A boron-based Ireland-Claisen approach to the synthesis of pordamacrine A

Article abstract of DOI:10.1016/j.tet.2016.11.030

A synthetic approach to pordamacrine A that features two key transformations is discussed. The first transformation applies an Ireland-Claisen rearrangement to establish sterically congested vicinal carbon centers. Although a hard enolization technique for accessing the silyl ketene acetal failed, a soft enolization, boron-based reaction was highly successful. The second step involves a proposed cascade palladium-catalyzed biscyclization to construct two carbocycles of the natural product. The overall strategy is presented, demonstrating the challenges of the cyclization events in this complex setting.

Full text of DOI:10.1016/j.tet.2016.11.030

Accepted Manuscript
A boron-based Ireland-Claisen approach to the synthesis of pordamacrine A
Curtis A. Seizert, Eric M. Ferreira
PII:
S0040-4020(16)31185-1
10.1016/j.tet.2016.11.030
TET 28244
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 30 August 2016
Revised Date: 27 October 2016
Accepted Date: 12 November 2016
Please cite this article as: Seizert CA, Ferreira EM, A boron-based Ireland-Claisen approach to the
synthesis of pordamacrine A, Tetrahedron (2016), doi: 10.1016/j.tet.2016.11.030.
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A boron-based Ireland-Claisen approach to
the synthesis of pordamacrine A
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Curtis A. Seizert and Eric M. Ferreira*
Department of Chemistry, University of Georgia, Athens, Georgia 30602, United States

1
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Tetrahedron
journal homepage: www.elsevier.com
A boron-based Ireland-Claisen Approach to the Synthesis of Pordamacrine A
Curtis A. Seizert and Eric M. Ferreira
Department of Chemistry, University of Georgia, Athens, Georgia 30602, United States
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A synthetic approach to pordamacrine A that features two key transformations is discussed. The
first transformation applies an Ireland-Claisen rearrangement to establish sterically congested
vicinal carbon centers. Although a hard enolization technique for accessing the silyl ketene
acetal failed, a soft enolization, boron-based reaction was highly successful. The second step
involves a proposed cascade palladium-catalyzed biscyclization to construct two carbocycles of
the natural product. The overall strategy is presented, demonstrating the challenges of the
cyclization events in this complex setting.
Available online
Keywords:
Ireland-Claisen rearrangement
Pordamacrine
Alkaloid
2009 Elsevier Ltd. All rights reserved
.
Cyclization
Boron
———
Corresponding author. Tel.: +1-706-542-4231; e-mail: emferr@uga.edu

2
Tetrahedron
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Introduction
Pordamacrine A (1, Fig. 1) is a heavily oxygenated,
hexacyclic alkaloid isolated from the leaves of daphniphyllum
macropodum in 2009.1 The natural product belongs to a family
of over 200 alkaloids produced by the daphniphyllum genus.2
These alkaloids appear to share the common biogenic ancestor
squalene, which is elaborated to the complex architecture of these
molecules through a polycyclization cascade postulated by
Heathcock3 and supported by a now classic synthesis of methyl
homosecodaphniphyllate.4
Along with other syntheses by
Heathcock,5 members of this family have been the targets of
numerous total syntheses and synthetic studies.6 At least part of
the reason for this is that the complex structures of these
alkaloids can provide a rich ground for reaction development,
owing to the likelihood of encountering difficulties during the
course of studies toward a total synthesis.
Fig. 2. Previous synthetic approaches to the yuzurimine alkaloids.
Background. Sigmatropic rearrangements occupy a privileged
position in the toolbox of synthetic chemists. Their impact is due
in part to their ability to enable difficult bond formations with
predictable stereoselectivity by rendering them intramolecular.
Among these transformations is the Ireland-Claisen
rearrangement.9,10 This reaction facilitates what is formally an
ester enolate allylation through the prior formation of an ester
linkage between the fragments that will ultimately be connected
by a C–C bond. The utility of this transformation is based on the
general reliability of methods for both forming the ester
precursor and accomplishing the rearrangement itself. Its use in
numerous total syntheses, oftentimes as a key step, underscores
the notion that the Ireland-Claisen rearrangement is indeed a
transformation of fundamental importance.11
Fig. 1. Representative daphniphylline alkaloids.
This opportunity is certainly true in the case of the yuzurimine
subfamily. Although a total synthesis of an alkaloid in this
subfamily has yet to be completed, several groups have
demonstrated interesting approaches (Fig. 2). Among these
efforts have been a pair of strategies by Coldham that employ an
intramolecular nitrone dipolar cycloaddition as a key step (eqs
1,2).6c,d The group of Bélanger centered their strategy around a
tandem intramolecular Vilsmeier-Haack/azomethine ylide
cycloaddition sequence (eq 3),6e and more recently Hakayawa
and Kigoshi took advantage of an intramolecular Wittig reaction
to close the yuzurimine central seven-membered ring (eq 4).6m
Herein, we describe our own synthetic approach toward the
yuzurimine alkaloid pordamacrine A, wherein a relatively
unexplored variant of the Ireland-Claisen rearrangement enabled
us to establish a crucial congested stereodiad within the
molecule. This effort is representative of the potential utility of
the Ireland-Claisen rearrangment using boron-based enolates,
which both our group7 and the Zemribo group8 have exploited in
recent synthetic and methods studies.
The classical conditions for effecting the reaction involve first
forming a silyl ketene acetal by low temperature hard enolization
of an allylic ester by a strong base such as LDA, and in situ
trapping of the enolate with a silylating agent. The resulting silyl
ketene acetal is then heated, either after prior purification or in
the same pot to induce the rearrangement itself.9 This protocol is
by far the most commonly utilized method for executing the
Ireland-Claisen rearrangement; however, other procedures exist.
A
limited body of work emerged in the early 1990s
demonstrating the viability of phosphorus12 (by hard enolization)
and boron13 and silicon14 (by soft enolization) ketene acetals in
the Ireland-Claisen rearrangement. Importantly, these methods
had not been tested with complex, polyfunctional substrates in
the context of total synthesis, until the recent elegant work of
Zemribo and coworkers on the successful approaches toward
pyrrolidine-based natural products.8 As described herein, the
boron-based strategy proved to be a successful alternative to
silicon in the context of our approach toward pordamacrine A.

3
Results and Discussion
functional group for oxidative addition in the proposed
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palladium cascade. This group was selected as we envisioned it
could readily arise from a carbonyl precursor. Because we
anticipated the final steps to allylic ester 14 from t-butyl ester 17
would be fairly straightforward, our synthetic route was based
around one major consideration – how to prepare the alkenyl
sulfonate moiety of acid 16 as a single positional alkene isomer.
