Rhodium-catalyzed endo -selective epoxide-opening cascades: formal synthesis of (-)-brevisin

Article abstract of DOI:10.1021/jacs.5b03570

[Rh(CO)₂Cl]₂ is as an effective catalyst for endo-selective cyclizations and cascades of epoxy-(E)-enoate alcohols, thus enabling the synthesis of oxepanes and oxepane-containing polyethers from di- and trisubstituted epoxides. Synth

Full text of DOI:10.1021/jacs.5b03570

Article
pubs.acs.org/JACS
Rhodium-Catalyzed Endo-Selective Epoxide-Opening Cascades:
Formal Synthesis of (−)-Brevisin
Kurt W. Armbrust, Matthew G. Beaver,† and Timothy F. Jamison*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
S
* Supporting Information
ABSTRACT: [Rh(CO)2Cl]2 is as an effective catalyst for endo-
selective cyclizations and cascades of epoxy-(E)-enoate
alcohols, thus enabling the synthesis of oxepanes and
oxepane-containing polyethers from di- and trisubstituted
epoxides. Syntheses of the ABC and EF ring systems of
(−)-brevisin via all endo-diepoxide-opening cascades using this
method constitute a formal total synthesis and demonstrate the
utility of this methodology in the context of the synthesis of
marine ladder polyether natural products.
demonstrated an important and unusual endo selectivity in the
INTRODUCTION
■
construction of trans-fused bis-oxepanes.11
The unique structural features, limited abundance, and potent
biological activity of the marine ladder polyether family of
natural products have inspired many innovative achievements
in total synthesis enabled by the development of new
methodology.1 Guided by the biogenesis proposed for these
compounds,2 several groups have investigated the feasibility of
all-endo3 epoxide-opening cascades as a potentially rapid and
general approach to these polyethers.4 An ongoing challenge,
these kinetically disfavored processes have been addressed in
part by previous methodology developed in our laboratory.5
Enabling expeditious synthesis of poly tetrahydropyran frag-
ments, template-guided, water-promoted cascades nevertheless
as yet do not appear to be amenable to the synthesis of
oxepanes, 7-membered rings that represent an important motif
present in every natural ladder polyether isolated to date.
Herein we demonstrate a new tactic that not only constructs
oxepane rings but also provides a new means for selective
initiation of epoxide-opening cascades, as embodied by a formal
synthesis of (−)-brevisin.
Our design is depicted in Scheme 1 and can be summarized
as follows: incorporation of an electronically tailored alkene at
Scheme 1. Substrate and Promoter Combination Designed
for Selective Initiation of All-Endo Epoxide-Opening
Cascades
In the same vein as the use of epoxides and allylic alcohols as
sites for selective initiation of polyene cyclizations toward
sterols,6 we envisioned that an appropriately substituted alkenyl
epoxide7 with a suitable activator might play a similar role in
epoxide-opening cascades. Previous examples of selective
initiation of epoxide-opening cascades include the Holton
synthesis of hemibrevetoxin B, wherein an electrophilic
selenium reagent triggered nucleophilic attack by an epoxide,8
the photochemical generation of an oxocarbenium described by
Floreancig and Houk,9 and bromonium formation in a epoxide-
opening cascade we utilized en route to dioxepandehydro-
thyrsiferol.10 Finally, although the Lewis acid promoted
epoxide-opening cascades developed by McDonald did not
utilize a site-selective initiation mechanism, they nevertheless
the distal12 epoxide would provide a specific site for
complexation and activation by a transition metal. The use of
transition metals to selectively activate alkenyl epoxides for
nucleophilic attack has excellent and diverse precedents.
