Scalable, divergent synthesis of meroterpenoids via "borono- sclareolide"

Article abstract of DOI:10.1021/ja303937y

A scalable, divergent synthesis of bioactive meroterpenoids has been developed. A key component of this work is the invention of "borono- sclareolide", a terpenyl radical precursor that enables gram-scale preparation of (+)-chromazonarol. Subsequent synthetic operations on this key intermediate permit rapid access to a variety of related meroterpenoids, many of which possess important biological activity.

Full text of DOI:10.1021/ja303937y

Communication
pubs.acs.org/JACS
Scalable, Divergent Synthesis of Meroterpenoids via “Borono-
sclareolide”
Darryl D. Dixon, Jonathan W. Lockner, Qianghui Zhou, and Phil S. Baran*
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
S
* Supporting Information
ABSTRACT: A scalable, divergent synthesis of bioactive
meroterpenoids has been developed. A key component of
this work is the invention of “borono-sclareolide”, a
terpenyl radical precursor that enables gram-scale prep-
aration of (+)-chromazonarol. Subsequent synthetic
operations on this key intermediate permit rapid access
to a variety of related meroterpenoids, many of which
possess important biological activity.
eroterpenoids are broadly defined as compounds of
M
mixed polyketide-terpenoid origin.1 Quinone/hydro-
quinone sesquiterpenoids2 are chiefly found in marine
organisms, with both antipodes occurring naturally.3 These
meroterpenoids have attracted attention due to their structural
diversity and biological activity ranging from anti-fungal to anti-
cancer and anti-HIV.4 This class of natural products generally
consists of a drimane or rearranged drimane sesquiterpenoid
attached to a quinone or hydroquinone moiety, exemplified by
the natural product (+)-yahazunol (1), discovered by Zubia and
co-workers from a sponge of the genus Dysidea.5 Hundreds of
meroterpenoids with related structures are known, and
synthetic pathways to these molecules have been investigated
extensively. This Communication describes the design and
execution of the first scalable, divergent approach to this natural
product family and analogues thereof.
Previous approaches to this class of natural products have
relied on the addition of a suitably protected arene nucleophile
to a terpene electrophile.6 Major drawbacks to this approach
are the use of protecting groups and subsequent redox
manipulations. Most of these syntheses consist of more than
12 steps and, in some cases, as many as 18 steps. Trammell and
Yamamoto, however, have utilized elegant biomimetic cycliza-
tions of polyprenoids to prepare a small set of meroterpenoids
efficiently.7 Strategies to divergently access this entire natural
product family from a single building block are still absent.8
With the above precedent in mind, the direct coupling of a
terpenoid donor with a non-terpenoid acceptor was envisioned,
as outlined in Figure 1A. It was reasoned that such a direct
coupling would minimize reliance on concession steps.9
Whereas the coupling of simple aryl- and alkylboronic acids
or trifluoroborates with electron-deficient heterocycle10 and
quinone11 radicophiles is known, the direct coupling of a
drimane skeleton and quinone has been less fruitful.
Theodorakis has employed a conceptually similar radical-
based strategy toward rearranged drimane sesquiterpenoids via
Figure 1. A global approach to meroterpenoids utilizing borono-
sclareolide (10).
light-induced decarboxylation, but this approach is less direct
due to ensuing functional group manipulations.12
In the initial plan (Figure 1A), the non-terpenoid unit found
in these natural products would be derived from 1,4-
benzoquinone, and the terpenoid unit would arise from a
radical precursor such as an alkylcarboxylic acid or alkyl halide.
Thus, a Minisci reaction with 5 as the terpenoid “donor” was
investigated (Figure 1B). Compound 5 is readily available via
Received: April 24, 2012
© XXXX American Chemical Society
A
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Journal of the American Chemical Society
Communication
a
Scheme 1. Brief, Scalable Synthesis of “Borono-sclareolide” (10) and (+)-Chromazonarol (11)
a
Reagents and conditions: (a) DIBAL, CH2Cl2, −78 °C, 1 h; (b) PIDA, I2, PhH, hν, 70 °C, 1 h; (c) AgF, py, rt, 12 h; (d) K2CO3, MeOH, 0 °C to rt,
2 h; 84% yield from 4; (e) THF, BH3·THF, 0 °C to rt, 12 h; 96% combined yield (3:1 dr of 10:13); (f) 10, 1,4-benzoquinone (2 equiv), AgNO3 (0.2
equiv), K2S2O8 (5.0 equiv), PhCF3/H2O, 60 °C, 2.5 h; 60% yield, 46% yield on 1.34 g scale.
hydrolysis13 of (+)-sclareolide (4), a common feedstock in the
perfume industry that can be purchased in kilogram quantities.