This requirement ruled out a scheme that involved the enolization
and trapping of a saturated ketone, because it was unlikely that
kinetic bases would be able to discriminate between the two
methine protons adjacent to this ketone. A reduction of
cyclopentenone 17 with concomitant trapping of the enolate
appeared to be a viable alternative; similar examples indicated
promise for this approach.17 Cyclopentenone 17 would arise
from esterification. Finally, we anticipated that cyclopentenone
Our retrosynthesis of pordamacrine A (1) is outlined in
Scheme 1. We planned to delay most of the elaboration of the
western half of the molecule until the last stages of the synthesis
because we anticipated that the high level of oxygenation present
on the cyclohexene ring could cause difficulties with the
transformations required to assemble the molecule’s carbocyclic
skeleton (7 → 1). This assembly would revolve around two main
steps. The first key step involved a proposed palladium-
catalyzed cascade cyclization to establish the cycloheptene and
cyclopentane rings of the natural product. Upon oxidative
addition of the alkenyl-X species, the closure of the central
seven-membered ring would occur by an intramolecular Pd-
catalyzed migratory insertion reaction, while the five-membered
ring formation would occur by the trapping of the resultant
captive neopentyl palladium species 8 by the pendant ester
enolate. This proposed process essentially represents a novel
enolate-coupling interception of the Heck reaction pathway.
18 would be expeditiously available via
a
catalytic,
multicomponent cyclocarbonylation reaction as described by
Moretó.18
Scheme 2. Model study of proposed cascade transformation -
retrosynthetic analysis of substrate 14.
In the forward sense, we prepared the t-butyl ester precursor
to the cyclocarbonylation reaction (19) by a straightforward, two
step transesterification sequence from commercially available
methyl hex-5-ynoate (21, Scheme 3). The cyclopentenone
synthesis gave acceptable yields of diester 17 after alkylation of
the acid reaction product with MeI and Cs2CO3. Although the
yield was modest, the low step count and scalability of the
reactions assured that we could produce the necessary amounts of
our substrates for the key steps to conduct studies. Reduction of
cyclopentenone 17 with Li(s-Bu)3BH followed by in situ
sulfonation of the resultant enolate with NfF cleanly provided
alkenyl nonaflate 22. Here, we opted to use the nonaflate group
rather than the more traditional triflate due to the former’s known
susceptibility to nucleophiles compared to the latter.19 Such a
side reaction could complicate the Pd-catalyzed cyclization step
in our planned synthesis. Finally, transesterification of t-butyl
ester 22 to allylic ester 14 proceeded straightforwardly in near
quantitative yield in two steps by HCl-catalyzed t-butyl ester
cleavage followed by DCC coupling20 with known allylic alcohol
15.21
Scheme 1. Proposed retrosynthetic approach to pordamacrine A.
There is an extensive body of literature on the use of the
intramolecular Heck reaction to form congested rings;15 to our
knowledge, however, there has been no report of the alkylation of
enols/enolates by neopentyl Pd species such as intermediate 8.
The alkylation of vinyl- and aryl-Pd species by enolates,
meanwhile, has been extensively explored,16 suggesting some
conceptual feasibility for this approach. The precursor to this
proposed cascade, amide 9, would arise from acid 10. The
synthesis of this acid could be achieved via an Ireland-Claisen
rearrangement of allylic ester 11. We believed this strategy
would be highly advantageous for the construction of the
congested, stereochemically complex γ,δ-unsaturated acid motif.
Finally, allylic ester 11 would be synthesized via standard
esterification between acid 12 and alcohol 13.
We acknowledged the fact that our tandem Pd-catalyzed
double cyclization reaction was fairly speculative, and therefore
we employed a model system to begin our investigations. We
simplified the approach by removing the additional oxygenation
on the cyclohexenyl system, reducing our target ester for the
Ireland-Claisen rearrangement to compound 14 (Scheme 2). In
this compound, we also chose to use an alkenyl sulfonate as the

4
Tetrahedron
low for compounds lacking α-alkoxy groups. Subsequent to
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those reports, boron ketene acetals have been shown to be
generated at low temperatures using strong boron electrophiles of
the type R2BI and R2BOTf in conjunction with a weak base, and
can be prepared as either isomer with high geometrical purity.22
The ability to achieve high geometrical purity offered the
potential for high diastereoselectivity in this particular desired
transformation. Since the cases outlined in Fig. 2 preceded the
reports of efficient methods for the generation of boron enolates
from esters, we felt it was necessary to reexamine this variant of
the Ireland-Claisen rearrangement with those methods in mind.
Scheme 3. Synthesis of diester 14.
Having thus secured a route to allylic ester 14, we turned our
attention to the pivotal Ireland-Claisen step (Scheme 4). The C–
C bond that would be formed in this step is between two
stereogenic centers, one tertiary and the other quaternary. In
addition, allylic ester 14 contains a distal ester moiety, capable of
both competing enolization and other side reactions. Partially
encouraging, this distal ester featured branching at the β position,
which should kinetically disfavor enolization to a small extent.
The widely demonstrated generality of this rearrangement
bolstered our confidence that it would provide us with our
desired product, acid 23. To our chagrin, the standard conditions
for effecting the rearrangement via a Z-ketene acetal (LDA,
HMPA, TBSCl; -78 to 66 °C)10 led to a complex mixture that
contained only traces of the expected acid (23). Unfortunately,
the intractable mixture of products obtained was unsuitable for
the progression of our synthetic studies. It was therefore
incumbent upon us to find alternative conditions for the
rearrangement step.
Fig. 3. Early cases of boron-based enolate Ireland-Claisen
rearrangements.
The diastereoselectivity of the Ireland-Claisen rearrangement
has been thoroughly investigated by Ireland and coworkers.9,23
On the basis of these studies, we determined that acid 23 would
arise via a chairlike transition state from (Z)-boron ketene acetal
30 (Scheme 5).24 Fortunately, highly Z-selective generation of
boron ketene acetals of n-alkyl esters is possible using c-Hx2BI in
conjunction with Et3N at -78 °C.22a To our delight, these
conditions (using 2.2 equiv of c-Hx2BI to enolize both esters)
followed by warming to room temperature effected smooth
rearrangement of allylic ester 14 to acid 23 as apparently a single
diastereomer about the formed bond. (The product existed as a
mixture of diastereomers epimeric at the distal methyl acetate
moiety).
