Si-directed regiocontrol in asymmetric Pd-catalyzed allylic alkylations using C1-ammonium enolate nucleophiles

Article abstract of DOI:10.1016/j.tet.2018.04.021

Cooperative catalysis enables the direct enantioselective α-allylation of linear prochiral esters using Si-substituted allyl electrophiles. The Si-substituent directs the regioselectivity of enantioselective bond formation and provides products containing synthetically versatile pentafluorophenyl ester and vinylsilane moieties. Critical to the efficacy of this process was the recognition that the ancillary ligand on palladium could be altered to prevent formation of a deleterious ether by-product, whilst retaining enantioselectivity through the Lewis base catalyst. Flexibility such as this is unique to cooperative catalysis events and provides efficient access to an array of enantioenriched products that are orthogonally functionalized and easily modified.

Full text of DOI:10.1016/j.tet.2018.04.021

Accepted Manuscript
Si-directed regiocontrol in asymmetric Pd-catalyzed allylic alkylations using C1-
ammonium enolate nucleophiles
James W.B. Fyfe, Omaru M. Kabia, Colin M. Pearson, Thomas N. Snaddon
PII:
S0040-4020(18)30400-9
10.1016/j.tet.2018.04.021
TET 29436
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 February 2018
Revised Date: 5 April 2018
Accepted Date: 6 April 2018
Please cite this article as: Fyfe JWB, Kabia OM, Pearson CM, Snaddon TN, Si-directed regiocontrol
in asymmetric Pd-catalyzed allylic alkylations using C1-ammonium enolate nucleophiles, Tetrahedron
(2018), doi: 10.1016/j.tet.2018.04.021.
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ACCEPTED MANUSCRIPT
4Graphical Abstract
Si-Directed regiocontrol in asymmetric Pd-
catalyzed allylic alkylations using C1-
ammonium enolate nucleophiles
Leave this area blank for abstract info.
James W. B. Fyfe, Omaru M. Kabia, Colin M. Pearson, Thomas N. Snaddon
Department of Chemistry, Indiana University, 800 E. Kirkwood Ave., Bloomington, Indiana 47405, United States

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Si-Directed regiocontrol in asymmetric Pd-catalyzed allylic alkylations using C1-
ammonium enolate nucleophiles
James W. B. Fyfe, Omaru M. Kabia, Colin M. Pearson, Thomas N. Snaddon*
Department of Chemistry, Indiana University, 800 E. Kirkwood Ave., Bloomington, Indiana 47405, United States
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Cooperative catalysis enables the direct enantioselective α-allylation of linear prochiral esters
using Si-substituted allyl electrophiles. The Si-substituent directs the regioselectivity of
enantioselective bond formation and provides products containing synthetically versatile
pentafluorophenyl ester and vinylsilane moieties. Critical to the efficacy of this process was the
recognition that the ancillary ligand on palladium could be altered to prevent formation of a
deleterious ether by-product, whilst retaining enantioselectivity through the Lewis base catalyst.
Flexibility such as this is unique to cooperative catalysis events and provides efficient access to
an array of enantioenriched products that are orthogonally functionalized and easily modified.
Available online
Keywords:
Cooperative catalysis
Allylic alkylation
Silicon
2018 Elsevier Ltd. All rights reserved
.
Palladium
Ammonium enolate
vinylsilanes in concert with catalytic asymmetric C(sp3)–C(sp3)
bond formation (Figure 1, bottom). The incorporation of both an
electrophilic pentafluorophenyl (Pfp) ester and a nucleophilic
vinylsilane in the enantioenriched products provides the
opportunity for orthogonal diversification.
1. Introduction
Transition metal-catalyzed asymmetric allylic alkylation is a
mainstay of organic synthesis. Vast quantities of research in this
field have led to the development of catalysis by numerous
transition metals and the further development of versatile ligand
classes to control chemo-, regio- and stereo-selectivity.1 The
versatility of this general class of reactions is now such that
C(sp3)–carbon bonds can be forged efficiently and in highly
enantioselective fashion using a wide range of nucleophiles.
However, challenges remain, and premier amongst these is the
direct employment of linear, prochiral esters as partner
nucleophiles.2
A major focus of our laboratory concerns the union of C1-
ammonium enolates with transition metal electrophiles via
cooperative catalysis.3 C1-Ammonium enolates are stereodefined
ester enolate equivalents that are accessible from simple activated
carboxylic acid derivatives.4,5 Within the sphere of transition
metal-catalyzed allylic alkylation reactions, their use addresses
many of the difficulties encountered when using linear, prochiral
esters as partner nucleophiles, where control over enolate
geometry, enantiofacial selectivity, and deleterious product
racemization are prevalent.3,6 Through this manifold,
enantioselectivity is governed by the Lewis base catalyst, while
linear and branched products are accessible through judicious
choice of the transition metal catalyst.
Figure 1. Si-based regiocontrol in Pd-catalyzed allylic allylation. (a)
Attack of nucleophile at carbon distal to silicon; (b) Attack of C1-
ammonium enolate at carbon distal to silicon.
Silicon-substituted electrophiles have been extensively
investigated in transition metal-catalyzed allylic alkylation
In this Article, we demonstrate the union of C1-ammonium
enolates with silicon-substituted π-(allyl)Pd(II) electrophiles.
Here, regiocontrol is directed by the silicon substituent (Figure 1,
top) and provides the means to form synthetically versatile

2
Tetrahedron
ACCEPTED MANUSCRIPT
reactions.7 Silicon-substituents have demonstrated a remarkable
regeneration of the Pfp ester. Competing pentafluorophenolate
capacity to direct nucleophilic attack to the distal carbon in the π-
(allyl)Pd(II) complexes, through both steric and electronic
factors,7g even when the distal carbon bears a substituent.7a
Although subsequent protodesilylation would provide the
corresponding branched products; however, our interest in Si-
based regiocontrol concerns the synthetic utility of vinylsilanes.8
These are remarkably diverse synthetic handles that provide a
convenient platform for further functionalization, for example via
oxidation,9 or Hiyama–Denmark cross coupling.10 In addition,
there is significant pharmaceutical interest in using silicon as a
bioisostere for carbon.11 Although encouraging, a lack of diverse
methods for the incorporation of silicon into relevant molecular
scaffolds has been cited as a significant limitation.11
attack was suppressed when P(2-furyl)3 was used as the ligand
and gave the product in 87% yield and 93:7 er (entry 10). Finally,
increasing the Hünig’s base stoichiometry to 1.25 equivalents
gave 97% yield with no loss of enantioselectivity (entry 11).
Notably, the reaction proceeds with exclusive formation of the E-
isomer, regardless of the geometry of the starting silyl-substituted
allyl mesylate (vide infra). As expected, performing the reaction
in the absence of either catalyst did not provide the desired
product.
Scheme 1. Evaluation of substrate scopea
2. Results and Discussion
Our investigations began by assessing the reaction of phenyl
acetic
acid
pentafluorophenyl
ester
and
(E)-3-
(dimethyl(phenyl)silyl)allyl methanesulfonate. Our previously
optimized cooperative catalysis conditions3a utilizing Buchwald’s
XantphosPd G3 precatalyst and Birman’s (R)-benzotetramisole
(BTM)12 gave the desired (R)-configured allylated product13 in
51% yield and 93:7 er as the alkene (E)-isomer (Table 1, entry 1).
Table 1. Ligand evaluation and reaction optimization.
aYields determined by 1H-NMR comparison with an internal standard
(1,2,4,5-tetramethylbenzene). bDetermined by chiral HPLC analysis in
comparison to the racemate. cOnly XantphosPd G3 precatalyst was used,
Pd2dba3 was omitted. d1.25 equiv iPr2NEt used.
aIsolated yields after silica gel chromatography. Enantiomeric ratio
determined by chiral HPLC in comparison to the racemate. bEnantiomeric
ratio determined following reduction to the corresponding alcohol.
cEnantiomeric ratio after 6 h reaction time.
Generating the catalyst in situ from Pd2dba3 precatalyst and
Xantphos gave the product in an improved 77% yield and with
comparable enantioselectivity (Table 1, entry 2). Thereafter, a
short survey of phosphine ligands possessing different steric and
electronic profiles revealed that a wide range of catalyst systems
were capable of effectively catalyzing the reaction, albeit with
slightly lower levels of enantioselection (entries 3-8). Returning
to Xantphos, a solvent screen revealed comparable results in 1,4-
dioxane; however, the reaction could not be pushed beyond
With optimized conditions in hand, we then sought to evaluate
the scope of the reaction with respect to both the aryl acetic acid
ester and three commonly encountered silicon substituents A-C
(Scheme 1), each of which provides opportunity for further
functionalization of the products. A range of aryl substituents
could be incorporated, encompassing a variety of electronic
demands. Although nucleophiles bearing electron-donating
groups performed well, the electron-withdrawing CF3 group
provided the products 5A-C with lower enantioenrichment. We
considered this was due to racemization of the products over time
(due to the enhanced acidity of the stereogenic proton in the
products). Running these reactions for a shorter time period (6 h
1
~75% conversion (entry 9). Interrogation of the H NMR spectra
of the crude material determined this was due to competing
attack of the pentafluorophenolate anion on the electrophilic allyl
mesylate, thus preventing turnover of the Lewis base catalyst and

3
vs. 24 h) restored the level of enantioenrichment with no loss in
Scheme 3. Functionalization of vinyl silanes.