Although Pd catalysis is the most well-known,13 we eschewed
this path because of the limited examples of oxygen
nucleophiles in this context and, more importantly, the
likelihood that an undesired stereochemical outcome would
be observed, i.e., net retention (double inversion) at the site of
Received: April 6, 2015
Published: May 18, 2015
© 2015 American Chemical Society
6941
DOI: 10.1021/jacs.5b03570
J. Am. Chem. Soc. 2015, 137, 6941−6946

Journal of the American Chemical Society
Article
epoxide opening, rather than the necessary inversion of
configuration. In contrast, [Rh(CO)2Cl]2 has been shown to
activate alkenyl epoxides for intermolecular opening by alcohol
and amine nucleophiles with inversion of stereochemistry.14
Further development by Ha and co-workers led to cyclizations
of trans-disubstituted enoate epoxy-alcohols and carbamates to
provide five- and six-membered saturated heterocycles.15 Prior
to our investigations, however, no examples of oxepane
formation via [Rh(CO)2Cl]2 catalysis, activation of trisub-
stituted epoxides, or its use in initiation of epoxide-opening
cascades had been reported.
Important in these designs was consideration of the natural
product (−)-brevisin (1), isolated by Wright and Baden in
2008 from the dinoflagellate Karenia brevis.16 The use of two
cascades as described above (and shown in Scheme 2) would
intercept two tricyclic intermediates (2 and 3) in the only
previous total synthesis of (−)-brevisin from Tachibana and co-
workers.17
Table 1. Trans-Disubstituted Epoxy Alcohol Cyclizations
under [Rh(CO)2Cl]2 and ( )-CSA Promotion
a
entry
substrate
activator
7/8
yield 7 (%)
b
d
1
2
3
4
6a, n = 0
6a, n = 0
6b, n = 1
[Rh(CO)2Cl]2
>20:1
1:1
94
−
81
c
( )-CSA
[Rh(CO)2Cl]2
>20:1
1:3
d
6b, n = 1
( )-CSA
−
a
b
c
Isolated yield. [Rh(CO)2Cl]2 (2.5 mol %), THF, rt. ( )-CSA (10
mol %), CH2Cl2, rt. [Rh(CO)2Cl]2 (5 mol %), THF, rt. ( )-CSA
(100 mol %), CH2Cl2, rt.
d
d
smaller ring (exo), THP 8b, consistent with results reported
Nicolaou and co-workers (Table 1, entry 4).20 The reversal of
regioselectivity by [Rh(CO)2Cl]2 relative to acid catalysis
supports an alternative mechanism for epoxide activation
beyond a typical Lewis acid. We found similar direct
comparisons in these studies to be useful measures of the
biasing ability of the enoate and [Rh(CO)2Cl]2 combination on
regioselectivity.
Scheme 2. Retrosynthetic Analysis of (−)-Brevisin (1)
Critical to the success of this method toward the synthesis of
the ABC tricycle of (−)-brevisin, distal methyl substitution was
well tolerated under [Rh(CO)2Cl]2 promotion, providing
complete endo selectivity for the synthesis of both tetrahy-
dropyran (7c) and oxepane (7d) from epoxy alcohols 6c and
6d respectively (Table 2, entries 1 and 3). In comparison,
Table 2. Trisubstituted Epoxy Alcohol Cyclizations under
[Rh(CO)2Cl]2 and ( )-CSA Promotion
a
entry
substrate
activator
7/8
yield 7 (%)
b
d
1
2
3
4
6c, n = 0
6c, n = 0
6d, n = 1
[Rh(CO)2Cl]2
>20:1
3.4:1
93
−
88
c
( )-CSA
[Rh(CO)2Cl]2
>20:1
d
6d, n = 1
( )-CSA
1:1.8
−
a
b
c
Isolated yield. [Rh(CO)2Cl]2 (1 mol %), THF, rt. ( )-CSA (10
mol %), CH2Cl2, rt. [Rh(CO)2Cl]2 (2.5 mol %), THF, rt. ( )-CSA
(100 mol %), CH2Cl2, rt.
d
d
RESULTS AND DISCUSSION
■
Before embarking on epoxide-opening cascades toward
(−)-brevisin, we first explored the feasibility of oxepane
formation from epoxy alcohols promoted by [Rh(CO)2Cl]2..