Scheme 4. Attempted Ireland-Claisen rearrangement of diester 14 using
hard enolization technique.
It was difficult to determine the cause of this failed reaction
based on the complex mixture of products that were observed. It
seemed likely, however, that the strongly basic conditions used to
create the silyl ketene acetal of allylic ester 14 played a role. We
therefore turned our attention to conditions that would employ a
milder base, i.e., soft enolization conditions. Among the
aforementioned systems utilizing soft enolization techniques,13,14
we were especially intrigued by boron.
Early work from Corey13a and Oh13b indicated the feasibility of
using boron-based enolates in the Ireland-Claisen rearrangement
(Fig. 3). In 1991, Corey and Lee described an enantioselective
process mediated by a bissulfonamidyl bromoborane (Fig. 3a).
Here, the control of the enolate geometry can be achieved with
solvent and base selection, and that enolate geometry transfers
effectively to the diastereoselection in the rearrangement. The
reaction times, however, were protracted, requiring 7 to 14 days
to reach completion. Oh and coworkers in 1992 demonstrated a
related process using common dialkylboron triflates (Figure 3b).
Reaction times were considerably shorter (reported to be less
than 5 min at 25 °C), but yields and diastereoselectivities were

5
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Scheme 5. Boron-mediated Ireland-Claisen rearrangement of diester 14.
To further study this rearrangement as well as ascertain its
diastereoselectivity, we turned our attention to allylic propionate
31 (Scheme 6). On treatment of propionate 31 to the conditions
similar to our more complex substrate, except with 1.1 equiv c-
Hx2BI/5 equiv Et3N, we obtained very similar yields. The
comparable yield suggests that the polyfunctional nature of
Scheme 7. Amidation and attempted proposed Pd-catalyzed
biscyclization.
We reasoned that a reliable method for terminating this
catalytic cycle, indeed one that was precedented in the context of
ring formation via migratory insertion, could provide insight into
this reaction. A reductive Heck cyclization appeared to be an
attractive option. To our knowledge, the formation of a seven-
membered ring terminated by alkylpalladium reduction in this
reaction manifold is unknown, but analogous five- and six-
membered ring formations from alkenyl halides have been
described.26 Under dilute conditions we treated amide 35b with
triethylammonium formate in the presence catalytic Pd(PPh3)4
(Scheme 8). Instead of cyclization, this reaction led only to
simple reduction of the alkenyl sulfonate moiety. It appears,
therefore, that formation of this seven-membered ring is
disfavored. Close examination of molecular models suggests a
reason for this lack of reactivity. For the seven-membered ring to
close, the alkenylpalladium species resulting from oxidative
addition and the exo-methylene group need to come into close
proximity. This forces the molecule to adopt a conformation that
places the dimethylamide moiety directly underneath the six-
membered ring, thereby creating severe non-bonded interactions
that may disfavor this reactive conformation. Based on this
conformational analysis, it seemed a fundamental feature of this
substrate created problems that even judicious choice of catalytic
conditions would be unlikely to solve.27
diester 14 was well tolerated.
To lend support to our
stereochemical assignment, we prepared the iodolactone of acid
32. The proximity of the indicated functional groups in
iodolactone 33 was determined by 2D NOE correlations,
supporting our stereochemical assignment of 23.
Scheme 6. Analogous stereochemical analysis -
rearrangement/iodolactonization of ester 31.
The acid moiety of rearrangement product 23 would likely
render it less suitable as a substrate for our tandem cyclization;
we anticipated the basic conditions would lead to a doubly
deprotonated species that may lead to unnecessary complications
(e.g., solubility profile, etc.). We therefore opted to transform it
to an amide, much like what we envisioned would be used in our
planned synthesis (Scheme 7). Mild amidation conditions failed
to give any detectable product, so we chose to activate acid 23 by
forming the acyl chloride (34), followed by in situ trapping with
Me2NH. The resulting amide existed as mixture of two products
(35a and 35b) that we suspected were epimeric at the cyclopentyl
stereocenter.25 Under a variety of conditions expected to effect
both the migratory insertion and enolate alkylation steps, we
obtained no evidence of seven-membered ring closure, with
isolable products always retaining the exo-methylene moiety.
We frequently observed palladium precipitation from the reaction
mixture in these experiments. One can envision a situation
where the captive neopentylpalladium species resulting from
migratory insertion does not undergo trapping by the pendant
Scheme 8. Pd-catalyzed reduction of nonaflate 35b.
Conclusion
We have described herein our studies toward the total
synthesis of pordamacrine A, featuring a successful execution of
the boron-based Ireland-Claisen rearrangement in a complex
enol/enolate nucleophile.
This intermediate could simply
undergo a β-alkyl elimination process, reversing the ring closure.
Without a readily available pathway to terminate the catalytic
cycle, the catalyst may simply precipitate from the reaction
mixture.
system.
Although the proposed cascade cyclization was
unsuccessful on the model system we investigated, important
insights were obtained about the structural limitations of the
synthetic approach. Regardless, this approach demonstrated the
potential utility of the boron-based Ireland-Claisen

6
Tetrahedron
rearrangement, as we were able to successfully employ this
and concentrated in vacuo to afford the carboxylic acid, which
ACCEPTED MANUSCRIPT
method in this structurally complex setting.
The
was used directly without further purification.
diastereoselectivity of the specific transformation was excellent,
predicated on the highly organized transition state by which this
process occurs. We believe that this example illustrates the
capacity of this rearrangement to establish complex
stereochemical arrays, and we anticipate that this method will
thus be of high use for the synthetic community. Further efforts
in related synthetic areas are underway.
To a solution of the carboxylic acid (assume 123 mmol) in
THF (40 mL) at -78 °C was added TFAA (34.1 mL, 245 mmol)
over 2 min. The solution was then allowed to warm to ambient
temperature. Once it had reached ambient temperature, the
solution was recooled to -78 °C, and a solution of t-BuOH (18.2
g, 245 mmol) in THF (10 mL) was added. The reaction mixture
was then sealed and stirred at 0 °C for 14 h. The reaction
mixture was then poured into a stirring solution of K2CO3 (50.9
g, 368 mmol) in H2O (200 mL) at a rate such that evolution of
CO2 was controlled. The resulting mixture was then extracted
with pentane (3 x 50 mL), and the combined organic extracts
were washed with H2O (2 x 200 mL), then dried with MgSO4 and
applied directly to a SiO2 column (3 x 15 cm), eluting with 9:1
pentane/Et2O. The combined product-containing fractions were
concentrated to give ester 19 (18.6 g, 90% yield over 2 steps) as a
colorless liquid.