ACCEPTED MANUSCRIPT
yield. The reaction could also be performed on preparative scale,
with 2A and 2C synthesized on gram scale in comparable yield
and enantioselectivity (see Supporting Information for details).
Overall, the reaction was tolerant to variation of both the aryl and
silyl substituents, and provides the desired products in good
yields and useful levels of enantioselection.
Next, we turned our attention to the derivatization of the Pfp
ester (Scheme 2). Here, the (Z)-isomer of the allyl mesylate was
employed as a demonstration of the energetic preference for
exclusive formation of the (E)-isomer products. A range of
nucleophilic quenches were then employed, successfully
affording amide 10, ester 11 and carboxylic acid 12 in good
yields and enantioselectivity without the need for any
intermediate purification.
Scheme 2. In situ functionalization of the ester moiety.
3. Conclusions
In summary, we have developed a cooperative catalysis
process that permits the direct, enantioselective α-allylation of
linear, prochiral esters using Si-substituted allyl electrophiles.
The Si-substituent directs the regioselectivity of the
enantioselective bond formation and provides products
containing synthetically versatile pentafluorophenyl ester and
vinylsilane moieties. This procedure is general across a range of
pentafluorophenyl acetic ester nucleophiles along with three
differentially Si-substituted allyl electrophiles. In situ quenching
of the reaction allowed efficient derivatization of the Pfp ester
group without the need for additional isolation/purification. We
have also demonstrated chemical transformations of the three
silyl moieties through halogenation, cross-coupling, and
oxidation protocols, thus emphasizing the versatility of the
reaction products for the efficient synthesis of enantioenriched
molecular scaffolds.
4. Experimental
4.1. General Information
To demonstrate the chemical utility of the installed silyl
functional groups, each of the three silicon substituents was
subjected to a different transformation. The phenyldimethylsilyl
group underwent facile halogenation with NIS giving 13 in
excellent yield (Scheme 3). Although use of MeCN as the
reaction solvent formed a 1:1 mixture of alkene isomers,
performing the reaction in hexafluoroisopropanol (HFIP)
afforded the (Z)-alkene isomer preferentially. This is an
interesting observation that differs from the expected retention of
stereochemistry reported by Zakarian and coworkers,14a who
utilized HFIP to suppress alkene isomerization. We speculate that
participation of the proximal Pfp-ester leads to the observed
stereodivergence in a manner described by Kishi and co-
workers.14b Hiyama–Denmark cross-coupling10,15 of the
benzyldimethylsilane afforded compound 14 in excellent yield
and enantioselectivity. This is complementary to our previously
reported work with cinnamyl carbonate electrophiles, as it
enables the bulk synthesis of the silylated intermediate which can
then be differentially modified via cross-coupling with a range of
aryl halides, allowing the type of late stage derivatization ideally
suited to the development of compound libraries. Finally, the
trimethylsilyl moiety could be converted to the corresponding
aldehyde via the intermediate silylated oxirane.9,16
1H and 13C NMR spectra were recorded at room temperature
on Varian Inova-instrumentation: Varian I400 (1H NMR at
400MHz and 13C NMR at 100 MHz), Varian VXR400 (1H NMR
at 400 MHz and 13C NMR at 100 MHz), and Varian I500 (1H
NMR at 500 MHz and 13C NMR at 125 MHz) using deuterium
lock. Data for 1H NMR spectra are quoted relative to chloroform
as an internal standard (7.26 ppm) and data for 13C NMR spectra
are quoted relative to CDCl3 as an internal standard (77.16 ppm)
and are reported in terms of chemical shift (δ ppm). Data are
reported as follows: chemical shift, integration, multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, br = broad, m =
multiplet), and coupling constants (Hz). In all cases 13C signals
for pentafluorophenyl were not observed due to splitting. Infrared
spectra (IR) were obtained on an Bruker Tensor II FT-IR
Spectrometer and recorded in wavenumbers (cm-1). High
Resolution Mass (HRMS) analysis was obtained using Electron
Impact Ionization (EI) or Chemical Ionization (CI) and reported
as m/z (relative intensity) for the [M]+ or [M+H]+ molecular ion.
GC-MS data was acquired using an Agilent 6890N Gas
Chromatograph and 5973 Inert Mass Selective Detector. Chiral
HPLC analyses were performed on an Agilent 1200 Series
system. All [α]D23 values were obtained in CHCl3 at c = 1.0.

4
Tetrahedron
ACCEPTED MANUSCRIPT
MHz): δ 169.6, 143.1, 140.0, 137.0, 132.2, 129.1, 128.4, 128.2,
128.1, 128.0, 124.1, 50.8, 40.2, 26.1, –3.4. 19F NMR (CDCl3,
376 MHz): δ –147.22 - –156.01 (m, 2F), –158.00 (t, J = 21.7 Hz,
1F), –162.40 (dd, J = 21.8, 17.2 Hz, 2F). HRMS: exact mass
calculated for [M+Na]+ C26H23F5O2Si requires m/z 513.1285,
found m/z 513.1276. HPLC analysis using a chiral column
(Chiralpak IA 3ꢀ column, 22 °C, 1.00 mL/min, 800:1
Hexane:Isopropanol, 210 nm, tmajor = 6.955 min, tminor = 7.61
min). [α]D23: –33.9.
4.2. General Procedure for synthesis of compounds 1A – 9C
To an oven dried 1 dram vial equipped with stirrer bar was
added Pd2dba3 (4.5 mg, 0.005 mmol, 5 mol%), P(2-furyl)3 (2.3
mg, 0.01 mmol, 10 mol%) and aryl acetic acid pentafluorophenyl
ester (0.1 mmol, 1 equiv). The vial was then sealed with a PTFE
lined cap and purged with nitrogen (× 3) before the addition of
1,4-dioxane (0.8 mL, 0.1 M). iPr2NEt (22 µL, 0.125 mmol, 1.25
equiv) was then added via a microsyringe and the reaction was
stirred at rt for 1 h before the addition of (+)-BTM (0.1 mL, 0.2
M, 0.02 mmol, 20 mol%) and the appropriate (silyl)allyl
methanesulfonate (0.1 mL, 1.25 M, 0.125 mmol, 1.25 equiv) as a
solution in 1,4-dioxane. The reaction was then allowed to stir at
rt for a further 24 h before being quenched with petroleum ether
(4 mL). The resulting solution was then passed through a plug of
acidic alumina, washing the vial and alumina plug with Et2O (2 ×
4 mL). The solution was then concentrated under vacuum and
purified by column chromatography (silica gel, 100:1
pentane:Et2O) to afford the desired product.
Pentafluorophenyl
(trimethylsilyl)pent-4-enoate, 2A
(E)-2-(4-methoxyphenyl)-5-
White solid (39 mg, 86% yield, 88:12 er). IR (film): 2956,
1775, 1518, 1247, 1093, 1028, 1002, 985, 871, 838. H NMR
1
(CDCl3, 400 MHz): δ 7.28 (d, J = 8.7 Hz, 2H), 6.90 (d, J = 8.7
Hz, 2H), 6.00 (dt, J = 18.6, 6.2 Hz, 1H), 5.80 (dt, J = 18.6, 1.4
Hz, 1H), 3.98 (dd, J = 9.3, 6.1 Hz, 1H), 3.81 (s, 3H), 3.02 – 2.87
(m, 1H), 2.69 – 2.56 (m, 1H), 0.02 (s, 9H). 13C NMR (CDCl3,
101 MHz): δ 169.9, 159.4, 141.9, 134.1, 129.1, 114.4, 55.4, 50.1,
40.3, –1.3. 19F NMR (CDCl3, 376 MHz): δ –151.04 - –153.93
(m, 2F), –158.15 (t, J = 21.6 Hz, 1F), –162.35 - –162.77 (m, 2F).
HRMS: exact mass calculated for [M+H]+ C21H22F5O3Si requires
m/z 445.1253, found m/z 445.1241. HPLC analysis using a chiral
column (Chiralpak IA 3ꢀ column, 22 °C, 0.75 mL/min, 99:1
Hexane:Isopropanol, 210 nm, tminor = 4.913min, tmajor = 5.143
min). [α]D23: –77.1.
Pentafluorophenyl
enoate, 1A
(E)-2-phenyl-5-(trimethylsilyl)pent-4-
White solid (28 mg, 68% yield, 91:9 er). IR (film): 2958,
1775, 1516, 1242, 1096, 985, 839, 747, 697, 511. 1H NMR
(CDCl3, 400 MHz): δ 7.41 – 7.35 (m, 4H), 7.35 – 7.30 (m, 1H),
6.00 (dt, J = 18.6, 6.3 Hz, 1H), 5.80 (dt, J = 18.6, 1.4 Hz, 1H),
4.03 (dd, J = 9.3, 6.1 Hz, 1H), 2.99 (dd, J = 7.9, 1.4 Hz, 1H),
2.64 (dtd, J = 14.5, 6.1, 1.5 Hz, 1H), 0.02 (s, 9H). 13C NMR
(CDCl3, 101 MHz): δ 169.7, 141.8, 137.1, 134.2, 129.1, 128.1,
128.0, 50.9, 40.2, –1.3. 19F NMR (CDCl3, 376 MHz): δ –150.26 -
–153.51 (m, 2F), –158.07 (t, J = 21.7 Hz, 1F), –162.49 (dd, J =
22.0, 17.0 Hz, 2F). HRMS: exact mass calculated for [M+H]+
C20H20F5O2Si requires m/z 415.1147, found m/z 415.1158. HPLC
analysis using a chiral column (Chiralpak IA 3ꢀ column, 22 °C,
0.75 mL/min, 98:2 Hexane:Isopropanol, 210 nm, tminor = 14.381
min, tmajor = 14.832 min). [α]D23: –67.9.