Subjecting trans-disubstituted epoxy alcohol 6b with the
required enoate π-activating group18 to conditions for [Rh-
(CO)2Cl]2 catalysis provided the desired oxepane 7b as the
only observable product (Table 1, entry 3). This combination
of alkenyl epoxide and Rh catalysis provides rapid access to
oxepanes from relatively simple starting materials19 via endo-
cyclization with stereospecific inversion observed at the formed
O−C bond.
promotion with ( )-CSA yielded a mixture of endo- and exo-
products, albeit with a slight improvement in regioselectivity
compared to disubstituted epoxides 6a and 6b. Encouraged by
these one-oxepane studies, we turned our attention to epoxide-
opening cascades.
Toward the EF fragment, the route illustrated in Scheme 3
allowed for rapid access to the desired cascade precursor 5.
Ozonolysis of known enoate 9,21 followed by nucleophilic
addition of isopropenyl magnesium bromide and a tandem
vinylation−Claisen process,22 afforded aldehyde 10. Olefination
of 1023 and subsequent asymmetric Shi epoxidation24 and
Noteworthy by contrast were the results observed under
Brønsted acid catalysis. For example, subjecting epoxy alcohol
6b to ( )-CSA activation conditions afforded primarily the
6942
DOI: 10.1021/jacs.5b03570
J. Am. Chem. Soc. 2015, 137, 6941−6946

Journal of the American Chemical Society
Article
activation, which we and others have employed in other all-
endo epoxide-opening cascades, provided none of the desired
product for enoate diepoxide 5, again highlighting the exquisite
selectivity of [Rh(CO)2Cl]2 catalysis (entries 3 and 4). The
ester functional group is critical to the success of the method;
vinyl diepoxide 13 under [Rh(CO)2Cl]2 catalysis provided
lower yields (entry 5). Alternatively, conditions utilized by
McDonald in methyl-11b or vinyl-directed11c epoxide-opening
cascades led to the desired product (3), but also in a lower yield
(entries 6−8). These results support the mechanistic
hypothesis of Rh(I) activation of alkenyl epoxides via π-
coordination and oxidative addition into the vinylic C−O bond
of the epoxide, which contrasts with the generally non-site-
selective epoxide activation with Lewis acids. Importantly, these
results represent the first examples of both a cascade process
and a seven-membered ring formation using this method. By
ozonolysis followed by Wittig reaction, (E)-enoate 11 was
converted to 3, corresponding to the EF-ring system of
(−)-brevisin (1).
Scheme 3. Synthesis of EF Diepoxy Cascade Precursors and
Formal Synthesis Target
a
Toward the ABC fragment, synthesis of the A ring proceeded
via the previously reported route to lactone 1417c (Scheme 4).
This lactone was elaborated by diastereoselective dihydrox-
ylation, and the incipient side chain installed through allyl
Grignard addition. Triethylsilane reduction of the intermediate
lactol and acetylation provided the fully elaborated A ring (15).
Elaboration of the allyl group of 15 was accomplished via
cross-metathesis with 18,26 giving trisubstituted alkene 19,
albeit in only 31% yield. Motivated by reports of higher yields
in the cross-metathesis of allyl groups with increased steric
hindrance,27 alkene 16 was prepared from 15 via cross-
metathesis with 2-methyl-2-butene.28 In comparison, cross-
metathesis of 18 and trisubstituted alkene 16 provided a
significantly higher yield, particularly when performed in the
absence of additional solvent. Despite the modest stereo-
selectivity, the 2:1 E/Z mixture of alkene isomers could be
separated by column chromatography. The enoate-directing
group was installed by desilylation of 19, alcohol oxidation, and
in situ stabilized-Wittig olefination. Asymmetric Shi epoxidation
and acetate ethanolysis provided the diepoxide cascade
precursor 21.
