Scalable asymmetric total syntheses of (+)-psoracorylifol B and (+)-ent-psoracorylifol C

Article abstract of DOI:10.1021/ol501120m

The first, asymmetric total syntheses of potent antimicrobial Psoracorylifol B (>1.3 g obtained, dr 10.5:1) with a 9.4% overall yield on a gram scale in 14 steps and ent-Psoracorylifol C with a 4.3% yield in 16 steps were achieved. The key features of our synthesis include (i) sequential, rarely explored Achmatowicz rearrangement/bicycloketalization to construct the 6,8-dioxabicyclo[3.2.1]octane core, and (ii) Cu-mediated S_N2′ methylation or Johnson-Claisen rearrangement to stereoselectively install the all-carbon quaternary stereocenter. This concise, highly efficient, and scalable synthetic route may provide expedited and practical access to psoracorylifols and their analogues for further biological activity evaluation.

Full text of DOI:10.1021/ol501120m

Letter
pubs.acs.org/OrgLett
Scalable Asymmetric Total Syntheses of (+)-Psoracorylifol B and
(+)-ent-Psoracorylifol C
Jingyun Ren,‡ Yuan Liu,‡ Liyan Song, and Rongbiao Tong*
Department of Chemistry, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China
S
* Supporting Information
ABSTRACT: The first, asymmetric total syntheses of potent antimicrobial Psoracorylifol B (>1.3 g obtained, dr 10.5:1) with a
9.4% overall yield on a gram scale in 14 steps and ent-Psoracorylifol C with a 4.3% yield in 16 steps were achieved. The key
features of our synthesis include (i) sequential, rarely explored Achmatowicz rearrangement/bicycloketalization to construct the
6,8-dioxabicyclo[3.2.1]octane core, and (ii) Cu-mediated SN2′ methylation or Johnson−Claisen rearrangement to
stereoselectively install the all-carbon quaternary stereocenter. This concise, highly efficient, and scalable synthetic route may
provide expedited and practical access to psoracorylifols and their analogues for further biological activity evaluation.
soracorylifols A−C (Figure 1) were isolated from the seeds
of Psoralea corylifolia L. (Buguchi, a well-known traditional
Structurally, these psoracorylifols shared a common all-carbon
quaternary stereocenter on the tetrahydropyran and a peripheral
phenol substituent. Psoracorylifol A (PsA, 1) was characterized
by the presence of a 2,6-trans-substituted tetrahydropyran, while
psoracorylifol B (PsB, 2) and psoracorylifol C (PsC, 3) feature a
unique 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO) frame-
work. These structural differences might account for the greater
antimicrobial potency of PsB and PsC when compared with that
of PsA. In fact, simple alkylated 6,8-DOBCOs such as
brevicomin, frontalin, and multistriatin are insect pheromones,5
while more complicated substitution of 6,8-DOBCO exists in
many biologically active and/or structurally diverse natural
products (cf. didemniserinolipid B6 and attenol B,7 Figure 1).
This privileged bicyclic acetal scaffold has been targeted as a
platform for the development of new synthetic methods/
strategies8 and recently investigated by Ley et al. to expand the
molecular diversity for drug-discovery programs.9 The combi-
nation of potent antimicrobial activity and unique and interesting
structures of PsB and PsC prompted us to undertake their total
syntheses. Herein, we reported the first, asymmetric total
syntheses of psoracorylifol B (2) and ent-psoracorylifol C (ent-
3) by exploitation of the Achmatowicz rearrangement/
bicycloketalization for the construction of the 6,8-DOBCO
framework.
P
Figure 1. Psoracorylifols A, B, and C and structurally related
didemniserinolipid B and attenol B.
