, C(=O)CH2CH3), 0.91 (3H,
d, J 7.5, CH(CH3)C=O). δC (75 MHz, CDCl3) 215.9, 133.7, 131.3,
80.3, 48.5, 36.3, 20.8, 14.2, 13.9, 10.6, 7.4.
To a stirred solution of enol silane 23 (1.00 g, 2.7 mmol) and propi-
onaldehyde (584 µL, 8.2 mmol) in CH2Cl2 (30 mL) at −100◦C was
added BF3 · OEt2 (516 µL, 4.1 mmol). The reaction mixture was stirred
at between −100◦C and −78◦C for 1.5 h before being quenched by
the addition of saturated aqueous NaHCO3 (50 mL). The mixture was
extracted with CH2Cl2 (3 × 50 mL), and the combined organic extracts
were dried (MgSO4) and concentrated under vacuum. The crude prod-
uct was purified by column chromatography (5% Et2O/CH2Cl2) to
give 3,4-syn-4,6-anti aldol adduct 24 (655.6 mg, 68%), RF 0.59 (5%
Et2O/CH2Cl2). δH (300 MHz, CDCl3) 5.34 (1H, t, J 6.9, CH=C), 4.17
(1H, d, J 9.6, CHOTBS), 3.90–3.84 (1H, m, CHOH), 3.03–2.92 (1H,
dq, J 9.9 and 7.2, CH(CH3)CO), 2.65–2.57 (1H, dq, J 7.2 and 2.4,
CH(CH3)COH), 2.07–1.96 (2H, m, CHAHBCH=C), 1.60–1.48 (1H,
m, CH(OH)CHAHB), 1.55 (3H, s, (CH3)C=CH), 1.48–1.31 (1H, m,
CH(OH)CHAHB), 1.13 (3H, d, J 7.2, CH(CH3)CHOH), 0.95 (3H, t,
J 7.5, CH3CH2CH=C), 0.98–0.93 (3H, t, J 7.5, CH(OH)CH2CH3),
0.81 (9H, s, (CH3)3C), 0.79 (3H, d, J 7.2, CH(CH3)CO), −0.03 (3H,
s, CH3Si), −0.04 (3H, s, CH3Si). δC (75.5 MHz, CDCl3) 216.6, 133.7,
131.4, 81.4, 72.6, 50.7, 48.0, 27.0, 25.8, 20.8, 18.1, 14.6, 13.7, 10.5,
10.3, 8.0, −4.7, −5.0.
7-(tert-Butyldimethylsilyloxy)-4,6,8-trimethylundec-8-en-3,5-dione 25
Dimethyl sulfoxide (DMSO; 400 µL, 5.6 mmol) was added dropwise to
a solution of oxalyl chloride (1.4 mL, 2.8 mmol) in CH2Cl2 (8 mL) at
−78◦C and the mixture was stirred for 15 min. Alcohol 24 (500 mg,
1.4 mmol) was then added as a solution in CH2Cl2 (10 + 5 mL) by
cannula. After 1 h, Et3N (1.17 mL, 8.4 mmol) was added, stirring was
continued at −78◦C for 15 min, and the reaction mixture was then slowly
warmed to −5◦C. The reaction mixture was quenched by the addition of
saturated aqueous NH4Cl (30 mL), allowed to warm to room tempera-
ture, andwasextractedwithCH2Cl2 (3 × 50 mL).Thecombinedorganic
extracts were washed with saturated aqueous NaHCO3 and brine (50 mL
each), dried (MgSO4), and concentrated under vacuum.The crude prod-
uct was purified by column chromatography (30% hexanes/CH2Cl2)
to give dione 25 (470.6 mg, 95%), RF 0.47 (30% hexanes/CH2Cl2).
δH (300 MHz, CDCl3) 5.37–5.31 (1H, m, CH=C), 4.00 (1H, d, J 9.9,
CHOTBS), 3.86 (1H, q, J 7.2, CH(CH3)CO), 2.84–2.74 (1H, dq, J 9.6
and 6.9, CH(OTBS)CH(CH3)CO), 2.58–2.49 (2H, m, CHAHBCH=C),
2.07–1.95 (2H, m, COCHAHB), 1.52 (3H, s, (CH3)C=CH), 1.26 (3H,
d, J 7.2, COCH(CH3)CO), 1.07 (3H, t, J 7.2, CH3CH2CH=C), 0.94
(3H, t, J 7.5, COCH2CH3), 0.81 (9H, s, (CH3)3C), 0.80 (3H, d, J 6.9,
CH(OTBS)CH(CH3)CO), −0.07 (3H, s, CH3Si), −0.08 (3H, s, CH3Si).
5-(tert-Butyldimethylsilyloxy)-4,6-dimethylnon-6-en-3-one 22
To a solution of alcohol 21 (987 mg, 5.4 mmol) in CH2Cl2 (40 mL)
cooled to −78◦C was added 2,6-lutidine (1.25 mL, 10.7 mmol) fol-
lowed by tert-butyldimethylsilyl trifluoromethanesulfonate (TBSOTf)
(1.85 mL, 8.0 mmol). The reaction mixture was stirred at −90◦C for
15 min, allowed to warm to −70◦C over 40 min, and was then stirred
at −70◦C for 5 min before being quenched with saturated aqueous
NaHCO3 (40 mL) and extracted with CH2Cl2 (3 × 50 mL). The com-
binedorganicextractsweredried(MgSO4), concentratedundervacuum,
and purified by column chromatography (50% CH2Cl2/hexanes) to give
product 22 (1.17 g, 73%) as a clear oil, RF 0.63 (50% CH2Cl2/hexanes).
δH (200 MHz, CDCl3) 5.32 (1H, t, J 7.3, CH=C), 4.03 (1H, d, J 9.8,
CHOTBS), 2.84–2.68 (1H, dq, J 9.8 and 7.0, CH(CH3)C=O), 2.61–2.45
(2H, m, CH3CHAHBCH), 2.09–1.93 (2H, m, C(=O)CHAHBCH3), 1.53
(3H, br m, (CH3)C=CH), 1.01 (3H, t, J 7.2, CH3CH2CH=C), 0.94
(3H, t, J 7.4, C(=O)CH2CH3), 0.80 (9H, s, (CH3)3C), 0.75 (3H, d,
J 7.0, CH(CH3)C=O), −0.06 (3H, s, CH3Si), −0.08 (3H, s, CH3Si).
δC (50 MHz, CDCl3) 215.0, 134.1, 131.0, 82.4, 49.1, 37.9, 25.7, 20.8,
18.0, 13.9, 13.7, 10.1, 7.3, −4.7, −5.5.
(Z)-5-(tert-Butyldimethylsilyloxy)-4,6-dimethyl-
3-[(trimethylsilyl)oxy]non-2,6-diene 23
4,6-Dimethyl-5-(1-oxopropoxy)-6-nonen-3-one 26
To a solution of dione 25 (50 mg, 0.14 mmol) in THF (470 µL) was
added tetrabutylammonium fluoride (423 mL of a 1 m solution in THF,
0.42 mmol).After stirring for 90 min at ambient temperature, the solvent
was removed under vacuum and the residue was taken up in CH2Cl2
(20 mL). The solution was washed with brine (10 mL) and the aqueous
phase was further extracted with CH2Cl2 (3 × 20 mL). The combined
organic extracts were washed with saturated aqueous NH4Cl (20 mL),
dried (MgSO4), and concentrated under vacuum. The crude product
was purified by column chromatography (5% Et2O/CH2Cl2) to give
the retro Claisen ester 26 (6.9 mg, 20%), RF 0.55 (5% Et2O/CH2Cl2).
δH (300 MHz, CDCl3) 5.56 (1H, t, J 6.9, CH=C), 5.23 (1H, d, J 10.2,
CHOC=O), 2.97–2.86 (1H, dq, J 10.5 and 7.2, CHCH(CH3)C=O),
2.53–2.45 (2H, dq, J 7.2 and 1.8, CH3CH2CH), 2.22 (2H, q, J 7.5,
CH3CH2C(=O)O), 2.08–1.99 (2H, m, C(=O)CH2CH3), 1.56 (3H, s,
TotheTBSether 22(1.86 g, 6.2 mmol)inCH2Cl2 (65 mL)at−78◦Cwas
added 2,6-lutidine (2.90 mL, 24.9 mmol) followed by trimethylsilyl tri-
fluoromethanesulfonate (TMSOTf) (3.38 mL, 18.7 mmol).The reaction
mixture was stirred at −78◦C for about 5 min before being allowed to
slowly warm to room temperature over several hours. The reaction mix-
ture was then stirred at room temperature for 16 h before being quenched
by the addition of saturated aqueous NaHCO3 (100 mL). The mixture
was extracted with CH2Cl2 (3 × 100 mL), the combined organic extracts
were washed with brine (100 mL), dried (Na2SO4), and concentrated
under vacuum. The crude product was purified by column chromato-
graphy (50% CH2Cl2/hexanes) to give enol ether 23 (2.11 g, 91%) as
a clear liquid, RF 0.95 (50% CH2Cl2/hexanes). δH (200 MHz, CDCl3)
5.25 (1H, t, J 7.4, CH=C), 4.49 (1H, q, J 6.6, (CH3)CH=C), 3.84 (1H,

Total Synthesis of a Hemiacetal Polypropionate
793
(CH3)C=CH), 1.07 (3H, t, J 7.5, CH3CH2C(=O)O), 1.04 (3H, t, J 7.5,
C(=O)CH2CH3), 0.95 (3H, t, J 7.5, CH3CH2CH), 0.92 (3H, d, J 6.9,
CH(CH3)C=O). δC (75.5 MHz, CDCl3) 212.8, 172.8, 133.9, 129.6,
81.2, 47.5, 35.4, 27.7, 20.9, 13.8, 13.7, 11.0, 9.1, 7.6.
reaction mixture was stirred at −78◦C for 30 min, at −30◦C for 2 h, and
was then allowed to sit in the freezer overnight. The reaction mixture
was quenched at approximately −5◦C by the slow addition of saturated
aqueous NH4Cl (70 mL) and the volatiles were removed under vacuum.