a
Reaction conditions: (a) O3, CH2Cl2, −78 °C; then Me2S, 82%; (b)
H2CC(CH3)MgBr, THF, −78 to 0 °C, 1:1 dr, 89%; (c) Triethylene
glycol divinyl ether, (1,10-phenanthroline)Pd(OAc)2, 80 °C, 7:1 E/Z,
63%; (d) LDA, (MeO)2P(O)CH2CHCHCO2Et, −78 °C to rt, 2:1
E/Z, 84%; (e) (−)-12, KHSO5, Bu4NHSO4, K2CO3, pH 10.5, DMM/
CH3CN (2:1), 22%; (f) TBAF, THF, rt, 69%; (g) O3, CH2Cl2/MeOH
(4:1), −78 °C; Ph3P, −78 °C to rt; (h) Ph3PCH3Br, KOt-Bu, THF, 0
°C to rt, 84% (over 2 steps).
TBAF desilylation rapidly provide cascade precursor 5 in six
steps from enoate 9.25
Investigation of cascade promoters for diepoxy alcohol 5
containing an (E)-enoate revealed [Rh(CO)2Cl]2 to be a highly
chemo-, stereo-, and regioselective promoter, in the desired
fashion. For example, [Rh(CO)2Cl]2 catalyzed the regioselec-
tive epoxide-opening cascade of (E)-enoate-diepoxy alcohol 5
to provide the desired product 11 in 38% isolated yield (Table
3, entry 1). Further optimization by employing 1,4-dioxane as
the solvent and performing the reaction at elevated temper-
atures (65 °C) provided a 61% yield. Lewis or Brønsted acid
Exposure of diepoxide 21 to catalytic [Rh(CO)2Cl]2 at
ambient temperature in THF led to full conversion and a 78%
yield of the desired ABC tricycle (22). Efforts directed toward
lowering the catalyst loading led to inferior yields. Brønsted
acid promotion with ( )-CSA did not provide any desired
product, further differentiating [Rh(CO)2Cl]2 from acid
promoted conditions. Completion of the formal synthesis of
(−)-brevisin (1) was achieved by benzylation of both hydroxyl
groups, oxidative cleavage of the pendant enoate via
dihydroxylation and diol cleavage,29 and finally aldehyde
reduction to provide alcohol 2, corresponding to the ABC-
ring system of (−)-brevisin (1).
To help further our understanding of these successful
diepoxide-opening reactions, we have put forth a mechanism
for the ABC-ring cascade, shown in Scheme 5. The proposed
epoxonium pathway invokes formation of a bicyclo[4.1.0]
epoxonium by [Rh(CO)2Cl]2 activation of the distal epoxy-
enoate, subsequent attack by the central epoxide, and then
rapid trapping by the A-ring hydroxyl. We favor the epoxonium
pathway versus a related stepwise transformation,30 as it
provides a more consistent explanation of the high yield
obtained under what would generally be regarded as mild
conditions.
Table 3. Investigation of Diepoxide Cascade towards EF
Fragment
product yield
entry substrate
conditions
(%)
a
a
1
2
3
4
5
6
7
8
5
[Rh(CO)2Cl]2, THF, rt
[Rh(CO)2Cl]2, Dioxane, 65 °C
BF3·OEt2, CH2Cl2, −78 °C
CSA, CH2Cl2, rt
11
11
11
11
3
38
61
5
bc
,
5
−
−
21
23
38
26
bc
,
5
b
13
13
13
13
[Rh(CO)2Cl]2, THF, rt
BF3·OEt2, CH2Cl2, −78 °C
Yb(OTf)3, CH2Cl2, rt
a
b
b
3
3
Eu(OTf)3, CH2Cl2, rt
3
a
b
Isolated yield. Yield determined by 1H NMR against mesitylene
c
standard. − represents no observed product.