Carboxylic acid 5 has been previously reported in a Minisci
reaction with naphthoquinone, resulting in a 20% yield of the
to lower yield), and degassing of the reaction mixture led to an
improved yield of 60%.
Utilizing this route, more than 3 g of 11 has been prepared to
date. The originally expected (+)-yahazunone (8) is not
observed in the crude reaction mixture and does not appear to
be an intermediate in the formation of 11. This result is very
unusual and suggests that a different mechanism may be
operable than originally envisioned. The presence of the cyclic
boronic acid has a drastic effect on the outcome of this reaction,
and the mechanism of this transformation is currently under
investigation.
desired adduct.14 Exposure of 5 to Ag+/S2O8 and 1,4-
2−
benzoquinone in various solvents failed to yield any of the
desired terpene-quinone product 8. Radical initiation or Pd-
based methods on iodide 6 were also investigated in a union
with 1,4-benzoquinone, and this also failed to yield yahazunone
(8). Trifluoroborate 7 (vide infra) also failed to react in the
10b
11
2−
expected manner with Mn(OAc)3
or Ag+/S2O8
.
In
With a highly efficient, scalable route to (+)-chromazonarol
(11), this key intermediate was enlisted in the preparation of
other related drimane meroterpenoid natural products (Scheme
2). Zonarol (14),19 isozonarol (15),20 zonarone (17),21 and
isozonarone (18)22 were isolated by Fenical and co-workers in
1973 from the brown seaweed Dictyopteris zonarioides.
striking contrast, the newly invented chemical entity “borono-
sclareolide” (10, Figure 1C) merged smoothly with 1,4-
benzoquinone, providing (+)-chromazonarol (11).7b,15
The preparation of borono-sclareolide (10) requires the
excision of carbon monoxide from 4 and incorporation of B-
OH in its place. Thus, DIBAL-mediated reduction of 4 resulted
in sclaral16 (12; Scheme 1), which upon exposure to the
23
Treatment of 11 with BCl3 in the presence of 2,6-di-tert-
hypoiodite-mediated C−C bond cleavage conditions of Suar
́
ez
butyl-4-methylpyridine at −78 °C afforded a 2.5:1.0:0.3 mixture
of (−)-isozonarol (15), (−)-zonarol (14), and tetrasubstituted
olefin 1624 in a combined 80% yield. After extensive screening,
treatment of 11 with silica gel-supported sodium periodate
yielded yahazunone (8)25,26 in 84% yield. Other oxidants
predominantly yielded o-quinone products (20 and 21, see
structures in Scheme 3) and only trace amounts of the oxidized
ring-opened product 8.
(+)-Yahazunol (1) can be obtained readily from crude 8 via
Pd-catalyzed hydrogenation in 76% yield over two steps from
11, which can then be purified via trituration with CH2Cl2. This
synthesis offers a drastic improvement over the previously
reported synthesis27 of 1 (18 steps from β-ionone, 3% overall vs
8 steps from (+)-sclareolide (4), 26% overall). Exposure of
crude 8 to SOCl2 in the presence of Et3N at −78 °C yielded a
9:1 mixture of (−)-zonarone (17) and (−)-isozonarone (18) in
a combined yield of 71% over two steps.
The anti-tumor and highly potent angiogenesis inhibitor,
(+)-8-epi-puupehedione (19), a synthetic analogue of puupe-
hedione, was also targeted (Scheme 3). The sequence of
Alvarez-Manzaneda to synthesize 19 was first explored.6b,15b,28
It was reported that treatment of 11 with Fremy’s salt
(K2NO(SO3)2) affords a single o-quinone product 20 in 85%
yield. When 11 was subjected to the published conditions, a 3:2
(PIDA/I2/hν) delivered iodoformate 6 (characterized by X-ray
crystallographic analysis). A two-step dehydroiodination/
hydrolysis procedure (AgF in pyridine followed by K2CO3 in
methanol) afforded the sponge metabolite (+)-drim-9(11)-en-
8α-ol (9)17 in 84% overall yield from 4, without the use of
chromatographic separation and on decagram scale for each
transformation. This route constitutes the highest yielding and
most efficient synthesis of 9 to date. Hydroboration of 9
resulted in a 3:1 mixture of diastereomers6c 10 and 13 in 96%
combined yield, which were readily separated by column
chromatography and characterized by X-ray crystallographic
analysis.
