Total synthesis of solandelactones A, B, E, and F exploiting a tandem petasis-claisen lactonization strategy

Article abstract of DOI:10.1021/jo800335g

(Chemical Equation Presented) Solandelactones A, B, E, and F were synthesized using Nozaki-Hiyama-Kishi coupling of iododiene 13 with aldehydes 14 and 99 obtained by oxidation of alcohols 92 and 94. Key steps in the synthesis of 92 and 94 were (i) a Nagao asymmetric acetate aldol reaction of aldehyde 77 with thionothiazolidine 78 to set in place an alcohol that becomes the (75) lactone center of solandelactones, (ii) a Simmons-Smith cyclopropanation of 80 directed by this alcohol, and (iii) Petasis methylenation of cyclic carbonate 90 in tandem with a Claisen rearrangement that generates the octenalactone portion of solandelactones. Synthesis of solandelactones A, B, E, and F confirmed their gross structure and absolute configuration at C7, 8, 10, and 14 but showed that alcohol configuration at C11 must be reversed in pairs, A/B and E/F, from the previous assignment made to these hydroid metabolites. Thus, solandelactones A and B are correctly represented by 2 and 1, respectively, whereas solandelactones E and F are 6 and 5. A biogenesis of solandelactones is proposed for these C₂₂ oxylipins that parallels a hypothesis put forward previously to explain the origin of C₂₀ cyclopropane-containing algal products.

Full text of DOI:10.1021/jo800335g

Total Synthesis of Solandelactones A, B, E, and F Exploiting a
Tandem Petasis-Claisen Lactonization Strategy
James D. White,* Christopher M. Lincoln, Jongtae Yang, William H. C. Martin, and
David B. Chan
Department of Chemistry, Oregon State UniVersity, CorVallis, Oregon 97331-4003
james.white@oregonstate.edu
ReceiVed February 15, 2008
Solandelactones A, B, E, and F were synthesized using Nozaki-Hiyama-Kishi coupling of iododiene
13 with aldehydes 14 and 99 obtained by oxidation of alcohols 92 and 94. Key steps in the synthesis of
92 and 94 were (i) a Nagao asymmetric acetate aldol reaction of aldehyde 77 with thionothiazolidine 78
to set in place an alcohol that becomes the (7S) lactone center of solandelactones, (ii) a Simmons-Smith
cyclopropanation of 80 directed by this alcohol, and (iii) Petasis methylenation of cyclic carbonate 90 in
tandem with a Claisen rearrangement that generates the octenalactone portion of solandelactones. Synthesis
of solandelactones A, B, E, and F confirmed their gross structure and absolute configuration at C7, 8, 10,
and 14 but showed that alcohol configuration at C11 must be reversed in pairs, A/B and E/F, from the
previous assignment made to these hydroid metabolites. Thus, solandelactones A and B are correctly
represented by 2 and 1, respectively, whereas solandelactones E and F are 6 and 5. A biogenesis of
solandelactones is proposed for these C22 oxylipins that parallels a hypothesis put forward previously to
explain the origin of C20 cyclopropane-containing algal products.
Solandelactones belong to the family of marine metabolites
known as oxylipins, a group that includes constanolactones A
(9) and B (10),4 halicholactone (11)5 and neohalicholactone (12)
(Figure 2).5 The eicosanoid oxylipins are believed to have their
origin in the C20 progenitor arachidonic acid; biosynthetic
pathways have been put forward that account for structural
variations within the class.4b,6 Solandelactones, as C22 metabo-
lites, present an immediate anomaly, however. There is also a
curious configurational divergence within the solandelactone,
constanolactone and halicholactone families that remains un-
explained. Thus, the disubstituted cyclopropane of solandelac-
tones has the same absolute configuration as that of halicholac-
tone (11) and neohalicholactone (12)7 but reversed configuration
when compared with the corresponding cyclopropane carbons
in constanolactones A (9) and B (10). On the other hand, the
Introduction
The growing interest attached to substances present in marine
invertebrates and algae has led to discovery of a large number
of new compounds and even to several unique structural classes
from the marine environment.1 However, the chemistry of
hydroids (class Hydrazoa) remains largely unexplored, and aside
from a few common steroids, phospholipids, aromatic polypep-
tides, and ꢀ-carbolines, little is known of the chemical con-
stituents of this family of organisms.2 In 1996, Shin and co-
workers reported the isolation of eight new substances, which
he named solandelactones A-H, from the hydroid Solanderia
secunda found near the island of Jaeju in Korea.3 Structures
1-8 (Figure 1) were assigned to these metabolites primarily
on the basis of detailed NMR analysis.
(1) Wessjohann, L. A.; Brandt, W. Chem. ReV. 2003, 103, 1625.
(2) (a) Fahy, E.; Andersen, R. J.; He, C.-H.; Clardy, J. J. Org. Chem. 1985,
50, 1149. (b) Aiello, A.; Fattorusso, E.; Magno, S.; Mayol, L. Tetrahedron 1987,
43, 5929. (c) Faulkner, D. J. Nat. Prod. Rep. 1995, 12, 223. and references cited
therein.
(4) (a) Nagle, D. G.; Gerwick, W. H. Tetrahedron Lett. 1990, 31, 2995. (b)
Nagle, D. G.; Gerwick, W. H. J. Org. Chem. 1994, 59, 7227.
(5) Niwa, H.; Wakamatsu, K.; Yamada, K. Tetrahedron Lett. 1989, 30, 4543.
(6) Brash, A. R. J. Am. Chem. Soc. 1989, 111, 1891.
(3) Seo, Y.; Cho, K. W.; Rho, J.-R.; Shin, J.; Kwon, B.-M.; Bok, S,-H.;
Song, J.-I. Tetrahedron 1996, 52, 10583.
(7) Kigoshi, H.; Niwa, H.; Yamada, K.; Stout, T. J.; Clardy, J. Tetrahedron
Lett. 199132, 2427.
10.1021/jo800335g CCC: $40.75
Published on Web 05/02/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 4139–4150 4139

White et al.
SCHEME 1
FIGURE 1. Shin’s structural assignments to solandelactones A-H.
FIGURE 2. Cyclopropane-containing C20 oxylipins.
lactonized C7 oxygen and the C14 alcohol of solandelactones
correspond stereochemically to C5 and C12 in constanolactones
but are reversed in configuration from the analogous centers,
C8 and C15, in 11 and 12.
progress, a publication by Davoren and Martin appeared
describing asymmetric synthesis of 6,10 that is, the structure
assigned by Shin to solandelactone F. However, NMR data for
Martin’s synthetic compound matched those of the epimer
solandelactone E, implying that C11 configuration of the E/F
pair should be reversed.
Our initial goal was synthesis of solandelactone E and F
having unsaturation in the eight-membered lactone, anticipating
that the saturated lactones A and B would become accessible
through reduction. This led to a strategy for synthesis of
solandelactones E and F shown in Scheme 1.11 The final step
in this plan is a Nozaki-Hiyama-Kishi coupling of iodoalkene
13 with aldehyde 14, for which the anticipated stereochemical
outcome with respect to the C11 center in solandelactones was
addressed in our synthesis of constanolactones A and B.8 Based
on that analogy, the Felkin product having (11S) configuration
corresponding to 5, the structure assigned by Shin to solan-
delactone E, was expected to be the major stereoisomer.
The absolute configuration of constanolactones A and B was
assigned unambiguously as (5R,6S,8S,12S) through total syn-
thesis, epimers A and B being given (9S) and (9R) designation,
respectively.8 Likewise, the absolute configuration of hali-
cholactone and neohalicholactone has been confirmed by
synthesis.9 The structural assignments made to solandelactones
by Shin and shown in Figure 1 placed heavy reliance on data
that included NOE correlation between protons at C10 and C11.3
A conformation about the C10-C11 bond was assumed on the
basis of NMR analysis that predicted (11R) configuration for
the series A, C, E, and G and reversed (11S) configuration for
solandelactones B, D, F, and H. These assignments, when taken
with the absence of stereochemical congruence among the
structural families represented in Figures 1 and 2, lent impetus
to a synthetic plan for solandelactones that would unambigu-
ously establish their stereochemistry. While our work was in
(8) (a) White, J. D.; Jensen, M. S. J. Am. Chem. Soc. 1993, 115, 2970. (b)
White, J. D.; Jensen, M. S. J. Am. Chem. Soc. 1995, 117, 6224.
(10) (a) Davoren, J. E.; Martin, S. F. J. Am. Chem. Soc. 2007, 129, 510. (b)
Davoren, J. E.; Harcken, C.; Martin, S. F. J. Org. Chem. 2008, 73, 391.
(11) White, J. D.; Martin, W. H. C.; Lincoln, C. M.; Yang, J. Org. Lett.
2007, 9, 3481.
(9) (a) Critcher, D. J.; Connolly, S.; Wills, M. Tetrahedron Lett. 1995, 36,
3763. (b) Critcher, D. J.; Connolly, S.; Wills, M. J. Org. Chem. 1997, 62, 6638.
4140 J. Org. Chem. Vol. 73, No. 11, 2008