The resultant slurry was extracted with CH2Cl2 (3 × 150 mL), the com-
bined organic extracts were washed with saturated aqueous NaHCO3
(100 mL), dried (MgSO4), and the solvent was removed under vacuum
to give a yellow oil. The crude product was purified by column chro-
matography (CH2Cl2) to give oxazolidinone 29 (3.42 g, 65%) as a clear
oil, RF 0.29 (CH2Cl2). δH (200 MHz, CDCl3) 7.38–7.19 (5H, m, ArH),
4.73–4.61 (1H, m, CH2CH(CH2)N), 4.20–4.16 (2H, m, CHCHAHBO),
3.81–3.64 (1H, m, C(=O)CH(CH3)CH2), 3.31–3.23 (1H, dd, J 13.4 and
3.4, CHCHAHBAr), 2.82–2.71 (1H, dd, J 13.4 and 9.6, CHCHAHBAr),
1.79–1.57 (2H, m, CHCH2CH2), 1.44–1.31 (2H, m, CH2CH2CH3),
1.22 (3H, d, J 6.8, CH(CH3)CH2), 0.91 (3H, m, CH2CH3).
2-Ethyl-2-hydroxy-3,5-dimethyl-6-(1-methylbuten-1-yl)tetrahydro-
4H-pyran-4-one 20
and 6-Ethyl-3,5-dimethyl-2-(1-methylbuten-1-yl)-2,3-dihydro-
4H-pyran-4-one 27
Todione24(150 mg, 0.42 mmol)wasaddedfreshlypreparedpyridinium
hydrofluoride buffered with excess pyridine [3 mL; stock prepared
from dry THF (10 mL), pyridine (5 mL), and pyridinium hydrofluo-
ride (2.1 g)] and H2O (40 µL). The reaction mixture was then stirred at
room temperature for 6 days, diluted with Et2O (25 mL), and washed
with saturated aqueous CuSO4 (20 mL). The aqueous phase was further
extractedwithEt2O(3 × 20 mL)andthecombinedorganicextractswere
washed with saturated aqueous NaHCO3 (30 mL), dried (MgSO4), and
concentrated under vacuum. The crude product was purified by column
chromatography (5% Et2O/CH2Cl2) to give dehydrated hemiacetal 27
(19 mg, 20%) as a clear oil, RF 0.63 (5% Et2O/CH2Cl2). δH (300 MHz,
CDCl3) 5.49 (1H, t, J 7.2, CH=C), 4.17 (1H, d, J 13.5, CCH(CH)OC),
2.58–2.46 (1H, dq, J 13.5 and 6.9, CHCH(CH3)C=O), 2.37–2.29 (2H,
qd, J 7.8 and 1.8, OC(=C)CHAHBCH3), 2.15–2.05 (2H, qd, J 7.2 and
6.9, CH3CH2CH=C), 1.72 (3H, s, C(=O)C(CH3)=C), 1.67 (3H, br s,
(CH3)C=CH), 1.12 (3H, t, J 7.8, OC(=C)CH2CH3), 0.99 (3H, t, J 7.5,
CH3CH2CH=C), 0.93 (3H, d, J 6.9, CH(CH3)C=O). δC (75.5 MHz,
CDCl3) 195.5, 173.2, 134.1, 130.8, 107.9, 89.8, 40.3, 25.8, 20.9, 13.7,
11.0, 10.8, 10.3, 9.3.
Further elution gave hemiacetal 20 (47.2 mg, 46%) as a clear oil,
RF 0.52 (5% Et2O/CH2Cl2). δH (300 MHz, C6D6) 5.31 (1H, t, J 6.9,
CH=C), 4.15 (1H, d, J 10.2, CCH(CH)OC), 2.29–2.22 (1H, qdd, J
6.3, 1.8, and 1.2, CH(CH3)COH), 2.20–2.09 (1H, dqd, J 10.5, 6.6, and
1.2, CHCH(CH3)C=O), 1.99–1.84 (2H, m, CH3CH2CH=C), 1.73 (1H,
br s, OC(OH)CH2CH3), 1.59 (3H, br s, (CH3)C=CH), 1.55–1.29 (2H,
m, C(OH)CHAHBCH3), 1.13 (3H, d, J 6.6, CH(CH3)C(OH)CH2), 0.97
(3H, d, J 6.6, CH(CH3)C=O), 0.86 (3H, t, J 7.5, CH3CH2CH=C),
0.81 (3H, t, J 7.5, C(OH)CH2CH3). δC (75.5 MHz, C6D6) 207.5, 132.6,
131.7, 102.8, 82.7, 49.9, 46.5, 33.2, 21.1, 14.0, 10.7, 10.1, 8.9, 8.2.
(2R)-2-Methylpentanol 30
To a solution of oxazolidinone 29 (3.27 g, 11.9 mmol) in Et2O (240 mL)
at −10◦C was added anhydrous EtOH (1.66 mL, 28.5 mmol) and LiBH4
(14.3 mL, 28.5 mmol). The reaction mixture was stirred at −10◦C for
1.5 h and then quenched by the addition of NaOH (1 M, 60 mL). The
resultant cloudy solution was stirred for 15 min at 0◦C and was then
poured into brine (200 mL). The mixture was extracted with Et2O
(4 × 100 mL), and the combined organic extracts were dried (Na2SO4)
and concentrated under vacuum. The crude residue was purified by col-
umn chromatography (30% Et2O/CH2Cl2) to give alcohol 30 (1.03 g,
85%) as a clear liquid, RF 0.33 (30% Et2O/CH2Cl2). δH (300 MHz,
CDCl3) 3.52–3.36 (2H, m, CHCHAHBOH), 1.64–1.58 (2H, br m,
(CH3)CHCH2CH2), 1.41–1.24 (2H, br m, CH3CH2CH2), 1.11–1.03
(1H, m, CH2CH(CH3)CH2), 0.90 (3H, d, J 6.6, CH(CH3)CH2). δC
(75.5 MHz, CDCl3) 68.4, 35.5, 35.4, 20.0, 16.5, 14.3.
Ethyl (2E,4R)-2,4-Dimethylheptenoate 32
To a solution of DMSO (3.26 mL, 46 mmol) in CH2Cl2 (80 mL) at
−78◦C was added oxalyl chloride (11.5 mL of a 2 M solution in CH2Cl2,
23 mmol) over 10 min. After 30 min, alcohol 30 (1.57 g, 15 mmol) in
CH2Cl2 (50 mL) was added by cannula and the resultant mixture was
stirred at −78◦C for 45 min. Triethylamine (12.8 mL, 92 mmol) was
then added over 10 min and the resultant white solution was stirred at
−78◦C for 30 min before being slowly warmed to room temperature.
(Carbethoxymethylene)triphenylphosphorane 31 (6.66 g, 18 mmol) in
CH2Cl2 (30 mL) was added and the reaction mixture was heated at
reflux (60◦C) for 6 days. The solvent was removed under vacuum, the
residue was triturated with hexanes, filtered to remove the insoluble
triphenylphosphineoxide, andconcentratedunderreducedpressure.The
resultant yellow liquid was purified by column chromatography (50%
CH2Cl2/hexanes) to afford the geometrically pure E-ester 32 (2.43 g,
86%), RF 0.48 (50% CH2Cl2/hexanes), [α]2D0 −4.2 (c 1.0 in CHCl3).
δH (300 MHz, CDCl3) 6.52 (1H, dd, J 9.9 and 1.2, (CH3)C=CH), 4.18
(2H, q, J 7.1, OCH2CH3), 2.54–2.33 (1H, m, CH3CHCH2), 1.82 (3H,
d, J 1.2, (CH3)=CCH), 1.39–1.21 (4H, m, CH3CH2CH2), 1.29 (3H, t,
J 7.1, OCH2CH3), 0.98 (3H, d, J 6.6, CH3CHCH2), 0.87 (3H, t, J 6.8,
CH3CH2CH2). δC (75.5 MHz, CDCl3) 168.5, 148.1, 126.2, 60.4, 39.1,
33.0, 20.6, 20.0, 14.3, 14.1, 12.5.