6943
DOI: 10.1021/jacs.5b03570
J. Am. Chem. Soc. 2015, 137, 6941−6946

Journal of the American Chemical Society
Article
a
Scheme 4. Synthetic Route to ABC Diepoxide-Opening Cascade Precursor and Formal Synthesis Target
a
(a) OsO4, NMO, Acetone/H2O (4:1), 95%; (b) CH2CHCH2MgBr, THF, −78 °C; (c) Et3SiH, TMSOTf, MeCN, 44% (over 2 steps); (d) Ac2O,
pyr, DMAP, CH2Cl2, 87%; (e) 2-methyl-2-butene, Hoveyda−Grubbs cat. (2nd generation), Benzoquinone, 87%; (f) L-(+)-DET, Ti(OiPr)4, TBHP,
CH2Cl2, −20 °C, 49%, 93% ee; (g) TBSCl, Et3N, CH2Cl2, 86%; (h) Hoveyda−Grubbs cat. (2nd generation), Benzoquinone, 80 °C, 78%, 2:1 E/Z;
(i) TBAF, THF, 84%; (j) pyr·SO3, DMSO, Et3N, CH2Cl2, rt; then Ph3PCHCO2Et, rt, 91%; (k) (+)-12, KHSO5, Bu4NHSO4, K2CO3, pH 10.5,
DMM/CH3CN (2:1), 84%, 3:1 dr; (l) Guanidine·HCl, NaOEt, EtOH, 77%; (m) [Rh(CO)2Cl]2 (10 mol %), THF, rt, 78%; (n) NaH, BnBr, TBAI,
THF, 60 °C, 75%; (o) K2OsO2(OH)4, Citric Acid, NMO, t-BuOH/H2O; (p) Ph3BiCO3, CH2Cl2, reflux; (q) NaBH4, MeOH, 0 °C, 60% (over 3
steps).
Scheme 5. Proposed Mechanism for Rh-Promoted Epoxide-
Opening Cascade of Diepoxide 22
Table 4. Proximal-Methyl (E)-Trisubstituted Epoxy Alcohols
Cyclizations under [Rh(CO)2Cl]2 and ( )-CSA Promotion
a
entry
substrate
activator
7:8
12:1
yield 7 (%)
b
d
1
2
3
4
6e, n = 0
6e, n = 0
6f, n = 1
[Rh(CO)2Cl]2
81
−
21
c
( )-CSA
1:>20
4:1
[Rh(CO)2Cl]2
e
6f, n = 1
( )-CSA
1: >20
−
a
b
c
Isolated yield. [Rh(CO)2Cl]2 (10 mol %), 1,4-Dioxane, 80 °C. ( )-
CSA (10 mol %), CH2Cl2, rt. [Rh(CO)2Cl]2 (10 mol %), THF, 60
d
e
°C. ( )-CSA (100 mol %), CH2Cl2, rt.
Further insight into the putative mechanism is suggested by
our initial cyclization studies of epoxides with proximal methyl
substitution. These substrates, which represent one of the most
challenging substitution patterns to achieve high endo selectivity
in epoxy alcohol cyclizations,31 have shown significant promise
thus far. For example, use of the enoate and [Rh(CO)2Cl]2
overrides the near-complete exo-selectivity observed with CSA
for proximal methyl substitution, (Table 4, entries 1 and 2).
Notably, however, measurable quantities of the exo products are
observed, in contrast to the previous substrates tested (vide
supra). Higher catalyst loadings and heating are required for full
conversion in these cases. While the yield and selectivity are
lower in the case of formation of oxepane 7f (Table 4, entry 3),
this result suggests nevertheless an alternative approach to
override the exo-directing methyl group in this very challenging
case of oxepane formation. These results together with the
diepoxide cascades further suggest that [Rh(CO)2Cl]2 is
activating alkenyl epoxides via a distinct mechanism relative
to Brønsted or Lewis acid catalysis.