Total Synthesis of Solandelactones A, B, E, and F
SCHEME 2
SCHEME 3
Construction of (E,Z)-iododiene 13 was foreseen from a 1,4-
dicarbonyl synthon 15 whose single stereogenic center originates
in (S)-(-)-malate ester 16. The first option considered for
assembling the ∆4,5-octenalactone portion 1412 recognized the
possibility of a ring-closing metathesis, but this strategy was
subsequently abandoned in favor of an approach based upon
Claisen rearrangement. Installation of the key C7 stereogenic
center in 14 would take place by a stereocontrolled addition to
aldehyde 17. The cyclopropane moiety 17 was initially envi-
sioned as the product of a previously disclosed tin-assisted
elimination of the triflate from alcohol 18.13 The latter is
available from (R)-(-)-malate 19, a design feature that enables
construction of the two halves of solandelactones from antipodal
starting materials.
Results and Discussion
Synthesis of Iododiene 13. Our previous synthesis of 13
employed an eleven-step sequence commencing from D-arabi-
nose, expunging two of the three stereogenic centers of the
pentose en route.8 This was clearly unsatisfactory as a multigram
preparation of 13. We therefore implemented a new route to
13 and selected dimethyl (S)-malate (16) as the point of
departure. Our intention was to preserve the configuration of
16 as surrogate for the C14 alcohol of the solandelactones while
building outward from the pair of methyl esters toward the hexyl
and (E)-iodoalkene termini, respectively (Scheme 2).
trityl residue,16 and alcohol 26 was then oxidized to aldehyde
27. This aldehyde was also unstable and was immediately treated
with chromous chloride and iodoform under Takai-Utimoto
conditions.17 Yields of 28 from this reaction were found to
depend on the scale as well as the provenance of reactants, but
a reliable 35-40% could be obtained from the two-step
sequence from alcohol 26.18 The need for TBS protection of
28 in the projected Nozaki-Hiyama-Kishi union with 14 was
uncertain at this point, and as a cautionary move we unmasked
only a portion of 28 to afford 13.
Synthesis of Lactone 14. First Generation Approach. A
strategic issue to be considered in an approach to 14 was the
sequence in which the cyclopropane and lactone rings should
be assembled. A plan in which the ∆4,5-octenalactone portion
of 14 would be fabricated using a late-stage ring-closing
metathesis, taken with the assumption that C7 configuration
could be installed through a stereocontrolled aldol-type reaction
of cyclopropanecarboxaldehyde 17, persuaded us that the
cyclopropane should be elaborated before the lactone.
Diester 16 was first reduced, as previously described,14 to
diol 20. Selective tritylation of the primary alcohol furnished
21 which was further protected as its TBS ether 22. Reduction
of this ester to an aldehyde with diisobutylaluminum hydride
was inefficient, and it was found more practical to take 22 to
alcohol 23 and then oxidize this substance with catalytic Ley’s
reagent15 to aldehyde 24. The latter proved to be unstable and
was promptly subjected to Wittig olefination with the ylide from
n-hexytriphenylphosphonium bromide. The resulting (Z)-alkene
25 was deprotected under conditions which removed only the
Two routes to cyclopropane 17 were explored, the first of
which employed (S)-(-)-glycidol (29) as the source of chirality
(12) For an earlier approach to the synthesis of this portion of solandelactones,
see: (a) Varadarajan, S.; Mohapatra, D. K.; Datta, A. Tetrahedron Lett. 1998,
39, 1075. (b) Mohapatra, D. K.; Yelleo, G. S. ARKIVOC 2003, 21.
(13) Lincoln, C. M.; White, J. D.; Yokochi, A. F. T. Chem. Commun. 2004,
2846.
(16) Bessodes, M.; Komiotis, D.; Antonakis, K. Tetrahedron Lett. 1986, 27,
579.
(14) Saito, S.; Hasegawa, T.; Inaba, M.; Nishida, R.; Fujii, T.; Nomizu, S.;
Moriwake, T. Chem. Lett. 1984, 1389.
(17) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki,
H. J. Am. Chem. Soc. 1986, 108, 6048.
(15) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis 1994,
639.
(18) For other routes to 13, see: (a) Da Silva, C. B.; Pale, P Tetrahedron:
Asymmetry 1998, 9, 3951. (b) Pietruszka, J.; Wilhelm, T. Synlett 2003, 1698.
J. Org. Chem. Vol. 73, No. 11, 2008 4141

White et al.
SCHEME 4
SCHEME 5
(Scheme 3). After protection of 29 as its trityl ether 30, the
epoxide was opened with the lithio alkyne prepared from
propargyl ether 31. Hexynol 32 was converted to bis TBS ether
33, from which the primary silyl ether was selectively cleaved
to yield 34. Reduction of alkynol 34 with Red-Al cleanly
afforded (E)-allylic alcohol 35 which was advanced to chloride
36. Exposure of 36 to lithio tri-n-butylstannane19 led to 37 from
which the silyl ether was cleaved to furnish enantiopure
homoallylic alcohol 38.
Suzuki showed that the triflate of homoallylic alcohol 39,
when exposed to a base, underwent elimination to give
cyclopropane 40 in very high enantiomeric excess (Scheme 4).20
A mechanism was proposed in which displacement of triflate
occurs with inversion via transition state 41 that orients
phenethyl and propenyl substituents in a 1,3-anti relationship.
Taylor later extended Suzuki’s observation by attaching a
silylmethylene unit at the alkene terminus.21 He found that an
E,Z mixture of 42 gave trans disubstituted cyclopropane 43 with
excellent stereoselectivity. Our belief that a carbocation stabi-
lized through stannyl participation in the elimination of the
triflate from 38 would also lead efficiently to a cyclopropane
was upheld when we subjected 38 to conditions essentially
identical to those employed by Suzuki on 39. The result was a
quantitative yield of trans and cis cyclopropanes 44 and 45 in
the ratio 7.6:1, respectively. Both 44 and 45 were enantiomeri-
cally pure as determined by chiral HPLC. The major cyclopro-
pane 44 is believed to result from elimination of triflate in a
1,3-anti conformation analogous to the transition state 41
proposed by Suzuki.20 Formation of the minor cis disubstituted
cyclopropane 45 from 38 presumably occurs through a transition
state that places the alkene and trityl ether in a 1,3-syn
orientation, and although this should be less favorable for steric
reasons than the 1,3-anti conformation analogous to 41, the
spacial interaction of substituents is not sufficiently large to
guide 38 uniquely toward 44. This suggested that a modified
version of 38, in which the trans double bond was replaced by
a cis alkene, would create a larger steric impediment to the
pathway proceeding via a 1,3-syn transition state because stannyl
and trityl groups would now be in closer proximity. Formation
of 44 relative to 45 should therefore be enhanced.
An attractive feature of the new route shown in Scheme 5
was that it could begin from the enantiomer of the starting
material used to prepare 13, namely dimethyl (R)-(+)-malate
(19). The latter was taken forward to aldehyde 46, which was
subjected to Gennari-Still condensation22 with phosphonate 47
to give (Z) unsaturated ester 48. The latter was reduced to allylic
alcohol 49 and the alcohol was converted to the corresponding
chloride. Displacement of this chloride with lithium tri-n-
butylstannane19 produced the (Z) allylstannane from which the
TBS group was removed to yield (R) alcohol 50. Exposure of
50 to triflic anhydride under the identical conditions used with
38 furnished 44 in excellent yield as the sole detectable product
(19) Tamborski, C.; Ford, F. E.; Soloski, E. J. J. Org. Chem. 1963, 28, 237.
(20) (a) Nagasawa, T.; Handa, Y.; Onoguchi, Y.; Ohba, S.; Suzuki, K. Synlett
1995, 739. (b) Nagasawa, T.; Handa, Y.; Onoguchi, Y.; Suzuki, K. Bull. Chem.
Soc. Jpn. 1996, 69, 31.
(21) Taylor, R. E.; Engelhardt, F. C.; Schmitt, M. J.; Yuan, H. J. Am. Chem.
Soc. 2001, 123, 2964.
(22) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
4142 J. Org. Chem. Vol. 73, No. 11, 2008

Total Synthesis of Solandelactones A, B, E, and F
FIGURE 3. Transition states for elimination of triflates from 38 and 50.
SCHEME 6
SCHEME 7
afforded cis allylic alcohol 57 which was converted to chloride
58. Displacement with lithio tri-n-butylstannane gave allylstan-
nane 59 from which the TBS ether was cleaved to yield 60.
Exposure of alcohol 60 to triflic anhydride in collidine-
triethylamine under the conditions used with 50 produced trans
and cis cyclopropanes 61 and 62 in the ratio 24:1. Here again,
a 1,3-anti transition state is highly favored over its syn
counterpart but a slightly diminished steric demand by the
p-methoxybenzyl group relative to trityl leads to a less decisive
outcome in favor of trans disubstituted cyclopropane 61.
The efficient preparation of enantiopure cyclopropane 44
allowed us to advance this substance along lines programmed
in Scheme 1 toward lactone 14 via aldehyde 17. Oxidative
cleavage of the vinyl substituent of 44 was accomplished in
good yield with potassium osmate and sodium periodate
(Scheme 7), but the resulting aldehyde 63 was unstable and
resisted full characterization. For that reason, 63 was im-
mediately subjected to an acetate aldol reaction with Phillips’
N-acetyloxazolidinethione 6423 under conditions specified by
Crimmins,24 our intention being to acquire (R) alcohol 65. In
the event, a stereoisomeric mixture of hydroxy amides was
using an assay in which the detection limit was 36:1. Charac-
terization of 44 by chiral stationary phase HPLC demonstrated
that this substance was enantiopure. Thus, results obtained with
38 and 50 are consistent with a prediction based on steric effects
operative in the transition states involved in triflate elimination
(Figure 3). Transition states 51 anti and 52 anti, analogous to
Suzuki’s 41, are clearly more favorable than their 1,3-syn
counterparts, and 52 syn is more highly strained than 51 syn
as a result of cis alkene geometry in the former.
The preference for a 1,3-anti conformation over its 1,3-syn
counterpart in steering elimination of triflate toward a trans
disubstituted cyclopropane was further supported by a sequence
shown in Scheme 6 in which the trityl ether of 50 was replaced
by a p-methoxybenzyl ether. Ether 53, prepared from (S)-(-)-
glycidol (29), was advanced as in Scheme 3 to alkyne 54 and
then, via triether 55, to alcohol 56. Semihydrogenation of 56
(23) Guz, N. R.; Phillips, A. J. Org. Lett. 2002, 4, 2253.
J. Org. Chem. Vol. 73, No. 11, 2008 4143