(4R)-3-(1-Oxopentyl)-4-phenylmethyloxazolidin-2-one 40
To a solution of the oxazolidinone 28 (10.0 g, 56.4 mmol) in dry THF
(100 mL) at −78◦C was added n-butyllithium (36.0 mL of a 1.6 M solu-
tion in hexanes, 57.5 mmol). The resultant yellow solution was treated
immediatelywithvalerylchloride(7.36 mL, 62.1 mmol)andthemixture
was stirred at −78◦C for 30 min. The reaction mixture was then warmed
to room temperature over 30 min, stirred for an additional 30 min, and
quenched at room temperature by the slow addition of saturated aque-
ous NH4Cl (100 mL). The volatiles were removed under vacuum and
the resultant slurry was extracted with CH2Cl2 (3 × 100 mL). The com-
bined organic extracts were washed with NaOH (1 M, 100 mL) and
brine (100 mL), dried (Na2SO4), and the solvent was removed under
vacuum to give the acylated oxazolidinone 40 (13.0 g, 88%). 1H and
13C NMR spectra indicated that the crude product consisted of only
one compound, and thus, purification was not required. δH (300 MHz,
CDCl3) 7.36–7.20 (5H, m, ArH), 4.71–4.63 (1H, m, CH2CH(CH2)N),
4.23–4.15 (2H, m, CHCHAHBO), 3.32–3.27 (1H, dd, J 13.2 and 3.3,
CHCHAHBAr), 3.04–2.84 (2H, m, C(=O)CH2CH2), 2.80–2.72 (1H,
dd, J 13.5 and 9.6, CHCHAHBAr), 1.73–1.60 (2H, m, CH2CH2CH2),
1.47–1.35 (2H, m, CH2CH2CH3), 0.95 (3H, t, J 7.2, CH2CH3).
(2E,4R)-2,4-Dimethylheptenol 41
To a solution of LiAlH4 (104 mg, 2.8 mmol) in THF (4.1 mL) cooled
to 0◦C was added, by cannula, ester 32 (460 mg, 2.5 mmol) in THF
(4.1 mL). The reaction mixture was warmed to room temperature and
stirred for 1.5 h before being cooled to 0◦C and quenched by the drop-
wise addition of H2O (0.1 mL), NaOH (0.1 mL, 15% aq.), and H2O
(0.3 mL). The mixture was dried (MgSO4), filtered (Et2O), and the fil-
trate was concentrated under vacuum to give the crude alcohol 41 in
quantitative yield. [α]D20 −14.6 (c 1.1 in CHCl3). δH (300 MHz, CDCl3)
5.14 (1H, dd, J 9.5 and 1.4, (CH3)C=CH), 3.96 (2H, d, J 0.9, CH2OH),
2.41–2.31 (1H, m, CH3CHCH2), 1.85–1.76 (1H, m, OH), 1.64 (3H, d,
J 1.4, (CH3)C=CH), 1.29–1.15 (4H, m, CH3CH2CH2), 0.90 (3H, d,
(4R)-3-(1-Oxo-2-methylpentyl)-4-phenylmethyloxazolidin-2-one 29
To a solution of diisopropylamine (5.4 mL, 38.3 mmol) inTHF (100 mL)
at −78◦C was added n-butyllithium (24 mL of a 1.6 M solution in hex-
anes, 38.3 mmol). The resultant mixture was warmed to 0◦C, stirred
for 30 min, and then recooled to −78◦C. Oxazolidinone 40 (5.00 g,
19.2 mmol) in THF (30 mL) was added to the lithium diisopropylamide
(LDA) solution by cannula and the resultant mixture was stirred at
−78◦C for 45 min. Methyl iodide (3.6 mL, 57.5 mmol) was added, the

794
T. Lister and M. V. Perkins
J 6.9, CH3CHCH2), 0.85 (3H, t, J 6.8, CH3CH2CH2). δC (75.5 MHz,
CDCl3) 133.1, 132.9, 68.9, 39.8, 31.7, 20.9, 20.5, 14.1, 13.7.
(1H, q, J 7.2, CH(CH3)OBz), 5.14 (1H, d, J 9.3, (CH3)C=CH), 4.20
(1H, d, J 9.9, CHOTBS), 2.99 (1H, dq, J 9.9 and 7.0, CHCHCH3), 2.42–
2.32 (1H, m, CH2CHCH3), 1.56 (3H, d, J 1.2, (CH3)C=CH), 1.54 (3H,
d, J 6.9, CH(CH3)OBz), 1.31–1.22 (4H, m, CH3CH2CH2), 0.93 (3H, d,
J 6.9, CHCHCH3), 0.89 (3H, d, J 6.6, CH2CHCH3), 0.87 (3H, t, J 6.6,
CH3CH2CH2), 0.82 (9H, s, (CH3)3C), −0.03 (6H, s, SiCH3ACH3B).
δC (75.5 MHz, CDCl3) 209.4, 165.7, 136.3, 133.1, 132.8, 129.8, 128.3,
81.3, 75.3, 46.3, 39.4, 31.6, 25.8, 20.8, 20.5, 18.0, 15.2, 14.6, 14.1, 10.5,
−4.8, −5.1 (one coincident vinyl carbon).
(2E,4R)-2,4-Dimethylheptenal 4
To a solution of DMSO (784 µL, 11 mmol) in CH2Cl2 (21 mL) at −78◦C
was added oxalyl chloride (2.64 mL of a 2 M solution in CH2Cl2,
5.3 mmol) over 2 min. After 30 min, the crude alcohol 41 (500 mg,
3.5 mmol) in CH2Cl2 (5 mL) was added by cannula and the resul-
tant mixture was stirred at −78◦C for 45 min. Triethylamine (2.94 mL,
21 mmol) was then added over 2 min, the resultant white solution was
stirred at −78◦C for 30 min then at 0◦C for 1 h, and finally at room
temperature for 30 min. The reaction mixture was quenched with the
additionofsaturatedaqueousNH4Cl(15 mL)andtheaqueousphasewas
extracted with CH2Cl2 (3 × 25 mL). The organic extracts were washed
with saturated aqueous NaHCO3 (20 mL) and brine (20 mL), dried
(MgSO4), and concentrated under vacuum to give the crude aldehyde,
which was contaminated with Et3N · HCl. This mixture was purified by
flash column chromatography (CH2Cl2) to give the volatile aldehyde
4 (424 mg, 86% from ester 32) as a clear oil, RF 0.39 (CH2Cl2). δH
(300 MHz, CDCl3) 9.38 (1H, s, CHO), 6.25 (1H, dd, J 9.9 and 1.2,
(CH3)C=CH), 2.77–2.63 (1H, m, CH3CHCH2), 1.74 (3H, d, J 1.2,
(CH3)C=CH), 1.52–1.21 (4H, m, CH3CH2CH2), 1.05 (3H, d, J 6.6,
CH3CHCH2), 0.89 (3H, t, J 7.1, CH3CH2CH2). δC (75.5 MHz, CDCl3)
195.6, 160.7, 137.9, 38.9, 33.3, 20.5, 19.8, 14.1, 9.3.
(4R,5S,6E,8R)-5-(tert-Butyldimethylsilyloxy)-4,6,8-trimethylundec-
6-en-3-one 34
To a solution of the protected adduct 42 (567 mg, 1.2 mmol) in THF
(15 mL) and MeOH (7.4 mL) at 0◦C was added SmI2 (approx. 50 mL of
a 1 M solution in THF, approx. 4.9 mmol) until a deep green colour
persisted. The reaction mixture was then quenched at 0◦C with the
addition of saturated aqueous K2CO3 (75 mL) and allowed to warm
to room temperature. The aqueous layer was extracted with Et2O
(3 × 50 mL), and the combined organic extracts were dried (MgSO4)
and concentrated under vacuum. The crude product was purified by col-
umn chromatography (30% CH2Cl2/hexanes) to afford the protected
hydroxy ketone 34 (400 mg, 95%) as a colourless oil, RF 0.33 (30%
20
CH2Cl2/hexanes), [α]D −17.4 (c 1.9 in CHCl3). (Found: m/z 363.2692.
C20H40O2Si requires [M + Na]+• 363.2695.) vmax/cm−1 (film) 1721,
1251, 1059, 837, 777. δH (300 MHz, CDCl3) 5.10 (1H, dd, J 9.3 and 1.2,
(CH3)C=CH), 4.03 (1H, d, J 9.6, CHOTBS), 2.75 (1H, dq, J 9.6 and
6.9, CHCHCH3), 2.52 (2H, qd, J 7.2 and 4.9, C(=O)CH2CH3), 2.41–
2.31 (1H, m, CH2CHCH3), 1.54 (3H, d, J 1.2, (CH3)C=CH), 1.32–1.17
(4H, m, CH3CH2CH2), 1.01 (3H, t, J 7.2, C(=O)CH2CH3), 0.88 (3H,
d, J 6.9, CH2CHCH3), 0.86 (3H, t, J 6.8, CH3CH2CH2), 0.80 (9H, s,
(CH3)3C), 0.75 (3H, d, J 6.6, CHCHCH3), −0.07 (6H, s, SiCH3ACH3B).
δC (75.5 MHz, CDCl3) 215.1, 135.9, 133.1, 82.3, 49.2, 39.5, 38.0, 31.7,
25.7, 20.9, 20.6, 18.0, 14.1, 13.9, 10.5, 7.2, −4.7, −5.5.