Pentafluorophenyl
methoxyphenyl)pent-4-enoate, 2B
(E)-5-(dimethyl(phenyl)silyl)-2-(4-
Colorless oil (45 mg, 89% yield, 92:8 er). IR (film): 2956,
1780, 1612, 1517, 1427, 1249, 1180, 1093, 1034, 991, 822, 786,
731, 699. H NMR (CDCl3, 400 MHz): δ 7.46 – 7.40 (m, 2H),
1
7.37 – 7.30 (m, 3H), 7.29 – 7.22 (m, 2H), 6.90 (d, J = 8.7 Hz,
2H), 6.06 (dt, J = 18.6, 6.3 Hz, 1H), 5.93 – 5.88 (m, 1H), 3.99
(dd, J = 8.7, 6.7 Hz, 1H), 3.81 (s, 3H), 3.13 – 2.91 (m, 1H), 2.84
– 2.60 (m, 1H), 0.29 (d, J = 2.1 Hz, 6H). 13C NMR (CDCl3, 101
MHz): δ 169.8, 159.4, 143.9, 138.7, 133.9, 132.0, 129.14,
129.09, 128.9, 127.8, 114.4, 55.4, 49.9, 40.3, –2.6. 19F NMR
(CDCl3, 376 MHz): δ –148.37 - – 154.93 (m, 2F), –158.11 (t, J =
21.6 Hz, 1F), –160.95 – –164.74 (m, 2F). HRMS: exact mass
calculated for [M+Na]+ C26H23F5O3SiNa requires m/z 529.1234,
found m/z 529.1215. HPLC analysis using a chiral column
(Chiralpak IA 3ꢀ column, 22 °C, 0.75 mL/min, 99:1
Hexane:Isopropanol, 210 nm, = tmajor 18.248 min, tminor = 22.005
min). [α]D23: –50.3.
Pentafluorophenyl
(E)-5-(dimethyl(phenyl)silyl)-2-
phenylpent-4-enoate, 1B
Colorless oil (45 mg, 95% yield, 94:6 er). IR (film): 2956,
1
1781, 1518, 1248, 1098, 991, 820, 731, 697. H NMR (CDCl3,
400 MHz): δ 7.45 (dd, J = 7.6, 1.8 Hz, 2H), 7.41 – 7.29 (m, 7H),
6.08 (dt, J = 18.6, 6.3 Hz, 1H), 5.93 (dt, J = 18.6, 1.4 Hz, 1H),
4.06 (dd, J = 8.8, 6.6 Hz, 1H), 3.05 (dddd, J = 14.8, 8.7, 6.2, 1.3
Hz, 1H), 2.72 (dtd, J = 14.4, 6.5, 1.4 Hz, 1H), 0.31 (d, J = 1.7 Hz,
6H). 13C NMR (CDCl3, 101 MHz): δ 169.6, 143.7, 138.6, 136.9,
133.2, 132.1, 129.09, 129.07, 128.09, 128.06, 127.9, 50.8, 40.3, –
2.58, –2.61. 19F NMR (CDCl3, 376 MHz): δ –149.99 - –153.78
(m, 2F), –158.03 (t, J = 21.6 Hz, 1F), –160.34 - –164.20 (m, 2F).
HRMS: exact mass calculated for [M+Na]+ C25H21F5O2SiNa
requires m/z 499.1129, found m/z 499.1120. HPLC analysis
using a chiral column (Chiralpak IA 3ꢀ column, 22 °C, 0.5
mL/min, 600:1 Hexane:Isopropanol, 210 nm, tminor = 12.108 min,
tmajor = 13.456 min). [α]D23: –34.3.
Pentafluorophenyl
methoxyphenyl)pent-4-enoate, 2C
(E)-5-(benzyldimethylsilyl)-2-(4-
Colorless oil (45 mg, 87% yield, 93:7 er). IR (film): 2956,
1780, 1517, 1493, 1249, 1180, 1092, 1034, 992, 907, 830, 732,
699, 553. H NMR (CDCl3, 400 MHz): δ 7.22 (d, J = 7.8 Hz,
1
2H), 7.14 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 7.3 Hz, 1H), 6.90 (d, J =
7.6 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 5.92 (dt, J = 18.7, 6.3 Hz,
1H), 5.71 (d, J = 18.6 Hz, 1H), 3.90 (dd, J = 8.8, 6.6 Hz, 1H),
3.77 (s, 3H), 2.91 (dt, J = 15.2, 7.8 Hz, 1H), 2.58 (dt, J = 13.9,
6.5 Hz, 1H), 2.04 (s, 2H), -0.05 (d, J = 1.7 Hz, 6H). 13C NMR
(CDCl3, 101 MHz): δ 169.8, 159.4, 143.2, 140.0, 132.1, 129.1,
Pentafluorophenyl (E)-5-(benzyldimethylsilyl)-2-phenylpent-
4-enoate, 1C
128.9, 128.4, 128.2, 124.1, 114.4, 55.4, 50.0, 40.3, 26.1, –3.4. 19
F
NMR (CDCl3, 376 MHz): δ –149.4 - –154.0 (m, 2F), –158.1 (t, J
= 21.7 Hz, 1F), –161.2 - –165.0 (m, 2F). HRMS: exact mass
calculated for [M+Na]+ C27H25F5O3SiNa requires m/z 543.1391,
found m/z 543.1367. HPLC analysis using a chiral column
(Chiralpak IB 3ꢀ column, 22 °C, 1.00 mL/min, 800:1
Hexane:Isopropanol, 210 nm, = tmajor 13.793 min, tminor = 20.379
min). [α]D23: –36.7.
Colorless oil (47 mg, 95% yield, 93:7 er). IR (film): 3026,
2955, 1781, 1518, 1493, 1248, 1096, 1028, 991, 831, 736, 697.
1H NMR (CDCl3, 400 MHz): δ 7.47 – 7.28 (m, 5H), 7.20 (t, J =
7.5 Hz, 2H), 7.07 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 6.7 Hz, 2H),
5.99 (dt, J = 18.7, 6.2 Hz, 1H), 5.77 (dt, J = 18.6, 1.4 Hz, 1H),
4.02 (dd, J = 8.8, 6.5 Hz, 1H), 3.10 – 2.90 (m, 1H), 2.76 – 2.55
(m, 1H), 2.10 (s, 2H), 0.02 (s, 6H). 13C NMR (CDCl3, 101

5
Pentafluorophenyl
(trimethylsilyl)pent-4-enoate, 3A
(E)-2-(naphthalen-2-yl)-5-
50.2, 40.2, –1.3. 19F NMR (CDCl3, 376 MHz): δ –149.99 - –
ACCEPTED MANUSCRIPT
154.32 (m, 2F), –157.78 (t, J = 21.7 Hz, 1F), –162.30 (dd, J =
21.8, 17.2 Hz, 2F). HRMS: exact mass calculated for [M+H]+
C20H19ClF5O2Si requires m/z 449.0758, found m/z 449.0751.
HPLC analysis using a chiral column (Chiralpak IA 3ꢀ column,
22 °C, 0.5 mL/min, 800:1 Hexane:Isopropanol, 210 nm, = tmajor
13.671 min, tminor = 17.323 min). [α]D23: –72.4.
White solid (34 mg, 72% yield, 89:11 er). IR (film): 1775,
1517, 1248, 1100, 988, 862, 839, 751, 481, 420. 1H NMR
(CDCl3, 400 MHz): δ 7.96 – 7.67 (m, 4H), 7.54 – 7.45 (m, 3H),
6.05 (dt, J = 18.6, 6.3 Hz, 1H), 5.84 (dt, J = 18.7, 1.4 Hz, 1H),
4.21 (dd, J = 9.2, 6.1 Hz, 1H), 3.09 (dddd, J = 14.6, 9.3, 6.5, 1.4
Hz, 1H), 2.82 – 2.63 (m, 1H), 0.02 (s, 9H). 13C NMR (CDCl3,
101 MHz): δ 169.7, 141.7, 134.5, 134.4, 133.6, 133.0, 128.9,
128.0, 127.8, 127.1, 126.6, 125.6, 51.0, 40.3, –1.3. 19F NMR
(CDCl3, 376 MHz): δ –151.95 - –152.66 (m, 2F), –157.99 (t, J =
21.7 Hz, 1F), –162.42 (dd, J = 21.9, 17.1 Hz, 2F). HRMS: exact
mass calculated for [M+H]+ C24H22F5O2Si requires m/z 465.1304,
found m/z 465.1291. HPLC analysis using a chiral column
(Chiralpak IB 3ꢀ column, 22 °C, 1.00 mL/min, 800:1
Hexane:Isopropanol, 210 nm, = tmajor 8.292 min, tminor = 8.941
min). [α]D23: –81.9.
