Synthetic Study Aiming at the Tricyclic Core of 12- epi-JBIR-23/24

Article abstract of DOI:10.1021/acs.orglett.1c00853

The synthetic study toward highly enantio- and diastereoselective synthesis of the tricyclic framework of 12-epi-JBIR-23/24, a natural product analogue showing inhibitory activity against four malignant pleural mesothelioma cell lines, is presented herein

Full text of DOI:10.1021/acs.orglett.1c00853

pubs.acs.org/OrgLett
Letter
Synthetic Study Aiming at the Tricyclic Core of 12-epi-JBIR-23/24
Yi Man, Chengying Zhou, Shaomin Fu,* and Bo Liu*
Cite This: Org. Lett. 2021, 23, 3151−3156
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: The synthetic study toward highly enantio- and diastereoselective synthesis of the tricyclic framework of 12-epi-JBIR-
23/24, a natural product analogue showing inhibitory activity against four malignant pleural mesothelioma cell lines, is presented
herein. In this synthesis, a rhodium-catalyzed asymmetric three-component Michael/aldol reaction introduces three consecutive
tertiary carbon centers, while the unique epoxyquinol core motif is successfully forged via [3,3]-sigmatropic rearrangement of an
allylic xanthate, vinylogous Pummerer rearrangement, and a selective mesylation/epoxidation cascade of a triol.
Scheme 1. Retrosynthetic Analysis of JBIR-23/-24
BIR-23 and -24 were isolated from Streptomyces sp. AK-
1a
JAB27 by Shin-ya and co-workers in 2009.
Structurally,
they contain a novel dodecahydrodibenzo[b,d]furan skeleton
bearing six stereogenic centers, three of which are located on
the compactly and highly oxygenated cyclohexane platform,
and a trienyl acid side chain (Scheme 1). Notably, both of
them display inhibitory activity against four malignant pleural
mesothelioma (MPM) cell lines. JBIR-23 not only shows
stronger antitumoral efficacy (10−50 μM) than JBIR-24 but
also prevents tumor growth in tumor-bearing nude mice for in
vivo studies.1b In spite of their intriguing structural motifs and
promising pharmacological properties, no total synthesis or
synthetic study toward JBIR-23 and -24 has yet been reported.
Herein, we present our endeavors on the synthesis of the
tricyclic core structure of 12-epi-JBIR-23 and -24.
Construction of the epoxyquinol motif of JBIR-23 and -24 is
challenging2 because its aromatization is feasible under both
basic and acidic conditions. Accordingly, to minimize the side
reactions, we consider introducing the brittle epoxyquinol core
at the late stage of synthesis, by devising an A−AB−ABC
synthetic strategy. As depicted in Scheme 1, we envision that
JBIR-23 and -24 could be advanced from compound 3 through
sequential ozonolysis and Wittig olefination or Horner−
Wadsworth−Emmon reaction as in our previous synthesis of
cuevaene A.3 We conceived that compound 3 could be
produced from 4 via oxidative rearrangement of a tertiary
allylic alcohol and selective epoxidation. Furthermore, ring C
of compound 4 could be installed through an intramolecular
nucleophilic addition of vinyl to ketone in 5. We consider that
5 could arise from 6 via necessary functional group
Received: March 11, 2021
Published: April 7, 2021
https://doi.org/10.1021/acs.orglett.1c00853
Org. Lett. 2021, 23, 3151−3156
© 2021 American Chemical Society
3151

Organic Letters
pubs.acs.org/OrgLett
Letter
manipulations involving ketalization and Wittig reaction. A Rh-
catalyzed enantioselective Michael addition between cyclo-
hexanone 7 and alkenyl zirconium 8,4 followed by aldol
reaction with aldehyde 9 in one pot, might generate 6. Finally,
9 could be derived from commercially available D-ribose 10.