CONCLUSIONS
■
In summary, the combination of an enoate group and
[Rh(CO)2Cl]2 catalysis is effective for not only the synthesis
of 6- and 7-membered oxygen heterocycles from epoxy alcohols
bearing a variety of substitution patterns but also cascades of
diepoxides where control of the sequence of epoxide opening
events is tantamount to success. The high yield, stereo-
specificity, functional group compatibility, and endo-selectivity
make this approach particularly well suited for target-directed
synthesis, as highlighted by the formal synthesis of (−)-brevisin.
Further application of this methodology toward other oxepane-
6944
DOI: 10.1021/jacs.5b03570
J. Am. Chem. Soc. 2015, 137, 6941−6946

Journal of the American Chemical Society
Article
Toganoh, M.; Rodríguez, J. R.; Do, B.; Neiwert, W. A.; Hardcastle, K.
I. J. Org. Chem. 2002, 67, 2515. (c) Bravo, F.; McDonald, F. E.;
Neiwert, W. A.; Hardcastle, K. I. Org. Lett. 2004, 6, 4487. (d) Valentine,
J. C.; McDonald, F. E.; Neiwert, W. A.; Hardcastle, K. I. J. Am. Chem.
Soc. 2005, 127, 4586. (e) McDonald, F. E.; Tong, R.; Valentine, J. C.;
Bravo, F. Pure Appl. Chem. 2007, 79, 281.
containing natural products is an active area of research, as is
investigation of other Rh(I) catalysts and alkene directing
groups.
ASSOCIATED CONTENT
* Supporting Information
■
S
(12) Distal is defined as the epoxide furthest from the terminating
alcohol nucleophile.
Experimental procedures and characterization data for all new
compounds. The Supporting Information is available free of
charge on the ACS Publications website at DOI: 10.1021/
jacs.5b03570.
(13) Tsuji, J.; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett. 1981, 22,
2575. (b) Trost, B. M.; Molander, G. A. J. Am. Chem. Soc. 1981, 103,
5969. (c) Trost, B. M.; Tenaglia, A. Tetrahedron Lett. 1988, 29, 2931.
(d) Trost, B. M.; McEachern, E. J.; Toste, F. D. J. Am. Chem. Soc.
1998, 120, 12702. (e) Trost, B. M.; McEachern, E. J. J. Am. Chem. Soc.
1999, 121, 8649. (f) Hirai, A.; Yu, X.-Q.; Tonooka, T.; Miyashita, M.
Chem. Commun. (Cambridge, U.K.) 2003, 2482. (g) Yu, X.-Q.;
Yoshimura, F.; Ito, F.; Sasaki, M.; Hirai, A.; Tanino, K.; Miyashita, M.
Angew. Chem., Int. Ed. 2008, 47, 750. (h) Arthuis, M.; Beaud, R.;
Gandon, V.; Roulland, E. Angew. Chem., Int. Ed. 2012, 51, 10510.
(14) (a) Ashworth, R. W.; Berchtold, G. A. Tetrahedron Lett. 1977,
18, 343. (b) Fagnou, K.; Lautens, M. Org. Lett. 2000, 2, 2319.
(15) (a) Ha, J. D.; Shin, E. Y.; Kang, S. K.; Ahn, J. H.; Choi, J.-K.
Tetrahedron Lett. 2004, 45, 4193. (b) Inoue, M.; Saito, F.; Iwatsu, M.;
Ishihara, Y.; Hirama, M. Tetrahedron Lett. 2007, 48, 2171.
(16) (a) Satake, M.; Campbell, A.; Van Wagoner, R. M.; Bourdelais,
A. J.; Jacocks, H.; Baden, D. G.; Wright, J. L. C. J. Org. Chem. 2009, 74,
989. (b) Van Wagoner, R. M.; Satake, M.; Bourdelais, A. J.; Baden, D.