Borono-sclareolide (10) was converted into trifluoroborate 7
(Figure 1B) since some alkylboronic acids are prone to undergo
oxidation.18 When 7 was treated with a slight excess of 1,4-
benzoquinone in the presence of AgNO3 and K2S2O8 in
PhCF3/H2O at 60 °C, the expected product 8 was not
observed. Instead, (+)-chromazonarol (11) was obtained in
∼10−20% yield. This transformation is surprising, as this
constitutes an overall redox-neutral process with respect to
both benzoquinone and 10 under strongly oxidizing conditions.
Remarkably, the use of borono-sclareolide (10) instead of 7, 2
equiv of 1,4-benzoquinone, 5 equiv of oxidant (less oxidant led
B
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a
Scheme 2. Divergent Synthesis of Meroterpenoids via 11
Scheme 4. (−)-Pelorol (30) and (+)-Dictyvaric Acid (31)
a
from 10
a
Reagents and conditions: (a) 1,4-dioxane, ArBr (23−26), 10 mol%
Pd(OAc)2, 15 mol% S-Phos, CsF, 50 °C, 12 h [23, 95% yield; 24, 84%
yield; 25, 72% yield; 26, 87% yield]; (b) EtOAc, 10% Pd/C, 200 psi
H2, rt, 12 h; 77% yield.
a
Reagents and conditions: (a) 2,6-di-tert-butyl-4-methylpyridine, BCl3,
CH2Cl2, −78 °C, 1 h; 80% combined yield (2.5:1.0:0.3 mixture of
15:14:16); (b) NaIO4/SiO2, CH2Cl2, rt, 30 min; 84% yield; (c) Pd/C,
H2, CH2Cl2, rt, 45 min; 76% yield from 11; (d) Et3N, SOCl2, CH2Cl2,
−78 °C, 1 h; 71% combined yield (9:1 mixture of 17:18) from 11.
To further establish the utility of borono-sclareolide (10) as a
versatile terpene donor, it was exposed to a variety of aryl
bromides (23−26) under Suzuki conditions developed by
Buchwald,31 resulting in excellent yields of the coupled product
(Scheme 4). The formal synthesis of the potent SHIP2
inhibitor (−)-pelorol (30) was accomplished by intercepting
Andersen’s intermediate 29 in 87% yield.32 Coupling between
10 and benzyl ester 25 followed by hydrogenation with 10%
Pd/C under 200 psi H2 yielded the previously unprepared
meroterpenoid (+)-dictyvaric acid (31) in 55% yield from 10.33
In summary, the power of borono-sclareolide (10) to
divergently and scalably access meroterpenoid natural products
has been demonstrated with the synthesis of 10 different
meroterpenoids: (+)-chromazonarol (11, 6 steps, 34% overall
yield), (−)-isozonarol (15) and (−)-zonarol (14, 7 steps, 25%
overall yield), (−)-yahazunone (8, 7 steps, 29% overall yield),
(+)-yahazunol (1, 8 steps, 26% overall yield), (−)-zonarone
(17) and (−)-isozonarone (18, 8 steps, 24% overall yield),
(+)-8-epi-puupehedione (19, 9 steps, 8% overall yield), the
formal synthesis of (−)-pelorol (30, 11 steps, 8.5% overall),
and synthesis of (+)-dictyvaric acid (31, 7 steps, 33% overall
yield). Notable elements of the syntheses include the following:
(1) expedient, scalable, four-step synthesis of (+)-drim-9(11)-
en-8α-ol (9); (2) invention of borono-sclareolide (10), a
privileged terpenoid donor fragment; (3) unprecedented
reactivity of 10 with 1,4-benzoquinone resulting in a redox-
neutral convergent union and annulation process; and (4) the
use of (+)-chromazonarol (11) as a divergent intermediate to
rapidly access meroterpenoid natural products.