Experimental Section
Materials and Methods. Reactions were performed under an
argon atmosphere unless otherwise noted. Dichloromethane,
tetrahydrofuran, N,N-dimethylformamide, and toluene were
purified by passing through activated alumina columns.
Triethylamine and diisopropylethylamine were distilled under Ar
from CaH2. Nonafluorobutanesulfonyl fluoride was purchased
from Synquest Laboratories (Alachua, FL) and purified
according to Lyapkalo and coworkers.28 All other reagents were
used as received unless otherwise noted. Commercially available
chemicals were purchased from Alfa Aesar (Ward Hill, MA),
Sigma-Aldrich (St. Louis, MO), or Strem Chemicals (Newport,
MA). Visualization was accomplished with UV light and
exposure to KMnO4 solutions followed by heating. Flash
chromatography was performed using Silicycle silica gel (230-
400 mesh). 1H NMR spectra were acquired on a Varian 400 MR
(at 400 MHz) and are reported in ppm relative to SiMe4 (δ 0.00).
13C NMR spectra were acquired on a Varian 400 MR (at 101
MHz) and are reported in ppm relative to SiMe4 (δ 0.0). 19F
NMR spectra were acquired on a Varian 400 MR (at 376 MHz)
and are reported in ppm relative to HF (δ 0.0). Infrared spectra
were recorded as films on a Nicolet iS-50 FTIR. High resolution
mass spectrometry data were acquired by the Colorado State
University Central Instrument Facility on an Agilent 6210 TOF
LC/MS; low resolution mass spectrometry data were acquired on
an Agilent 6100 Single Quad LC/MS.
Data for ester 19. TLC: Rf = 0.36 (19:1 hexanes/EtOAc,
1
KMnO4 stain solution). H NMR (400 MHz, CDCl3): δ = 2.33 (t,
J = 7.4 Hz, 2H), 2.23 (td, J = 6.9, 2.5 Hz, 2H), 1.94 (t, J = 2.5
Hz, 1H), 1.79 (app. quintet, J = 7.2 Hz, 2H), 1.43 (s, 9H). 13C
NMR (101 MHz, CDCl3): δ = 172.4, 83.5, 80.3, 68.8, 34.2, 28.1,
23.8, 17.8. IR (film): ν = 3296, 3005, 2975, 2935, 2119, 1723,
1367, 1144 cm-1. HRMS (DART): m/z calc’d for (M + NH4)+
[C10H16O2 + NH4]+: 186.1489, found 186.1493.
Cyclopentenone
17
(tert-butyl
4-(4-(2-methoxy-2-
oxoethyl)-5-oxocyclopent-1-en-1-yl)butanoate). In a 250 mL
round bottom flask charged with a large stirbar, a mixture of
NiBr2 (1.09 g, 5.00 mmol), NaI (3.00 g, 20.0 mmol), and Fe
powder (10 ꢀm particle size, 2.79 g, 50.0 mmol) was stirred
under vacuum for 10 min at room temperature. The flask was
then backfilled with CO, fitted with a CO balloon, and charged
with acetone (25 mL). The resulting suspension was stirred for
30 min, during which the color changed from dark red to pale
green. A portion of water (1.00 mL, 55.5 mmol) was added at
the end of this period. Next, a solution of alkyne 19 (8.41 g, 50.0
mmol), allyl bromide (5.19 mL, 60.0 mmol), and i-Pr2NEt (0.218
mL, 1.25 mmol) in acetone (10 mL) was added via syringe pump
at a rate of 8.0 mL/h. The stirring during the addition was
extremely vigorous to keep the solution saturated with CO. At
the end of the addition, the reaction mixture was stirred for an
additional 1 h at room temperature. The solvent was then
removed in vacuo. The resulting residue was dissolved in
CH2Cl2 (50 mL), and filtered through a plug of celite, rinsing
with CH2Cl2. The filtrate was washed sequentially with 10% aq.
HCl (3 x 50 mL), H2O (50 mL), and brine (50 mL), dried with
MgSO4, and concentrated in vacuo. The resulting crude product
was used in the next step without further purification.
Notes on handling c-Hx2BI. Dicyclohexyliodoborane is a
very water and oxygen sensitive compound that must at all times
be handled and stored under an inert atmosphere. The pure
reagent is a clear, colorless liquid at room temperature. Material
kept in septum-capped bottles, either neat or in solution,
discolors on the order of days to weeks, and strongly colored
reagent gives inferior results. After careful experimentation, we
found the following protocol to be useful: after synthesis of the
reagent by the method of Brown,22a the crude material was
distilled into a Schlenk flask. On completion of the distillation,
the product-containing flask was stoppered under an Ar purge
and immediately evacuated. The flask was taken into an N2
atmosphere glove-box, transferred to a brown glass bottle, and
stored at room temperature. Material stored in this way showed
no evidence of decomposition after several months had elapsed.
The reagent was removed from the glove-box in a syringe as
needed and added to a reaction mixture or diluted with hexanes
to make a stock solution that was used immediately.
The crude product was dissolved in DMF (50 mL) at 23 °C,
and treated sequentially with dry Cs2CO3 (9.77 g, 30.0 mmol)
and MeI (6.24 mL, 100 mmol). The resulting solution was
stirred 14 h at ambient temperature then poured into H2O (100
mL) and extracted with pentane (3 x 50 mL). The pentane
extracts were washed with 10% aq. LiCl (50 mL), followed by
brine (50 mL), dried with Na2SO4, and concentrated in vacuo.
The resulting residue was purified by flash column
chromatography (9:1 hexanes/EtOAc eluent) to give diester 17
(3.79 g, 26% yield) as a colorless liquid.