(2S,4R,5S,6E,8R)-2-Benzoyloxy-4,6,8-trimethyl-5-hydroxyundec-
6-en-3-one 33
To a solution of dicyclohexylboron chloride (2.2 mL, 10 mmol) in Et2O
(14.1 mL) at −78◦C was added Me2NEt (1.3 mL, 12 mmol) followed
by ketone 19 (1.38 g, 6.7 mmol) in Et2O (14.1 mL). The reaction mix-
ture was warmed to 0◦C and stirred for 2 h before being recooled to
−78◦C. The aldehyde 4 (493 mg, 3.5 mmol) in Et2O (2 + 2 + 1 mL)
was added by cannula and stirring was continued at −78◦C for 2 h
then at −23◦C for 14 h. The reaction mixture was quenched at 0◦C
with the addition of MeOH (14.1 mL), pH 7 buffer solution (14.1 mL),
and H2O2 (14.1 mL, 30% aq.), and stirring was maintained for 1 h at
room temperature. The mixture was partitioned between H2O (100 mL)
and CH2Cl2 (3 × 100 mL), the combined organic extracts were dried
(MgSO4), and the solvent was removed under reduced pressure. The
crude residue was purified by column chromatography (CH2Cl2) to give
adduct 33 (483 mg, 60%, >95% d.s.) as a white solid, RF 0.42 (CH2Cl2).
[α]2D0 13.7 (c 2.3 in CHCl3). (Found: m/z 369.2034. C21H30O4 requires
[M + Na]+• 369.2042.) vmax/cm−1 (film) 3514, 1721, 1453, 1317, 1270,
1116, 1027, 997, 713. δH (300 MHz, CDCl3) 8.11–8.07 (2H, m, ArH),
7.60–7.55 (1H, m, ArH), 7.49–7.42 (2H, m, ArH), 5.45 (1H, q, J 7.2,
CH(CH3)OBz), 5.19 (1H, d, J 9.6, (CH3)C=CH), 4.17 (1H, d, J 7.5,
CH(OH)CH), 3.04 (1H, dq, J 9.6 and 7.1, CH3CHCH), 2.40–2.35 (1H,
m, CH3CHCH2), 1.99 (1H, br s, OH), 1.60 (3H, d, J 1.2, (CH3)C=CH),
1.57 (3H, d, J 7.2, CH(CH3)OBz), 1.29–1.21 (4H, m, CH3CH2CH2),
1.03 (3H, d, J 6.9, CHCHCH3), 0.90 (3H, d, J 6.3, CH2CHCH3), 0.86
(3H, t, J 6.6, CH3CH2CH2). δC (75.5 MHz, CDCl3) 211.1, 165.8, 136.6,
133.2, 132.6, 129.8, 129.6, 128.4, 80.2, 75.1, 45.6, 39.5, 31.8, 20.8, 20.5,
15.5, 14.5, 14.2, 10.8.
(2Z,4R,5S,6E,8R)-5-(tert-Butyldimethylsilyloxy)-4,6,8-trimethyl-
2-trimethylsilyloxyundec-2,6-diene 35
To a solution of the protected ketone 34 (250 mg, 0.73 mmol) in CH2Cl2
(6.1 mL) at −78◦C was added 2,6-lutidine (282 µL, 2.4 mmol) followed
by TMSOTf (330 µL, 1.8 mmol). After stirring for 5 min at −78◦C,
the reaction mixture was warmed to room temperature and stirring
was continued for 14 h. The reaction mixture was quenched with the
addition of saturated aqueous NaHCO3 (20 mL) and the aqueous phase
was extracted with CH2Cl2 (3 × 40 mL).The combined organic extracts
were washed with brine (40 mL), dried (MgSO4), and the solvent was
removed under reduced pressure. The crude residue was purified by col-
umn chromatography (30% CH2Cl2/hexanes) to give the geometrically
pure enol ether 35 (288 mg, 99%) as a colourless oil, RF 0.70 (30%
20
CH2Cl2/hexanes). [α]D 8.4 (c 2.0 in CHCl3). (Found: m/z 435.3097.
C23H48O2Si2 requires [M + Na]+• 435.3091.) vmax/cm−1 (film) 1677,
1461, 1253, 1197, 1069, 896, 838, 775. δH (300 MHz, CDCl3) 4.99 (1H,
d, J 9.3, (CH3)C=CH), 4.49 (1H, q, J 6.7, (CH3)CH=C), 3.84 (1H, d, J
9.0, CHOTBS), 2.41–2.32 (1H, m, CH2CHCH3), 2.16 (1H, dq, J 9.0 and
7.2, CHCHCH3), 1.54 (3H, d, J 1.5, (CH3)C=CH), 1.48 (3H, d, J 6.7,
(CH3)CH=C), 1.35–1.19 (4H, m, CH3CH2CH2), 0.88 (3H, d, J 6.9,
CH2CHCH3), 0.88 (3H, t, J 6.9, CH3CH2CH2), 0.83 (9H, s, (CH3)3C),
0.75 (3H, d, J 6.9, CHCHCH3), 0.21 (9H, s, (CH3)3Si), −0.02 (3H, s,
CH3Si), −0.05 (3H, s, CH3Si). δC (75.5 MHz, CDCl3) 153.1, 134.5,
134.2, 101.5, 80.7, 44.9, 39.7, 31.6, 25.8, 21.0, 20.6, 18.2, 15.7, 14.2,
11.2, 10.9, 1.0, −4.8, −5.3.
(2S,4R,5S,6E,8R)-2-Benzoyloxy-5-(tert-butyldimethylsilyloxy)-
4,6,8-trimethylundec-6-en-3-one 42
To a solution of alcohol 33 (450 mg, 1.3 mmol) in CH2Cl2 (13 mL) at
−78◦C was added 2,6-lutidine (303 µL, 2.6 mmol) followed byTBSOTf
(450 µL, 2.0 mmol). After stirring for 30 min at −78◦C, the reaction
mixture was quenched with saturated aqueous NaHCO3 (50 mL) and
the aqueous phase was extracted with CH2Cl2 (3 × 50 mL). The com-
bined organic extracts were dried (MgSO4) and concentrated under
vacuum, and the crude residue was purified by column chromatography
(CH2Cl2) to give the protected adduct 42 (602 mg, 94%) as a colourless
oil, RF 0.73 (CH2Cl2). [α]2D0 2.7 (c 1.6 in CHCl3). (Found: m/z 483.2925.
C27H44O4Si requires [M + Na]+• 483.2907.) vmax/cm−1 (film) 1724,
1268, 1116, 1070, 837, 711. δH (300 MHz, CDCl3) 8.10–8.06 (2H, m,
ArH), 7.56 (1H, tt, J 7.4 and 1.6, ArH), 7.46–7.41 (2H, m, ArH), 5.44
(3S,4R,6R,7S,8E,10R)-7-(tert-Butyldimethylsilyloxy)-3-hydroxy-
4,6,8,10-tetramethyltridec-8-en-5-one 36
To a solution of enol ether 35 (227 mg, 0.55 mmol) and propionaldehyde
(118 µL, 1.7 mmol)inCH2Cl2 (5.5 mL)at−78◦CwasaddedBF3 · OEt2
(105 µL, 0.83 mmol). The reaction mixture was stirred at −78◦C for
1.5 h before being quenched with saturated aqueous NaHCO3 (20 mL).
The aqueous phase was extracted with CH2Cl2 (3 × 50 mL), and the
combined organic extracts were dried (MgSO4) and concentrated under

Total Synthesis of a Hemiacetal Polypropionate
795
vacuum.Thecrude residue was purified by column chromatography (5%
Et2O/CH2Cl2) to give adduct 36 (164 mg, 75%, 87% d.s.) as a colour-
less oil, RF 0.37 (5% Et2O/CH2Cl2), [α]2D0 2.9 (c 2.1 in CHCl3). (Found:
m/z 421.3115. C23H46O3Si requires [M + Na]+• 421.3114.) vmax/cm−1
(film) 3476, 1703, 1460, 1256, 1061, 837, 778. δH (300 MHz, CDCl3)
5.12 (1H, dd, J 9.3 and 1.2, (CH3)C=CH), 4.15 (1H, d, J 9.6, CHOTBS),
3.90–3.84 (1H, m, CHOH), 2.98 (1H, br s, OH), 2.96 (1H, dq, J 9.8 and
7.1, CHCHCH3), 2.60 (1H, qd, J 7.2 and 2.6, C(=O)CHCH3), 2.41–
2.32 (1H, m, CH2CHCH3), 1.62–1.47 (1H, m, CHCHACHBCH3), 1.56
(3H, d, J 1.2, (CH3)C=CH), 1.44–1.32 (1H, m, CHCHACHBCH3),
1.31–1.20 (4H, m, CH3CH2CH2), 1.13 (3H, d, J 7.2, C(=O)CHCH3),
0.95 (3H, t, J 7.5, CHCH2CH3), 0.88 (3H, d, J 6.6, CH2CHCH3),
0.86 (3H, t, J 6.9, CH3CH2CH2), 0.81 (9H, s, (CH3)3C), 0.78 (3H,
d, J 6.9, CHCHCH3), −0.03 (3H, s, CH3Si), −0.04 (3H, s, CH3Si).