a
Scheme 3. 8-epi-Puupehedione (19) from 11
a
Reagents and conditions: (a) DMF, IBX, rt, 30 min (1:1 mixture of
20:21); (b) 20, EtOH, NaBH4, rt, 15 min; (c) 22, chloranil, t-BuOH,
100 °C, 16 h; 24% from 11.
ratio of o-quinone products 20 and 21 was observed, slightly
favoring 20 along with unreacted 11. Even with a large excess of
Fremy’s salt, the oxidation did not go to completion and always
resulted in a mixture of o-quinone products. After screening
various oxidants, it was found that the conditions reported by
Pettus29 (IBX in DMF) resulted in a very rapid and
reproducible reaction giving a ∼1:1 mixture of 20 and 21
that was readily separable by column chromatography.
Reduction of 21 with NaBH4 and subsequent oxidation of
crude puupehenol15b (22) with chloranil in refluxing tert-
butanol afforded 19 in 24% from 11.30 The direct oxidation of
20 under various conditions failed to produce 19 in appreciable
amounts.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and analytical data (1H and 13C
NMR, CIF) for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
C
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Journal of the American Chemical Society
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(11) (a) Fujiwara, Y.; Domingo, V.; Seiple, I. B.; Gianatassio, R.; Del
Bel, M.; Baran, P. S. J. Am. Chem. Soc. 2011, 133, 3292. (b) Lockner, J.
W.; Dixon, D. D.; Risgaard, R.; Baran, P. S. Org. Lett. 2011, 13, 5628.
(12) (a) Ling, T.; Xiang, A. X.; Theodorakis, E. A. Angew. Chem., Int.
Ed. 1999, 38, 3089. (b) Ling, T.; Poupon, E.; Rueden, E. J.; Kim, S. H.;
Theodorakis, E. A. J. Am. Chem. Soc. 2002, 124, 12261.
(13) Corey, E. J.; Sauers, R. R. J. Am. Chem. Soc. 1959, 81, 1739.
(14) (a) Boehm, P.; Cooper, K.; Hudson, A. T.; Elphick, J. P.;
McHardy, N. J. Med. Chem. 1981, 24, 295. (b) Hudson, A. T.; Pether,
M. J.; Randall, A. W.; Fry, M.; Latter, V. S.; McHardy, N. Eur. J. Med.
Chem. 1986, 21, 271.
(15) (a) Villamizar, J.; Plata, F.; Canudas, N.; Tropper, E.; Fuentes,
J.; Orcajo, A. Synth. Commun. 2006, 36, 311. (b) Alvarez-Manzaneda,
E. J.; Chahboun, R.; Cabrera, E.; Alvarez, E.; Haidour, A.; Ramos, J.
M.; Alvarez-Manzaneda, R.; Hmamouchi, M.; Bouanou, H. J. Org.
Chem. 2007, 72, 3332. (c) Nakamura, S.; Ishihara, K.; Yamamoto, H. J.
Am. Chem. Soc. 2000, 122, 8131. (d) Cimino, G.; De Stefano, S.;
Minale, L. Experientia 1975, 31, 1117. (e) Dave, M.-N.; Kusumi, T.;
Ishitsuka, M.; Iwashita, T.; Kakisawa, H. Heterocycles 1984, 22, 2301.
(f) Barrero, A. F.; Alvarez-Manzaneda, E. J.; Herrador, M. M.;
Chahboun, R.; Galera, P. Bioorg. Med. Chem. Lett. 1999, 9, 2325.
(16) Margaros, I.; Montagnon, T.; Vassilikogiannakis, G. Org. Lett.
2007, 9, 5585.
AUTHOR INFORMATION
■
Corresponding Author
pbaran@scripps.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this work was provided by LEO Pharma.
Bristol-Myers Squibb and Amgen supported graduate fellow-
ships to J.W.L., and the Shanghai Institute of Organic
Chemistry supported a postdoctoral fellowship for Q.Z. We
are grateful to Prof. Arnold Rheingold and Dr. Curtis E. Moore
(UCSD) for X-ray crystallographic analysis and Dr. G. Siuzdak
(TSRI) for mass spectrometry assistance.