Chinese medicine for treatment and cure of gynecological
bleeding, vitiligo, psoriasis, and bone fractures)1 by Yue et al. in
2006.2 These compounds have shown significant antimicrobial
activity in vitro as potent inhibitors against two strains of
Helicobacter pylori (ATCC 43504 and SS1) with MICs of 12.5−
25 μg/mL. The remarkable inhibition of H. pylori-ATCC 43504
holds great potential for clinical use because H. pylori infections
causing diseases such as gastritis, peptic ulcer, and gastric cancer
are often resistant to metronidazole (MIC = 128 μg/mL against
H. pylori-ATCC43504), which is a main ingredient for
combination therapies of various H. pylori infections.3 In 2007,
Yoshikawa et al. independently isolated psoracorylifols B and C
again from the same seeds of Psoralea corylifolia, although both
compounds did not show the expected inhibitory effects on the
release of β-hexosaminidase from RBL-2H3 cells.4
At the outset of our studies, we recognized that PsB was
reported as a diastereomer of the enantiomer of PsC (ent-3)
(except for the opposite all-carbon chiral center, Scheme 1).2,4
To fully exploit this structural relationship and ease the synthetic
work, we proposed to synthesize the enantiomer of PsC from a
common intermediate (e.g., 4, Scheme 1) used for the synthesis
Received: April 18, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol501120m | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Synthetic Plan for Psoracorylifol B (2) and ent-
Psoracorylifol C (ent-3)
Scheme 2. Synthesis of the Key 6,8-DOBCO (6) on
Multigram Scale
and 5-bromo-2-furaldehyde 12 was effectively promoted by
KHMDS at −78 °C to give the alkene 13 in 88% yield with
excellent E/Z selectivity (E/Z > 20/1). In the course of
reproducing this olefination, the E/Z selectivity was found to be
dependent on the reaction temperature as well as the counterion
of the base, since NaHMDS and LiHMDS under various
conditions gave lower E/Z selectivity.20 Next, iron-catalyzed
Kochi cross-coupling21 of 13 with i-PrMgBr yielded the 2,5-
disubstituted furan 14, which underwent Sharpless asymmetric
dihydroxylation with AD mix-β using t-BuOH/H2O (1:1) as the
mixed solvents at 0 °C for 4 days to provide the desired furyl diol
8 in 84% yield as the single diastereomer (98% ee by HPLC).
Treatment of the furyl diol 8 with m-CPBA initiated the oxidative
ring expansion (Achmatowicz rearrangement) and provided
pyranone acetal 7, which upon treatment of 10-camphorsulfonic
acid (CSA) in the same reaction vessel underwent dehydrative
bicycloketalization to give the key 6,8-DOBCO (6) in 72% yield,
corresponding to the core bicyclic skeleton of PsB and ent-PsC.
In particular, the efficiency and robustness of the synthetic route
to the 6,8-DOBCO (6.7 g obtained) were demonstrated by
performing these reactions on a multigram scale without a
significant drop in yields as compared to the corresponding
milligram-scale reactions.