White et al.
SCHEME 8
FIGURE 4. Coordinated and noncoordinated dipole-minimized transi-
tion states for the reaction of 63 with 64 leading to 65 and its epimer.
SCHEME 9
obtained from this reaction in which the desired (R) isomer 65
predominated over its epimer by only a ratio of 2:1. The isomers
could not be separated but, after silylation to afford 66, reductive
cleavage of the chiral auxiliary produced 67 which could be
obtained in pure form by chromatography.
The relatively poor stereoselectivity observed in the reaction
of aldehyde 63 with the enolate of 64 is surprising in light of
results reported by Phillips.23 Our supposition that 63 would
react in a bisected conformation via the chair transition state
shown in Figure 4 appears to be only partially correct. Thus,
although titanium-sulfur coordination would lead to si face
attack at the aldehyde by the enolate of 64 and to a transition
state that produces 65, one or more competing pathways such
as a noncoordinated dipole-minimized chair assemblage must
intervene. The latter would result in re face attack at aldehyde
63 and leads to epi-65.
a route to the octenalactone that did not hinge upon ring-closing
metathesis. These two paradigms were our guides in planning
a new pathway to 14.
The way forward from 67 to ∆4,5-octenalactone 14 was
predicated upon elaborating both the primary alcohol and the
secondary silyl ether while retaining the primary trityl ether.
To this end, 67 was oxidized to aldehyde 68 which was treated
with Lombardo’s reagent to give alkene 69 (Scheme 8).
Removal of silyl protection from 69 and acylation of the
resulting homoallylic alcohol 70 with 4-pentenoyl chloride (71)
furnished ester 72, our prospective substrate for ring-closing
metathesis. Unfortunately, no hint of lactone formation could
be discerned from more than a dozen experiments that exposed
72 to metathesis catalysts under a variety of conditions.25 In
most instances, oligomers were produced from intermolecular
reactions at each of the terminal alkenes.
Our failure to close diene 72 to eight-membered lactone 73,
together with poor stereoselectivity in the acetate aldol reaction
of 63 with 64, caused us to revise our strategy for obtaining
14. It was decided that a revised plan should install a hydroxyl
group corresponding to (7R) configuration of the solandelactones
as early as possible, ideally before construction of the cyclo-
propane moiety. Foregoing results also persuaded us to devise
Synthesis of Lactone 14. Second Generation Approach.
The key features of the new route to 14 are expressed in Scheme
9. The ∆4,5-octenalactone segment of 14 is projected as the
rearrangement product of cyclic ketene acetal 74, while cyclo-
propane 75 is the result of a directed Simmons-Smith reaction
on allylic alcohol 76. Petrzilka was the first to demonstrate, in
his elegant synthesis of phoracantholide J, that thermal rear-
rangement of a vinyl substituted cyclic ketene acetal can lead
26
to an unsaturated medium ring lactone, and Holmes subse-
quently extended this variant of the Claisen rearrangement to a
∆4,5-octenalactone in his synthesis of laurencin.27 More recently,
the same tactic has appeared in a synthesis of discodermolide
by Paterson.28 A noteworthy difference between the plan shown
in Scheme 9 and our first generation approach to 14 is early
introduction of the (7R) oxygen function of solandelactones via
an acetate aldol reaction on an achiral substrate, thus removing
the possibility of a mismatched coupling.
(26) (a) Petrzilka, M. HelV. Chim. Acta 1978, 61, 3075. (b) Baudat, R.;
Petrzilka, M. HelV. Chim. Acta 1979, 62, 1406.
(24) (a) Crimmins, M. T.; King, B. W.; Tabet, E. A. J. Am. Chem. Soc.
1997, 119, 7883. (b) Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chaudhary,
K. J. Org. Chem. 2001, 66, 894.
(27) (a) Robinson, R. A.; Clark, J. S.; Holmes, A. B. J. Am. Chem. Soc.
1993, 115, 10400. (b) Burton, J. W.; Clark, J. S.; Derrer, S.; Stork, T. C.; Bendall,
J. G.; Holmes, A. B. J. Am. Chem. Soc. 1997, 119, 7483.
(28) Paterson, I.; Florence, G. J.; Gerlach, K.; Scott, J. P.; Sereinig, N. J. Am.
Chem. Soc. 2001, 123, 9535.
(25) A possible explanation for this failure lies in the barrier, estimated to
be 7.9 kcal/mol by a Hartree-Fock/6-31G** calculation, for conversion of the
more stables trans ester conformation to s-cis conformation 72 required for RCM.
4144 J. Org. Chem. Vol. 73, No. 11, 2008

Total Synthesis of Solandelactones A, B, E, and F
SCHEME 10
SCHEME 11
Trans-R,ꢀ-unsaturated aldehyde 77, obtained from cis-2-
29
butene-1,4-diol,
was reacted with the titanium enolate of
Nagao’s (4S)-3-acetyl-4-isopropyl-2-thionothiazolidine (78)30 to
give (R) hydroxy amide 79 as a single diastereomer in excellent
yield (Scheme 10). The thiazolidine auxiliary was cleaved from
79 with N,O-dimethylhydroxylamine and the resulting Weinreb
amide 80 was treated with diiodomethane and diethylzinc. This
variant of the directed Simmons-Smith reaction due to Charette31
afforded cyclopropane 81 as the sole detectable isomer. To
prevent retro aldol fission of 81, the alcohol was masked as its
TES ether 82 before reduction of the amide function. The
unstable aldehyde 83 from reduction of 82 was reacted promptly
with vinylmagnesium bromide to give allylic alcohol 84 as an
inseparable 1:1 mixture of diastereomers, and removal of TES
protection from 84 produced stereoisomeric diols 85. Because
the configuration of the allylic hydroxyl group in 85 was likely
to be inconsequential to the lactone construction envisioned in
Scheme 9, the mixture of stereoisomers was carried forward
without separation.
Our initial approach to ketene acetal 74 from diol 85 took its
cue from Holmes’ work27 and employed acid-catalyzed con-
densation of the diol with R-phenylselenoacetaldehyde diethyl
acetal (86)32 (Scheme 11). Subsequent elimination of the
selenoxide from oxidation of 87 and in situ exposure of ketene
acetal 88 to hot xylene produced lactone 89. In practical terms,
however, access to 89 by this pathway was problematic due to
the sensitivity of cyclopropylcarbinol 85 as well as acetal 87 to
PPTS. A more reliable synthesis of lactone 89 was achieved
via cyclic carbonate 90 along lines described by Holmes.33
Treatment of 90, prepared from 85 with triphosgene, with a
toluene solution of Petasis reagent34 at 110 °C resulted in
methylenation of the carbonate followed by in situ rearrange-
ment of 88 to give 89 in a reproducible yield of 60-65%. The
only significant byproduct (ca. 10%) from this sequence was
enol ether 91 resulting from methylenation of lactone 89 with
residual Petasis reagent. Removal of silyl protection from 89
gave alcohol 92 but aldehyde 14 from oxidation of 92 proved
to be a sensitive compound that could not be fully characterized
without decomposition. It was therefore prepared as needed and
used in situ for subsequent coupling with iododiene 13.
Octenalactone 89 is nominally an entrance point to saturated
lactone 93 needed for the synthesis of solandelactones A and
B, but neither hydrogenation of 89 over Wilkinson’s catalyst
nor catalyzed transfer hydrogenation produced any trace of 93.
In most cases, the cyclopropane of 89 was destroyed in these
reactions. By contrast, reduction of 89 with diimide led smoothly
to saturated lactone 93, and removal of silyl protection gave
(29) Vlieghe, P.; Clerc, T.; Pannecouque, C.; Witvrouw, M.; De Clercq, E.;
Salles, J. P.; Kraus, J. L. J. Med. Chem. 2001, 44, 3014.
(30) Nagao, Y.; Hagiwara, Y.; Kumagai, T.; Ochiai, M.; Inoue, T.; Hash-
imoto, K.; Fujita, E. J. Org. Chem. 1986, 51, 2391.
(31) Charette, A. B.; Lebel, H. J. Org. Chem. 1995, 60, 2966.
(32) Carling, R. W.; Holmes, A. B. J. Chem. Soc., Chem. Commun. 1986,
325.
(33) Anderson, E. A.; Davidson, J. E. P.; Harrison, J. R.; O’Sullivan, P. T.;
Burton, J. W.; Collins, I.; Holmes, A. B. Tetrahedron 2002, 58, 1943.
(34) Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc. 1990, 112, 6392.
J. Org. Chem. Vol. 73, No. 11, 2008 4145