δC (75.5 MHz, CDCl3) 218.5, 136.2, 132.8, 81.4, 72.5, 50.7, 48.1, 39.4,
31.7, 27.0, 25.7, 20.8, 20.5, 18.1, 14.7, 14.1, 10.6, 10.5, 8.0, −4.7, −5.0.
silica (5% Et2O/CH2Cl2) to give hemiacetal 7 (23.1 mg, 54%) as a
crystalline solid and dihydropyrone 10 (8.2 mg, 21%) as a colourless oil.
20
Hemiacetal 7, RF 0.38 (5% Et2O/CH2Cl2), [α]D 27.1 (c 0.6
in CHCl3). (Found: m/z 305.2084. C17H30O3 requires [M + Na]+•
305.2093.) vmax (film)/cm−1 3468, 1719, 1457, 1169, 1033, 996. δH
(300 MHz, CDCl3) 5.16 (1H, dd, J 9.3 and 1.2, (CH3)C=CH), 4.07
(1H, d, J 10.2, OCHCHCH3), 2.68 (1H, br q, J 6.7, CH(CH3)COH),
2.48 (1H, dqd, J 10.2, 6.6, and 1.2, OCHCHCH3), 2.55–2.38 (1H,
m, CH2CHCH3), 1.98 (1H, d, J 1.8, OH), 1.90–1.78 (1H, m,
C(OH)CHAHBCH3), 1.75–1.63 (1H, m, C(OH)CHACHBCH3), 1.69
(3H, d, J 1.5, (CH3)C=CH), 1.38–1.17 (4H, m, CH3CH2CH2), 1.07
(3H, d, J 6.6, CH(CH3)COH), 1.02 (3H, t, J 7.5, C(OH)CH2CH3), 0.91
(3H, d, J6.9, CH2CHCH3), 0.88(3H, t, J6.6, CH3CH2CH2), 0.86(3H, d,
J 6.6, OCHCHCH3). δC (75.5 MHz, CDCl3) 209.8, 137.4, 131.1, 103.5,
83.2, 50.2, 47.1, 39.9, 33.5, 32.2, 21.0, 20.9, 14.6, 11.2, 10.0, 8.9, 8.5.
20
Dihydropyrone 10, RF 0.63 (5% Et2O/CH2Cl2), [α]D 38.9 (c 0.54
in CHCl3). (Found: m/z 287.1980. C17H28O2 requires [M + Na]+•
287.1987.) vmax/cm−1 (film) 1665, 1618, 1458, 1392, 1365, 1179, 1063.
δH (300 MHz, CDCl3) 5.24 (1H, dd, J 9.6 and 1.2, (CH3)C=CH),
4.15 (1H, d, J 13.8, OCHCHCH3), 2.51 (1H, dq, J 13.8 and 6.9,
OCHCHCH3), 2.55–2.41 (1H, m, CH2CHCH3), 2.33 (2H, q, J 7.3,
CCH2CH3), 1.72 (3H, s, (CH3)C=C), 1.67 (3H, d, J 1.2, (CH3)C=CH),
1.34–1.21 (4H, m, CH3CH2CH2), 1.12 (3H, t, J 7.7, CCH2CH3), 0.94
(3H, d, J 7.2, CH2CHCH3), 0.92 (3H, d, J 6.9, OCHCHCH3), 0.89 (3H,
t, J 7.5, CH3CH2CH2). δC (75.5 MHz, CDCl3) 195.5, 173.3, 138.7,
129.7, 107.8, 89.8, 40.4, 39.5, 31.9, 25.7, 20.6, 20.6, 14.2, 11.2, 10.9,
10.3, 9.3.
(6R,7S,8E,10R)-7-(tert-Butyldimethylsilyloxy)-
4,6,8,10-tetramethyltridec-8-en-3,5-dione 37
To a solution of DMSO (64 µL, 0.90 mmol) in CH2Cl2 (1.3 mL) at
−78◦C was added dropwise oxalyl chloride (226 µL of a 2 M solution
in CH2Cl2, 0.46 mmol). After 30 min, alcohol 36 (62.3 mg, 0.15 mmol)
was added by cannula as a solution in CH2Cl2 (0.3 + 0.1 mL) and
the resultant mixture was stirred at −78◦C for 45 min. Triethylamine
(189 µL, 1.4 mmol) was added dropwise and the resultant white solu-
tion was stirred at −78◦C for 30 min then at 0◦C for 1 h. The reaction
mixture(0◦C)waspouredintorapidlystirred1 MNaHSO4 (1.5 mL), the
layers were separated, and the aqueous phase was extracted with Et2O
(3 × 20 mL). The combined organic extracts were concentrated under
vacuum and the residue was diluted with Et2O (20 mL) then washed
successively with 1 M NaHSO4 (3 × 10 mL), H2O (10 mL), saturated
aqueous NaHCO3 (10 mL), and brine (10 mL). The organic layer was
then dried (MgSO4) and concentrated under vacuum. The crude residue
was purified by column chromatography (30% CH2Cl2/hexanes) to
give product 37 (61.4 mg, 99%) as a mixture of dione and enol forms.
δH (300 MHz, CDCl3) 5.12 (1H, m, (CH3)C=CH), 4.14 (0.1H, d, J
9.6, CHOTBS), 4.09 (0.3H, d, J 9.6, CHOTBS), 3.99 (0.6H, d, J 9.6,
CHOTBS), 3.86 (0.6H, q, J 7.1, C(=O)CHCH3), 3.74 (0.1H, q, J 7.1,
C(=O)CHCH3), 3.02–2.92 (0.4H, m, CHCHCH3), 2.78 (0.6H, dq, J 9.6
and 6.9, CHCHCH3), 2.53 (1.3H, qd, J 7.2 and 5.4, C(=O)CH2CH3),
2.48–2.30 (1.7H, m, C(=O)CH2CH3, CH2CH(CH3)CH), 1.88 (0.9H,
s, C(CH3)=COH), 1.58 (0.9H, d, J 1.2, (CH3)C=CH), 1.55–1.54
(2.1H, m, (CH3)C=CH), 1.26 (2.1H, d, J 7.2, CH(CH3)C=O), 1.14–
1.00 (4H, m, CH3CH2CH2), 0.91–0.74 (21H, m, CH3CH2CH2,
CH2CH(CH3)CH, CHCH(CH3), C(=O)CH2CH3, (CH3)3C), −0.03
(0.3H, s, CH3Si), −0.03 (0.3H, s, CH3Si), −0.06 (1.8H, s, CH3Si),
−0.08 (1.8H, s, CH3Si), −0.09 (0.9H, s, CH3Si), −0.11 (0.9H, s,
CH3Si); enol OH 0.3H missing. δC (75.5 MHz, CDCl3) 210.5, 209.1,
195.9, 193.7, 136.4, 136.3, 136.0, 133.4, 132.8, 105.4, 82.7, 82.3, 81.2,
62.5, 61.6, 49.6, 48.0, 41.2, 39.5, 39.4, 35.2, 34.9, 31.7, 29.8, 25.8, 25.8,
25.6, 20.9, 20.8, 20.5, 18.0, 14.8, 14.2, 14.1, 12.8, 12.2, 12.1, 10.4, 10.3,
9.2, 7.7, 7.5, −4.7, −4.8, −5.1, −5.3, −5.7.
(4R,5S,6E,8R)-4,6,8-Trimethyl-5-(1-oxopropoxy)undec-
6-en-3-one 15
DBU (20 µL) was added to a solution of hemiacetal 7 (8.5 mg,
0.03 mmol) in benzene (10 mL) and the resultant mixture was stirred
at room temperature for 30 min. The solvent was then removed under
vacuum and the residue was immediately purified by column chromato-
graphy (buffered silica, 5% Et2O/CH2Cl2) to give ketol ester 15 and the
starting hemiacetal (5.0 mg, 60%) as an inseparable mixture, RF 0.56
(5% Et2O/CH2Cl2). By subtracting the peaks due to hemiacetal 7, the
spectra for ester 15 were recorded as follows. δH (300 MHz, CDCl3)
5.33 (1H, d, J 6.6, (CH3)C=CH), 5.21 (1H, d, J 10.5, OCHCHCH3),
2.91 (1H, dq, J 10.5 and 7.1, OCHCHCH3), 2.49 (2H, qd, J 7.2 and
1.2, C(=O)CH2CH3), 2.21 (2H, q, J 7.5, CH3CH2CO2), 1.57 (3H,
d, J 1.5, (CH3)C=CH), 1.25 (4H, m, CH3CH2CH2), 1.07 (3H, t,
J 7.5, CH3CH2CO2), 1.04 (3H, t, J 7.2, C(=O)CH2CH3), 0.93 (3H,
d, J 6.9, CHCHCH3), 0.90 (3H, d, J 6.6, CH2CHCH3), 0.85 (3H,
t, J 6.6, CH3CH2CH2). δH (300 MHz, C6D6) 5.52 (1H, d, J 10.2,
OCHCHCH3), 5.33 (1H, d, J 9.9, (CH3)C=CH), 2.76 (1H, dq, J 10.2
and 7.2, CHCHCH3), 2.29–2.22 (1H, m, CH2CHCH3), 2.19 (2H, q,
J 7.2, C(=O)CH2CH3), 1.96 (2H, q, J 7.5, CH3CH2CO2), 1.51 (3H,
d, J 0.9, (CH3)C=CH), 1.35–1.25 (1H, m, CH3CH2CH2), 1.20–1.15
(3H, m, CH3CH2CH2), 1.02 (3H, t, J 7.5, CH3CH2CO2), 0.88 (3H, t,
J 7.2, CH2CH3), 0.87 (3H, d, J 7.0, CHCHCH3), 0.84 (3H, d, J 7.0,
CHCHCH3), 0.77 (3H, d, J 7.2, CHCHCH3).