of PsB via divergent transformations. Structural analysis of PsB
and ent-PsC clearly revealed that the primary synthetic challenges
included (i) stereoselective construction of the all-carbon
quaternary stereocenter10 and (ii) efficient preparation of the
unique 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO) frame-
work. For the first synthetic challenge, we envisioned that on
the basis of elegant work by Kobayashi11 the all-carbon
quaternary stereocenter could be constructed by Cu-mediated
SN2′ methylation of allyl picolinate 4 (Scheme 1), although the
stereoselectivity and stereochemical outcome could not be
predicted and controlled at this stage. However, it might be
advantageous to access both PsB and ent-PsC from a nonselective
reaction mixture if their separation by column chromatography
was not difficult. For the 6,8-DOBCO framework of PsB and ent-
PsC, it was noted that in 2010 Hashimoto12 et al. reported an
efficient Rh-catalyzed 1,3-dipolar cycloaddition13 of α-diazo-
carbonyl compounds with aldehydes to construct the fully
substituted 6,8-DOBCO framework of PsB and PsC. Unfortu-
nately, this elegant strategy has not yet led to the total synthesis
of PsB or PsC. Nonetheless, in continuation of our interest in the
synthetic utilities of Achmatowicz rearrangement,14 we envi-
sioned that the 6,8-DOBCO core structure (6) could be
constructed by sequential Achmatowicz rearrangement/bicyclo-
ketalization (AR/BCK, 8 → 6), a protocol originally developed
by Ogasawara15 for the enantio- and diastereoselective synthesis
of hexoses from furfural. To our surprise, this AR/BCK strategy
has been rarely exploited in the synthesis of 6,8-DOBCO, which
instead was prepared conventionally by dehydrative ketalization
of the corresponding dihydroxyl ketone.16 Given that the
structure of type 8 could be synthesized straightforwardly
through Julia−Kocienski olefination17 and Sharpless asymmetric
dihydroxylation,18 we first explored this strategy for the synthesis
of the 6,8-DOBCO framework of PsB and ent-PsC. If
implementation of these two key tactics (SN2′ methylation and
AR/BCK) were successful, we expected that the total syntheses
of PsB and ent-PsC could be achieved in a concise, highly
enantioselective fashion.
To construct the all-carbon quaternary stereocenter via
Kobayashi’s SN2′ methylation, the 6,8-DOBCO (6) needed to
be properly functionalized with the introduction of two carbons
(Scheme 3). Specifically, Pd/C-mediated hydrogenation of 6
followed by Horner−Wadsworth−Emmons (HWE)22 olefina-
Scheme 3. Completion of Total Syntheses of Psoracorylifol B
and ent-Psoracorylifol C
Our synthesis (Scheme 2) began with the preparation of
sulfone 11 for Julia−Kocienski olefination. Specifically, 4-
hydroxylbenzaldehyde (9) was converted to 11 in 4 steps
through silylation with triisopropylsilyl chloride (TIPSCl),
NaBH4 reduction, Mitsunobu reaction19 with 1-phenyl-1H-
tetrazol-5-yl thiol (PTSH) in the presence of PPh3/DIAD
(diisopropyl azodicarboxylate), and oxidation with m-CPBA (3-
chloroperbenzoic acid). The Julia−Kocienski olefination of 11
B
dx.doi.org/10.1021/ol501120m | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
tion to provide the conjugated ester 15 in 66% combined yield
over two steps as an E/Z mixture (3/1). Although separation of
these two E/Z stereoisomers by flash column chromatography
was difficult, the resulting allylic alcohols 16 (16a and 16b) from
reduction with diisobutylaluminum hydride (DIBAL-H) in-
dicated noticeably different Rf values based on TLC and could be
separated by careful flash column chromatography. However, the
E/Z mixture 16 was used for subsequent transformations
because Kobayashi et al. found that stereoselectivity in the
course of SN2′ substitution was independent of the E/Z
stereochemistry of the allyl picolinate.11 DCC-mediated
esterification of allylic alcohol 16 with picolinic acid provided
quantitatively the desired picolinate 17 as the key substrate for
the SN2′ methylation. To our delight, picolinate 17 underwent
regio- and stereoselective SN2′ substitution with MeMgBr in the
presence of CuBr-Me2S/ZnCl2 to furnish psoracorylifol B as a
10.5:1 diastereomeric mixture (2/ent-3 = 10.5:1) after
desilylation with TBAF. It was noteworthy that the SN2′
methylation on a gram-scale proceeded smoothly with similar
efficiency and stereoselectivity to deliver 1.34 g of PsB (dr
10.5:1). The formation of PsB as the major product in the course
of SN2′ methylation was unexpected and could not be fully
rationalized because the methyl addition from the bottom face
(concave, path b) of the bicyclic acetal 17 was seemingly
disfavored. Suspicion of misassignment of PsC as PsB was
eliminated by single crystal X-ray diffraction analysis of the 4-
nitrobenzoate derivative of PsB (Figure 2.). The high
Scheme 4. Total Syntheses of ent-PsC (ent-3) via Johnson−
Claisen Rearrangement/Reductive Decarboxylation
of 18a and 18b in 68% combined yield, which could be separated
by flash column chromatography (Scheme 4). Interestingly,
Johnson−Claisen rearrangement of the single E-isomer 16a was
found to give surprisingly a 3.3:1 diastereomeric mixture of 20a
and 20b favoring 20a, while under the same conditions Z-isomer
16b resulted in only a 1.5:1 mixture favoring 20a. Oxidation of
18a with oxone in DMF25 gave an excellent yield of the desired
carboxylic acid 19a, which was subjected to the modified Barton’s
reductive decarboxylation26 to furnish (+)-ent-PsC in 64% yield
as the single diastereomer after desilylation.20 In contrast to the
SN2′ methylation method in Scheme 3, this route delivered ent-
PsC as the major product in 5 steps from the common
intermediate 16 with 27.6% overall yield. It was noteworthy that
Kobayashi11d reported a conceptionally similar strategy to
diastereoselectively install the opposite stereochemistry of the
quaternary carbon via ester methylation and picolinate allylic
SN2′ substitution.