G.; Wright, J. L. C. J. Nat. Prod. 2010, 73, 1177.
(17) (a) Kuranaga, T.; Ohtani, N.; Tsutsumi, R.; Baden, D. G.;
Wright, J. L. C.; Satake, M.; Tachibana, K. Org. Lett. 2011, 13, 696.
For a discussion of fragment synthesis, see: (b) Kuranaga, T.; Satake,
M.; Baden, D. G.; Wright, J. L. C; Tachibana, K. Tetrahedron Lett.
2010, 51, 4673. (c) Ohtani, N.; Tsutsumi, R.; Kuranaga, T.; Shirai, T.;
Wright, J. L.; Baden, D. G.; Satake, M.; Tachibana, K. Heterocycles
2010, 80, 825.
(18) “π-Activating group” refers to the group distal to the furthest
epoxide relative to the trapping nucleophile.
(19) See the Supporting Information for complete details of synthetic
procedures and compound characterization towards epoxy alcohols
6a−6f.
AUTHOR INFORMATION
Corresponding Author
* tfj@mit.edu
■
Present Address
†Amgen, 360 Binney Street, Cambridge, MA 02142.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the NIGMS (GM72566 and fellowship to M.G.B.,
F32GM095014) and the NSF (Graduate Research Fellowship
to K.W.A.) for financial support of this work. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
We also thank Li Li and Eric A. Standley (both MIT) for
HRMS analyses, which were conducted on an instrument
purchased with the assistance of NSF Grant CHE-0234877.
NMR spectroscopy was carried out on instruments purchased
in part with funds provided by the NSF (CHE-9808061 and
CHE-8915028). We are grateful to Elizabeth H. Kelley and Eric
A. Standley (both MIT) for insightful discussions and input
during the preparation of this manuscript.
REFERENCES
■
(20) Alkenes other than enoates are superior π-activating groups for
endo-selective epoxy-alcohol cyclizations promoted by Brønsted acids.
See: (a) Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.; Hwang, C.-K.
J. Am. Chem. Soc. 1989, 111, 5330. (b) Nicolaou, K. C.; Prasad, C. V.
C.; Somers, P. K.; Hwang, C.-K. J. Am. Chem. Soc. 1989, 111, 5335.
(21) Enoate 9 was prepared in three steps from commercially
available 2-deoxy-D-ribose. See: Nicolaou, K. C.; Wallace, P. A.; Shi, S.;
Ouellette, M. A.; Bunnage, M. E.; Gunzner, J. L.; Agrios, K. A.; Shi, G.;
Gartner, P.; Yang, Z. Chem.Eur. J. 1999, 5, 618.
(1) (a) Nakata, T. Chem. Rev. 2005, 105, 4314. (b) Inoue, M. Chem.
Rev. 2005, 105, 4379. (c) Nicolaou, K. C.; Frederick, M. O.; Aversa, R.
J. Angew. Chem., Int. Ed. 2008, 47, 7182.
(2) (a) Nakanishi, K. Toxicon 1985, 23, 473. (b) Nicolaou, K. C.
Angew. Chem., Int. Ed. Engl. 1996, 35, 588.
(3) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
(4) Vilotijevic, I.; Jamison, T. F. Angew. Chem., Int. Ed. 2009, 48,
5250.
(5) (a) Vilotijevic, I.; Jamison, T. F. Science 2007, 317, 1189. (b) Van
Dyke, A. R.; Jamison, T. F. Angew. Chem., Int. Ed. 2009, 48, 4430.
(c) Morten, C. J.; Jamison, T. F. J. Am. Chem. Soc. 2009, 131, 6678.
(d) Morten, C. J.; Byers, J. A.; Van Dyke, A. R.; Vilotijevic, I.; Jamison,
T. F. Chem. Soc. Rev. 2009, 38, 3175.
(6) (a) Abe, I.; Rohmer, M.; Prestwich, G. D. Chem. Rev. 1993, 93,
2189. (b) Van Tamelen, E. E. Acc. Chem. Res. 1975, 8, 152.