Pentafluorophenyl
chlorophenyl)pent-4-enoate, 4B
(E)-5-(dimethyl(phenyl)silyl)-2-(4-
Colorless oil (45 mg, 88% yield, 92:8 er). IR (film): 2957,
1781, 1518, 1492, 1248, 1092, 992, 908, 821, 730, 699. 1H
NMR (CDCl3, 400 MHz): δ 7.43 – 7.38 (m, 2H), 7.37 – 7.30 (m,
5H), 7.28 (d, J = 8.5 Hz, 2H), 6.02 (dt, J = 18.6, 6.3 Hz, 1H),
5.94 – 5.86 (m, 1H), 4.02 (dd, J = 8.4, 7.0 Hz, 1H), 3.01 (dddd, J
= 14.6, 8.5, 6.2, 1.3 Hz, 1H), 2.68 (dtd, J = 14.7, 6.6, 1.4 Hz,
1H), 0.29 (d, J = 1.8 Hz, 6H). 13C NMR (CDCl3, 101 MHz): δ
169.3, 143.2, 138.5, 135.3, 134.1, 133.9, 132.7, 129.5, 129.3,
129.2, 127.9, 50.1, 40.2, –2.6. 19F NMR (CDCl3, 376 MHz): δ –
148.37 - –154.93 (m, 2F), –157.70 (t, J = 21.6 Hz, 1F), –162.21
(dd, J = 21.7, 17.2 Hz, 2F). HRMS: exact mass calculated for
[M+Na]+ C25H20ClF5O2SiNa requires m/z 533.0739, found m/z
533.0744. HPLC analysis using a chiral column (Chiralpak IA 3ꢀ
column, 22 °C, 0.75 mL/min, 800:1 Hexane:Isopropanol, 210
nm, = tminor 17.075 min, tmajor = 21.525 min). [α]D23: –38.6.
Pentafluorophenyl
(naphthalen-2-yl)pent-4-enoate, 3B
(E)-5-(dimethyl(phenyl)silyl)-2-
Colorless oil (48 mg, 90% yield, 88:12 er). IR (film): 3054,
2956, 1781, 1518, 1248, 1096, 991, 839, 818, 786, 730, 699, 475.
1H NMR (CDCl3, 400 MHz): δ 7.80 – 7.42 (m, 4H), 7.34 – 6.81
(m, 8H), 5.88 – 5.74 (m, 1H), 5.71 – 5.53 (m, 1H), 3.94 (t, J =
7.8 Hz, 1H), 2.84 (dt, J = 14.9, 7.4 Hz, 1H), 2.65 – 2.39 (m, 1H),
-0.00 (d, J = 1.8 Hz, 4H). 13C NMR (CDCl3, 101 MHz): δ 143.7,
134.3, 133.9, 133.0, 132.3, 129.1, 128.9, 128.1, 127.9, 127.8,
127.3, 126.6, 126.4, 125.6, 50.9, 40.3, –2.6. 19F NMR (CDCl3,
376 MHz): δ –152.20 - –152.50 (m, 2F), –157.94 (t, J = 21.6 Hz,
1F), –162.36 (dd, J = 21.9, 17.3 Hz, 2F). HRMS: exact mass
calculated for [M+Na]+ C29H23F5O2SiNa requires m/z 549.1285,
found m/z 549.1307. HPLC analysis using a chiral column
(Chiralpak IA 3ꢀ column, 22 °C, 0.5 mL/min, 99:1
Hexane:Isopropanol, 210 nm, = tmajor 8.710 min, tminor = 10.080
min). [α]D23: –50.2.
Pentafluorophenyl
chlorophenyl)pent-4-enoate, 4C
(E)-5-(benzyldimethylsilyl)-2-(4-
Colorless oil (49 mg, 93% yield, 89:11 er). IR (film): 2955,
1781, 1518, 1492, 1248, 1092, 992, 830, 761, 733, 698, 476. 1H
NMR (CDCl3, 400 MHz): δ 7.36 (d, J = 8.5 Hz, 2H), 7.28 (d, J =
8.5 Hz, 2H), 7.20 (t, J = 7.5 Hz, 2H), 7.07 (t, J = 7.3 Hz, 1H),
6.95 (d, J = 6.9 Hz, 2H), 5.94 (dt, J = 18.6, 6.2 Hz, 1H), 5.76 (dt,
J = 18.6, 1.4 Hz, 1H), 3.98 (dd, J = 8.6, 6.8 Hz, 1H), 3.07 – 2.90
(m, 1H), 2.64 (dtd, J = 12.9, 6.8, 1.4 Hz, 1H), 2.10 (s, 2H), 0.02
(s, 6H). 13C NMR (CDCl3, 101 MHz): δ 169.3, 142.5, 139.9,
135.4, 134.1, 132.7, 129.4, 129.2, 128.3, 128.2, 124.1, 50.1, 40.1,
26.0, –3.4. 19F NMR (CDCl3, 376 MHz): δ –148.03 - –153.51
(m, 2F), –157.68 (t, J = 21.6 Hz, 1F), –162.19 (dd, J = 21.8, 17.3
Hz, 2F). HRMS: exact mass calculated for [M]+ C26H22ClF5O2Si
requires m/z 524.0992, found m/z 524.0975. HPLC analysis
using a chiral column (Chiralpak IA 3ꢀ column, 22 °C, 0.4
mL/min, 600:1 Hexane:Isopropanol, 210 nm, = tmajor 22.250 min,
tminor = 27.271 min). [α]D23: –38.8.
Pentafluorophenyl (E)-5-(benzyldimethylsilyl)-2-(naphthalen-
2-yl)pent-4-enoate, 3C
Colorless oil (50 mg, 92% yield, 91:9 er). IR (film): 3059,
3024, 2955, 1780, 1518, 1493, 1248, 1095, 992, 831, 816, 733,
698, 475. 1H NMR (CDCl3, 400 MHz): δ 7.96 – 7.76 (m, 4H),
7.57 – 7.44 (m, 3H), 7.15 (t, J = 7.5 Hz, 2H), 7.04 (t, J = 7.4 Hz,
1H), 6.92 (d, J = 7.0 Hz, 2H), 6.02 (dt, J = 18.6, 6.2 Hz, 1H),
5.79 (d, J = 18.6 Hz, 1H), 4.18 (dd, J = 8.7, 6.5 Hz, 1H), 3.27 –
2.97 (m, 1H), 2.76 (dtd, J = 14.4, 6.3, 1.4 Hz, 1H), 2.08 (s, 2H),
0.00 (s, 6H). 13C NMR (CDCl3, 101 MHz): δ 169.6, 143.0,
140.0, 134.3, 133.6, 133.0, 132.3, 128.9, 128.3, 128.2, 128.0,
127.9, 127.2, 126.6, 126.4, 125.6, 124.1, 50.9, 40.3, 26.1, –3.4.
19F NMR (CDCl3, 376 MHz): δ –152.36 (d, J = 17.5 Hz, 2F), –
157.91 (t, J = 21.7 Hz, 1F), –162.32 (dd, J = 21.8, 17.3 Hz, 2F).
HRMS: exact mass calculated for [M+Na]+ C30H25F5O2SiNa
requires m/z 563.1442, found m/z 563.1437. HPLC analysis
using a chiral column (Chiralpak IA 3ꢀ column, 22 °C, 0.5
mL/min, 99:1 Hexane:Isopropanol, 210 nm, = tminor 7.544 min,
tmajor = 8.355 min). [α]D23: –51.2.
Pentafluorophenyl
(E)-2-(
4-(trifluoromethyl)phenyl)-5-
(trimethylsilyl)pent-4-enoate, 5A
White solid (33 mg, 69% yield, 89:11 er). IR (film): 2957,
1783, 1519, 1325, 1168, 1129, 1100, 1069, 993, 863, 837, 734.
1H NMR (CDCl3, 400 MHz): δ 7.65 (d, J = 7.9 Hz, 2H), 7.49 (d,
J = 7.9 Hz, 2H), 6.04 – 5.90 (m, 1H), 5.86 – 5.73 (m, 1H), 4.11
(dd, J = 8.9, 6.3 Hz, 1H), 3.01 (ddd, J = 15.1, 8.5, 6.1 Hz, 1H),
2.75 – 2.60 (m, 1H), 0.03 (s, 9H). 13C NMR (CDCl3, 101 MHz):
2
δ 169.1, 141.0, 140.9, 135.1, 130.5 (q, JC-F = 32.7 Hz), 128.5,
126.0 (q, 3JC-F = 3.8 Hz), 124.1 (q, 1JC-F = 272.0 Hz), 50.7, 40.2, –
1.3. 19F NMR (CDCl3, 376 MHz): δ –62.74 (s, 3F), –150.26 - –
154.66 (m, 2F), –157.56 (t, J = 21.7 Hz, 1F), –162.17 (dd, J =
21.7, 17.2 Hz, 2F). HRMS: exact mass calculated for [M-CH3]+
C20H15F8O2Si requires m/z 476.0708, found m/z 467.0718. HPLC
analysis using a chiral column (Chiralpak IA 3ꢀ column, 22 °C,
1.0 mL/min, 98:2 Hexane:Isopropanol, 210 nm, = tmajor 10.524
min, tminor = 13.282 min). [α]D23: –46.3.