Figure 2. ORTEP diagram of 4-nitrobenzoate derivative of psoracor-
ylifol B (2).
diastereoselectivity of SN2′ methylation for 17 (path b) might
arise from blocking the top-face attack (path a) by coordination
of Zn2+ with tetrahydropyran oxygen and picolinate. However,
the dependence of diastereoselectivity on the alkene geometry
(e.g., 16a → PsB only, 16b → PsB + ent-PsC, Scheme 3) was very
surprising to us and in sharp contrast to Kobayashi’s findings.11
More studies are needed to address the stereoselectivity issues in
the course of this SN2′ substitution. All spectroscopic data of
synthetic PsB and ent-PsC were in good agreement with those
reported for natural PsB and PsC,20 except for the optical
rotation. The opposite sign of optical rotation of ent-PsC
supported the absolute configuration proposed for the natural
PsC.
We recognized that ent-PsC (ent-3) was synthesized as a minor
product from both 16b and a 3:1 mixture of 16a/16b in the final
SN2′ substitution (Scheme 3). To achieve a more efficient
synthesis of ent-PsC, we designed a new synthetic route that
exploited the Johnson−Claisen23 rearrangement of the allylic
alcohol 16 and reductive decarboxylation24 to construct the all-
carbon quaternary stereocenter (Scheme 4).
In summary, we have achieved the first, asymmetric total
syntheses of potent antimicrobial Psoracorylifol B with a 9.4%
overall yield on a gram-scale in 14 steps and ent-Psoracorylifol C
with a 4.3% yield in 16 steps. The conciseness and efficiency were
enabled by exploitation of two key reactions to solve two major
synthetic challenges: (i) the novel Achmatowicz rearrangement/
bicycloketalization sequence to construct the core 6,8-dioxa-
bicyclo[3.2.1]octane substructure and (ii) SN2′ methylation of
allylic picolinate or Johnson−Claisen rearrangement of the allylic
alcohol to stereoselectively install the all-carbon quaternary
stereocenter. Our synthetic studies confirmed the relative and
absolute configurations of PsB and PsC and provided expedited
and practical chemical access to these structurally novel
antimicrobial agents PsB and ent-PsC and their analogues for
further biological activity evaluation.
ASSOCIATED CONTENT
* Supporting Information
■
S
Treatment of allylic alcohol 16 (E/Z = 3/1) with a catalytic
amount of propionic acid in MeC(OEt)3 under reflux and
subsequent DIBAL-H reduction of the Johnson−Claisen
rearrangement adducts produced a 3.5:1 diastereomeric mixture
Detailed experimental procedures, characterizations and copies
1
of H and 13C NMR spectra of new compounds, and X-ray
crystallographic data. This material is available free of charge via
the Internet at http://pubs.acs.org.