White et al.
SCHEME 12
SCHEME 13
alcohol 94 in virtually quantitative yield. As was the case with
92, oxidation of 94 yielded an unstable aldehyde that was best
used in situ for coupling with 13.
basis it is again assigned 11(S) configuration. This configuration
was previously assigned to solandelactone B3 but is now shown
to belong to solandelactone A. Conversely, the minor alcohol
from 99 represents solandelactone B. In light of these results,
it is likely that C11 configuration of stereochemical pairs C/D
and G/H must be reversed from the assignment made by Shin.
With the absolute configuration of solandelactones A, B, E,
and F firmly established, a biogenesis of these substances can
be offered along lines put forward to explain the origin of C20
eicosanoids derived from arachidonic acid. A proposal initially
made by Corey to account for the biogenesis of prostanoids35
was subsequently extended by Brash to include oxylipins that
would be precursors of cyclopropane containing metabolites
such as the constanolactones.36 A key intermediate in the
Corey-Brash postulate is an allene oxide formed from arachi-
donic acid via oxidation to a (8R) hydroperoxide with lipoxy-
genase. Supporting evidence for an allene oxide intermediate
was obtained by Brash who isolated and characterized the
compound from an incubation of (8R)-cis,trans,cis,cis-8-hydro-
peroxyeicosa-5,9,11,14-tetraenoic acid with an acetone powder
prepared from the marine coral Plexaura homomalla.37
By analogy with the Corey-Brash proposal, biogenesis of
solandelactones 1-8 would take place from all cis-docosa-
7,10,13,16-tetraenoic acid (100) and would invoke (10R)
hydroperoxide 101 (Scheme 14). The derived allene oxide 102
is positioned for attack (with inversion) by the cis ∆7,8 double
bond, which would lead to cyclopropylcarbinyl cation 103. This
intermediate has the cyclopropane absolute configuration of the
solandelactones. Lactone formation from 103, followed by
enzymatic oxidation at C14 and reduction of the C11 ketone of
104, would produce solandelactones A and B. Solandelactones
C-H presumably arise from a C22 carboxylic acid analogous
to 100 but which contains additional cis alkenes at C4,5 or
C19,20 or at both sites. The fact that all known solandelactones
possess (7R) configuration would be consistent with a pathway
Our initial approach to constanolactones A (9) and B (10)
coupled 95, the TBDPS protected version of 13 with aldehyde
96 in a Nozaki-Hiyama-Kishi reaction that gave 97 and 98 in
the ratio 2:1, respectively (Scheme 12). The major product 97
was shown by NMR to correspond in configuration to con-
stanolactone A and is the result of Felkin addition to 96 by the
organochromium species from 95. However, a problem emerged
in the final deprotection of 97 and 98; the TBDPS ether could
not be cleaved without destruction of the cyclopropane. The
problem was solved by removing the silyl protection from 95and
using 13 for NHK coupling with 96. In that case, constanolactones
A and B were obtained directly in the proportion 1.4:1. This showed
that protonation by the free alcohol of the organochromium species
from 13 is not a competing reaction and convinced us that 13,
rather than its TBS ether 28, should be employed for NHK coupling
with aldehyde 14 and its saturated counterpart from 93.
Therefore, aldehyde 14, obtained by oxidation of 92 was
reacted with iododiene 13 under conditions that had been used
in the direct preparation of constanolactones A and B (scheme
13). Two stereoisomeric alcohols were produced in the ratio
3.5:1, the major alcohol corresponding precisely in the chemical
shift and coupling constants of its C11 proton to the C9
hydrogen of constanolactone A (9). Thus, the major alcohol
from 14 has (11S) configuration and is again the result of Felkin
addition. As found previously by Martin, the NMR spectra
for this alcohol did not match the data reported by Shin for
solandelactone F3 but instead were identical to the data for
natural solandelactone E. Likewise, the C11 proton signal in
the NMR spectrum of the minor alcohol from aldehyde 14
matched the C9 proton of constanolactone B and confirmed that
this isomer was solandelactone F. Thus, the assignment of C11
configuration made to solandelactones E and F by Shin must
be reversed, a conclusion that was reached independently by
Davoren and Martin in their synthesis of solandelactone E.10
An analogous NHK coupling to that conducted on 14 was
carried out on aldehyde 99 obtained from 94 and led to major
and minor alcohols in the ratio 1.5:1, respectively. The C11
proton signal in the NMR spectrum of the major isomer matched
constanolactone A (9) as well as solandelactone E, and on that
(35) (a) Corey, E. J.; Matsuda, S. P. T. Tetrahedron Lett. 1987, 28, 4247.
(b) Corey, E. J.; d’Alarcao, M.; Matsuda, S. P. T.; Lansbury, P. T.; Yamada, Y.
J. Am. Chem. Soc. 1987, 109, 289.
(36) Baertschi, S. W.; Brash, A. R.; Harris, T. M. J. Am. Chem. Soc. 1989,
111, 5003.
(37) Gerwick, W. H Chem. ReV. 1993, 93, 1807.
4146 J. Org. Chem. Vol. 73, No. 11, 2008

Total Synthesis of Solandelactones A, B, E, and F
SCHEME 14
°C under argon. KHMDS (6.81 mL, 0.60 M in toluene) was added
slowly, and after 30 min a solution of 46 (1.88 g, 4.08 mmol) in
THF (5 mL) was added. The mixture was stirred for 1 h, then the
reaction was quenched with saturated aqueous NH4Cl (10 mL) and
the mixture was extracted with Et2O (2 × 25 mL). The combined
organic extracts were dried (Na2SO4), filtered, and concentrated
under reduced pressure. The residue was purified by column
chromatography (2-10% EtOAc in hexane) to yield 48 (1.88 g,
89%) as a colorless oil:[R23D]-5.8 (c 1.0, CHCl3); IR (neat) 3.86,