Our synthesis commenced with D-ribose 10, which was
transformed to aldehyde 9 through a three-step sequence
involving acetonide protection,5 selective oxidation of the
primary alcohol, and silyl protection of the secondary alcohol
(Scheme 2). Taking inspiration from asymmetric Michael
With 13 in hand, we embarked on the construction of ring B
of the tricyclic core. Accordingly, desilylation of 13 in the
presence of TBAF and HOAc afforded 6. Treatment of 6 with
TEMPO/PhI(OAc)2 at 50 °C resulted in selective oxidation of
the semiacetal and then ester migration, providing 14 in 83%
yield together with a five-membered lactone in 15% yield (see
the Supporting Information for details). After numerous trials,
we fortunately identified that treating 14 with CH3ONa,
followed by a CSA-mediated cyclization, could generate
compound 15 in 81% yield.6 Although 15 embraced a cis-
fused 6/5 bicyclic skeleton, not in accordance with that of
either JBIR-23 or JBIR-24, we envisioned the desired trans-
fused 6/5 bicycle could be achieved through equilibration at
the final stage of synthesis.
Scheme 2. Synthesis of 15
The stage was now set for establishment of ring C with the
epoxyquinol substructure. Initially, an alkene was devised to be
installed at C14 to facilitate RCM reaction, leading to ring C.
Thus, oxidation of 15 secured the corresponding ketone 16
(Scheme 3). However, the ketone at C14 was inert to various
olefination reagents involving Tebbe reagent, Peterson reagent,
and phosphorus ylide. Then we resorted to an oxidative
rearrangement of tertiary allylic alcohol to construct the enone
motif in ring C, instead of the RCM strategy. In practice, in the
presence of the ketone at C14, treating 16 with DIBAL-H
enabled chemoselective reduction of the ester into an aldehyde
to give 17. Such abnormal selectivity indicated steric hindrance
surrounding the ketone at C14, accounting for the inert
reactivity of its olefination. Compound 17 was further
advanced to the vinyl iodide 18 via Wittig reaction. Then,
we extensively screened classical NHK reaction conditions, but
no productive reactivity could be identified.7 Satisfactorily,
exposure of vinyl iodide 18 into nBuLi/LiCl at −78 °C induced
expedient lithium/halide exchange, and the resulting vinyl
lithium attacked the ketone (C14) to deliver 19 as a single
stereoisomer in 83% yield.8 The relative configuration of
tricyclic compound 19 was confirmed by NOE analysis. Next,
we started to investigate installation of the enone via 1,3-
oxidative rearrangement of allylic alcohol.9 Preliminary
experimentations under typical conditions, such as PCC,
PDC, and Dess−Martin periodinane, led to either decom-
position of 19 or a complex mixture, plausibly due to the
instability of 19 under acidic conditions. Thus, different bases
were tested to suppress acidity in the oxidative rearrangement
process, and the combination of PCC and Et3N generated
reaction,4 we initially treated the enone 7 with 8 in the
presence of [Rh(COD)Cl]2 (3.8 mol %) and (R)-BINAP (7.6
mol %) by following Oi’s methodology4a and generated a
Michael adduct with excellent 97% ee. We were then
encouraged to conduct a cascade Michael/aldol reaction, in
which the resulting alkenylzirconium 12 was treated with the
aldehyde 9. Pleasingly, compound 13 was achieved in 80%
overall yield with excellent diastereoselectivity (>20:1 dr).
Scheme 3. Synthesis of 21 and Attempt to Synthesize α,β-Unsaturated Ketone 22 through a Cleavage of Acetonide
3152
https://doi.org/10.1021/acs.orglett.1c00853
Org. Lett. 2021, 23, 3151−3156

Organic Letters
pubs.acs.org/OrgLett
Letter
Scheme 4. Synthesis of Compound 32
Scheme 5. Synthesis of the Tricycle 42
compounds 20 and 21 in 72% and 15% yield, respectively,
based on the recovery of starting material (see the Supporting
Information for details). Allylic oxidation with MnO2 could
transform 20 into 21, albeit in moderate yield. To our dismay,
although considerable protonic acids and Lewis acids were
investigated, we failed to remove the acetonide-protecting
groups in either 20 or 21 (see the Supporting Information for
details).