C
dx.doi.org/10.1021/ol501120m | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Y.; Hyodo, T.; Kobayashi, Y. Org. Lett. 2008, 10, 1719. (c) Kobayashi, Y.;
Feng, C.; Ikoma, A.; Ogawa, N.; Hirotsu, T. Org. Lett. 2014, 16, 760.
(d) Kawashima, H.; Kaneko, Y.; Sakai, M.; Kobayashi, Y. Chem.Eur. J.
2014, 20, 272.
(12) Kurosaki, Y.; Shimada, N.; Anada, M.; Nambu, H.; Hashimoto, S.
Bull. Korean Chem. Soc. 2010, 31, 694.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: rtong@ust.hk.
Author Contributions
‡These authors contributed equally.
(13) For leading references, see: (a) Padwa, A.; Fryxell, G. E.; Zhi, L. J.
Am. Chem. Soc. 1990, 112, 3100. (b) Doyle, M. P.; Forbes, D. C.;
Protopopova, M. N.; Stanley, S. A.; Vasbinder, M. M.; Xavier, K. R. J.
Org. Chem. 1997, 62, 7210. (c) Jiang, B.; Zhang, X.; Luo, Z. Org. Lett.
2002, 4, 2453. (d) Lu, C.-D.; Chen, Z.-Y.; Liu, H.; Hu, W.-H.; Mi, A.-Q.
Org. Lett. 2004, 6, 3071. (e) Russell, A. E.; Brekan, J.; Gronenberg, L.;
Doyle, M. P. J. Org. Chem. 2004, 69, 5269. (f) DeAngelis, A.; Panne, P.;
Yap, G. P. A.; Fox, J. M. J. Org. Chem. 2008, 73, 1435.
(14) (a) Achmatowicz, O., Jr.; Bukowski, P.; Szechner, B.;
Zwierzchowska, Z.; Zamojski, A. Tetrahedron 1971, 27, 1973.
(b) Zhu, L.; Song, L.; Tong, R. Org. Lett. 2012, 14, 5892. For leading
reviews on Achmatowicz rearrangement, see: (c) Lipshutz, B. H. Chem.
Rev. 1986, 86, 795. (d) Harris, J. M.; Li, M.; Scott, J. G.; O’Doherty, G. A.
Achmatowicz Approach to 5,6-Dihydro-2H-pyran-2-one Containing
Natural Products. In Strategy and Tactics in Organic Synthesis; Harmata,
M., Ed.; Elsevier: London, 2004; Vol. 5, pp 221−253.
(15) (a) Taniguchi, T.; Ohnishi, H.; Ogasawara, H. Chem. Commun.
1996, 1477. (b) Takeuchi, M.; Taniguchi, T.; Ogasawara, K. Synthesis
1999, 2, 341. (c) Burke, M. D.; Berger, E. M.; Schreiber, S. L. J. Am.
Chem. Soc. 2004, 126, 14095. For other representative examples using
the dihydroxylation/Achmatowicz rearrangement approach to natural
product synthesis, see: (d) Balachari, D.; O’Doherty, G. A. Org. Lett.
2000, 2, 863. (e) Balachari, D.; O’Doherty, G. A. Org. Lett. 2000, 2, 4033.
(f) Ahmed, Md. M.; O’ Doherty, G. A. Tetrahedron Lett. 2005, 46, 4151.
(16) (a) Mundy, B. P.; Lipkowitz, K. B.; Dirks, G. W. Heterocycles 1977,
6, 51. (b) Mori, K. Tetrahedron 1989, 45, 3233. (c) Kotsuki, H. Synlett
1992, 97. (d) Jun, J.-G. Synlett 2003, 1759. Also see refs 6−9.
(17) (a) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A.
Synlett 1998, 26. For a recent review, see: (b) Chatterjee, B.; Bera, S.;
Mondal, D. Tetrahedron: Asymmetry 2014, 25, 1.