Pentafluorophenyl
(trimethylsilyl)pent-4-enoate, 4A
(E)-2-(4-chlorophenyl)-5-
White solid (33 mg, 72% yield, 88:12 er). IR (film): 2956,
1774, 1517, 1248, 1097, 985, 870, 838, 525. H NMR (CDCl3,
1
400 MHz): δ 7.35 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H),
5.97 (dt, J = 18.6, 6.2 Hz, 1H), 5.85 – 5.72 (m, 1H), 4.01 (dd, J =
9.0, 6.4 Hz, 1H), 2.97 (dddd, J = 14.4, 9.0, 6.4, 1.3 Hz, 1H), 2.63
(dtd, J = 14.3, 6.2, 1.4 Hz, 1H), 0.03 (s, 9H). 13C NMR (CDCl3,
101 MHz): δ 169.3, 141.2, 135.5, 134.7, 134.1, 129.4, 129.2,
Pentafluorophenyl
(E)-5-(dimethyl(phenyl)silyl)-2-(4-
(trifluoromethyl)phenyl)pent-4-enoate, 5B

6
Tetrahedron
ACCEPTED MANUSCRIPT
Colorless oil (45 mg, 81% yield, 86:14 er). IR (film): 2958,
exact mass calculated for [M+Na]+ C26H23F5O2SiNa requires m/z
1782, 1619, 1519, 1324, 1167, 1127, 1111, 1068, 992, 838, 820,
731, 699. 1H NMR (CDCl3, 400 MHz): δ 7.64 (d, J = 8.0 Hz,
2H), 7.47 (d, J = 8.0 Hz, 2H), 7.44 – 7.39 (m, 2H), 7.37 – 7.29
(m, 3H), 6.12 – 5.95 (m, 1H), 5.95 – 5.86 (m, 1H), 4.12 (t, J =
7.7 Hz, 1H), 3.10 – 2.98 (m, 1H), 2.78 – 2.65 (m, 1H), 0.30 (s,
6H). 13C NMR (CDCl3, 101 MHz): δ 169.0, 142.8, 139.6 (d, 1JC-F
513.1285, found m/z 513.1263. HPLC analysis using a chiral
column (Chiralpak IA 3ꢀ column, 22 °C, 0.75 mL/min, 99:1
Hexane:Isopropanol, 210 nm, = tmajor 12.367 min, tminor = 14.733
min). [α]D23: –41.8.
Pentafluorophenyl
tolyl)pent-4-enoate, 6C
(E)-5-(benzyldimethylsilyl)-2-(4-
2
= 245.4 Hz), 133.9, 133.0, 130.5 (d, JC-F = 32.9 Hz), 129.2,
128.6, 127.9, 126.0 (d, 3JC-F = 3.8 Hz), 50.5, 40.2, –2.7. 19F NMR
(CDCl3, 376 MHz): δ –62.69 (s, 3F), –152.25 - –152.76 (m, 2F),
–157.55 (t, J = 21.7 Hz, 1F), –161.78 - –162.39 (m, 2F). HRMS:
exact mass calculated for [M+H]+ C26H21F8O2Si requires m/z
545.1178, found m/z 545.1159. HPLC analysis using a chiral
column (Chiralpak IB 3ꢀ column, 22 °C, 1.0 mL/min, 800:1
Hexane:Isopropanol, 210 nm, = tminor 9.576 min, tmajor = 10.205
min). [α]D23: –19.2.
Colorless oil (46 mg, 91% yield, 93:7 er). IR (film): 2955,
1781, 1518, 1493, 1248, 1093, 992, 830, 699, 476. H NMR
1
(CDCl3, 400 MHz): δ 7.29 – 7.19 (m, 6H), 7.09 (t, J = 7.4 Hz,
1H), 6.98 (d, J = 6.6 Hz, 2H), 6.02 (dt, J = 18.6, 6.2 Hz, 1H),
5.85 – 5.72 (m, 1H), 4.01 (dd, J = 8.9, 6.4 Hz, 1H), 3.09 – 2.94
(m, 1H), 2.67 (dtd, J = 14.3, 6.3, 1.4 Hz, 1H), 2.40 (s, 3H), 2.13
(s, 2H), 0.05 (s, 6H). 13C NMR (CDCl3, 101 MHz): δ 169.8,
143.2, 140.0, 137.8, 134.0, 132.1, 129.7, 128.4, 128.2, 127.9,
124.1, 50.4, 40.3, 26.1, 21.3, –3.4. 19F NMR (CDCl3, 376 MHz):
δ –151.79 - –152.94 (m, 2F), –158.08 (t, J = 21.7 Hz, 1F), –
162.46 (dd, J = 21.6, 17.2 Hz, 2F). HRMS: exact mass calculated
for [M+Na]+ C27H25F5O2SiNa requires m/z 527.1442, found m/z
527.1427. HPLC analysis using a chiral column (Chiralpak IB 3ꢀ
column, 22 °C, 1.0 mL/min, 800:1 Hexane:Isopropanol, 210 nm,
= tmajor 6.925 min, tminor = 9.236 min). [α]D23: –44.4.
Pentafluorophenyl
(E)-5-(benzyldimethylsilyl)-2-(4-
(trifluoromethyl)phenyl)pent-4-enoate, 5C
Colorless oil (43 mg, 79% yield, 89:11 er). IR (film): 2957,
1
1783, 1519, 1493, 1324, 1127, 1068, 993, 831, 733, 699. H
NMR (CDCl3, 400 MHz): δ 7.66 (d, J = 8.1 Hz, 2H), 7.48 (d, J =
8.1 Hz, 2H), 7.20 (t, J = 7.6 Hz, 2H), 7.07 (t, J = 7.4 Hz, 1H),
6.96 (d, J = 6.7 Hz, 2H), 5.95 (dt, J = 18.6, 6.2 Hz, 1H), 5.84 –
5.73 (m, 1H), 4.09 (dd, J = 8.6, 6.7 Hz, 1H), 3.10 – 2.97 (m, 1H),
2.74 – 2.61 (m, 1H), 2.10 (s, 2H), 0.02 (s, 6H). 13C NMR
(CDCl3, 101 MHz): δ 169.0, 142.2, 140.8, 139.9, 133.0, 130.5 (d,
Pentafluorophenyl
(E)-2-(2-fluorophenyl)-5-
(trimethylsilyl)pent-4-enoate, 7A
Colorless oil (33 mg, 76% yield, 90:10 er). IR (film): 2956,
3
4
2JC-F = 32.6 Hz), 128.5, 128.3 (d, JC-F = 10.2 Hz), 126.0 (q, JC-F
= 3.7 Hz), 124.2, 50.6, 40.2, 26.0, –3.4. CF3 carbon not observed.
19F NMR (CDCl3, 376 MHz): δ –62.70 (s, 3F), –152.56 (d, J =
17.3 Hz, 2F), –157.49 (t, J = 21.7 Hz, 1F), –162.08 (dd, J = 21.7,
17.2 Hz, 2F). HRMS: exact mass calculated for [M+H]+
C27H23F8O2Si requires m/z 559.1334, found m/z 559.1308.
HPLC analysis using a chiral column (Chiralpak IB 3ꢀ column,
22 °C, 1.0 mL/min, 800:1 Hexane:Isopropanol, 210 nm, = tmajor
8.383 min, tminor = 9.898 min). [α]D23: –18.4.
1
1784, 1518, 1493, 1248, 1102, 990, 863, 836, 754. H NMR
(CDCl3, 400 MHz): δ 7.40 – 7.28 (m, 2H), 7.17 (td, J = 7.6, 1.3
Hz, 1H), 7.15 – 7.06 (m, 1H), 5.99 (dt, J = 18.6, 6.3 Hz, 1H),
5.86 – 5.61 (m, 1H), 4.40 (t, J = 7.6 Hz, 1H), 2.99 (dddd, J =
14.3, 7.9, 6.3, 1.3 Hz, 1H), 2.78 – 2.59 (m, 1H), 0.01 (s, 9H). 13C
1
NMR (CDCl3, 101 MHz): δ 169.1, 160.5 (d, JC-F = 247.0 Hz),
3
141.3, 134.7, 129.7 (d, JC-F = 8.4 Hz), 129.1 (d, JC-F = 3.4 Hz),
124.6 (d, JC-F = 3.6 Hz), 124.4 (d, 2JC-F = 14.6 Hz), 115.8 (d, 2JC-F
= 22.2 Hz), 43.4 (d, 3JC-F = 2.5 Hz), 39.2, –1.3. 19F NMR (CDCl3,
376 MHz): δ –117.55 - –117.66 (m, 1F), –152.54 (dd, J = 20.4,
3.6 Hz, 2F), –157.97 (t, J = 21.6 Hz, 1F), –162.45 (dd, J = 21.8,
17.2 Hz, 2F). HRMS: exact mass calculated for [M+H]+
C20H19F6O2Si requires m/z 433.1053, found m/z 433.1045. HPLC
analysis using a chiral column (Chiralpak IA 3ꢀ column, 22 °C,
1.0 mL/min, 98:2 Hexane:Isopropanol, 210 nm, = tminor 9.993
min, tmajor = 10.413 min). [α]D23: –75.2.