Learning from the above failure, we perceived that the cis-
fused 6/5 ring junction between ring C and the acetonide
moiety was stable to weak acidity, while the BC bicycle was
prone to aromatization under typical acidic conditions. To
comprise the stability of the BC bicycle and requirement of
deprotection of acetonide, we planned to achieve a compound
with trans-diol on ring C instead of compound 19 with a cis-
diol moiety.
Reduction of the ester 15 with DIBAL-H furnished 23 in
89% yield (Scheme 4). Exposure of 23 to Cs2CO3 in MTBE
triggered epimerization to a thermodynamically favorable
trans-fused acetonide, which was in situ advanced to the
vinyl iodide 24 after sequential Wittig reaction and oxidation
of the secondary alcohol. Subsequent treatment of 24 with
tBuLi provided 25 as a single diastereomer in 90% yield. The
stereochemistry of 25 was assigned by NOE analysis. Unlike its
epimer 19, compound 25 underwent various oxidative
rearrangement conditions without delivering the desired 26
or 27, disappointingly (see the Supporting Information for
details). Such a failure could be attributed to the twisty boat-
like conformation of ring C in 25, which prompted us to resort
to [3,3]-rearrangement. However, although an array of
attempts involving Eschenmoser−Claisen rearrangement,10
Johnson−Claisen rearrangement,11 Overman rearrangement,12
3153
https://doi.org/10.1021/acs.orglett.1c00853
Org. Lett. 2021, 23, 3151−3156

Organic Letters
pubs.acs.org/OrgLett
Letter
and aliphatic Claisen rearrangement13 were surveyed, either
recovery of 25 or the formation of undesired aromatized
compounds was discovered. Alternatively, we prepared the
xanthate 28 from 25, as a precursor of [3,3]-sigmatropic
rearrangement. Heating 28 in benzene at 90 °C afforded the
dithiolcarbonate 30 predominantly in 72% yield via TS-29
(path A),14 while the unexpected retro-Ene-type fragmentation
occurred simultaneously to produce 2-alkenyl methyl sulfide
32 in 24% yield via TS-31 (path B).15 Exposing 30 to
ethanolamine under air achieved the disulfide 33,16 which was
treated by P(NEt2)3 to smoothly furnish 32, with the
stereochemistry at C18 maintained.17 The relative config-
urations of 30, 32, and 33 were established by extensive
spectroscopic analysis including NOE analysis (see the
Supporting Information for details).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c00853.
■
sı
Experimental procedures, Tables 1−5, and nmr spectra
of new compounds (PDF)
Original HRMS spectra for compounds 9, 24, S2, 15−
18, 21, 23, 24, 25, 28, 30, 32, 34a, 34b, and 38 (PDF)
FAIR data, including the primary NMR FID files, for
compounds 6, 9, 12−21, 23−25, 28, 30, 32−34, 37−
39, and 42 (ZIP)
AUTHOR INFORMATION
Corresponding Authors
■
After considerable experiments, we discovered a strategy
involving vinylogous Pummerer rearrangement to establish the
enone moiety in ring C.18 In practice, oxidation of 32 with
H2O2 gave the sulfoxide 34 in 90% yield as a 2:1 separable
mixture of diastereomers (Scheme 5). Treatment of 34 with
TFAA in the presence of 2,6-lutidine resulted in the vinylogous
Pummerer rearrangement,19 affording 37 after hydrolysis. For
37, NOE interactions between H13/14-OH, H15/12-OMe,
and H8/H17 were shown in Scheme 5. These results indicate
that 37 is a unique cage-like compound. Treating 37 with
MeI20 produced the cyclohexanone 38 in 75% yield, showing a
result of simultaneous desulfurization, elimination to form
enone, and deprotection of acetonide. Direct conversion of the
trans-diol 38 into an epoxide failed after numerous attempts,
while the aromatization byproduct was observed instead.