(2R,4S,5R,6E,8R)-2-Benzoyloxy-5-hydroxy-4,6,8-trimethylundec-
6-en-3-one 39
(2S,3R,5R,6S)-6-[(1E,3R)-1,3-Dimethylhex-1-enyl]-2-ethyl-
2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one 7
and (2S,3R)-2-[(1E,3R)-1,3-Dimethylhex-1-enyl)-6-ethyl-
3,5-dimethyl-2,3-dihydro-4H-pyran-4-one 10
The previously described procedure used for the preparation of 33 was
followed using ketone 38 (1.38 g, 6.7 mmol), dicyclohexylboron chlo-
ride (2.2 mL, 10 mmol), Me2NEt (1.3 mL, 12 mmol), and aldehyde 4
(493 mg, 3.5 mmol). Standard oxidative workup and purification by
column chromatography (5% Et2O/CH2Cl2) gave adduct 39 (891 mg,
To a Teflon cylinder that contained the dione/enols 37 (61.4 mg,
0.16 mmol) was added buffered pyridinium hydrofluoride [0.5 mL;
stock solution prepared from dry THF (10 mL), pyridine (5 mL), and
pyridinium hydrofluoride (2.1 g, 30%)] and H2O (20 µL). The resul-
tant solution was stirred at room temperature for 6 days and was
then diluted with Et2O (10 mL) and partitioned with saturated aque-
ous CuSO4 (8 mL). The layers were separated and the aqueous phase
was further extracted with Et2O (3 × 10 mL). The combined organic
extracts were washed with saturated aqueous NaHCO3 (10 mL), dried
(MgSO4), and the solvent was removed under reduced pressure. The
crude residue was purified by column chromatography on deactivated
20
73%, >95% d.s.) as a white solid, RF 0.35 (CH2Cl2), [α]D −38.7 (c
0.4 in CHCl3). (Found: m/z 369.2030. C21H30O4 requires [M + Na]+•
369.2042.) vmax/cm−1 (film) 3537, 1730, 1718, 1285, 1267, 1118, 715.
δH (300 MHz, CDCl3) 8.09 (2H, m, ArH), 7.59 (1H, m, ArH), 7.46
(2H, m, ArH), 5.46 (1H, q, J 7.0, CH(CH3)OBz), 5.20 (1H, d, J 9.6,
(CH3)C=CH), 4.18 (1H, dd, J 9.5 and 3.5, CH(OH)CH), 3.04 (1H,
dq, J 9.5 and 7.1, CHCHCH3), 2.43–2.33 (1H, m, CH2CHCH3), 1.90
(1H, d, J 3.5, OH), 1.60 (3H, d, J 1.2, (CH3)C=CH), 1.58 (3H, d,
J 6.9, CH(CH3)OBz), 1.29–1.14 (4H, m, CH3CH2CH2), 1.04 (3H,

796
T. Lister and M. V. Perkins
d, J 7.2, CHCHCH3), 0.93 (3H, d, J 6.6, CH2CHCH3), 0.86 (3H, t,
J 6.9, CH3CH2CH2). δC (75.5 MHz, CDCl3) 211.1, 165.9, 136.9, 133.2,
132.6, 129.8, 129.6, 128.4, 80.5, 75.1, 45.5, 39.7, 31.8, 20.8, 20.6, 15.6,
14.5, 14.1, 10.6.
(3S,4R,6S,7R,8E,10R)-7-(tert-Butyldimethylsilyloxy)-3-hydroxy-
4,6,8,10-tetramethyltridec-8-en-5-one 46
The previously described procedure used for the preparation of 36
was followed using enol ether 45 (366 mg, 0.89 mmol), propion-
aldehyde (191 µL, 2.7 mmol), and BF3 · OEt2 (168 µL, 1.3 mmol).
Standard workup and purification of the crude product by column
chromatography (5% Et2O/CH2Cl2) gave adduct 46 (235 mg, 67%,
(2R,4S,5R,6E,8R)-2-Benzoyloxy-5-(tert-butyldimethylsilyloxy)-
4,6,8-trimethylundec-6-en-3-one 43
20
85% d.s.) as a colourless oil, RF 0.37 (5% Et2O/CH2Cl2), [α]D
The previously described procedure used for the preparation of 42 was
followed using alcohol 39 (688 mg, 2.0 mmol), 2,6-lutidine (463 µL,
4.0 mmol), and TBSOTf (684 mL, 3.0 mmol). Standard workup and
purification of the crude product by column chromatography (CH2Cl2)
gave the protected adduct 43 (880 mg, 96%) as a colourless oil, RF
−21.7 (c 1.1 in CHCl3). (Found: m/z 421.3114. C23H46O3Si requires
[M + Na]+• 421.3114.) vmax/cm−1 (film) 3469, 1702, 1459, 1255, 1060,
998, 877, 836, 777. δH (300 MHz, CDCl3) 5.09 (1H, dd, J 9.6 and
1.2, (CH3)C=CH), 4.16 (1H, d, J 9.9, CHOTBS), 3.90–3.84 (1H, m,
CHOH), 2.98 (1H, dq, J 9.8 and 7.1, CHCHCH3), 2.97 (1H, d, J 3.9,
OH), 2.60 (1H, qd, J 7.2 and 2.6, C(=O)CHCH3), 2.44–2.30 (1H, m,
CH2CHCH3), 1.62–1.47 (1H, m, CHCHACHBCH3), 1.55 (3H, d, J 1.2,
(CH3)C=CH), 1.45–1.33 (1H, m, CHCHACHBCH3), 1.27–1.17 (4H,
m, CH3CH2CH2), 1.13 (3H, d, J 7.2, C(=O)CHCH3), 0.95 (3H, t, J
7.4, CHCH2CH3), 0.92 (3H, d, J 6.6, CH2CHCH3), 0.84 (3H, t, J 7.1,
CH3CH2CH2), 0.80 (9H, s, (CH3)3C), 0.80 (3H, d, J 7.0, CHCHCH3),
−0.04 (6H, s, (CH3)2Si). δC (75.5 MHz, CDCl3) 218.5, 136.4, 132.7,
81.7, 72.6, 50.8, 47.8, 39.7, 31.8, 27.0, 25.8, 20.7, 20.4, 18.1, 14.6, 14.1,
10.5, 10.5, 8.0, −4.6, −5.0.
20
0.68 (CH2Cl2), [α]D −16.9 (c 2.1 in CHCl3). (Found: m/z 483.2902.
C27H44O4Si requires [M + Na]+• 483.2907.) vmax/cm−1 (film) 1724,
1267, 1116, 1070, 836, 778, 711. δH (300 MHz, CDCl3) 8.09 (2H, m,
ArH), 7.57 (1H, t, J 7.5, ArH), 7.44 (2H, m, ArH), 5.44 (1H, q, J 7.0,
CH(CH3)OBz), 5.10 (1H, dd, J 9.6 and 1.4, (CH3)C=CH), 4.21 (1H, d,
J 9.9, CHOTBS), 3.01 (1H, dq, J 9.9 and 7.1, CHCHCH3), 2.43–2.31
(1H, m, CH2CHCH3), 1.55 (3H, d, J 1.4, (CH3)C=CH), 1.53 (3H, d,
J 7.2, CH(CH3)OBz), 1.28–1.12 (4H, m, CH3CH2CH2), 0.94 (3H, d, J
6.9, CHCHCH3), 0.93 (3H, d, J 6.9, CH2CHCH3), 0.85 (3H, t, J 6.6,
CH3CH2CH2), 0.81 (9H, s, (CH3)3C), −0.03 (3H, s, CH3Si), −0.03
(3H, s, CH3Si). δC (75.5 MHz, CDCl3) 209.5, 165.7, 136.5, 133.1,
132.7, 129.8, 128.4, 81.6, 75.3, 46.0, 39.7, 31.8, 25.8, 20.7, 20.4, 18.0,
15.2, 14.5, 14.1, 10.4, −4.7, −5.1 (1 coincident vinyl carbon).