Pentafluorophenyl
enoate, 6A
(E)-2-(4-tolyl)-5-(trimethylsilyl)pent-4-
White solid (39 mg, 90% yield, 91:9 er). IR (film): 2961,
1775, 1517, 1243, 1097, 1003, 986, 872, 839, 820, 544. 1H
NMR (CDCl3, 400 MHz): δ 7.27 (d, J = 9.1 Hz, 2H), 7.20 (d, J =
7.9 Hz, 2H), 6.03 (dt, J = 18.6, 6.2 Hz, 1H), 5.91 – 5.76 (m, 1H),
4.02 (dd, J = 9.4, 6.0 Hz, 1H), 3.09 – 2.91 (m, 1H), 2.71 – 2.55
(m, 1H), 2.38 (s, 3H), 0.06 (s, 9H). 13C NMR (CDCl3, 101
MHz): δ 169.8, 141.9, 137.8, 134.1, 134.1, 129.7, 127.8, 50.5,
40.3, 21.3, –1.3. 19F NMR (CDCl3, 376 MHz): δ –152.42 (d, J =
17.3 Hz, 2F), –158.16 (t, J = 21.7 Hz, 1F), –162.55 (dd, J = 21.7,
17.3 Hz, 2F). HRMS: exact mass calculated for [M+H]+
C21H22F5O2Si requires m/z 429.1304, found m/z 429.1287. HPLC
analysis using a chiral column (Chiralpak IA 3ꢀ column, 22 °C,
1.0 mL/min, 98:2 Hexane:Isopropanol, 210 nm, = tmajor 8.818
min, tminor = 9.590 min). [α]D23: –65.9.
Pentafluorophenyl
(E)-5-(dimethyl(phenyl)silyl)-2-(2-
fluorophenyl)pent-4-enoate, 7B
Colorless oil (35 mg, 71% yield, 88:12 er). IR (film): 2957,
1
1783, 1518, 1493, 1248, 1108, 991, 820, 755, 731, 699, 469. H
NMR (CDCl3, 400 MHz): δ 7.47 – 7.42 (m, 2H), 7.40 – 7.29 (m,
5H), 7.18 (td, J = 7.6, 1.2 Hz, 1H), 7.12 (ddd, J = 9.7, 8.3, 1.2
Hz, 1H), 6.08 (dt, J = 18.5, 6.4 Hz, 1H), 5.90 (dt, J = 18.5, 1.4
Hz, 1H), 4.43 (t, J = 7.6 Hz, 1H), 3.05 (dddd, J = 14.1, 7.6, 6.2,
1.4 Hz, 1H), 2.80 – 2.72 (m, 1H), 0.30 (d, J = 3.6 Hz, 6H). 13C
1
NMR (CDCl3, 101 MHz): δ 169.0, 160.6 (d, JC-F = 246.8 Hz),
Pentafluorophenyl
(E)-5-(dimethyl(phenyl)silyl)-2-(4-
143.3, 138.5, 133.9, 132.5, 129.7 (d, 3JC-F = 8.2 Hz), 129.2 (d, JC-
tolyl)pent-4-enoate, 6B
F = 3.6 Hz), 129.1, 127.8, 124.7 (d, JC-F = 3.7 Hz), 124.2 (d, 2JC-F
2
3
= 14.9 Hz), 115.9 (d, JC-F = 22.2 Hz), 43.3 (d, JC-F = 2.4 Hz),
39.2, –2.6. 19F NMR (CDCl3, 376 MHz): δ –116.03 - –119.61
(m, 1F), –151.07 - –153.51 (m, 2F), –157.88 (t, J = 21.7 Hz, 1F),
–162.37 (dd, J = 21.8, 17.1 Hz, 2F). HRMS: exact mass
calculated for [M+Na]+ C25H20F6O2SiNa requires m/z 517.1035,
found m/z 517.1017. HPLC analysis using a chiral column
(Chiralpak IA 3ꢀ column, 22 °C, 0.25 mL/min, 600:1
Hexane:Isopropanol, 210 nm, = tminor 23.334 min, tmajor = 26.967
min). [α]D23: –36.3.
Colorless oil (45 mg, 91% yield, 92:8 er). IR (film): 2957,
1
1783, 1520, 1100, 1002, 822, 700. H NMR (CDCl3, 400 MHz):
δ 7.39 – 7.33 (m, 2H), 7.29 – 7.21 (m, 3H), 7.16 (dd, J = 8.5, 1.7
Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 6.11 – 5.93 (m, 1H), 5.83 (d, J
= 18.6 Hz, 1H), 3.94 (dd, J = 8.8, 6.5 Hz, 1H), 3.03 – 2.86 (m,
1H), 2.60 (dt, J = 13.8, 6.4 Hz, 1H), 2.28 (s, 3H), 0.23 (s, 6H).
13C NMR (CDCl3, 101 MHz): δ 169.7, 143.9, 138.7, 137.8,
133.9, 131.9, 129.7, 129.1, 127.9, 127.8, 50.4, 40.3, –2.6. 19F
NMR (CDCl3, 376 MHz): δ –151.00 - –153.65 (m, 2F), –158.13
(t, J = 21.7 Hz, 1F), –162.51 (dd, J = 21.9, 17.2 Hz, 2F). HRMS:

7
Pentafluorophenyl
fluorophenyl)pent-4-enoate, 7C
(E)-5-(benzyldimethylsilyl)-2-(2-
7.10 (m, 1H), 7.04 – 6.99 (m, 2H), 6.00 (dt, J = 18.6, 6.3 Hz,
ACCEPTED MANUSCRIPT
1H), 5.82 (dt, J = 18.7, 1.4 Hz, 1H), 4.03 (dd, J = 8.7, 6.7 Hz,
1H), 3.10 – 2.94 (m, 1H), 2.72 – 2.62 (m, 1H), 2.15 (s, 2H), 0.07
(d, J = 1.4 Hz, 6H). 13C NMR (CDCl3, 101 MHz): δ 169.1,
142.4, 139.9, 139.0, 132.8, 131.31, 131.27, 130.6, 128.3, 128.2,
126.7, 124.1, 123.0, 50.4, 40.1, 26.0, –3.3. 19F NMR (CDCl3,
376 MHz): δ –149.96 - –154.90 (m, 2F), –157.63 (t, J = 21.7 Hz,
1F), –162.14 (dd, J = 21.8, 17.3 Hz, 2F). HRMS: exact mass
calculated for [M+Na]+ C26H22BrF5O2SiNa requires m/z
591.0390, found m/z 591.0414. HPLC analysis using a chiral
column (Chiralpak IB 3ꢀ column, 22 °C, 1.00 mL/min, 800:1
Hexane:Isopropanol, 210 nm, = tmajor 9.700 min, tminor = 13.405
min). [α]D23: –72.1.
Colorless oil (43 mg, 85% yield, 90:10 er). IR (film): 2957,
1785, 1521, 1493, 1107, 1004, 995, 833, 757. H NMR (CDCl3,
1
400 MHz): δ 7.38 – 7.29 (m, 2H), 7.22 – 7.14 (m, 3H), 7.12 (ddd,
J = 9.7, 8.2, 1.2 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), 6.96 – 6.90 (m,
2H), 5.98 (dt, J = 18.6, 6.4 Hz, 1H), 5.83 – 5.66 (m, 1H), 4.38 (t,
J = 7.6 Hz, 1H), 3.00 (dddd, J = 14.2, 7.7, 6.2, 1.4 Hz, 1H), 2.79
– 2.59 (m, 1H), 2.07 (s, 2H), 0.00 (d, J = 1.3 Hz, 6H). 13C NMR
1
(CDCl3, 101 MHz): δ 169.1, 160.6 (d, JC-F = 247.0 Hz), 142.6,
140.0, 132.6, 129.7 (d, JC-F = 8.4 Hz), 129.2 (d, JC-F = 3.4 Hz),
3
2
128.3, 128.2, 124.7 (d, JC-F = 3.6 Hz), 124.3 (d, JC-F = 14.7 Hz),
2
3
124.1, 115.8 (d, JC-F = 22.2 Hz), 43.3 (d, JC-F = 2.4 Hz), 39.2,
26.0, –3.4. 19F NMR (CDCl3, 376 MHz): δ –117.47 (dd, J = 10.7,
5.6 Hz, 1F), –151.61 - –154.93 (m, 2F), –157.87 (t, J = 21.7 Hz,
1F), –162.36 (dd, J = 21.9, 17.3 Hz, 2F). HRMS: exact mass
calculated for [M+Na]+ C26H22F6O2SiNa requires m/z 531.1191,
found m/z 531.1189. HPLC analysis using a chiral column
(Chiralpak IA 3ꢀ column, 22 °C, 0.75 mL/min, 98:2
Hexane:Isopropanol, 210 nm, = tminor 18.069 min, tmajor = 18.811
min). [α]D23: –33.7.