By following a circuitous strategy to bypass the facility of
aromatization, the ketone in 38 was reduced to give the triol
39, in which the rigid tricycle scaffold made ring C exist with a
stable half-chair conformation. Thus, selective mesylation of
the C17 hydroxyl in 39 was achieved in the presence of the
other two hydroxyls at C16 and C18, and basic treatment of the
intermediate in one pot realized formation of the epoxide 41.
Due to its lability, compound 41 was immediately subjected to
allylic oxidation to afford 42, an epimer of core 3, in 49%
overall yield from 39. Notably, compound 42 is difficult to
prepare in large quantities due to the instability of 40 and 41.
Actually, an array of acidic conditions aiming at achievement of
equilibration between 42 and 3 were examined but
unfortunately unsuccessful (see the Supporting Information
for details). Thus, we conceive of constructing the trans-fused
6/5/6 tricycle, i.e., 3, from the cis-fused 6/5/6 tricycle, i.e., 42,
through a precisely tailored chiral catalyst under neutral
conditions.21 The related studies are currently ongoing in our
laboratory, and further results will be described in the future.
In summary, we have completed synthesis of the tricyclic
core of 12-epi-JBIR-23 and -24 through a A−AB−ABC ring
construction sequence. Key features include a tandem
asymmetric Michael/aldol reaction to establish three consec-
utive tertiary carbon centers and [3,3]-sigmatropic rearrange-
ment of an allylic xanthate, followed by vinylogous Pummerer
rearrangement and a selective mesylation/epoxidation cascade
of a triol, to access the brittle epoxyquinol motif. Inspired by
this achievement, further endeavors toward total synthesis of
JBIR-23 and -24 are currently in progress in our laboratory and
will be disclosed in due course.
Shaomin Fu − Key Laboratory of Green Chemistry &
Technology of Ministry of Education, College of Chemistry,
Sichuan University, Chengdu 610064, China;
Email: fsm09@aliyun.com
Bo Liu − Key Laboratory of Green Chemistry & Technology of
Ministry of Education, College of Chemistry, Sichuan
University, Chengdu 610064, China; orcid.org/0000-
0002-6235-1573; Email: chembliu@scu.edu.cn
Authors
Yi Man − Key Laboratory of Green Chemistry & Technology
of Ministry of Education, College of Chemistry, Sichuan
University, Chengdu 610064, China
Chengying Zhou − Key Laboratory of Green Chemistry &
Technology of Ministry of Education, College of Chemistry,
Sichuan University, Chengdu 610064, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00853
Author Contributions
The manuscript was written through contributions of all
authors.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge financial support from the NSFC (21871191,
21921002, U19A2014). This work was supported by the
Research Fund for the Doctoral Program of Higher Education
of China (No. 20130181110022). We also thank the Analytical
& Testing Center of Sichuan University for NMR recording.
REFERENCES
■
(1) (a) Motohashi, K.; Hwang, J.-H.; Sekido, Y.; Takagi, M.; Shin-ya,
K. JBIR-23 and −24, Novel Anticancer Agents from Streptomyces sp.
AK-AB27. Org. Lett. 2009, 11, 285. (b) Hwang, J.-H.; Takagi, M.;
Murakami, H.; Sekido, Y.; Shin-ya, K. Induction of tubulin
polymerization and apoptosis in malignant mesothelioma cells by a
new compound JBIR-23. Cancer Lett. 2011, 300, 189.
(2) (a) Mehta, G.; Islam, K. Enantioselective total synthesis of
epoxyquinone natural products (−)-phyllostine, (+)-epoxydon,
(+)-epiepoxydon and (−)-panepophenanthrin: access to versatile
chiral building blocks through enzymatic kinetic resolution.