Data for diester 17. 1H NMR (400 MHz, CDCl3): δ = 7.28 (br.
s, 1H), 3.66 (s, 3H), 2.86 (ddd, J = 18.8, 6.7, 3.1 Hz, 1H), 2.82
(dd, J = 16.5, 4.1 Hz, 1H), 2.68 (dddd, J = 9.3, 6.7, 4.1, 2.7 Hz,
1H), 2.40 (dd, J = 16.5, 9.3 Hz, 1H), 2.29 (app. dt, J = 18.8, 2.3
Ester 19 (tert-butyl hex-5-ynoate). To a solution of methyl
ester 21 (methyl hex-5-ynoate, 15.5 g, 123 mmol) in MeOH (160
mL) and H2O (40 mL) at ambient temperature was added KOH
pellets (85%, 15.5 g, 184 mmol). The solution was stirred for 30
min, at which point TLC indicated consumption of the starting
material. The solution was quenched with sat. aq. NH4Cl, and
the MeOH was removed by rotary evaporation. The resulting
biphasic mixture was diluted with 10% aq. HCl (100 mL) and
extracted with EtOAc (3 x 100 mL). The combined organic
extracts were washed with brine (100 mL), dried with MgSO4,

7
Hz, 1H), 2.21 (t, J = 7.4 Hz, 2H), 2.22-2.16 (comp. m, 2H), 1.76
(app. quintet, J = 7.4 Hz, 2H), 1.42 (s, 9H). 13C NMR (101 MHz,
CDCl3): δ = 209.2, 172.6, 172.4, 156.2, 144.7, 80.2, 51.7, 41.6,
35.0, 34.9, 33.6, 28.1, 24.3, 23.0.
1H), 3.67 (s, 3H), 3.34-3.24 (m, 1H), 2.64 (dd, J = 15.7, 3.9 Hz,
ACCEPTED MANUSCRIPT
1H), 2.39-2.14 (comp. m, 8H), 1.83-1.63 (comp. m, 3H). 13C
NMR (101 MHz, CDCl3): δ = 178.8, 171.9, 143.8, 133.5, 51.7,
40.0, 36.9, 33.2, 28.9, 26.4, 26.0, 21.7. 19F NMR (376 MHz,
CDCl3): δ = -80.7 (t, J = 9.5 Hz, 3F), -110.2 (tq, J = 15.0, 2.7 Hz,
2F), -120.9 (m, 2F), -125.9 (m, 2F). IR (film): ν = 3000 (br),
2957, 1739, 1711, 1419, 1235, 1197, 1141, 1033 cm-1. HRMS
(ESI): m/z calc’d for (M + Na)+ [C16H17F9O7S + Na]+: 547.0443,
found 547.0446.
Alkenyl nonaflate 22 (tert-butyl 4-(3-(2-methoxy-2-
oxoethyl)-2-(((perfluorobutyl)sulfonyl)oxy)cyclopent-1-en-1-
yl)butanoate). To a solution of cyclopentenone 17 (3.79 g, 12.8
mmol) in THF (20 mL) at -78 °C was added Li(s-Bu)3BH (13.4
mL, 1.0 M in THF, 13.4 mmol) over 5 min. The resulting
solution was stirred 10 min then treated with NfF (2.98 mL, 16.6
mmol). The resulting biphasic mixture was stirred 60 s, then
removed from the dry ice/acetone bath and allowed to warm 5
min before placing in a -20 °C bath. The reaction mixture
became homogeneous in 5 min, and an additional portion of NfF
was added (0.460 mL, 2.56 mmol). The reaction mixture was
stirred an additional 30 min, and then quenched with H2O (1.0
mL). The resulting solution was cooled to -78 °C and treated
slowly (caution: exothermic!) with H2O2 (30% in H2O, 5.50 mL,
51.2 mmol). The dry ice bath was removed, and the solution
heated under its own exotherm to ~40 °C. The quenched reaction
mixture was poured into H2O (150 mL) and 1 M aq. NaOH (50
mL), and the resulting mixture was extracted with pentane (3 x
Ester 14 ((2-methylcyclohex-1-en-1-yl)methyl 4-(3-(2-
methoxy-2-oxoethyl)-2-
(((perfluorobutyl)sulfonyl)oxy)cyclopent-1-en-1-
yl)butanoate).
To a solution of (2-methylcyclohex-1-en-
1yl)methanol21 (15, 1.21 g, 9.55 mmol), acid 16 (5.15 g, 9.09
mmol), and DMAP (56.0 mg, 0.455 mmol) in CH2Cl2 (9.1 mL) at
0 °C was added DCC (2.06 g, 10.0 mmol) in one portion. A
precipitate began to form almost immediately. The reaction was
stirred at 0 °C for 30 min and then warmed to ambient
temperature, stirring for an additional 12 h. At this point, TLC
indicated that acid 16 remained, so additional charges of alcohol
15 (126 mg, 0.909 mmol) and DCC (206 mg, 1.00 mmol) were
added. The reaction mixture was stirred an additional 12 h, until
TLC showed consumption of acid 16. The reaction mixture was
then diluted with hexanes (20 mL) and filtered (through plug?
50 mL).
The combined organic extracts were washed
sequentially with H2O (100 mL), 1 M aq. NaOH (50 mL), and
brine (50 mL), dried with MgSO4, and concentrated in vacuo.
The resulting residue was purified by flash column
chromatography (9:1 hexanes/EtOAc eluent) to give alkenyl
nonaflate 22 (6.19 g, 83% yield) as a colorless liquid.
frit?), rinsing with hexanes (20 mL).
The filtrate was
concentrated, and the crude product was further purified by flash
column chromatography (9:1 hexanes/EtOAc eluent) to give
ester 14 (6.02 g, 98% yield) as a pale yellow liquid.
Data for alkenyl nonaflate 22. TLC: Rf = 0.09 (9:1
hexanes/EtOAc, KMnO4 stain solution). 1H NMR (400 MHz,
CDCl3): δ = 3.68 (s, 3H), 3.31 (br. s, 1H), 2.65 (dd, J = 15.7, 3.9
Hz, 1H), 2.44-2.09 (comp. m, 8 H), 1.80-1.57 (comp. m, 3H),
1.44 (s, 9H). 13C NMR (101 MHz, CDCl3): δ = 172.3, 171.9,
143.6, 134.0, 80.4, 51.7, 40.0, 37.1, 34.9, 28.9, 28.0, 26.4, 26.1,
22.2. 19F NMR (376 MHz, CDCl3): δ = -80.7 (t, J = 9.5 Hz, 3F),
-110.3 (tq, J = 15.0, 2.7 Hz, 2F), -120.9 (m, 2F), -125.9 (m, 2F).
IR (film): ν = 2978, 2955, 2855, 1729, 1238, 1199, 1143, 909
cm-1. HRMS (DART): m/z calc’d for (M + NH4)+ [C20H25F9O7S +
NH4]+: 598.1516, found 598.1540.