3059, 3033, 2953, 2928, 2884, 2856, 1724, 1647, 1597, 1491, 1471,
in which lactone formation to give 104 takes place in concert
with epoxide opening of allene oxide 102 by the cis-7,8-alkene.
However, in the case of constanolactone biosynthesis, a δ-hy-
droxy acid has been implicated prior to lactonization.36 An
alternative biogenesis of solandelactones to that shown in
Scheme 14 has been suggested by Shin3 based on a previous
proposal by Gerwick.37
In summary, total syntheses of solandelactones A, B, E, and
F have been completed. Their previously assigned absolute
configuration at C7, 8, 10, and 14 has been confirmed but
configuration at C11 in pairs A/B and E/F must be reversed
from the attribution made by Shin3 in the course of his structural
elucidation of the solandelactones.
1
1448, 1407, 1361, 1323, 1255, 1174 cm-1; H NMR (300 MHz,
CDCl3) δ -0.01 (s, 3H), 0.03 (s, 3H), 0.80-0.95 (m, 9H),
2.96-3.05 (m, 1H), 3.06-3.13 (m, 1H), 3.69 (s, 3H), 3.83-3.99
(m, 1H), 5.78-5.83 (m, 1H), 5.78-5.83 (m, 1H), 7.19-7.34 (m,
9H), 7.42-7.49 (m, 6H); 13C NMR (75 MHz, CDCl3) δ -4.9, -4.6,
18.0, 25.8, 34.5, 51.0, 67.1, 70.8, 86.5, 120.6, 126.9, 127.7, 128.3,
128.6, 128.7, 144.1, 146.4, 166.7; MS (CI) m/z 485 (M - [OCH3])+,
473, 439, 407, 333, 327, 291, 277, 271, 257; HRMS (CI) m/z
485.2503 (calcd for C31H37O3Si (M - [OCH3])+: 485.2512).
(2R,4Z)-2-(tert-Butyldimethylsilanyloxy)-1-trityloxyhex-4-en-
6-ol (49). A solution of 48 (1.85 g, 3.58 mmol) in CH2Cl2 (20 mL)
was cooled to 0 °C under argon and DIBAl-H (1.40 mL, 7.88 mmol)
was added slowly. The mixture was stirred for 45 min, then the
reaction was quenched with saturated aqueous Na+/K+ tartrate (20
mL). After 1 h of vigorous stirring, the aqueous phase was extracted
with CH2Cl2 (3 × 25 mL) and the combined organic extracts were
dried (Na2SO4), filtered and concentrated under reduced pressure.
The residue was purified by column chromatography (5-40%
Experimental Section
tert-Butyl[(S,1E,5Z)-1-iodoundeca-1,5-dien-3-yloxy]dimethyl-
silane (28).18b To a solution of 26 (23 mg, 80.3 µmol) and
4-methylmorpholine-N-oxide (14.0 mg, 120 µmol) in CH2Cl2 (3.5
mL) was added 4 Å molecular sieves (93 mg, powdered). After 10
min, TPAP (5.6 mg, 16.1 µmol) was added to the mixture and
stirring was continued for 1 h. The mixture was diluted with pentane
(7 mL), filtered through a short column of silica gel (20% EtOAc
in pentane), and concentrated under reduced pressure to give 27
(19.6 mg), which was used for the next step without further
purification.
CrCl2 was added to a flask that contained 27 obtained above
and CHI3 (63.2 mg, 0.161 mmol). THF (1 mL) was added to the
flask under Ar at 0 °C and the mixture was stirred for 16 h at 0 °C.
The reaction was quenched with saturated NaCl solution and the
mixture was extracted with Et2O (3 × 6 mL). The combined organic
extracts were dried over MgSO4, filtered, and concentrated under
reduced pressure. Column chromatography (petroleum ether) gave
EtOAc in hexane) to yield 49 (1.33 g, 76%) as a colorless oil: R22
D
+ 2.8 (c 1.0, CHCl3); IR (neat) 3348, 3086, 3059, 3023, 2958,
2928, 2883, 2856, 1597, 1491, 1471, 1448, 1388, 1361, 1322, 1255,
1220, 1184, 1154 cm-1; 1H NMR (300 MHz, CDCl3) δ -0.03 (s,
3H), 0.02 (s, 3H), 0.85 (s, 9H), 1.56 (brs, 1H), 2.32-2.54 (m, 2H),
2.98 (dd, J ) 6.6, 9.1 Hz, 1H), 3.10 (dd, J ) 4.9, 9.1 Hz, 1H),
3.79-3.89 (m, 1H), 4.04-4.17 (m, 2H), 5.64-5.74 (m, 1H),
5.47-5.58 (m, 1H), 7.20-7.34 (m, 9H), 7.42-7.49 (m, 6H); 13C
NMR (75 MHz, CDCl3) δ -4.7, -4.6, 18.1, 25.8, 33.0, 58.5, 67.0,
71.1, 86.6, 127.0, 127.7, 128.7, 128.8, 130.6, 144.0; MS (CI) m/z
488 (M - H)+, 484, 471, 411, 333, 297, 271, 257; HRMS (CI)
m/z 411.2360 (calcd for C25H35O3Si (M - [C6H5])+: 411.2356).
(2R,4Z)-6-(Tri-n-butylstannyl)-1-trityloxyhex-4-en-2-ol (50).
TBAF (2.43 mL, 1.0 M in THF) was added dropwise Via syringe
to a stirred solution of (2R,4Z)-2-(tert-butyldimethylsilanyloxy)-6-
(tri-n-butylstannyl)-1-trityloxyhex-4-ene (906 mg, 1.18 mmol) and
collidine (227 µL) in THF (18 mL) at 0 °C under argon, and the
mixture was stirred at ambient temperature for 21 h. The mixture
was placed in a separatory funnel containing CH2Cl2 (50 mL) and
saturated aqueous NH4Cl (20 mL), and the separated aqueous phase
was extracted with CH2Cl2 (4 × 20 mL). The combined organic
extracts were dried (Na2SO4), filtered, and concentrated under
reduced pressure, and the residue was purified by column chro-
matography (2-10% EtOAc in hexane) to give 50 (516 mg, 63%)
as a colorless oil: R22D -2.4 (c 1.0, CHCl3); IR (neat) 3460, 3086,
1
28 (12.1 mg, 37%): H NMR (400 MHz, CDCl3) δ 0.04 (s, 3H),
0.05 (s, 3H), 0.89 (s, 9H), 0.89 (t, J ) 7.0 Hz, 3H), 1.25-1.36 (m,
6H), 2.00 (q, J ) 7.1 Hz, 2H), 2.23 (m, 1H), 4.09 (q, J ) 6.0 Hz,
1H), 5.29-5.50 (m, 2H), 6.21 (dd, J ) 0.9, 14.4 Hz, 1H), 6.53
(dd, J ) 5.7, 14.4 Hz, 1H), ; 13C NMR (100 MHz, CDCl3) δ -4.6,
-4.4, 14.3, 18.4, 22.8, 26.0, 27.7, 29.5, 31.8, 35.9, 75.3, 75.9, 124.3,
132.9, 149.0.
(3S,1E,5Z)-3-Hydroxy-1-iodoundeca-1,5-diene (13). To a solu-
tion of 28 (11.5 mg, 28 µmol) in THF (0.2 mL) at room temperature
was added TBAF (56 µL, 1 M THF, 56 µmol). After 30 min, the
reaction was quenched with saturated NH4Cl solution and the
mixture was extracted with CH2Cl2 (5 × 6 mL). The combined
organic extracts were dried over Na2SO4, filtered, and concentrated
under reduced pressure. Column chromatography (12% ethyl
acetate/pentane) gave 13 (8.0 mg, 97%) as a colorless oil whose
NMR data were in agreement with those previously reported.8b
Methyl (2Z,5R)-5-(tert-Butyldimethylsilanyloxy)-6-trityloxy-
hex-2-enoate (48). A solution of 47 (1.30 g, 4.08 mmol) and 18-
crown-6 (5.40 g, 20.4 mmol) in THF (60 mL) was cooled to -78
J. Org. Chem. Vol. 73, No. 11, 2008 4147