Tetrahedron Lett. 2004, 45, 7683. (b) O’Byrne, A.; O’Reilly, S.;
Tighe, C.; Evans, P.; Ciuffini, L.; Santoro, M. G. Temporary thio-
derivatization in the synthesis of (+)-4-acetylbromoxone. Tetrahedron
Lett. 2012, 53, 5936. (c) Carreno, M. C.; Merino, E.; Ribagorda, M.;
3154
https://doi.org/10.1021/acs.orglett.1c00853
Org. Lett. 2021, 23, 3151−3156

Organic Letters
pubs.acs.org/OrgLett
Letter
Somoza, I.; Urbano, A. Enantioselective Synthesis of Natural
Polyoxygenated Cyclohexanes and Cyclohexenes from [(p-Tolylsul-
finyl) methyl]-p-quinols. Chem. - Eur. J. 2007, 13, 1064. (d) Man, Y.;
Fu, S.; Chen, J.; Liu, B. Total synthesis and structural revision of an
isopanepoxydone analog isolated from Lentinus strigellus. Org. Biomol.
Chem. 2018, 16, 5043.
Y.; Ogura, Y.; Enomoto, M.; Kuwahara, S. Synthesis of the N-Acyl
Amycolose Moiety of Amycolamicin and Its Methyl Glycosides. J.
Org. Chem. 2019, 84, 7474. (c) Trost, B. M.; Biannic, B.; Brindle, C.
S.; O’Keefe, B. M.; Hunter, T. J.; Ngai, M.-Y. A Highly Convergent
Total Synthesis of Leustroducsin B. J. Am. Chem. Soc. 2015, 137,
11594. (d) Wang, Y.-G.; Kobayashi, Y. Formal Total Synthesis of
Fostriecin. Org. Lett. 2002, 4, 4615.
(9) (a) Cheung, W. S.; Wong, H. N. C. Total synthesis of
(−)-hispanolone and an improved approach towards prehispanolone.
Tetrahedron 1999, 55, 11001. (b) Majetich, G.; Nishide, H.; Phillips,
R.; Yu, J. Conformational Biasing in 1, 3-Oxidative Rearrangements of
Dienols. Heterocycles 2007, 74, 225. (c) Vatele, J.-M. Copper-
Catalyzed Aerobic Oxidative Rearrangement of Tertiary Allylic
Alcohols Mediated by TEMPO. Synlett 2009, 2009, 2143. (d) Li,
J.; Tan, C.; Gong, J.; Yang, Z. Palladium-Catalyzed Oxidative
Rearrangement of Tertiary Allylic Alcohols to Enones with Oxygen
in Aqueous Solvent. Org. Lett. 2014, 16, 5370. (e) Corey, E. J.;
Crouse, D. Application of bisthiocarb-anions to the elaboration of 2-
cyclohexenone systems. J. Org. Chem. 1968, 33, 298.
(10) (a) Kawamoto, Y.; Karube, F.; Kobayashi, T.; Ito, H.
Enantioselective Total Synthesis of Mollebenzylanol A. Org. Lett.
2020, 22, 7609. (b) Yoshida, M.; Kasai, T.; Mizuguchi, T.; Namba, K.
Total Synthesis of (−)-HM-3 and (−)-HM-4 Utilizing a Palladium-
Catalyzed Addition of an Arylboronic Acid to an Allenic Alcohol
Followed by Eschenmoser−Claisen Rearrangement. Synlett 2014, 25,
1160.
(11) (a) Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom,
T. J.; Li, T.-T.; Faulkner, D. J.; Petersen, M. R. Simple stereoselective
version of the Claisen rearrangement leading to trans-trisubstituted
olefinic bonds. Synthesis of squalene. J. Am. Chem. Soc. 1970, 92, 741.
(b) Bin, H.-Y.; Wang, K.; Yang, D.; Yang, X.-H.; Xie, J.-H.; Zhou, Q.-
L. Scalable Enantioselective Total Synthesis of (−)-Goniomitine.
Angew. Chem., Int. Ed. 2019, 58, 1174.
(3) Chen, Y.; Huang, J.; Liu, B. Total syntheses of the proposed
structures of cuevaene A. Tetrahedron Lett. 2010, 51, 4655.