Pentafluorophenyl
(trimethylsilyl)pent-4-enoate, 9A
(E)-2-(3-chlorophenyl)-5-
Colorless oil (30 mg, 67% yield, 85:15 er). IR (film): 2955,
1783, 1518, 1248, 1094, 991, 860, 836, 690. 1H NMR (CDCl3,
400 MHz): δ 7.35 – 7.30 (m, 1H), 7.30 – 7.25 (m, 2H), 7.24 –
7.18 (m, 1H), 5.94 (dt, J = 18.6, 6.2 Hz, 1H), 5.76 (dt, J = 18.5,
1.4 Hz, 1H), 3.97 (dd, J = 9.0, 6.3 Hz, 1H), 2.94 (dddd, J = 14.4,
9.0, 6.4, 1.3 Hz, 1H), 2.61 (dtd, J = 14.3, 6.2, 1.4 Hz, 1H), 0.00
(s, 9H). 13C NMR (CDCl3, 101 MHz): δ 169.1, 141.1, 138.9,
134.9, 130.3, 128.4, 128.3, 126.2, 50.5, 40.1, –1.3. 19F NMR
(CDCl3, 376 MHz): δ –150.53 - –155.20 (m, 2F), –157.75 (t, J =
21.7 Hz, 1F), –162.27 (dd, J = 21.8, 17.2 Hz, 2F). HRMS: exact
mass calculated for [M-CH3]+ C19H15ClF5O2Si requires m/z
433.0445, found m/z 433.0443. HPLC analysis using a chiral
column (Chiralpak IB 3ꢀ column, 22 °C, 1.00 mL/min, 1600:1
Hexane:Isopropanol, 210 nm, = tminor 6.751 min, tmajor = 7.726
min). [α]D23: –47.8.
Pentafluorophenyl
(E)-2-(3-bromophenyl)-5-
(trimethylsilyl)pent-4-enoate, 8A
Colorless oil. (37 mg, 75% yield, 86:14 er) IR (film): 2955,
1
1783, 1518, 1248, 1091, 991, 836, 690. H NMR (CDCl3, 400
MHz): δ 7.55 (t, J = 1.8 Hz, 1H), 7.49 (dt, J = 7.7, 1.7 Hz, 1H),
7.33 (dt, J = 7.8, 1.5 Hz, 1H), 7.32 – 7.25 (m, 1H), 6.00 (dt, J =
18.5, 6.2 Hz, 1H), 5.82 (dt, J = 18.5, 1.3 Hz, 1H), 4.03 (dd, J =
9.0, 6.3 Hz, 1H), 3.06 – 2.92 (m, 1H), 2.73 – 2.60 (m, 1H), 0.07
(s, 9H). 13C NMR (CDCl3, 101 MHz): δ 169.1, 141.1, 139.2,
134.9, 131.3, 130.5, 126.6, 123.0, 50.4, 40.1, –1.3. 19F NMR
(CDCl3, 376 MHz): δ –148.91 - –154.39 (m, 2F), –157.71 (t, J =
21.7 Hz, 1F), –162.23 (dd, J = 21.6, 17.2 Hz, 2F). HRMS: exact
mass calculated for [M-CH3] C19H15BrF5O2Si requires m/z
476.9939, found m/z 476.9934. HPLC analysis using a chiral
column (Chiralpak IA 3ꢀ column, 22 °C, 0.5 mL/min, 1600:1
Hexane:Isopropanol, 210 nm, = tminor 14.278 min, tmajor = 16.110
min). [α]D23: –50.4
Pentafluorophenyl
chlorophenyl)pent-4-enoate, 9B
(E)-5-(dimethyl(phenyl)silyl)-2-(3-
Colorless oil (45 mg, 88% yield, 88:12 er). IR (film): 2956,
1782, 1518, 1428, 1248, 1094, 1025, 991, 838, 820, 783, 731,
698. 1H NMR (CDCl3, 400 MHz): δ 7.43 – 7.36 (m, 2H), 7.35 –
7.23 (m, 6H), 7.23 – 7.16 (m, 1H), 6.04 – 5.94 (m, 1H), 5.87 (dt,
J = 18.5, 1.2 Hz, 1H), 3.98 (dd, J = 8.5, 6.8 Hz, 1H), 2.98 (dddd,
J = 14.6, 8.6, 6.0, 1.1 Hz, 1H), 2.73 – 2.60 (m, 1H), 0.27 (s, 6H).
13C NMR (CDCl3, 101 MHz): δ 169.1, 143.1, 138.8, 138.4,
134.9, 133.9, 132.8, 130.3, 129.2, 128.4, 128.4, 127.9, 126.2,
50.3, 40.1, –2.6. 19F NMR (CDCl3, 376 MHz): δ –150.53 - –
153.58 (m, 2F), –157.67 (t, J = 21.7 Hz, 1F), –162.19 (dd, J =
21.9, 17.2 Hz, 2F). HRMS: exact mass calculated for [M+Na]+
C25H20ClF5O2SiNa requires m/z 533.0739, found m/z 533.0714.
HPLC analysis using a chiral column (Chiralpak IA 3ꢀ column,
22 °C, 0.75 mL/min, 800:1 Hexane:Isopropanol, 210 nm, = tminor
11.206 min, tmajor = 16.342 min). [α]D23: –32.6.
Pentafluorophenyl
(E)-5-(dimethyl(phenyl)silyl)-2-(3-
bromophenyl)pent-4-enoate, 8B
Colorless oil (47 mg, 84% yield, 87:13 er). IR (film): 2956,
1
1782, 1518, 1427, 1248, 1108, 1092, 991, 820, 731, 698. H
NMR (CDCl3, 400 MHz): δ 7.51 (d, J = 1.8 Hz, 1H), 7.47 (dt, J
= 7.4, 1.7 Hz, 1H), 7.47 – 7.39 (m, 2H), 7.36 – 7.31 (m, 2H),
7.30 – 7.20 (m, 3H), 6.02 (dt, J = 18.5, 6.0 Hz, 1H), 5.94 – 5.87
(m, 1H), 4.01 (dd, J = 8.5, 6.8 Hz, 1H), 3.01 (dddd, J = 14.6, 8.5,
6.0, 1.1 Hz, 1H), 2.76 – 2.63 (m, 1H), 0.30 (s, 6H). 13C NMR
(CDCl3, 101 MHz): δ 169.1, 143.1, 139.0, 133.9, 132.8, 131.3,
130.6, 129.2, 127.9, 126.7, 123.0, 50.3, 40.1, –2.6. 19F NMR
(CDCl3, 376 MHz): δ –152.23 - –152.66 (m, 2F), –157.65 (t, J =
21.7 Hz, 1F), –162.17 (dd, J = 21.8, 17.3 Hz, 2F). HRMS: exact
mass calculated for [M+Na]+ C25H20BrF5O2SiNa requires m/z
577.0234, found m/z 577.0259. HPLC analysis using a chiral
column (Chiralpak IA 3ꢀ column, 22 °C, 1.00 mL/min, 600:1
Hexane:Isopropanol, 210 nm, = tminor 6.372 min, tmajor = 7.963
min). [α]D23: –31.2.
Pentafluorophenyl
chlorophenyl)pent-4-enoate, 9C
(E)-5-(benzyldimethylsilyl)-2-(3-
Colorless oil (44 mg, 84% yield, 87:13 er). IR (film): 2955,
1782, 1598, 1518, 1493, 1248, 1094, 991, 831, 733, 698. H
1
NMR (CDCl3, 400 MHz): δ 7.35 (d, J = 2.6 Hz, 1H), 7.34 – 7.30
(m, 2H), 7.26 – 7.20 (m, 1H), 7.19 (t, J = 7.7 Hz, 2H), 7.11 –
7.01 (m, 1H), 6.98 – 6.91 (m, 2H), 5.94 (dt, J = 18.6, 6.3 Hz,
1H), 5.75 (dt, J = 18.6, 1.4 Hz, 1H), 3.97 (dd, J = 8.7, 6.7 Hz,
1H), 2.97 (dddd, J = 14.9, 8.6, 6.4, 1.4 Hz, 1H), 2.64 (dtd, J =
Pentafluorophenyl
(E)-5-(benzyldimethylsilyl)-2-(3-
14.5, 6.5, 1.5 Hz, 1H), 2.08 (s, 2H), 0.00 (d, J = 1.1 Hz, 6H). 13
C
bromophenyl)pent-4-enoate, 8C
NMR (CDCl3, 101 MHz): δ 169.1, 142.4, 139.9, 138.8, 134.9,
132.8, 130.3, 128.4, 128.3, 128.2, 126.2, 124.1, 50.4, 40.1, 26.0,
–3.3. 19F NMR (CDCl3, 376 MHz): δ –151.04 - –154.09 (m, 2F),
–157.65 (t, J = 21.6 Hz, 1F), –161.25 - –165.38 (m, 2F). HRMS:
exact mass calculated for [M+Na]+ C26H22ClF5O2SiNa requires
m/z 547.0985, found m/z 547.0908. HPLC analysis using a chiral
Colorless oil (51 mg, 89% yield, 88:12 er). IR (film): 2955,
1782, 1518, 1493, 1248, 1091, 991, 831, 733, 698. H NMR
(CDCl3, 400 MHz): δ 7.58 (d, J = 1.9 Hz, 1H), 7.54 (dt, J = 7.5,
1.7 Hz, 1H), 7.37 – 7.30 (m, 2H), 7.26 (t, J = 7.7 Hz, 2H), 7.16 –
1

8
Tetrahedron
ACCEPTED MANUSCRIPT
column (Chiralpak IB 3ꢀ column, 22 °C, 1.00 mL/min, 800:1
methanesulfonate (0.1 mL, 1.25 M, 0.125 mmol, 1.25 equiv).