Data for ester 14. TLC: Rf = 0.27 (9:1 hexanes/EtOAc,
KMnO4 stain solution). 1H NMR (400 MHz, CDCl3): δ = 4.56 (s,
2H), 3.66 (s, 3H), 3.34-3.22 (m, 1H), 2.63 (dd, J = 15.7, 3.9 Hz,
1H), 2.38-2.11 (comp. m, 8H), 2.02-1.92 (comp. m, 4H), 1.82-
1.63 (comp. m, 3H), 1.67 (s, 3H), 1.66-1.50 (comp. m, 4H). 13C
NMR (101 MHz, CDCl3): δ = 173.2, 171.9, 143.7, 133.8, 133.6,
125.0, 64.9, 51.7, 40.0, 37.0, 33.7, 31.9, 28.9, 27.7, 26.4, 26.1,
22.78, 22.75, 22.1, 19.0. 19F NMR (376 MHz, CDCl3): δ = -80.7
(t, J = 10.2 Hz, 3F), -110.3 (t, J = 15.0 Hz, 2F), -120.9 (m, 2F), -
125.9 (m, 2F). IR (film): ν = 2933, 2859, 1737, 1419, 1235,
1198, 1142, 1033, 852 cm-1. HRMS (DART): m/z calc’d for (M +
NH4)+ [C24H29F9O7S + NH4]+: 650.1829, found 650.1823.
Carboxylic acid 16 (4-(3-(2-methoxy-2-oxoethyl)-2-
(((perfluorobutyl)sulfonyl)oxy)cyclopent-1-en-1-yl)butanoic
acid). An apparatus to generate HCl gas was assembled by
charging a 50 mL Schlenk flask with ~50 g NaCl. The flask was
capped with a rubber septum and the side arm fitted with PVC
tubing connected to a long 18 gauge needle. The needle was
immersed in a solution of ester 22 (5.00 g, 9.11 mmol) in CH2Cl2
(91 mL) at ambient temperature in a 250 mL round bottom flask
fitted with a rubber septum and an outlet needle. The solution
was sparged with HCl gas by slowly adding H2SO4 (98%, 6.0
mL) to the Schlenk flask containing NaCl at a rate so as to
control the evolution of gas. Near the end of the addition, the
HCl gas needle was raised above the level of the solution and the
outlet needle was removed to create a slight positive pressure of
HCl in the flask. When the addition was complete, the needle
was removed altogether, and the flask was sealed with parafilm
and stirred 16 h at ambient temperature. At the end of this time,
TLC indicated consumption of the starting material. The reaction
mixture was then poured into H2O (50 mL), the organic phase
separated, and the aqueous phase extracted with CH2Cl2 (2 x 20
mL). The combined organic extracts were dried with Na2SO4
and concentrated in vacuo to afford acid 16 (4.45 g, 99% yield)
as a pale brown liquid.
Acid
(((perfluorobutyl)sulfonyl)oxy)cyclopent-1-en-1-yl)-2-(1-
methyl-2-methylenecyclohexyl)butanoic acid). stirred
23
(4-(3-(2-methoxy-2-oxoethyl)-2-
A
solution of ester 14 (876 mg, 1.39 mmol) and Et3N (1.94 mL,
13.9 mmol) in CH2Cl2 (14 mL) was cooled to -78 °C. Neat c-
Hx2BI (0.698 mL, 3.04 mmol) was added dropwise to the
reaction mixture at -78 °C, and the resulting mixutre was stirred
at this temperature for 60 min. At this time, the reaction mixture
was allowed to warm to ambient temperature over approx. 15
min. The solution was stirred at this temperature 20 h. At this
time, TLC indicated consumption of starting material, and the
reaction mixture was quenched by pouring into 4:1 sat. aq.
NH4Cl/1.0 M aq. Na2SO3 (25 mL), rinsing the flask with Et2O
(10 mL), and the mixture was acidified (pH 1) with 2 M aq. HCl.
The biphasic mixture was then extracted with Et2O (3 x 10 mL).
The combined organic extracts were then washed with brine (10
mL), dried with Na2SO4 and concentrated in vacuo. The
resulting residue was dissolved in MeOH (14 mL) and treated
with H2O2 (1.39 mL, 30% in H2O, 13.9 mmol). This mixture was
allowed to stand 1 h at ambient temperature, then diluted with
EtOH (25 mL) and concentrated to azeotropically remove H2O.
The residue was then gently heated with a heat gun under high
vacuum (<0.1 torr) for 1-2 min to remove most of the
Data for acid 16. TLC: Rf = 0.01 (9:1 hexanes/EtOAc, KMnO4
1
cyclohexanol. The crude product was analyzed by H NMR (d1
1
stain solution). H NMR (400 MHz, CDCl3): δ = 11.25 (br. s,

8
Tetrahedron
= 10 s) to obtain a dr of the reaction and then purified by flash
HRMS (DART): m/z calc’d for (M + H)+ [C26H34NO6F9S + H]+:
ACCEPTED MANUSCRIPT
column chromatography (19:1 hexanes/EtOAc
→
89:10:1
660.2036, found 660.2040.
hexanes/EtOAc/AcOH eluent) to give acid 23 (581 mg, 66%
yield) as a clear, colorless liquid. (For the H NMR spectrum,
excepting the signals at 1.08 and 1.10 ppm, the remaining signals
of the two diastereomers either appeared as coalesced signals or
complex multiplets.)
Alkene 37 (methyl 2-(3-(4-(dimethylamino)-3-(1-methyl-2-
methylenecyclohexyl)-4-oxobutyl)cyclopent-2-en-1-yl)acetate.
A solution of alkenyl nonaflate 35b (33.6 mg, 0.0509 mmol) in
toluene (5.1 mL) was sparged with Ar for 15 min. This solution
was transferred to an Ar flushed vial charged with a stirbar and
Pd(PPh3)4 (5.9 mg, 0.00509 mmol). To this solution was added
1
Data for acid 23. TLC: Rf
=
0.24 (89:10:1
hexanes/EtOAc/AcOH, KMnO4). 1H NMR (400 MHz, CDCl3): δ
= 4.72 (s, 1H), 4.62 (s, 1H), 3.68 (s, 3H), 3.40-3.22 (m, 1H),
2.92-2.81 (m, 1H), 2.75-2.61 (comp. m, 2H), 2.50-2.01 (comp.
m, 7H), 1.89-1.63 (comp. m, 4H), 1.62-1.42 (comp. m, 3H),
1.34-1.13 (comp. m, 3H), 1.10 (s, 1.5H), 1.08 (s, 1.5H). 13C
NMR (101 MHz, CDCl3): δ = 178.9, 178.8, 172.1, 171.9, 153.6,
153.5, 143.9, 143.4, 134.1, 133.6, 108.4, 108.3, 51.8, 51.7, 49.0,
48.6, 44.6, 41.7, 41.6, 40.1, 40.0, 37.12, 37.05, 37.0, 32.8, 29.24,
29.18, 28.0, 27.9, 26.6, 26.5, 26.2, 25.7, 24.1, 23.9, 21.73, 21.70,
21.6, 21.5, 20.2. 19F NMR (376 MHz, CDCl3): δ = -80.7 (m, 3F),
-110.2 (m, 2F), -120.9 (m, 2F), -125.9 (m, 2F). IR (film): ν =
3000 br, 2937, 2859, 1736, 1704, 1421, 1238, 1200, 1144, 907
cm-1. MS (ESI): m/z calc’d for (M + H)+ [C24H29F9O7S + H]+:
633.2, found 633.2.