(4) (a) Oi, D.; Sato, T.; Inoue, Y. Asymmetric 1, 4-addition of
alkenylzirconium reagents to α, β-unsaturated ketones catalyzed by
chiral rhodium complexes. Tetrahedron Lett. 2004, 45, 5051. (b) El-
Batta, A.; Hage, T. R.; Plotkin, S.; Bergdahl, M. Direct Copper(I)
Iodide Dimethyl Sulfide Catalyzed Conjugate Addition of Alkenyl
Groups from Vinylzirconocene Reagents. Org. Lett. 2004, 6, 107.
(c) Nicolaou, K. C.; Tang, W.; Dagneau, P.; Faraoni, R. A. Catalytic
Asymmetric Three-Component 1, 4-Addition/Aldol Reaction:
Enantioselective Synthesis of the Spirocyclic System of Vannusal A.
Angew. Chem., Int. Ed. 2005, 44, 3874. (d) Jin, M. Y.; Li, J.; Huang, R.;
Zhou, Y.; Chung, L. W.; Wang, J. Catalytic asymmetric
trifluoromethylthiolation of carbonyl compounds via a diastereo and
enantioselective Cu-catalyzed tandem reaction. Chem. Commun. 2018,
54, 4581. (e) Rodríguez-Fernández, M.; Yan, X.; Collados, J. F.;
White, P. B.; Harutyunyan, S. R. Lewis Acid Enabled Copper-
Catalyzed Asymmetric Synthesis of Chiral β-Substituted Amides. J.
Am. Chem. Soc. 2017, 139, 14224. (f) Ng, E. W. H.; Low, K.-H.; Chiu,
P. Synthesis and Applications of Unquaternized C-Bound Boron
Enolates. J. Am. Chem. Soc. 2018, 140, 3537. (g) Wang, J. Y. J.;
Palacin, T.; Fletcher, S. P. β-Chloroaldehydes from Trapping
Zirconium Enolates Produced in Asymmetric 1, 4-Additions. Org.
Lett. 2019, 21, 378. (h) Miura, T.; Murakami, M. Rhodium-catalysed
1, 4-addition of diarylindium hydroxides to α, β-unsaturated carbonyl
compounds. Chem. Commun. 2005, 5676. (i) Wei, Y.; Shi, M.
Asymmetric Reactions Catalyzed by Chiral Tertiary Phosphines. Chin.
J. Chem. 2020, 38, 1395. (j) Feringa, B. L.; Pineschi, M.; Arnold, L. A.;
Imbos, R.; de Vries, A. H. M. Highly Enantioselective Catalytic
Conjugate Addition and Tandem Conjugate Addition−Aldol
Reactions of Organozinc Reagents. Angew. Chem., Int. Ed. Engl.
1997, 36, 2620.
(12) (a) Overman, L. E. Mercury (II)-and Palladium (II)-Catalyzed
[3, 3]-Sigmatropic Rearrangements. Angew. Chem., Int. Ed. Engl. 1984,
23, 579. (b) Doherty, A. M.; Kornberg, B. E.; Reily, M. D. A study of
the 3, 3-sigmatropic rearrangement of chiral trichloroacetamidic
esters. J. Org. Chem. 1993, 58, 795. (c) Overman, L. E. Thermal and
mercuric ion catalyzed [3, 3]-sigmatropic rearrangement of allylic
trichloroacetimidates. 1, 3 Transposition of alcohol and amine
functions. J. Am. Chem. Soc. 1974, 96, 597.
(5) Moon, H. R.; Choi, W. J.; Kim, H. O.; Jeong, L. S. Improved and
alternative synthesis of D- and L-cyclopentenone derivatives, the
versatile intermediates for the synthesis of carbocyclic nucleosides.
Tetrahedron: Asymmetry 2002, 13, 1189.
(13) (a) Nelson, S. G.; Bungard, C. J.; Wang, K. Catalyzed Olefin
Isomerization Leading to Highly Stereoselective Claisen Rearrange-
ments of Aliphatic Allyl Vinyl Ethers. J. Am. Chem. Soc. 2003, 125,
13000. (b) Lastra-Barreira, B.; Francos, J.; Crochet, P.; Cadierno, V.