(18) (a) Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.;
Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968. (b) Kolb, H. C.;
VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483.
(19) For reviews: (a) Swamy, K. C. K.; Kumar, N. N. B.; Balaraman, E.;
Kumar, K. V. P. Chem. Rev. 2009, 109, 2551. (b) Mitsunobu, O. Synthesis
1981, 1. (c) Ahn, C.; Correia, R.; DeShong, P. J. Org. Chem. 2002, 67,
1751.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was financially supported by HKUST and Research
Grant Council of Hong Kong (ECS 605912 and GRF 605113).
The authors thank Prof. Dr. Ian Williams and Dr. Herman Sung
(HKUST) for the single crystal X-ray diffraction analysis and
Prof. Jian-Min Yue (Shanghai Institute of Materia Medica,
Chinese Academy of Sciences, China) for the authentic NMR
spectra for Psoracorylifols B and C.
REFERENCES
■
(1) (a) Chopra, B.; Dhingra, A. K.; Dhar, K. L. Fitoterapia 2013, 90, 44.
(b) Wei, S.-M.; Yan, Z.-Z.; Zhou, J. J. Ethnopharmacol. 2011, 137, 568.
(2) Yin, S.; Fan, C.-Q.; Dong, L.; Yue, J.-M. Tetrahedron 2006, 62,
2569.
(3) Kwon, D. H.; Kato, M.; El-Zaatari, F.; Osato, M. S.; Graham, D. Y.
FEMS Microbiol. Lett. 2000, 188, 197.
(4) Matsuda, H.; Sugimoto, S.; Morikawa, T.; Matsuhira, K.;
Mizugachi, E.; Nakamura, S.; Yoshikawa, M. Chem. Pharm. Bull. 2007,
55, 106.
(5) (a) Silverstein, R. M.; Brownlee, R. G.; Bellas, T. E.; Wood, D. L.;
Browne, L. E. Science 1968, 159, 889. (b) Kinzer, G. W.; Fentiman, A. F.,
Jr.; Page, T. F., Jr.; Foltz, R. L.; Vite, J. P.; Pitman, G. B. Nature 1969, 221,
447. (c) Pearce, G. T.; Gore, W. E.; Silverstein, R. M. J. Org. Chem. 1976,
41, 2797.
́ ́
(6) (a) Gonzalez, N.; Rodríguez, J.; Jimenez, C. J. Org. Chem. 1999, 64,
5705. For selected total synthesis, see: (b) Kiyota, H.; Dixon, D. J.;
Luscombe, C. K.; Hettstedt, S.; Ley, S. V. Org. Lett. 2002, 4, 3223.
(c) Marvin, C. C.; Voight, E. A.; Burke, S. D. Org. Lett. 2007, 9, 5357.
(d) Marvin, C. C.; Voight, E. A.; Suh, J. M.; Paradise, C. L.; Burke, S. D. J.
Org. Chem. 2008, 73, 8452.
(7) (a) Takada, N.; Suenaga, K.; Yamada, K.; Zheng, S.-Z.; Chen, H.-S.;
Uemura, D. Chem. Lett. 1999, 1025. For selected total synthesis, see:
(b) Suenaga, K.; Araki, K.; Sengoku, T.; Uemura, D. Org. Lett. 2001, 3,
527. (c) Araki, K.; Suenaga, K.; Sengoku, T.; Uemura, D. Tetrahedron
2002, 58, 1983. (d) de Wedhe, P. V.; Aoun, D.; Boiteau, J.-G.; Eustache,
J. Org. Lett. 2002, 4, 4105. (e) Enders, D.; Lenzen, A. Synlett 2003, 2185.
(f) LaCruz, T. E.; Rychnovsky, S. D. J. Org. Chem. 2007, 72, 2602.
(g) Fuwa, H.; Sasakin, M. Org. Lett. 2008, 10, 2549.