White et al.
1
3059, 3022, 2955, 2924, 2870, 2853, 1637, 1597, 1491, 1448, 1418,
1376, 1220, 1183, 1153 cm-1 1H NMR (300 MHz, CDCl3)
1652, 1475, 1424, 1110 cm-1; H NMR (CDCl3) δ 1.07 (9H, s),
2.60 (1H, dd, J ) 16.7, 9.1 Hz), 2.70 (1H, dd, J ) 16.7, 2.2 Hz),
3.20 (3H, s), 3.69 (3H, s), 3.89 (1H, s), 4.24 (2H, m), 4.61 (1H,
m), 5.82 (1H, m), 5.89 (1H, ddd, J ) 15.5, 3.3, 0.9 Hz), 7.43-7.36
(6H, m), 7.70-7.67 (4H, m); 13C NMR (CDCl3) δ 19.3, 26.9 (x3),
31.9, 38.4, 61.3, 63.8, 68.3, 127.7 (×4), 129.6, 129.7 (×2), 130.6,
133.7, 135.6 (×4), 173.3; MS (CI) m/z 450 (M+ + Na), 410 (M+-
OH); HRMS m/z 450.2057 (calcd for C24H33NO4NaSi 450.2077).
;
δ 0.82-0.92 (m, 15H), 1.22-1.36 (m, 6H), 1.42-1.54 (m, 6H),
1.69 (d, J ) 9.2 Hz, 2H), 2.18-2.27 (m, 2H), 2.30 (d, J ) 3.8 Hz,
1H), 3.11 (dd, J ) 6.9, 9.3 Hz, 1H), 3.22 (dd, J ) 3.8, 9.3 Hz,
1H), 3.77-3.88 (m, 1H), 4.97-5.07 (m, 1H), 5.59-5.72 (m, 1H),
7.22-7.35 (m, 9H), 7.43-7.49 (m, 6H); 13C NMR (75 MHz,
CDCl3) δ 9.3, 10.7, 13.7, 27.3, 29.1, 31.2, 67.3, 71.0, 86.6, 118.6,
127.0, 127.8, 128.7, 131.4, 143.9; MS (CI) m/z 648 (M)+, 603,
523, 467, 405, 349, 291, 257; HRMS (CI) m/z 648.2973 (calcd for
C37H52O2120Sn: 648.2989).
(3R)-3-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
3-hydroxy-N-methoxy-N-methylpropionamide (81). To a solution
of 80 (0.427 g, 1.16 mmol) in CH2Cl2 (12 mL) at -15 °C was
added diethylzinc (5.8 mL, 5.8 mmol, 1 M in hexanes) followed
by diiodomethane (0.467 mL, 5.80 mmol). The solution was
allowed to warm to room temperature over 1 h and was stirred for
a further 2 h. The reaction was quenched with a saturated solution
of NH4Cl (10 mL) and the mixture was extracted with CH2Cl2 (3
× 20 mL). The organic extract was dried over Na2SO4, and the
solvent was removed to give pure 81 (0.427 g, 97%) as a colorless
oil: [R]23D +13.4 (c 0.65 CHCl3); IR (neat) 3458 (br), 2933, 2851,
(1R,2S)-1-(Trityloxymethyl)-2-vinylcyclopropane (44). Triflic
anhydride (246 µL, 1.46 mmol) was added dropwise Via syringe
to a stirred solution of 50 (630 mg, 0.973 mmol) and collidine (192
µL, 1.46 mmol) in CH2Cl2 (10 mL) at -78 °C under argon, and
the mixture was stirred for 1 h. Et3N (443 µL, 3.42 mmol) was
added dropwise Via syringe, and the mixture was stirred for an
additional 19 h at -78 °C. The mixture was allowed to warm to
ambient temperature and concentrated under reduced pressure. The
residue was purified by column chromatography (2-4% EtOAc in
hexane, containing 1% Et3N) to yield 44 (302 mg, 91%) (Chiral
OD, 0.85 mL/min, 100% hexanes): [R23D] -45.3 (c 1.0, CHCl3);
IR (neat) 3083, 3059, 3021, 2993, 2955, 2915, 2868, 1635, 1597,
1647, 1428, 1114 cm-1; H NMR (CDCl3) δ 0.52 (1H, ddd, J )
1
8.3, 8.3, 5.1 Hz), 0.68 (1H, ddd, J ) 8.3, 8.3, 5.1 Hz), 1.07-0.87
(2H, m), 1.08 (9H, s), 2.75 (1H, dd, J ) 16.6, 9.8 Hz), 2.97 (1H,
brd, J ) 16.6 Hz), 3.23 (3H, s), 3.32 (1H, dd, J ) 10.6, 7.3 Hz),
3.46 (1H, dt, J ) 9.2, 2.2 Hz), 3.67 (3H, s), 3.82 (1H, dd, J )
10.6, 5.2 Hz), 4.33 (1H, brs), 7.47-7.37 (6H, m), 7.73-7.66 (4H,
m); 13C NMR (CDCl3) δ 8.7, 18.7, 19.3, 22.7, 26.9 (×3), 32.1,
38.1, 61.4, 66.6, 72.3, 127.7 (×4), 129.7 (×3), 133.8, 135.6 (×4),
173.9; MS (CI) m/z 441 (M+), 408, 398, 384; HRMS m/z 441.2335
(calcd for C25H35NO4Si 441.2077).
1
1491, 1448, 1402, 1317, 1218, 1182, 1153 cm-1; H NMR (300
MHz, CDCl3) δ 0.66 (t, J ) 6.9 Hz, 2H), 1.07-1.23 (m, 1H),
1.24-1.34 (m, 1H), 2.94 (dd, J ) 6.5, 9.6 Hz, 1H), 3.07 (dd, J )
6.1, 9.6 Hz, 1H), 4.88 (dd, J ) 1.7, 10.3 Hz, 1H), 5.06 (ddd, J )
0.5, 1.7, 17.1 Hz, 1H), 5.45 (ddt, J ) 8.5, 10.2, 17.1 Hz, 2H),
7.20-7.34 (m, 9H), 7.44-7.49 (m, 6H); 13C NMR (75 MHz,
CDCl3) δ 11.9, 20.4, 20.6, 66.7, 86.2, 111.9, 126.9, 127.7, 128.7,
141.2, 144.3; MS (CI) m/z 340 (M)+, 263, 243, 228, 183, 165,
143, 105, 91; HRMS (CI) m/z 340.1828 (calcd for C25H24O:
340.1827).
(3R)-3-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
N-methoxy-N-methyl-3-triethylsilanyloxypropionamide (82). To
a solution of 81 (0.408 g, 0.91 mmol) in CH2Cl2 (6 mL) at 0 °C
were added 2,6-lutidine (0.20 mL, 1.82 mmol) and TESOTf (0.308
mL, 1.37 mmol). The solution was stirred at 0 °C for 45 min, the
reaction was quenched with a saturated solution of NaHCO3 (10
mL), and the mixture was extracted with CH2Cl2 (3 × 20 mL).
The organic extract was washed with brine, dried over Na2SO4,
and the solvent was removed. Column chromatography (10%
EtOAc in pentane) gave 82 (0.500 g, 98%) as a pale-yellow oil:
[R]23D -2.3 (c 2.0 CHCl3); IR (neat) 2958, 2879, 1671, 1472, 1429,
1111, 1075 cm-1; 1H NMR (CDCl3) δ 0.49 (1H, ddd, J ) 9.4, 4.5,
4.4 Hz), 0.62 (1H, m), 0.64 (6H, q, J ) 8.1 Hz), 0.99 (9H, t, J )
8.1 Hz), 1.00-0.93 (2H, m), 1.09 (9H, s), 2.60 (1H, dd, J ) 14.4,
4.4 Hz), 3.48 (1H, dd, J ) 14.4, 8.3 Hz), 3.69 (3H, s), 3.70 (1H,
dd, J ) 10.6, 5.6 Hz), 3.81 (1H, ddd, J ) 8.1, 8.1, 4.5 Hz),
7.45-7.37 (6H, m), 7.73-7.67 (4H, m); 13C NMR (CDCl3) δ 6.5
(x3), 6.9 (x3), 9.0, 18.4, 19.2, 23.7, 26.9 (x3), 32.0, 40.7, 61.2,
66.5, 72.2, 127.7 (×4), 129.6 (×3), 133.9, 135.6 (×4), 173.3; MS
(CI) m/z 578 (M+ + Na), 346 (M+ - OTES); HRMS m/z 578.3074
(calcd for C31H49NO4NaSi2 578.3098).
(3R)-3-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
3-triethylsilanyloxypropionaldehyde (83). To a solution of 82
(0.120 g, 0.220 mmol) in THF (2 mL) at -78 °C was added
DIBAL-H (0.26 mL, 1 M solution in THF) over a period of 5 min.
After 10 min, the reaction was quenched with a saturated solution
of Rochelle’s salt (8 mL), and the mixture was allowed to warm to
room temperature and extracted with CH2Cl2 (3 × 20 mL). The
organic extract was dried over Na2SO4, and the solvent was removed
to give 83 as a colorless oil: [R]23D -7.8 (c 1.2 CHCl3); IR (neat):
2950, 2872, 1722, 1469, 1112 cm-1; 1H NMR (CDCl3) δ 0.50 (1H,
ddd, J ) 9.4, 4.5, 4.4 Hz), 0.66-0.56 (7H, m), 1.00-0.89 (11H,
m), 1.07 (9H, s), 2.64 (1H, ddd, J ) 15.5, 5.2, 2.5 Hz), 2.70 (1H,
ddd, J ) 15.5, 6.5, 2.5 Hz), 3.40 (1H, dd, J ) 10.4, 6.3 Hz),
3.74-3.64 (2H, m), 7.46-7.39 (6H, m), 7.71-7.67 (4H, m), 9.87
(1H, t, J ) 2.5 Hz); 13C NMR (CDCl3) δ 5.3 (×3), 6.9 (×3), 9.2,
18.5, 19.2, 23.6, 26.9 (×3), 52.1, 66.3, 71.3, 127.7 (×4), 129.7
(×3), 133.8, 135.6 (×4), 201.9; MS (CI) m/z 519 (M+ + Na);
HRMS m/z 519.2761 (calcd for C29H44O3NaSi2 519.2727). This
(3R)-6-(tert-Butyldiphenylsilanyloxy)-3-hydroxy-1-(4S-isopro-
pyl-2-thionothiazolidin-3-yl)hex-4-en-1-one (79). To a solution
of 78, (0.645 g, 3.42 mmol) in CH2Cl2 (25 mL) at 0 °C was added
titanium tetrachloride (416 µL, 3.80 mmol). After 5 min, the
solution was cooled to -78 °C and diisopropylethylamine (662 µL,
3.80 mmol) was added dropwise over 5 min. The solution was
stirred at -78 °C for 2 h and 77 (740 mg, 2.28 mmol) in CH2Cl2
(7 mL) was added Via cannula over 5 min. The dark solution was
stirred at -78 °C for a further 6 h, then the reaction was quenched
with a saturated solution of NH4Cl (10 mL), and the mixture was
extracted with CH2Cl2 (3 × 20 mL). The organic phase was dried
over Na2SO4 and the solvent was removed. Column chromatography
(10% to 25% EtOAc in pentane) gave 79 (1.154 g, 94%) as a yellow
oil: [R]23D +172.5 (c 1.8; CHCl3); IR (neat) 3462 (br), 3067, 2959,
2852, 1695, 1471, 1247, 1105 cm-1; 1H NMR (CDCl3) δ 1.03 (3H,
d, J ) 6.7 Hz), 1.13-1.08 (12H, m), 2.41 (1H, oct, J ) 6.4 Hz),
2.83 (1H, brs), 3.06 (1H, dd, J ) 11.4, 0.9 Hz), 3.36 (1H, ddd, J
) 17.7, 8.8, 0.8 Hz), 3.54 (1H, dd, J ) 11.4, 7.9 Hz), 3.66 (1H,
dd, J ) 17.7, 3.0 Hz), 4.27 (2H, s), 4.73 (1H, m), 5.18 (1H, ddd,
J ) 7.9, 6.4, 0.9 Hz), 5.85 (1H, dd, J ) 15.7, 3.9 Hz), 5.90 (1H,
dd, J ) 15.7, 3.2 Hz), 7.49-7.40 (6H, m), 7.73-7.69 (4H, m);
13C NMR (CDCl3) δ 17.9, 19.1, 19.3, 26.9 (x3), 30.7, 30.9, 36.4,
45.3, 63.8, 68.3, 71.4, 127.7 (x4), 129.7, 130.2, 130.3, 133.6, 135.6
(×4), 172.5, 203.0; MS (CI) m/z 550 (M+ + Na), 510 (M+ - OH);
HRMS m/z 550.1849 (calcd for C28H37NO3NaSiS2 550.1882).
(3R)-6-(tert-Butyldiphenylsilanyloxy)-3-hydroxyhex-4-enoic Acid
Methoxymethylamide (80). To a solution of 79 (220 mg, 0.41
mmol) in CH2Cl2 (5 mL) at room temperature were added imidazole
(300 mg, 4.40 mmol) and HN(OCH3)CH3•HCl (215 mg, 2.21 mmol,
azeotroped from benzene three times). The heterogeneous solution
was stirred at room temperature for 16 h, the reaction was quenched
with a saturated solution of NH4Cl (10 mL) and the mixture was
extracted with CH2Cl2 (3 × 20 mL). The organic extract was dried
over Na2SO4 and the solvent was removed. Column chromatography
(25% EtOAc in pentane) gave 80 (0.126 g, 71%) as a pale-yellow
oil: [R]23 +19.1 (c 2.2 CHCl3); IR (neat) 3437 (br), 2925, 2856,
D
4148 J. Org. Chem. Vol. 73, No. 11, 2008