REFERENCES
■
(1) (a) Cornforth, J. W. Chem. Ber. 1968, 4, 102. (b) Geris, R.;
Simpson, T. J. Nat. Prod. Rep. 2009, 26, 1063.
(2) Marcos, I. S.; Conde, A.; Moro, R. F.; Basabe, P.; Diez, D.;
Urones, J. G. Mini-Rev. Org. Chem. 2010, 7, 230.
(3) Yong, K. W. L.; Jankam, A.; Hooper, J. N. A.; Suksamrarn, A.;
Garson, M. J. Tetrahedron 2008, 64, 6341.
(4) (a) Kohmoto, S.; McConnell, O. J.; Wright, A.; Koehn, F.;
Thompson, W.; Lui, M.; Snader, K. M. J. Nat. Prod. 1987, 50, 336.
(b) Sova, V. V.; Fedoreev, S. A. Khim. Prirod. Soedin. 1990, 497.
(c) Longley, R. E.; McConnell, O. J.; Essich, E.; Harmody, D. J. Nat.
Prod. 1993, 56, 915. (d) Nasu, S. S.; Yeung, B. K. S.; Hamann, M. T.;
Scheuer, P. J.; Kelly-Borges, M.; Goins, K. J. Org. Chem. 1995, 60,
7290. (e) El Sayed, K. A.; Dunbar, D. C.; Perry, T. L.; Wilkins, S. P.;
Hamann, M. T.; Greenplate, J. T.; Wideman, M. A. J. Agric. Food
Chem. 1997, 45, 2735. (f) Faulkner, D. J. Nat. Prod. Rep. 1998, 15, 113.
(g) Bourguet-Kondracki, M.-L.; Lacombe, F.; Guyot, M. J. Nat. Prod.
1999, 62, 1304. (h) El Sayed, K. A.; Bartyzel, P.; Shen, X.; Perry, T. L.;
Zjawiony, J. K.; Hamann, M. T. Tetrahedron 2000, 56, 949.
(17) (a) Wada, K.; Tanaka, S.; Marumo, S. Agric. Biol. Chem. 1983,
47, 1075. (b) Vlad, P. F.; Aryku, A. N.; Chokyrian, A. G. Russ. Chem.
Bull. 2004, 53, 443. (c) Vlad, P. F.; Kuchkova, K. I.; Aryku, A. N.;
Deleanu, K. Russ. Chem. Bull. 2005, 54, 2656.
(18) (a) Snyder, H. R.; Kuck, J. A.; Johnson, J. R. J. Am. Chem. Soc.
1938, 60, 105. (b) Davies, A. G. J. Chem. Res. 2008, 361.
(19) Villamizar, J.; Orcajo, A. L.; Fuentes, J.; Tropper, E.; Alonso, R.
J. Chem. Res., Synop. 2002, 395.
(20) (a) Welch, S. C.; Rao, A. S. C. P. Tetrahedron Lett. 1977, 505.
(b) Welch, S. C.; Rao, A. S. C. P. J. Org. Chem. 1978, 43, 1957.
(21) Schroder, J.; Magg, C.; Seifert, K. Tetrahedron Lett. 2000, 41,
̈
5469.
(22) Fenical, W.; Sims, J. J.; Squatrito, D.; Wing, R. M.; Radlick, P. J.
Org. Chem. 1973, 38, 2383.
(23) Snyder, S. A.; Treitler, D. S.; Brucks, A. P. J. Am. Chem. Soc.
2010, 132, 14303.
(24) (a) Djura, P.; Stierle, D. B.; Sullivan, B.; Faulkner, D. J.; Arnold,
E.; Clardy, J. J. Org. Chem. 1980, 45, 1435. (b) Villamizar, J.; Fuentes,
J.; Tropper, E.; Orcajo, A. L.; Alonso, R. Synth. Commun. 2003, 33,
1121.
(25) Since the majority of hydroquinone natural products are isolated
along with their quinone counterparts, 8 is assumed to be an as-yet
unisolated natural product.
(i) Hamann, M. T. Curr. Pharm. Des. 2003, 9, 879. (j) Pina, I. C.;
̃
Sanders, M. L.; Crews, P. J. Nat. Prod. 2003, 66, 2. (k) Takamatsu, S.;
Hodges, T. W.; Rajbhandari, I.; Gerwick, W. H.; Hamann, M. T.;
Nagle, D. G. J. Nat. Prod. 2003, 66, 605. (l) Kraus, G. A.; Nguyen, T.;
Bae, J.; Hostetter, J.; Steadham, E. Tetrahedron 2004, 60, 4223.