Ruthenium (II) Complexes with η6-Coordinated 3-Phenylpropanol
and 2-Phenylethanol as Catalysts for the Tandem Isomerization/
Claisen Rearrangement of Diallyl Ethers in Water. Organometallics
2018, 37, 3465. (c) Higashino, T.; Sakaguchi, S.; Ishii, Y.
Rearrangement of Allyl Homoallyl Ethers to γ, δ-Unsaturated
Carbonyl Compounds Catalyzed by Iridium Complexes. Org. Lett.
2000, 2, 4193. (d) Jones, G. B.; Huber, R. S.; Chau, S. The claisen
rearrangement in synthesis: acceleration of the Johnson orthoester
protocol en route to bicyclic lactones. Tetrahedron 1993, 49, 369.
(14) (a) Taguchi, T.; Kawazoe, Y.; Yoshihira, K.; Kanayama, H.;
Mori, M.; Tabata, K.; Harano, K. Rearrangement and trans-
elimination against the Chugaev reaction rule. Tetrahedron Lett.
1965, 6, 2717. (b) Chatzopoulos-Ouar, F.; Descotes, G. Synthesis and
photolysis of S-methyl S-alkenyl dithiocarbonates in the monoterpene
series. J. Org. Chem. 1985, 50, 118. (c) Overman, L. E.; Roberts, S.
W.; Sneddon, H. F. Catalytic Asymmetric Synthesis of Allylic Thiol
Derivatives. Org. Lett. 2008, 10, 1485. (d) Carey, J. S.; MacCormick,
S.; Stanway, S. J.; Teerawutgulrag, A.; Thomas, E. J. Effective 1, 5-, 1,
6- and 1, 7-remote stereocontrol in reactions of alkoxy- and hydroxy-
substituted allylstannanes with aldehydes. Org. Biomol. Chem. 2011, 9,
3896.
(6) (a) Hiroya, K.; Ichihashi, Y.; Suwa, Y.; Ikai, T.; Inamoto, K.; Doi,
T. Facile synthesis of asymmetric quaternary centers based on
diastereoselective protection of the carbonyl group at the symmetrical
position. Tetrahedron Lett. 2010, 51, 3728. (b) Hiroya, K.; Suwa, Y.;
Ichihashi, Y.; Inamoto, K.; Doi, T. Total Synthesis of Optically Active
Lycopladine A by Utilizing Diastereoselective Protection of Carbonyl
Group in a 1,3-Cyclohexanedione Derivative. J. Org. Chem. 2011, 76,
4522. (c) Daloze, D.; Braekman, J. C.; Georget, P.; Tursch, B.
Chemical Studies of Marine Invertebrates. XXII. Two Novel
Sesquiterpenes from Soft Corals of the Genera Lemnalia and
Paralemnalia (Coelenterata, Octocorallia, Alcyonacea). Bull. Soc.
Chim. Belg. 1977, 86, 47. (d) Suarez, R. M.; Montserrat Martinez,
M.; Sarandeses, L. A.; Perez Sestelo, J. Synthetic studies on
neomarinone: practical and efficient stereoselective synthesis of the
side chain. Tetrahedron Lett. 2007, 48, 6493. (e) Wang, T.; Chen, J.;
Zhao, K. 1,3-Diastereocontrolled O-Displacement of Enolates. J. Org.
Chem. 1995, 60, 2668.
(7) (a) Tian, Q.; Zhang, G. Recent Advances in the Asymmetric
Nozaki−Hiyama−Kishi Reaction. Synthesis 2016, 48, 4038. (b) Wang,
B.; Xie, Y.; Yang, Q.; Zhang, G.; Gu, Z. Total Synthesis of Aquatolide:
Wolff Ring Contraction and Late-Stage Nozaki−Hiyama−Kishi
Medium-Ring Formation. Org. Lett. 2016, 18, 5388. (c) Okude, Y.;
Hirano, S.; Hiyama, T.; Nozaki, H. Grignard-type carbonyl addition
of allyl halides by means of chromous salt. A chemospecific synthesis
of homoallyl alcohols. J. Am. Chem. Soc. 1977, 99, 3179.