HCO2 Et3NH+ (7.6 mg, 0.0509 mmol), and the solution was
-
immediately heated to 120 °C in a preheated oil bath. The
reaction mixture was stirred for 15 min at this temperature and
then allowed to cool to ambient temperature. The solution was
then passed through a short pad of SiO2, rinsing with Et2O (10
mL). The filtrate was concentrated in vacuo and purified by flash
column chromatography (9:1 hexanes/EtOAc
→
2:1
hexanes/EtOAc) to give pure alkene 37 (8.5 mg, 45% yield) as a
pale yellow liquid.
Data for alkene 37. TLC: Rf = 0.33 (2:1 hexanes/EtOAc,
KMnO4). 1H NMR (400 MHz, CDCl3): δ = 5.29 (br. s, 1H), 4.71
(s, 1H), 4.63 (s, 1H), 3.67 (s, 3H), 3.17-2.98 (m, 1H), 3.13 (app.
d, J = 8.6 Hz, 1H), 3.04 (s, 3H), 2.90 (s, 3H), 2.39-2.08 (comp.
m, 7H), 2.04-1.85 (comp. m, 3H), 1.80-1.71 (m, 1H), 1.70-1.33
(comp. m, 7H), 1.15 (s, 3H). 13C NMR (101 MHz, CDCl3): δ =
174.7, 173.4, 153.5, 145.4, 127.0, 108.2, 51.4, 43.4, 42.2, 42.0,
40.4, 38.3, 36.1, 35.6, 34.3, 33.7, 30.3, 29.7, 27.8, 26.3, 23.2,
21.9. IR (film): ν = 2929, 1736, 1634, 1438, 1394, 1254, 1165,
1132 cm-1. MS (ESI): m/z calc’d for (M + H)+ [C22H35NO3 + H]+:
362.2690, found 362.2682.
Amides 35a/35b (methyl 2-(3-(4-(dimethylamino)-3-(1-
methyl-2-methylenecylcohexyl)-4-oxobutyl)-2-
(((perfluorobutyl)sulfonyl)oxy)cyclopent-2-en-1-yl)acetate.
To a solution of acid 23 (2.20 mg, 3.26 mmol) in CH2Cl2 (13
mL) was added DMF (1.26 mL, 16.3 mmol), followed by
(COCl)2 (0.651 mL, 7.69 mmol). Toward the end of this
addition, a colorless crystalline precipitate formed. The reaction
mixture was stirred 5 min at -10 °C, then Me2NH•HCl (1.33 g,
16.3 mmol) was added in one portion, followed by i-Pr2NEt (3.41
mL, 19.6 mmol) over 30 s. The solution became clear yellow,
and it was stirred 30 min at -10 °C before being allowed to warm
to ambient temperature. The reaction mixture was then diluted
with hexanes (50 mL) and Et2O (50 mL). The resulting solution
was washed sequentially with 1 M aq. HCl (50 mL), H2O (50
mL) and brine (50 mL), dried with Na2SO4, and concentrated in
vacuo. The resulting residue was purified by flash column
chromatography (4:1 hexanes/EtOAc → 2:1 hexanes/EtOAc
eluent) to give amides 35a (739 mg, <32% yield) and 35b (1.00
g, 44% yield), both as pale yellow liquids. Amide 35a was
contaminated with an unidentified impurity that could not be
removed.
Acid 32 (2-(1-methyl-2-methylenecyclohexyl)propanoic
acid). A stirred solution of (2-methylcyclohex-1-en-1-yl)methyl
propionate7 (31, 187 mg, 1.03 mmol) and Et3N (0.710 mL, 5.13
mmol) in CH2Cl2 (10.3 mL) was cooled to -78 °C. Neat c-Hx2BI
(0.260 mL, 1.13 mmol) was added dropwise to the reaction
mixture at -78 °C, and the latter was stirred at this temperature
for 60 min. At this time, the reaction mixture was allowed to
warm to ambient temperature over approx. 15 min. The solution
was stirred at this temperature 20 h. At this time, TLC indicated
consumption of starting material, and the reaction mixture was
quenched by pouring into 4:1 sat. aq. NH4Cl/1.0 M aq. Na2SO3
(25 mL), rinsing the flask with Et2O (10 mL), and the mixture
was acidified (pH 1) with 2 M aq. HCl. The biphasic mixture
was then extracted with Et2O (3 x 10 mL). The combined
organic extracts were then washed with brine (10 mL), dried with
Na2SO4 and concentrated. The resulting residue was dissolved in
MeOH (10 mL) and treated with H2O2 (1.03 mL, 30% in H2O, 10
mmol). This mixture was allowed to stand 1 h at ambient
temperature, then diluted with EtOH (25 mL) and concentrated to
azeotropically remove H2O. The residue was then gently heated
with a heat gun under high vacuum (<0.1 torr) for 1-2 min to
remove most of the cyclohexanol. The crude product was
dissolved in CDCl3 (4.0 mL), an internal standard of 1,2-
dichloroethane was added (20.2 L, 0.256 mmol) and analyzed
Data for amide 35a. TLC: Rf = 0.14 (4:1 hexanes/EtOAc,
KMnO4). 1H NMR (400 MHz, CDCl3): δ = 4.73 (s, 1H), 4.62 (d,
J = 1.2 Hz, 1H), 3.68 (s, 3H), 3.36-3.24 (m, 1H), 3.11 (dd, J =
11.0, 2.4 Hz, 1H), 3.03 (s, 3H), 2.90 (s, 3H), 2.65 (dd, J = 15.7,
3.9 Hz, 1H), 2.50-1.22 (comp. m, 17H), 1.14 (s, 3H). 19F NMR
(376 MHz, CDCl3): δ = -80.6 (m, 3F), -110.3 (m, 2F), -120.9 (m,
2F), -125.9 (m, 2F). IR (film): ν = 2938, 2861, 1737, 1666, 1635,
1418, 1236, 1199, 1143, 1121, 1009 cm-1. HRMS (DART): m/z
calc’d for (M + H)+ [C26H34NO6F9S + H]+: 660.2036, found
660.2039.