(c) Johnson, W. S.; Gravestock, M. B.; McCarry, B. E. J. Am. Chem.
Soc. 1971, 93, 4332. (d) Gravestock, M. B.; Johnson, W. S.; McCarry,
B. E.; Parry, R. J.; Ratcliffe, B. E. J. Am. Chem. Soc. 1978, 100, 4274.
(e) Corey, E. J.; Luo, G.; Lin, L. S. J. Am. Chem. Soc. 1997, 119, 9927.
(7) For a recent review on vinyl epoxides in organic synthesis, see:
He, J.; Ling, J.; Chiu, P. Chem. Rev. 2014, 114, 8037.
(8) Zakarian, A.; Batch, A.; Holton, R. A. J. Am. Chem. Soc. 2003, 125,
7822.
(22) Wei, X.; Lorenz, J. C.; Kapadia, S.; Saha, A.; Haddad, N.;
Busacca, C. A.; Senanayake, C. H. J. Org. Chem. 2007, 72, 4250.
(23) The phosphonate ester was prepared in two steps by the
literature method: Mitton-Fry, M. J.; Cullen, A. J.; Sammakia, T.
Angew. Chem., Int. Ed. 2007, 46, 1066.
(24) Zhu, Y.; Wang, Q.; Cornwall, R. G.; Shi, Y. Chem. Rev. 2014,
114, 8199.
(25) Diepoxide 13 was synthesized from aldehyde 10 via a related
sequence in seven steps. See the Supporting Information for details.
(26) Yang, D.; Xu, M. Org. Lett. 2001, 3, 1785.
(27) (a) Netscher, T. J. Organomet. Chem. 2006, 691, 5155.
(b) Wang, Z. J.; Jackson, W. R.; Robinson, A. J. Org. Lett. 2013, 15,
3006.
(28) Chatterjee, A. K.; Sanders, D. P.; Grubbs, R. H. Org. Lett. 2002,
4, 1939.
(9) Wan, S.; Gunaydin, H.; Houk, K. N.; Floreancig, P. E. J. Am.
(29) (a) Barton, D. H. R.; Kitchin, J. P.; Lester, D. J.; Motherwell, W.
B.; Papoula, M. T. B. Tetrahedron 1981, 37, 73. (b) Anaya, J.; Barton,
D. H. R.; Gero, S. D.; Grande, M.; Martin, N.; Tachdijian, C. Angew.
Chem., Int. Ed. Engl. 1993, 32, 867. (c) See the Supporting
Information for a discussion regarding the optimization of this
oxidative cleavage sequence.
Chem. Soc. 2007, 129, 7915.
(10) (a) Tanuwidjaja, J.; Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc.
2009, 131, 12084. (b) Underwood, B. S.; Tanuwidjaja, J.; Ng, S.-S.;
Jamison, T. F. Tetrahedron 2013, 69, 5205.
(11) (a) McDonald, F. E.; Wang, X.; Do, B.; Hardcastle, K. I. Org.
Lett. 2000, 2, 2917. (b) McDonald, F. E.; Bravo, F.; Wang, X.; Wei, X.;
6945
DOI: 10.1021/jacs.5b03570
J. Am. Chem. Soc. 2015, 137, 6941−6946

Journal of the American Chemical Society
Article
(30) Morten, C. J.; Byers, J. A.; Jamison, T. F. J. Am. Chem. Soc. 2011,
133, 1902.
(31) Use of specific π-activating groups can also lead to endo-selective
cyclizations, albeit with erosion of trans-stereochemistry in the
products. See: Matsukura, H.; Morimoto, M.; Koshino, H.; Nakata,
T. Tetrahedron Lett. 1997, 38, 5545.
6946
DOI: 10.1021/jacs.5b03570
J. Am. Chem. Soc. 2015, 137, 6941−6946