(5) (a) Perez-García, E.; Zubía, E.; Ortega, M. J.; Carballo, J. L. J. Nat.
́
Prod. 2005, 68, 653. (b) Ochi, M.; Kotsuki, H.; Muraoka, K.;
Tokoroyama, T. Bull. Chem. Soc. Jpn. 1979, 52, 629.
(6) (a) Akita, H.; Nozawa, M.; Shimizu, H. Tetrahedron: Asymmetry
́
1998, 9, 1789. (b) Alvarez-Manzaneda, E. J.; Chahboun, R.; Perez, I.
B.; Cabrera, E.; Alvarez, E.; Alvarez-Manzaneda, R. Org. Lett. 2005, 7,
1477. (c) Alvarez-Manzaneda has reported the hydroboration of 8 to
yield the diol as a single diastereomer after oxidative workup, but we
were unable to reproduce this result. See ref 6b.
(7) (a) Trammell, G. L. Tetrahedron Lett. 1978, 1525. (b) Ishibashi,
H.; Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 11122.
(c) Although our synthesis is longer than Yamamoto’s (6 steps vs 3
steps), our overall yield is higher (34% vs 10%) and does not require
synthesis of a chiral ligand.
(8) Boger, D. L.; Brotherton, C. E. J. Org. Chem. 1984, 49, 4050. For
some recent examples of divergent synthesis, see: (a) Richter, J. M.;
Ishihara, Y.; Masuda, T.; Whitefield, B. W.; Llamas, T.; Pohjakallio, A.;
Baran, P. S. J. Am. Chem. Soc. 2008, 130, 17938. (b) Seiple, I. B.; Su, S.;
Young, I. S.; Nakamura, A.; Yamaguchi, J.; Jørgensen, L.; Rodriguez, R.
(26) Using other solvents (EtOAc or THF) or solid support
(Florisil) for the oxidation greatly decreased the rate of reaction (days
vs 30 min).
(27) Laube, T.; Schroder, J.; Stehle, R.; Seifert, K. Tetrahedron 2002,
̈
58, 4299.
(28) (a) Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.;
́
Cortes, M.; Armstrong, V. Tetrahedron 1999, 55, 15181. (b) Maiti, S.;
Sengupta, S.; Giri, C.; Achari, B.; Banerjee, A. K. Tetrahedron Lett.
2001, 42, 2389. (c) Armstrong, V.; Barrero, A. F.; Alvarez-Manzaneda,
́
́
E. J.; Cortes, M.; Sepulveda, B. J. Nat. Prod. 2003, 66, 1382.
(29) Magdziak, D.; Rodriguez, A. A.; Van De Water, R. W.; Pettus, T.
R. R. Org. Lett. 2002, 4, 285.
(30) Oxidation conditions by Alvarez-Manzaneda15b produced 19 in
25% yield compared to the reported yield of 81%.
(31) Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2004, 43, 1871.
A.; O’Malley, D. P.; Gaich, T.; Kock, M.; Baran, P. S. J. Am. Chem. Soc.
̈
(32) Yang, L.; Williams, D. E.; Mui, A.; Ong, C.; Krystal, G.; van
Soest, R.; Andersen, R. J. Org. Lett. 2005, 7, 1073.
(33) Song, F. H.; Fan, X.; Xu, X. L.; Zhao, J. L.; Han, L. J.; Shi, J. G.
Chin. Chem. Lett. 2004, 15, 316.
2011, 133, 14710. (c) Snyder, S. A.; Gollner, A.; Chiriac, M. I. Nature
2011, 474, 461.
(9) Gaich, T.; Baran, P. S. J. Org. Chem. 2010, 75, 4657.
(10) (a) Seiple, I. B.; Su, S.; Rodriguez, R. A.; Gianatassio, R.;
Fujiwara, Y.; Sobel, A. L.; Baran, P. S. J. Am. Chem. Soc. 2010, 132,
13194. (b) Molander, G. A.; Colombel, V.; Braz, V. A. Org. Lett. 2011,
13, 1852.
D
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