1
by H NMR (d1 = 10 s) to obtain a crude yield and dr of the
reaction. The chloroform solution was concentrated, and the
residue was purified by flash column chromatography (19:1
hexanes/EtOAc → 89:10:1 hexanes/EtOAc/AcOH eluent) to give
acid 32 (127 mg, 68% yield) as a waxy, colorless solid.
Data for amide 35b. TLC: Rf = 0.07 (4:1 hexanes/EtOAc,
KMnO4). H NMR (400 MHz, CDCl3): δ = 4.73 (s, 1H), 4.64 (s,
1
1H), 3.68 (s, 3H), 3.36-3.18 (m, 1H), 3.17 (dd, J = 11.2, 2.5 Hz,
1H), 3.07 (s, 3H), 2.90 (s, 3H), 2.63 (dd, J = 15.7, 3.9 Hz, 1H),
2.46-2.17 (comp. m, 6H), 2.16-2.05 (m, 1H), 2.03-1.83 (comp.
m, 2H), 1.78-1.36 (comp. m, 8H), 1.14 (s, 3H). 13C NMR (101
MHz, CDCl3): δ = 174.2, 153.1, 142.8, 134.8, 108.3, 51.7, 44.4,
42.2, 39.9, 38.2, 37.1, 36.0, 35.6, 33.6, 28.8, 27.8, 26.6, 25.9,
25.8, 23.1, 21.6. 19F NMR (376 MHz, CDCl3): δ = -80.6 (m, 3F),
-110.3 (m, 2F), -120.9 (m, 2F), -125.8 (m, 2F). IR (film): ν =
2933, 2859, 1739, 1418, 1236, 1198, 1142, 1032, 1010 cm-1.
Data for acid 32. TLC: Rf
=
0.32 (89:10:1
1
hexanes/EtOAc/AcOH, KMnO4 stain solution). H NMR (400
MHz, CDCl3): δ 4.72 (s, 1H), 4.63 (s, 1H), 3.02 (q, J = 7.0 Hz,
1H), 2.39 (td, J = 14.1, 3.9 Hz, 1H), 2.17 (dt, J = 14.1, 2.4 Hz,
1H), 1.77 (app. d, J = 13.7 Hz, 2H), 1.55-1.40 (comp. m, 2H),
1.37-1.22 (m, 1H), 1.20-1.11 (m, 1H), 1.09 (d, J = 7.0 Hz, 3H),
1.08 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 181.5, 153.8, 108.2,

9
D. J. Nat. Prod. Rep. 2014, 31, 550-562. (j) Williams, D. R.;
42.3, 41.3, 37.0, 32.8, 28.1, 21.6, 21.1, 11.2. IR (film): ν = 2967,
2943, 2916, 1733, 1213, 1155, 1027, 963 cm-1. HRMS (ESI+)
m/z calc’d for (M + H)+ [C11H18O2 + H]+: 183.1380, found
183.1385.
ACCEPTED MANUSCRIPT
Mondal, O. K.; Bawel, S. A.; Nag, P. P. Org. Lett. 2014, 16,
1956-1959. (k) Diaba, F.; Martínez-Laporta, A.; Coussanes, G.;
Fernández, I.; Bonjoch, I. Tetrahedron 2015, 71, 3642-3651. (l)
Guo, J.-J.; Li, Y.; Cheng, B.; Xu, T.; Tao, C.; Yang, X.; Zhang,
D.; Yan, G.; Zhai, H. Chem. Asian J. 2015, 10, 865-868. (m)
Hayakawa, I.; Niida, K.; Kigoshi, H. Chem. Commun. 2015, 51,
11568-11571. (n) Ma, D.; Cheng, H.; Huang, C.; Xu, L.
Lactone
33
(7a-(iodomethyl)-3,3a-
dimethylhexahydrobenzofuran-2(3H)-one). To a solution of
acid 32 (57.9 mg, 0.318 mmol) and KI (106 mg, 0.636 mmol) in
a biphasic mixture of 5% aq. NaHCO3 (1.00 mL) and CH2Cl2
(1.00 mL) at ambient temperature under air was added H2O2
(63.6 L, 30 % in H2O, 0.636 mmol) dropwise. The solution
was stirred for 5 min at ambient temperature, at which time TLC
indicated consumption of the acid starting material. The reaction
was then partitioned between CH2Cl2 (20 mL) and H2O (20 mL).
The organic layer was separated and washed with brine (10 mL),
dried with Na2SO4 and concentrated to afford lactone 33 (88.4
mg, 90% yield) as a colorless, crystalline solid, which did not
require further purification. The stereochemistry of lactone 33
was assigned on the basis of NOE data.
Data for lactone 33. 1H NMR (400 MHz, CDCl3): δ 3.60 (d, J
= 11.2 Hz, 1H), 3.44 (d, J = 11.2 Hz, 1H), 3.01 (q, J = 7.2 Hz,
1H), 2.52 (br. d, J = 14.1 Hz, 1H), 1.76-1.08 (comp. m, 7H), 1.05
(d, J = 7.2 Hz, 3H), 0.91 (s, 3H). 13C NMR (101 MHz, CDCl3): δ
177.0, 83.5, 44.3, 42.0, 34.6, 32.2, 22.4, 21.0, 19.4, 9.2, 8.7. IR
(film): ν = 3357 (br), 2952, 2923, 2854, 1760, 1175, 1118, 1049,
1023, 974, 931 cm-1.
Tetrahedron Lett. 2015, 56, 2492-2495. (o) Shvartsbart, A.;
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Acknowledgments
The University of Georgia and Colorado State University are
acknowledged.
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24. Here we adopt the convention of giving boron the highest priority
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25. Diazomethane derivatization, which nearly always maintains the
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esters with nearly identical 1H NMR spectra.
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Tetrahedron
27. Of note, the reductive Heck reaction has seen highly limited
ACCEPTED MANUSCRIPT
application using sulfonate-based oxidants compared to halogen-
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28. Vogel, M. A. K.; Stark, C. B. W.; Lyapkalo, I. M. Synlett 2007,
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