Total Synthesis of Solandelactones A, B, E, and F
material was unstable and was used promptly in the next step
without further purification.
chromatography (10% EtOAc in pentane) gave 89 (0.011 g, 43%,
63% brsm) as a colorless oil: [R]23 -173.3 (c 0.45 CHCl3); IR
D
(neat): 2958, 2929, 2855, 1746, 1478, 1425, 1110, 1074 cm-1: 1H
NMR (CDCl3) δ 0.50 (1H, ddd, J ) 8.8, 5.2, 5.2 Hz), 0.64 (1H,
ddd, J ) 8.8, 4.9, 4.9 Hz), 0.88 (1H, m), 0.97 (1H, m), 1.05 (9H,
s), 2.34-2.23 (2H, m), 2.12 (1H, m), 2.60 (1H, ddd, J ) 13.5,
10.6, 5.7 Hz), 2.73 (1H, ddd, J ) 13.5, 6.1, 3.4 Hz), 2.86 91H, m),
3.40 (1H, dd, J ) 10.6, 6.9 Hz), 3.75 (1H, dd, J ) 10.6, 4.9 Hz),
3.94 (1H, dt, J ) 10.4, 1.3 Hz), 5.83-5.72 (2H, m), 7.45-7.36
(6H, m), 7.68-7.64 (4H, m); 13C NMR (CDCl3) δ 8.6, 19.2, 19.6,
20.4, 24.5, 26.9 (×3), 37.8, 66.1, 81.8, 127.7 (×4), 128.4, 129.7
(×2), 132.7, 133.8 (×2), 135.6 (×4), 177.0; MS (CI) m/z 457 (M+
+ Na); HRMS m/z 452.2604 (calcd for C27H38NO3Si 452.2621).
(8R)-8-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
3,4,7,8-tetrahydrooxocin-2-one (92). To 89 (0.012 g, 0.027 mmol)
in THF (1.5 mL) was added TBAF (0.068 mL, 1 M in THF) at
room temperature. After 1 h, the reaction was quenched with an
aqueous solution of NH4Cl (0.5 mL) and was extracted with CH2Cl2
(4 × 10 mL). The combined organic extracts were dried over
Na2SO4, and the solvent was removed. Column chromatography
(50% EtOAc in pentane) gave 92 (0.004 g, 74%) as a colorless
oil: [R]23D +5.8 (c 0.4 CHCl3); IR (neat) 3435, 2923, 2850, 1742,
1433, 1330, 1212, 1013 cm-1: 1H NMR (CDCl3) δ 0.55 (1H, dt, J
) 10.5, 5.2 Hz), 0.75 (1H, dt, J ) 10.5, 5.2 Hz), 1.00 (1H, ddd, J
) 13.0, 8.6, 4.7 Hz), 1.11 (1H, m), 2.11 (1H, m), 2.31 (1H, ddd,
J ) 13.2, 7.6, 1.6 Hz), 2.62 (1H, ddd, J ) 13.5, 10.3, 6.5 Hz),
2.73 (1H, ddd, J ) 13.5, 6.0, 2.9 Hz), 2.85 (1H, m), 3.46 (1H, dd,
J ) 11.2, 7.3 Hz), 3.55 (1H, dd, J ) 11.2, 6.7 Hz), 4.04 (1H, dt,
J ) 8.5, 1.9 Hz), 5.73 (1H, m), 5.79 (1H, m); 13C NMR (CDCl3)
δ 8.7, 19.7, 20.7, 24.5, 34.3, 37.7, 66.0, 80.9, 128.1, 132.8, 177.0;
HRMS (CI) m/z 197.1179 (calcd for C11H17O3 197.1178).
(5R)-5-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
5-triethylsilanyloxypent-1-en-3-ol (84). To a solution of 83 (0.116
g, 0.220 mmol) in THF (3 mL) at -78 °C was added vinylmag-
nesium bromide (0.44 mL, 1 M solution in THF). After 40 min,
some starting material was still apparent by tlc analysis and an
additional quantity of vinylmagnesium bromide (0.22 mL) was
added. After a further 10 min, the reaction was quenched with a
saturated solution of NH4Cl, and the mixture was allowed to warm
to room temperature and extracted with CH2Cl2 (3 × 20 mL). The
organic extract was dried over Na2SO4 and the solvent was removed.
Column chromatography (10% EtOAc in pentane) gave 84 (0.074
g, 85%, 1:1 mixture of diastereomers) as a pale-yellow oil: IR (neat)
3459 (br s), 2960, 2870, 1652, 1424, 1110 cm-1; 1H NMR (CDCl3)
δ 0.63-0.50 (4H, m), 0.68 (12H, q, J ) 8.1 Hz), 1.00 (18H, t, J
) 8.1 Hz), 1.00-0.88 (4H, m), 1.09 (18H, s), 1.91-1.79 (4H, m),
3.50-3.28 (6H, m), 3.74 (2H, m), 4.38 (1H, m), 4.56 (1H, m),
5.11 (2H, m), 5.30 (2H, m), 5.89 (2H, ddd, J ) 17.2, 10.9, 5.2
Hz), 7.49-7.39 (12H, m), 7.73-7.67 (8H, m); 13C NMR (CDCl3)
δ 5.3, 6.9, 10.0, 10.4, 18.5, 19.0, 19.2, 22.9, 23.9, 26.9, 43.5, 44.4,
66.4, 66.5, 69.9, 72.0, 74.9, 113.8, 127.7, 129.7, 133.8, 135.6, 140.9,
141.22; MS (CI) m/z 547 (M+ + Na); HRMS m/z 547.3014 (calcd
for C31H48O3NaSi2 547.3040).
(5R)-5-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
5-hydroxypent-1-en-3-ol (85). To 84 (18 mg, 0.034 mmol) was
added a mixture of AcOH, THF and H2O (6:2:1, 2.0 mL). The
solution was stirred for 1 h at room temperature and the reaction
was quenched with NaHCO3. The mixture was extracted with
CH2Cl2 (3 × 20 mL), and the organic extract was dried over Na2SO4
to give 85 as a colorless oil that was carried forward to the next
reaction without further purification: IR (neat) 3367 (br s), 2927,
(8R)-8-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopro-
pyl]octahydrooxocin-2-one (93). To a solution of 89 (42 mg, 0.10
mmol) in pyridine (4 mL) was added potassium azodicarboxylate
(378 mg, 1.94 mmol). AcOH (0.23 mL) in MeOH was added to
this solution over 1 h at rt. The mixture was stirred at rt for 13 h
diluted with Et2O (10 mL) and was washed with saturated aqueous
NaHCO3, aqueous CuSO4 and brine. The separated organic phase
was dried over Na2SO4 and the solvent was removed under reduced
pressure. Column chromatography (10:1 pentane:EtOAc) gave 93
1
2853, 1733, 1472, 1428, 1263, 1115, 1076, 823 cm-1: H NMR
(CDCl3) δ 0.48 (2H, m), 0.56 (2H, ddd, J ) 9.6, 4.6, 4.6 Hz),
1.03-0.86 (4H, m), 1.08 (18H, s), 1.97-1.76 (4H, m), 3.27 (2H,
dq, J ) 8.6, 3.6 Hz), 3.40 (2H, dd, J ) 10.9, 7.3 Hz), 3.76 (2H,
m), 4.40 (1H, m), 4.53 (1H, m), 5.14 (1H, d, J ) 10.6 Hz), 5.17
(1H, d, J ) 10.6 Hz), 5.29 (1H, d, J ) 17.2 Hz), 5.33 (1H, d, J )
17.2 Hz), 5.92 (2H, m), 7.49-7.39 (12H, m), 7.72-7.67 (8H, m);
13C NMR (CDCl3) δ 1.1, 8.0, 8.1, 18.7, 18.7, 19.2, 23.6, 24.0, 26.9,
29.7, 42.2, 43.1, 66.4, 70.4, 73.2, 73.4, 76.3, 114.3, 127.7, 129.7,
133.8, 135.6, 140.7; MS (CI) m/z 433 (M+ + Na); HRMS m/z
433.2166 (calcd for C25H34O3NaSi 433.2175).
(30.8 mg, 73%) as a colorless oil: [R]23 +2.6 (c 1.5, CHCl3): IR
D
1
(neat) 3071, 2930, 2858, 1731, 1428, 1232, 1112 cm-1; H NMR
(CDCl3) δ 0.50 (1H, dt, J ) 5.0, 7.4 Hz), 0.57 (1H, dt, J ) 8.2,
5.0 Hz), 1.05 (9H, s), 1.08-0.9 (2H, m), 1.58-1.47 (3H, m),
1.92-1.78 (4H, m), 2.47-2.37 (2H, m), 3.42 (1H, dd, J ) 10.6,
6.5 Hz), 3.73 (1H, dd, J ) 10.6, 5.3 Hz), 3.95 (1H, dt, J ) 7.6, 6.5
Hz), 7.46-7.35 (6H, m), 7.70-7.62 (4H, m); 13C NMR (CDCl3) δ
8.4, 19.2, 21.2, 24.2, 26.9, 29.0, 26. 5, 32.6, 37.2, 66.1, 82.5, 127.7,
129.7, 133.8, 135.6, 176.6; MS (CI) m/z 437 (M + H), 379 (M+ -
t-Bu); HRMS m/z 437.2504 (calcd for C27H37O3Si 437.2511).
(8R)-8-[1S,2R-(Hydroxymethyl)cyclopropyl]octahydrooxocin-
2-one (94). To a solution of 93 (30 mg, 0.069 mmol) in THF (5
mL) was added TBAF (170 µL, 1 M in THF). After 30 min, the
solution was diluted with Et2O and washed with brine. The
separated organic phase was dried over Na2SO4 and the solvent
was removed. Column chromatography (10:1 pentane:EtOAc) gave
(4R)-4-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
6-vinyl-[1,3]-dioxan-2-one (90). To 85 (0.105 g, 0.26 mmol) in
CH2Cl2 (2 mL) at -78 °C were added 4 Å molecular sieves, Et3N
(0.154 mL, 1.52 mmol), pyridine (0.120 g, 1.52 mmol), and
triphosgene (0.386 g, 1.30 mmol). The solution was stirred for 30
min, the reaction was quenched with an aqueous solution of NH4Cl
(2 mL), and the separated organic phase was washed with an
aqueous solution of CuSO4, water, and brine. The organic phase
was dried over Na2SO4, and the solvent was removed to give 90
(113 mg, 98%) as a colorless oil: IR (neat) 2963, 2912, 2843, 1742,
1
1424, 1260, 1105 cm-1: H NMR (CDCl3) δ 0.74-0.58 (4H, m),
1.12-0.90 (22H, m), 1.89-1.76 (2H, m), 2.24-2.13 (2H, m),
3.42-3.29 (2H, m), 3.87-3.76 (4H, m), 4.81 (1H, m), 5.07 (1H,
m), 5.44-5.30 (4H, m), 5.92-5.78 (2H, m), 7.45-7.35 (12H, m),
7.67-7.61 (8H, m); 13C NMR (CDCl3) δ 8.2, 8.6, 18.3, 18.5, 19.3,
20.4, 20.6, 26.6, 26.9, 31.5, 33.5, 65.6, 65.7, 76.2, 76.8, 77.1, 77.4,
78.6, 79.7, 82.1, 118.2, 118.3, 127.8, 129.8, 133.5, 133.6, 134.3,
134.4, 135.6, 148.8, 149.0; MS (CI) m/z 459 (M+ + Na); HRMS
m/z 459.1978 (calcd for C26H32O4NaSi 459.1968). This material
was carried forward to the next reaction without further purification.
(8R)-8-[1S,2R-(tert-Butyldiphenylsilanyloxymethyl)cyclopropyl]-
3,4,7,8-tetrahydrooxocin-2-one (89). To 90 (0.025 g, 0.06 mmol)
in toluene (2 mL) was added dicyclopentadienyldimethyltitanium
(0.044 g of a 33% by wt solution in toluene). The solution was
stirred in the dark at 100 °C for 2 h. The reaction vessel was cooled
to room temperature and the solvent was removed. Column
94 (13.6 mg, 99%) as a colorless oil: [R]22 +4.5 (c 1.5, CHCl3);
D
IR (neat) 3049 (br), 2922, 2851, 1713, 1456, 1238, 1056, 731 cm-1
;
1H NMR (CDCl3) δ 0.55 (1H, dt, J ) 8.3, 5.1 Hz), 0.67 (1H, dt,
J ) 8.6, 5.1 Hz), 0.85 (1H, m), 1.01 (1H, ddd, J ) 9.1, 8.4, 4.7
Hz), 1.57-1.49 (3H, m), 1.70 (1H, m), 1.89-1.79 (4H, m), 2.43
(1H, dd, J ) 6.4, 5.9 Hz), 3.43 (1H, dd, J ) 11.7, 7.0 Hz), 3.57
(1H, dd, J ) 11.7, 6.4 Hz), 4.07 (1H, q, J ) 7.0 Hz); 13C NMR
(CDCl3) δ 8.5, 19.3, 21.5, 24.2, 26.5, 29.1, 32.7, 37.1, 66.0, 81.7,
176.7; MS (EI) m/z 198 (M+), 181 (M+ - OH); HRMS m/z
198.1247 (calcd for C11H18O3 198.1256).
Solandelactones E (6) and F (5). To 92 (0.004 g, 0.020 mmol)
in CH2Cl2 (1 mL) were added 4 Å molecular sieves (0.024 g) and
4-methylmorpholine N-oxide (0.0036 g, 0.030 mmol). Tetrapro-
J. Org. Chem. Vol. 73, No. 11, 2008 4149