(4-epi,6S,7R,8E,10R)-7-(tert-Butyldimethylsilyloxy)-
4,6,8,10-tetramethyltridec-8-en-3,5-dione 47
The previously described procedure used for the preparation of 37 was
followed using DMSO (107 µL, 1.5 mmol), oxalyl chloride (376 µL
of a 2 M solution in CH2Cl2, 0.75 mmol), alcohol 46 (100 mg,
0.25 mmol), and triethylamine (315 µL, 2.3 mmol). Standard workup
and purification of the crude product by column chromatography
(30% CH2Cl2/hexanes) gave the pure product 47 (99 mg, 99%) as a
mixture of dione and enol forms. δH (300 MHz, CDCl3) 5.08 (1H,
m, (CH3)C=CH), 4.14 (0.2H, d, J 9.6, CHOTBS), 4.09 (0.3H, d,
J 9.6, CHOTBS), 3.99 (0.5H, d, J 9.6, CHOTBS), 3.86 (0.5H, q,
J 7.1, C(=O)CHCH3), 3.75 (0.2H, q, J 7.1, C(=O)CHCH3), 3.05–2.94
(0.5H, m, CHCHCH3), 2.80 (0.5H, dq, J 9.6 and 6.9, CHCHCH3),
2.54 (1.3H, qd, J 7.2 and 5.4, C(=O)CH2CH3), 2.49–2.30 (1.7H, m,
C(=O)CH2CH3, CH2CH(CH3)CH), 1.87 (0.9H, s, (CH3)C=COH),
1.57 (0.6H, d, J 1.2, (CH3)C=CH), 1.55–1.54 (2.4H, m, (CH3)C=CH),
1.26 (2.1H, d, J 7.2, CH(CH3)C=O), 1.14–1.00 (4H, m, CH3CH2CH2),
0.93–0.74 (21H, m, CH3CH2CH2, CH2CH(CH3)CH, CHCH(CH3),
C(=O)CH2CH3, (CH3)3C), −0.03 (1.5H, s, CH3Si), −0.06 (1.5H, s,
CH3Si), −0.08 (1.8H, s, CH3Si), −0.10 (0.6H, s, CH3Si), −0.11 (0.6H,
s, CH3Si); enol OH 0.3H missing. δC (75.5 MHz, CDCl3) 210.5, 209.1,
207.4, 195.9, 193.8, 136.6, 136.5, 136.1, 133.4, 132.7, 105.0, 83.1, 82.6,
81.6, 62.5, 61.6, 49.2, 47.7, 40.9, 39.7, 39.6, 35.2, 34.9, 31.8, 29.8, 25.8,
25.8, 25.5, 20.6, 20.6, 20.4, 18.0, 14.7, 14.1, 12.8, 12.2, 12.1, 10.5, 10.3,
10.2, 9.2, 7.7, 7.5, −4.5, −4.6, −4.7, −5.0, −5.2, −5.7.
(4S,5R,6E,8R)-5-(tert-Butyldimethylsilyloxy)-4,6,8-trimethylundec-
6-en-3-one 44
The previously described procedure used for the preparation of 34
was followed using protected adduct 43 (600 mg, 1.3 mmol) and SmI2
(approx. 55 mL of a 1 M solution in THF, approx. 5.2 mmol). Standard
workup and purification of the crude product by column chromato-
graphy (30% CH2Cl2/hexanes) afforded the protected hydroxy ketone
44 (393 mg, 89%) as a colourless oil, RF 0.34 (30% CH2Cl2/hexanes),
[α]2D0 0.8 (c 2.5 in CHCl3). (Found: m/z 363.2691. C20H40O2Si requires
[M + Na]+• 363.2695.) vmax/cm−1 (film) 1721, 1251, 1057, 836, 777.
δH (300 MHz, CDCl3) 5.07 (1H, dd, J 9.6 and 1.2, (CH3)C=CH), 4.03
(1H, d, J 9.9, CHOTBS), 2.77 (1H, dq, J 9.9 and 7.0, CHCHCH3),
2.53 (2H, qd, J 7.2 and 6.9, C(=O)CH2CH3), 2.44–2.28 (1H, m,
CH2CHCH3), 1.56 (3H, d, J 1.2, (CH3)C=CH), 1.37–1.11 (4H, m,
CH3CH2CH2), 1.01 (3H, t, J 7.2, C(=O)CH2CH3), 0.91 (3H, d, J 6.9,
CH2CHCH3), 0.84 (3H, t, J 6.8, CH3CH2CH2), 0.79 (9H, s, (CH3)3C),
0.77 (3H, d, J 7.2, CHCHCH3), −0.06 (3H, s, CH3Si), −0.07 (3H, s,
CH3Si). δC (75.5 MHz, CDCl3) 215.1, 136.1, 133.0, 82.7, 48.9, 39.7,
38.0, 31.8, 25.7, 20.7, 20.5, 18.0, 14.1, 13.9, 10.3, 7.2, −4.6, −5.5.
(2Z,4S,5R,6E,8R)-5-(tert-Butyldimethylsilyloxy)-4,6,8-trimethyl-
2-(trimethylsilyloxy)undec-2,6-diene 45
(2R,3S,5S,6R)-6-[(1E,3R)-1,3-Dimethylhex-1-enyl]-2-ethyl-
2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one 8
and (2R,3S)-2-[(1E,3R)-1,3-Dimethylhex-1-enyl]-6-ethyl-
3,5-dimethyl-2,3-dihydro-4H-pyran-4-one 10
The previously described procedure used for the preparation of
35 was followed using the protected hydroxy ketone 44 (330 mg,
0.97 mmol), 2,6-lutidine (451 µL, 3.9 mmol), and TMSOTf (526 µL,
2.9 mmol). Standard workup and purification of the crude product by
column chromatography (30% CH2Cl2/hexanes) gave the geometri-
cally pure enol ether 45 (386 mg, 97%) as a colourless oil, RF 0.67
The previously described procedure used for the preparation of 7 was
followed using the dione/enols 47 (99 mg, 0.25 mmol), buffered pyri-
dinium hydrofluoride (1.0 mL), and H2O (40 µL). Standard workup
and purification of the crude product by column chromatography on
deactivated silica (5% Et2O/CH2Cl2) gave hemiacetal 8 (29.8 mg,
43%) as a crystalline solid and dihydropyrone 11 (11.2 mg, 17%) as
a colourless oil.
20
(30% CH2Cl2/hexanes), [α]D −28.10 (c 1.1 in CHCl3). (Found: m/z
435.3079. C23H48O2Si2 requires [M + Na]+• 435.3091.) vmax/cm−1
(film) 1677, 1459, 1253, 1197, 1068, 875, 838, 775. δH (300 MHz,
CDCl3) 4.97 (1H, dd, J 9.6 and 1.2, (CH3)C=CH), 4.49 (1H, q, J
6.7, (CH3)CH=C), 3.83 (1H, d, J 9.3, CHOTBS), 2.44–2.30 (1H, m,
CH2CHCH3), 2.17 (1H, dq, J 9.3 and 7.0, CHCHCH3), 1.52 (3H, d, J
1.2, (CH3)C=CH), 1.48 (3H, d, J 6.9, (CH3)CH=C), 1.29–1.15 (4H,
m, CH3CH2CH2), 0.92 (3H, d, J 6.9, CH2CHCH3), 0.87 (3H, t, J 6.9,
CH3CH2CH2), 0.83 (9H, s, (CH3)3C), 0.76 (3H, d, J 6.9, CHCHCH3),
0.21 (9H, s, (CH3)3Si), −0.02 (3H, s, CH3Si), −0.06 (3H, s, CH3Si).
δC (75.5 MHz, CDCl3) 153.2, 134.5, 134.5, 101.5, 81.1, 44.5, 39.9, 31.7,
25.8, 20.8, 20.7, 18.2, 15.8, 14.2, 11.2, 10.6, 1.0, −4.8, −5.3.
20
Hemiacetal 8, RF 0.43 (5% Et2O/CH2Cl2), [α]D −65.9 (c 2.0
in CHCl3). (Found: m/z 305.2082. C17H30O3 requires [M + Na]+•
305.2093.) vmax/cm−1 (film) 3357, 1718, 1457, 1173, 1042, 953.
δH (300 MHz, CDCl3) 5.15 (1H, dd, J 9.3 and 1.2, (CH3)C=CH),
4.07 (1H, d, J 10.5, OCHCHCH3), 2.68 (1H, qt, J 6.6 and 1.2,
CH(CH3)COH), 2.49 (1H, dqd, J 10.5, 6.6, and 1.2, OCHCHCH3),
2.41 (1H, m, CH2CHCH3), 2.08 (1H, d, J 2.1, OH), 1.90–1.78 (1H,
m, C(OH)CHAHBCH3), 1.74–1.58 (1H, m, C(OH)CHACHBCH3), 1.68

Total Synthesis of a Hemiacetal Polypropionate
797
(3H, d, J1.2, (CH3)C=CH), 1.32–1.16(4H, m, CH3CH2CH2), 1.06(3H,
d, J 6.6, CH(CH3)COH), 1.02 (3H, t, J 7.4, C(OH)CH2CH3), 0.95 (3H,
d, J 6.6, CH2CH(CH3), 0.86 (3H, t, J 6.6, CH3CH2CH2), 0.86 (3H, d,
J 6.6, OCHCHCH3). δC (75.5 MHz, CDCl3) 209.5, 137.1, 131.0, 103.1,
83.0, 49.7, 46.5, 39.7, 33.2, 31.8, 20.7, 20.6, 14.1, 10.7, 9.6, 8.5, 8.2.
m, CH3CH2CH2), 1.01 (3H, t, J 7.2, CH3CH2CO2), 0.91–0.83 (9H, m,
3 × CH3), 0.77 (3H, d, J 7.2, CHCHCH3). δH (75.5 MHz, CDCl3) 212.8,
172.7, 138.7, 128.7, 81.3, 47.6, 39.6, 35.3, 31.9, 27.7, 20.6, 20.6, 14.1,
13.7, 11.5, 9.1.