(8) For some recent syntheses of brevicomin, see: (a) List, B.; Shabat,
D.; Barbas, C. F.; Lerner, R. A. Chem.Eur. J. 1998, 4, 881. (b) Burke, S.
D.; Muller, N.; Beaudry, C. M. Org. Lett. 1999, 1, 1827. (c) Hu, S.;
Jayaraman, S.; Oehlschlager, A. C. J. Org. Chem. 1999, 64, 2524.
(d) Raghavan, S.; Joseph, S. C. Tetrahedron Lett. 2003, 44, 8237. (e) Pal,
P.; Shaw, A. K. Tetrahedron 2011, 67, 4036. (f) Sabitha, G.; Reddy, A.
M.; Sankara Reddy, S. S.; Singh Yadav, J. Helv. Chem. Acta 2013, 96,
1610.
(9) (a) Milroy, L.-G.; Zinzalla, G.; Prencipe, G.; Michel, P.; Ley, S. V.;
Gunaratnam, M.; Beltran, M.; Neidle, S. Angew. Chem., Int. Ed. 2007, 46,
2493 and references cited therein. (b) Milroy, L.-G.; Zinzalla, G.;
Loiseau, F.; Qian, Z.; Prencipe, G.; Pepper, C.; Fegan, C.; Ley, S. V.
ChemMedChem 2008, 3, 1922.
(10) For leading references, see: (a) Trost, B. M.; Jiang, C. Synthesis
2006, 369. (b) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed.
1998, 37, 388. (c) Douglas, C. J.; Overman, L. E. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5363.
(20) See Supporting Information for more details.
(21) (a) Tamura, M.; Kochi, J. K. J. Am. Chem. Soc. 1971, 93, 1487.
(b) Haner, J.; Jack, K.; Nagireddy, J.; Raheem, M. A.; Durham, R.; Tam,
W. Synthesis 2011, 731. For leading reviews, see: (c) Sherry, B. D.;
Furstner, A. Acc. Chem. Res. 2008, 41, 1500. (d) Furstner, A.; Martin, R.
̈
̈
Chem. Lett. 2005, 34, 624. (e) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L.
Chem. Rev. 2004, 104, 6217.
(22) For a review, see: Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989,
89, 863.
(23) (a) Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom, T.
J.; Li, T.-T.; Faulkner, D. J.; Petersen, M. R. J. Am. Chem. Soc. 1970, 92,
741. For selected reviews, see: (b) Fernandes, R. A.; Chowdhury, A. K.;
Kattanguru, P. Eur. J. Org. Chem. 2014, 2833. (c) Castro, A. M. M. Chem.
Rev. 2004, 104, 2939.
(24) (a) Barton, D. H. R.; Crich, D.; Motherwell, W. B. J. Chem. Soc.,
Chem. Commun. 1983, 939. For a recent review, see: (b) Saraiva, M. F.;
Couri, M. R. C.; Le Hyaric, M.; de Almeida, M. V. Tetrahedron 2009, 65,
3563.
(25) Travis, B. R.; Sivakumar, M.; Hollist, G. O.; Borhan, B. Org. Lett.
2003, 5, 1031.
(26) (a) Ko, E. J.; Savage, G. P.; Williams, C. M.; Tsanaktsidis, J. Org.
Lett. 2011, 13, 1944. (b) Ho, J.; Zheng, J.; Meana-Paneda, R.; Truhlar, D.
̃
G.; Ko, E. J.; Savage, G. P.; Williams, C. M.; Coote, M. L.; Tsanaktsidis, J.
J. Org. Chem. 2013, 78, 6677.
(11) (a) Kaneko, Y.; Kiyotsuka, Y.; Acharya, H. P.; Kobayashi, Y. Chem.
Commun. 2010, 46, 5482. (b) Kiyotsuka, Y.; Acharya, H. P.; Katayama,
D
dx.doi.org/10.1021/ol501120m | Org. Lett. XXXX, XXX, XXX−XXX