White et al.
pylammonium perruthenate (0.0016 g, 0.0046 mmol) was added
and, after 20 min at room temperature, the solution was passed
through a short plug of silica gel. Removal of the solvent gave 14
(0.040 g) and 4-methylmorpholine oxide (0.0072 g, 0.060 mmol).
After 10 min, tetra-n-propylammonium perruthenate (0.0032 g,
0.0092 mmol) was added, and after 20 min at room temperature,
the solution was passed through a short plug of silica gel. Removal
of the solvent gave 99 (0.008 g, quant) as a colorless oil. This
aldehyde was unstable and was carried forward to the next reaction
without further purification.
1
(0.004 g, quant) as a colorless oil: H NMR (CDCl3) δ 1.28 (1H,
m), 1.33 (1H, dt, J ) 9.5, 4.7 Hz), 1.79 (1H, dddd, J ) 10.6, 6.6,
6.6, 4.0 Hz), 1.94 (1H, ddd, J ) 8.8, 8.8, 4.0 Hz), 2.13 (1H, dddd,
J ) 12.3, 6.6, 5.0 3.0 Hz), 2.32, 1H, ddd, J ) 14.1, 8.1, 1.3 Hz),
2.60 (1H, dddd, J ) 14.1, 10.3, 7.2, 1.4 Hz), 2.74 (1H, ddd, J )
13.4, 5.9, 3.0 Hz), 2.84 (1H, m), 4.28 (1H, ddd, J ) 10.6, 6.7, 1.9
Hz), 5.74 (1H, m), 5.81 (1H, dddd, J ) 11.0, 9.6, 6.9, 1.6 Hz),
9.21 (1H, d, J ) 4.6 Hz); 13C NMR (CDCl3) δ 12.5, 24.4, 25.0,
27.5, 34.0, 37.7, 77.8, 127.6, 133.2, 176.5, 199.9. This compound
was unstable and was carried forward without further purification.
A mixture of 14 prepared above and 13 was thoroughly dried
by azeotropic removal of benzene (twice). To the mixture was added
degassed DMSO (0.5 mL), chromium(II) chloride (6.6 mg, 0.054
mmol) and nickel(II) chloride (0.05 mg), and the green solution
was stirred at room temperature for 18 h. The reaction was quenched
by addition of saturated aqueous NaCl and the mixture was extracted
with EtOAc (3 × 5 mL). The combined organic extracts were dried
over Na2SO4, after which column chromatography (50% EtOAc
in pentane) gave solandelactone E (6, 3.7 mg, 53%) and solan-
A mixture of 99 prepared above and 13 was thoroughly dried
by azeotropic removal of benzene (twice). To the mixture was added
degassed DMSO (1 mL), chromium(II) chloride (13 mg, 0.11
mmol) and nickel(II) chloride (2.0 mg). The green solution was
stirred at room temperature for 12 h and the reaction was quenched
by addition of saturated aqueous NH4Cl. The mixture was extracted
with EtOAc (3 × 5 mL), and the combined organic extracts were
dried over Na2SO4. Column chromatography (50% EtOAc in
pentane) gave solandelactone A (2, 4.7 mg, 32%) and solandelac-
tone B (1, 1.3 mg, 9%) as colorless oils. 2: [R]23 +0.8 (c 0.13
D
MeOH); IR (neat) 3416, 2935, 2851, 1721, 1457, 1141, 1097, 1064
1
cm-1; H NMR (CDCl3) δ 0.60 (1H, ddd, J ) 8.6, 5.5 Hz), 0.68
(1H, ddd, J ) 8.6, 5.2 Hz), 0.89 (1H, t, J ) 6.2 Hz), 0.99 (1H,
ddd, J ) 8.9, 8.9, 4.6 Hz), 1.16 (1H, ddd, J ) 8.6, 8.6, 4.9 Hz),
1.39-1.22 (6H, m), 1.60-1.50 (4H, m), 1.69 (1H, m), 1.90-1.82
(3H, m), 2.09-2.00 (2H, m), 2.35-2.29 (2H, m), 2.44 (2H, dd, J
) 6.8, 6.2 Hz), 3.65 (1H, dd, J ) 7.4, 4.0 Hz), 4.10 (1H, dt, J )
6.5, 7.9 Hz), 4.18 (1H, m), 5.38 (1H, dt, J ) 11.0, 7.6 Hz), 5.59
(1H, dt, J ) 11.0, 7.4 Hz), 5.76 (1H, dd J ) 15.4, 7.2 Hz), 5.81
(1H, dd, J ) 15.4, 4.2 Hz); 13C NMR (CDCl3) δ 7.9, 14.1, 21.5,
22.6, 23.1, 24.2, 26.5, 27.5, 29.1, 29.3, 31.5, 32.7, 35.3, 37.1, 71.5,
74.6, 81.5, 124.1, 131.7, 133.2, 134.1, 176.6; HRMS (CI) m/z
delactone F (5, 1.0 mg, 15%) as colorless oils. 6; [R]23 +2.7 (c
D
0.03 MeOH); IR (neat): 3401, 2921, 2848, 1746, 1455, 1214, 1099,
1
1057 cm-1: H NMR (CDCl3) δ 0.61 (1H, dt, J ) 10.0, 5.0 Hz),
0.75 (1H, dt, J ) 10.0, 5.0 Hz), 0.89 (3H, t, J ) 6.7 Hz), 1.01 (1H,
m), 1.14 (1H, ddd, J ) 12.6, 8.5, 4.7 Hz), 1.38-1.30 (6H, m),
2.05 (2H, m), 2.12 (2H, m), 2.35-2.22 (4H, m), 2.63 (1H, ddd, J
) 14.1, 10.6, 6.0 Hz), 2.73 (1H, ddd, J ) 13.0, 5.3, 3.2 Hz), 2.86
(1H, m), 3.67 (1H, dd, J ) 7.4, 3.5 Hz), 4.04 (1H, ddd, J ) 10.5,
8.1, 2.1 Hz), 4.19 (1H, m), 5.38 (1H, dt, J ) 12.0, 6.7 Hz), 5.59
(1H, dt, J ) 12.0, 6.7 Hz), 5.84-5.72 (4H, m); 13C NMR (CDCl3)
δ 8.1, 14.1, 20.7, 22.6, 23.4, 24.5, 27.5, 29.3, 31.5, 34.3, 35.3, 37.8,
71.5, 74.5, 80.9, 124.1, 128.1, 131.7, 132.8, 133.2, 134.1, 177.0;
MS (CI) m/z 385 (M+ + Na), 345 (M+-OH; HRMS m/z 385.2371
(calcd for C22H34O4Na 385.2355). 5: [R]23D +2.0 (c 0.01 MeOH);
365.2701 (calcd for C22H37O4: 365.2691). 1: [R]23 +2.5 (c 0.08
D
1
MeOH); IR (neat) 3387, 2928, 1718, 1565, 1461, 1098 cm-1; H
NMR (CDCl3) δ 0.73-0.68 (2H, m), 0.88 (1H, t J ) 6.6 Hz), 0.98
(1H, m), 1.06 (1H, m), 1.38-1.23 (6H, m), 1.72-1.49 (6H, m)
1.79 (1H, m), 1.86 (1H, m), 2.09-2.00 (2H, m), 2.36-2.27 (2H,
m), 2.46-2.39 (2H, m), 3.67 (1H, dd J ) 7.46, 4.8 Hz), 4.06 (1H,
m), 4.17 (1H, m), 5.37 (1H, ddt, J ) 10.7, 7.3, 1.3 Hz), 5.59 (1H,
dtt, J ) 10.9, 6.9, 0.8 Hz), 5.80-5.74 (2H, m); 13C NMR (CDCl3)
δ 9.0, 14.1, 20.5, 22.6, 23.3, 24.2, 26.5, 27.5, 29.1, 29.3, 31.5, 32.8,
35.4, 37.2, 71.6, 74.8, 81.6, 124.0, 131.6, 133.6, 134.0, 176.6;
HRMS m/z 365.2682 (calcd for C22H37O4: 365.2691).
IR (neat) 3449, 2922, 2844, 1739, 1450, 1378, 1325, 1009 cm-1
;
1H NMR (CDCl3) δ 0.71 (1H, dt, J ) 7.6, 5.6 Hz), 0.78 (1H, dt,
J ) 7.3, 5.3 Hz), 0.89 (3H, t, J ) 6.7 Hz), 1.06-1.00 (2H, m),
1.37-1.22 (6H, m), 2.07-2.02 (2H, m), 2.12 (1H, m), 2.18 (1H,
ddd, J ) 13.9, 8.0, 1.2 Hz), 2.38-2.26 (4H, m), 2.58 (1H, ddd, J
) 14.0, 10.1, 6.2 Hz), 2.73 (1H, ddd, J ) 13.0, 5.9, 3.0 Hz), 2.85
(1H, m), 3.67 (1H, dd, J ) 6.0, 4.3 Hz), 4.01 (1H, dt, J ) 10.6,
1.7 Hz), 4.18 (1H, m), 5.38 (1H, dt, J ) 10.6, 7.7 Hz), 5.59 (1H,
dt, J ) 10.6, 7.2 Hz), 5.82-5.72 (2H, m); 13C NMR (CDCl3) δ
9.0, 14.0, 19.8, 22.6, 23.6, 24.4, 27.4, 29.3, 31.5, 34.3, 35.3, 37.7,
71.5, 74.8, 80.7, 124.0, 128.0, 131.7, 132.8, 133.6, 134.0; MS (CI)
m/z 385 (M+ + Na); HRMS m/z 385.2364 (calcd for C22H34O4Na
385.2355). Solandelactones E and F undergo mutarotation in MeOH
due to methanolysis of the lactone.
Acknowledgment. Financial support for this work was
provided by the National Science Foundation (grant no 0413994-
CHE).
Supporting Information Available: Experimental proce-
dures and characterization data of compounds not described in
the Experimental Section; 1H and 13C NMR spectra of all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Solandelactone A (2) and B (1). To a solution of 94 (0.008 g,
0.040 mmol) in CH2Cl2 (2 mL) were added 4 Å molecular sieves
JO800335G
4150 J. Org. Chem. Vol. 73, No. 11, 2008