(15) Eto, M.; Nishimoto, M.; Kubota, S.; Matsuoka, T.; Harano, K.
Retro-Ene type fragmentation of allylic dithiolcarbonates. Tetrahedron
Lett. 1996, 37, 2445.
(8) (a) Yu, T.; Sun, Y.; Tu, C.; Chen, T.; Fu, S.; Liu, B. Total
synthesis of crotophorbolone. Chem. Sci. 2020, 11, 7177. (b) Meguro,
3155
https://doi.org/10.1021/acs.orglett.1c00853
Org. Lett. 2021, 23, 3151−3156

Organic Letters
pubs.acs.org/OrgLett
Letter
(16) Yamashita, M.; Hayashi, H.; Suzuki, M.; Kuzuhara, D.; Yuasa,
J.; Kawai, T.; Aratani, N.; Yamada, H. Bisanthra-thianthrene:
synthesis, structure and oxidation properties. RSC Adv. 2016, 6,
70700.
(17) (a) Harpp, D. N.; Gleason, J. G. Organic Sulfur Chemistry. X.
Selective Desulfurization of Disulfides. Scope and Mechanism. J. Am.
Chem. Soc. 1971, 93, 2437. (b) Kojima, K.; Yakushiji, F.; Katsuyama,
A.; Ichikawa, S. Total Synthesis of Echinomycin and Its Analogues.
Org. Lett. 2020, 22, 4217.
(18) (a) Sharma, A. K.; Swern, D. Trifluoroacetic anhydride: A new
activating agent for dimethyl sulfoxide in the synthesis of
iminosulfuranes. Tetrahedron Lett. 1974, 15, 1503. (b) Bonjoch, J.;
Catena, J.; Valls, N. Total Synthesis of ( )-Deethylibophyllidine:
Studies of a Fischer Indolization Route and a Successful Approach via
a Pummerer Rearrangement/Thionium Ion-Mediated Indole Cycliza-
tion. J. Org. Chem. 1996, 61, 7106.
(19) (a) Denancé, M.; Legay, R.; Gaumont, A.-C.; Gulea, M.
Pummerer-type reactions in the (2-methylsulfanyl-2-phosphonyl)
thiopyran 1-oxide series. Tetrahedron Lett. 2008, 49, 4329.
(b) Shimizu, Y.; Shi, S.-L.; Usuda, H.; Kanai, M.; Shibasaki, M.
Catalytic Asymmetric Total Synthesis of ent-Hyperforin. Angew.
Chem., Int. Ed. 2010, 49, 1103. (c) Nishimura, T.; Unni, A. K.;
Yokoshima, S.; Fukuyama, T. J. Am. Chem. Soc. 2011, 133, 418.
(20) Gosselin, P. Acid catalyzed hydrolysis of a dienyl sulfide.
Application to the synthesis of α-damascone. Tetrahedron 1988, 44,
1979.
(21) (a) Li, Q.; Levi, S. M.; Jacobsen, E. N. Highly Selective β-
Mannosylations and β-Rhamnosylations Catalyzed by Bis-thiourea. J.
Am. Chem. Soc. 2020, 142, 11865. (b) Mayfield, A. B.; Metternich, J.
B.; Trotta, A. H.; Jacobsen, E. N. Stereospecific Furanosylations
Catalyzed by Bis-thiourea Hydrogen-Bond Donors. J. Am. Chem. Soc.
2020, 142, 4061. (c) Jeanneret, A. R.; Johnson, S. E.; Galan, M. C.
Conformationally Constrained Glycosyl Donors as Tools to Control
Glycosylation Outcomes. J. Org. Chem. 2020, 85, 15801. (d) Adero, P.
O.; Amarasekara, H.; Wen, P.; Bohé, L. David Crich, D. The
Experimental Evidence in Support of Glycosylation Mechanisms at
the SN1−SN2 Interface. Chem. Rev. 2018, 118, 8242.
3156
https://doi.org/10.1021/acs.orglett.1c00853
Org. Lett. 2021, 23, 3151−3156