20
Dihydropyrone 11, RF 0.63 (5% Et2O/CH2Cl2), [α]D −57.6 (c
Acknowledgments
0.75 in CHCl3). (Found: m/z 287.1983. C17H28O2 requires [M + Na]+•
287.1987.) vmax/cm−1 (film) 1666, 1618, 1456, 1390, 1366, 1179, 1063.
δH (300 MHz, CDCl3) 5.23 (1H, dd, J 9.6 and 0.9, (CH3)C=CH),
4.16 (1H, d, J 13.2, OCHCHCH3), 2.52 (1H, dq, J 13.2 and 6.9,
OCHCHCH3), 2.44 (1H, m, CH2CHCH3), 2.33 (2H, q, J 7.5,
CCH2CH3), 1.72 (3H, s, (CH3)C=C), 1.68 (3H, d, J 1.5, (CH3)C=CH),
1.31–1.17 (4H, m, CH3CH2CH2), 1.12 (3H, t, J 7.7, CCH2CH3), 0.98
(3H, d, J 6.6, CH2CHCH3), 0.95 (3H, d, J 6.9, OCHCHCH3), 0.87 (3H,
t, J 6.9, CH3CH2CH2). δC (75.5 MHz, CDCl3) 195.5, 173.3, 138.9,
129.8, 107.9, 90.0, 40.2, 39.6, 31.9, 25.8, 20.7, 20.6, 14.1, 11.2, 11.0,
10.3, 9.3.
We thank the Australian Research Council (Flinders Univer-
sity Small ARC Grant to M.V.P.) for support. We also thank
Ms Catherine M. Sincich, Professor William Fenical, and the
late Professor D. John Faulkner, Center for Marine Biotech-
nology and Biomedicine, Scripps Institution of Oceanogra-
1
phy, for kindly providing copies of the original H NMR
spectra for hemiacetal 1 and ester 2 from the Hochlowski
and Faulkner[3] isolation.
(4S,5R,6E,8R)-5-Hydroxy-4,6,8-trimethylundec-6-en-3-one 13
References
To a solution of the unprotected adduct 39 (100 mg, 0.22 mmol) in
THF (2.6 mL) and MeOH (1.3 mL) at 0◦C was added SmI2 (approx.
9 mL of a 1 M solution in THF, approx. 0.87 mmol) until a deep green
colour persisted. The reaction mixture was then quenched at 0◦C with
the addition of saturated aqueous K2CO3 (13 mL) and allowed to
warm to room temperature. The aqueous layer was extracted with Et2O
(3 × 15 mL), and the combined organic extracts were dried (MgSO4)
and concentrated under vacuum. The crude product was purified by col-
umn chromatography (10% Et2O/CH2Cl2) to afford β-hydroxy ketone
13 with an indeterminate amount of benzoyloxy derived contami-
nant, RF 0.39 (Et2O/CH2Cl2). δH (300 MHz, CDCl3) 5.17 (1H, d,
J 9.6, (CH3)C=CH), 4.09 (1H, d, J 9.3, CH(OH)CH), 3.99 (1H, s,
OH), 2.78 (1H, dq, J 9.3 and 7.2, CHCHCH3), 2.56 (2H, qd, J 7.2
and 3.6, C(=O)CH2CH3), 2.37 (1H, m, CH2CHCH3), 1.61 (3H, d, J
1.5, (CH3)C=CH), 1.25 (4H, m, CH3CH2CH2), 1.05 (3H, t, J 7.2,
C(=O)CH2CH3), 0.93 (6H, d, J 6.9, CH2CHCH3, CHCHCH3), 0.86
(3H, t, J 6.8, CH3CH2CH2).
[1] M. T. Davies-Coleman, M. J. Garson, Nat. Prod. Rep. 1998,
15, 477.
[2] (a) M. J. Garson, J. M. Goodman, I. Paterson, Tetrahedron Lett.
1994, 35, 6929. doi:10.1016/0040-4039(94)85044-5
(b) M. J. Garson, Chem. Rev. 1993, 93, 1699.
(c) D. C. Manker, M. J. Garson, D. J. Faulkner, J. Chem. Soc.,
Chem. Commun. 1988, 1061. doi:10.1039/C39880001061
[3] J. E. Hochlowski, D. J. Faulkner, J. Org. Chem. 1984, 49,
3838.
[4] U. N. Sundram, K. F. Albizati, Tetrahedron Lett. 1992, 33, 437.
doi:10.1016/S0040-4039(00)93961-3
[5] I. Paterson, D. J. Wallace, Tetrahedron Lett. 1994, 35, 9477.
doi:10.1016/S0040-4039(00)78576-5
[6] I. Paterson, D. J. Wallace, S. M. Velazquez, Tetrahedron Lett.
1994, 35, 9083. doi:10.1016/0040-4039(94)88434-X
[7] T. Lister, Honours Thesis 2002 (Flinders University: Adelaide).
[8] (a) S. E. Denmark, S. M. Pham, Org. Lett. 2001, 3, 2201.
doi:10.1021/OL0160497
(4S,5R,6E,8R)-4,6,8-Trimethyl-5-(1-oxopropoxy)undec-6-en-3-one 16
(b) L. N. Mander, S. P. Sethi, Tetrahedron Lett. 1984, 25, 5953.
doi:10.1016/S0040-4039(01)81731-7
Pyridine (17 µL, 0.21 mmol) followed by propionyl chloride (17 µL,
0.20 mmol) were added to a solution of the β-hydroxy ketone 13 (11 mg,
0.04 mmol) in CH2Cl2 (284 µL) and the resultant mixture was stirred
at room temperature for 2 h. Dichloromethane (10 mL) was added to
the reaction mixture, the organic phase was washed with HCl (4 mL,
2 M) and saturated aqueous NaHCO3 (4 mL), dried (MgSO4), and the
solvent was removed under reduced pressure. The crude product was
purified by column chromatography (CH2Cl2) to give ester 16 (7.5 mg,
[9] The product obtained from the subsequent Mukaiyama aldol
coupling (compound 24) was a different syn isomer to that
obtained in low yield from the Tiiv aldol coupling.
[10] D. A. Evans, M. G. Yang, M. J. Dart, J. L. Duffy, A. S. Kim,
J. Am. Chem. Soc. 1995, 117, 9598.
[11] R. W. Hoffmann, G. Dahmann, Chem. Ber. 1994, 127, 1317.
[12] R. E. Zelle, M. P. DeNinno, H. G. Selnick, S. Danishefsky,
J. Org. Chem. 1986, 51, 5032.
20
18% over two steps) as a colourless oil, RF 0.34 (CH2Cl2), [α]D −6.0 (c
0.5 in CHCl3). (Found: m/z 305.2084. C17H30O3 requires [M + Na]+•
305.2093.) vmax/cm−1 (film) 1741, 1718, 1458, 1376, 1181, 1004. δH
(300 MHz, CDCl3) 5.33 (1H, dd, J 9.6 and 1.5, (CH3)C=CH), 5.22 (1H,
d, J 10.2, OCHCH), 2.91 (1H, dq, J 10.2 and 7.1, CHCHCH3), 2.49
(2H, qd, J 7.2 and 1.5, C(=O)CH2CH3), 2.34 (1H, m, CH2CHCH3),
2.21 (2H, q, J 7.5, CH3CH2CO2), 1.57 (3H, d, J 1.5, (CH3)C=CH),
1.27–1.11 (4H, m, CH3CH2CH2), 1.07 (3H, t, J 7.7, CH3CH2CO2),
1.03 (3H, t, J 7.4, C(=O)CH2CH3), 0.94 (3H, d, J 7.2, CHCHCH3),
0.92 (3H, d, J 6.6, CH2CHCH3), 0.85 (3H, t, J 6.7, CH3CH2CH2). δH
(300 MHz, C6D6) 5.53 (1H, d, J 10.5, OCHCHCH3), 5.32 (1H, d, J 9.6,
(CH3)C=CH), 2.75 (1H, dq, J 10.2 and 7.2, CHCHCH3), 2.29–2.15
(1H, m, CH2CHCH3), 2.19 (2H, q, J 7.2, C(=O)CH2CH3), 1.96 (2H,
q, J7.5, CH3CH2CO2), 1.51(3H, d, J1.5, (CH3)C=CH), 1.20–1.08(4H,
[13] The 1H NMR spectrum was reported[3] to be recorded in CDCl3,
but copies of the original spectra sent to us were marked CCl4.
The 1H NMR spectrum of compound 7 recorded in CCl4
(with external C6D6 lock) was identical to that reported for
hemicacetal 1 in ref. [3].
[14] The 13C NMR (C6D6) spectrum reported[3] for hemacetal 1
was identical to that found for hemiacetal 7 except for C7 (81.5
compared with 82.8 ppm). Unfortunately, original copies of the
13C NMR spectra could not be located for direct comparison.
It is possible that the reported shifts for the C7 signals of
hemiacetal 1 and ester 2 were inadvertently interchanged.
[15] Copies of the original 1H NMR spectra of hemiacetal 1 and
ester 2 in both C6D6 and CCl4 were obtained for comparison.