Hexane:Isopropanol, 210 nm, = tmajor 8.900 min, tminor = 10.485
After stirring for 24 h at rt H2O (0.5 mL) and Et3N (70 µL, 0.5
mmol, 5 equiv) and DMAP (2.4 mg, 0.02 mmol, 0.2 equiv) were
added and the reaction mixture was heated to 65 °C for 18 h. The
reaction was then acidified with 1 M HCl (3 mL) and extracted
with Et2O (4 mL). The organics were dried and concentrated
under vacuum before being purified by column chromatography
(silica gel, 10-30% Et2O/petroleum ether) to afford the desired
product as a colorless oil (25 mg, 70% yield, 85:15 er). IR (film):
2954, 1703, 1612, 1511, 1248, 1206, 1179, 1035, 830, 795, 699.
1H NMR (CDCl3, 400 MHz): δ 7.23 – 7.19 (m, 2H), 7.17 (t, J =
7.6 Hz, 2H), 7.10 – 7.01 (m, 1H), 6.94 – 6.89 (m, 2H), 6.87 –
6.82 (m, 2H), 5.88 (dt, J = 18.6, 6.3 Hz, 1H), 5.65 (dt, J = 18.6,
1.4 Hz, 1H), 3.78 (s, 3H), 3.59 (t, J = 7.7 Hz, 1H), 2.87 – 2.75
(m, 1H), 2.59 – 2.48 (m, 1H), 2.03 (s, 2H), -0.05 (d, J = 2.3 Hz,
6H). 13C NMR (CDCl3, 101 MHz): δ 179.8, 159.1, 144.1, 140.1,
131.3, 130.1, 129.2, 128.3, 128.2, 124.0, 114.2, 55.4, 50.3, 40.1,
26.1, –3.3. HRMS: exact mass calculated for [M]+ C21H26O3Si
requires m/z 354.1646, found m/z 354.1650. HPLC analysis
using a chiral column (Chiralpak IB 3ꢀ column, 22 °C, 1.00
mL/min, 98:2 Hexane:Isopropanol, 210 nm, = tmajor 10.249 min,
tminor = 12.010 min). [α]D23: –57.6.
min). [α]D23: –34.5.
4.3. Synthesis of compounds from Scheme 2
(R,E)-N-benzyl-5-(benzyldimethylsilyl)-2-(4-
methoxyphenyl)pent-4-enamide, 10
Prepared according to the General Procedure using 4-
methoxyphenyl acetic acid pentafluorophenyl ester (33 mg, 0.1
mmol,
1
equiv)
and
(Z)-3-(benzyldimethylsilyl)allyl
methanesulfonate (0.1 mL, 1.25 M, 0.125 mmol, 1.25 equiv).
After stirring for 24 h at rt, benzylamine (14 µL, 0.13 mmol, 1.3
equiv) and DIPEA (26 µL, 0.15 mmol, 1.5 equiv) were added
and the reaction mixture continued stirring at rt for a further 18 h.
The reaction was then subjected to the workup described in the
General Procedure and purified by column chromatography
(silica gel, 10-30% Et2O/petroleum ether) to afford the desired
product as a colorless oil (34 mg, 77% yield, 94:6 er). IR (film):
3292, 3026, 2953, 1645, 1611, 1510, 1453, 1248, 1179, 1035,
1
831, 699. H NMR (CDCl3, 400 MHz): δ 7.32 – 7.22 (m, 3H),
7.22 – 7.13 (m, 5H), 7.04 (t, J = 7.3 Hz, 1H), 6.91 (d, J = 7.5 Hz,
2H), 6.86 (d, J = 8.6 Hz, 2H), 5.90 (dt, J = 18.6, 6.4 Hz, 1H),
5.74 – 5.51 (m, 2H), 4.51 – 4.24 (m, 2H), 3.80 (s, 3H), 3.35 (t, J
= 7.5 Hz, 1H), 2.99 (dt, J = 13.8, 6.8 Hz, 1H), 2.53 (dt, J = 14.4,
7.3 Hz, 1H), 2.04 (s, 2H), –0.04 (s, 6H). 13C NMR (CDCl3, 101
MHz): δ 173.2, 159.0, 145.3, 140.2, 138.4, 131.6, 130.7, 129.2,
128.8, 128.4, 128.2, 127.7, 127.5, 124.0, 114.3, 55.4, 52.4, 43.7,
40.6, 26.2, –3.3. HRMS: exact mass calculated for [M]+
C28H33O2NSi requires m/z 443.2275, found m/z 443.2260. HPLC
analysis using a chiral column (Chiralpak IA 3ꢀ column, 22 °C,
1.00 mL/min, 90:10 Hexane:Isopropanol, 210 nm, = tminor 10.588
min, tmajor = 17.343 min). [α]D23: –45.6.
4.4. Synthesis of compounds from Scheme 3
Pentafluorophenyl
enoate, 13
(R,Z)-2-(4-chlorophenyl)-5-iodopent-4-
To an oven dried 1 dram vial equipped with stirrer bar was
added pentafluorophenyl (R,E)-2-(4-chlorophenyl)-5-
(dimethyl(phenyl)silyl)pent-4-enoate (60 mg, 0.12 mmol, 1
equiv) and HFIP (0.4 mL, 0.3 M) and cooled to 0 °C. N-
iodosuccinimide (41 mg, 0.18 mmol, 1.5 equiv) was then added
and stirred for 20 minutes. The reaction mixture was then
quenched with H2O (2 mL) and extracted with DCM (3 mL). The
organic phase was then washed with sat. sodium thiosulfate,
dried and concentrated under vacuum before being purified by
column chromatography (silica gel, 1% Et2O/petroleum ether) to
afford the desired product as a colorless oil (55 mg, 92% yield,
89:11 er, 4:1 Z:E). IR (film): 2924, 1782, 1520, 1493, 1103,
Methyl
(R,E)-5-(benzyldimethylsilyl)-2-(4-
methoxyphenyl)pent-4-enoate, 11
Prepared according to the General Procedure using 4-
methoxyphenyl acetic acid pentafluorophenyl ester (33 mg, 0.1
mmol,
1
equiv)
and
(Z)-3-(benzyldimethylsilyl)allyl
1
methanesulfonate (0.1 mL, 1.25 M, 0.125 mmol, 1.25 equiv).
After stirring for 24 h at rt methanol (0.5 mL) and Et3N (70 µL,
0.5 mmol, 5 equiv) and DMAP (2.4 mg, 0.02 mmol, 0.2 equiv)
were added and the reaction mixture was heated to 65 °C for 18
h. The reaction was then subjected to the workup described in the
General Procedure and purified by column chromatography
(silica gel, 10-30% Et2O/petroleum ether) to afford the desired
product as a colorless oil (32 mg, 86% yield, 91:9 er). IR (film):
2951, 2836, 1734, 1612, 1510, 1247, 1151, 1034, 829, 794, 698.
1H NMR (CDCl3, 400 MHz): δ 7.23 – 7.15 (m, 4H), 7.06 (t, J =
7.4 Hz, 1H), 6.95 – 6.90 (m, 2H), 6.89 – 6.79 (m, 2H), 5.89 (dt, J
= 18.7, 6.4 Hz, 1H), 5.64 (dt, J = 18.6, 1.4 Hz, 1H), 3.78 (s, 3H),
3.64 (s, 3H), 3.59 (dd, J = 8.5, 7.0 Hz, 1H), 2.83 (dddd, J = 15.2,
8.3, 6.5, 1.4 Hz, 1H), 2.58 – 2.46 (m, 1H), 2.05 (s, 2H), -0.04 (d,
J = 2.6 Hz, 6H). 13C NMR (CDCl3, 101 MHz): δ 174.3, 158.9,
144.5, 140.1, 130.9, 130.8, 129.0, 128.3, 128.2, 124.0, 114.1,
55.4, 52.0, 50.4, 40.7, 26.2, –3.3. HRMS: exact mass calculated
for [M]+ C22H28O3Si requires m/z 368.1802, found m/z 368.1807.
HPLC analysis using a chiral column (Chiralpak IA 3ꢀ column,
22 °C, 0.5 mL/min, 98:2 Hexane:Isopropanol, 210 nm, = tminor
11.436 min, tmajor = 12.024 min). [α]D23: –65.7.
1095, 1049, 997, 760. H NMR (CDCl3, 400 MHz, Z isomer): δ
7.56 – 7.45 (m, 4H), 6.55 – 6.50 (m, 1H), 6.29 (q, J = 7.0 Hz,
1H), 4.42 (t, J = 7.7 Hz, 1H), 3.07 – 2.96 (m, 1H), 2.86 – 2.78
(m, 1H). 13C NMR (CDCl3, 101 MHz, Z isomer): δ 169.9, 137.9,
136.5, 134.4, 130.8, 129.9, 86.4, 49.2, 38.9. 19F NMR (CDCl3,
376 MHz): δ –154.75 (d, J = 17.0 Hz, 2F), –160.07 (t, J = 21.1
Hz, 1F), –164.68 (dd, J = 21.4, 17.0 Hz, 2F). HRMS: exact mass
calculated for [M]+ C17H10ClF5O2I requires m/z 502.9329, found
m/z 502.9347. HPLC analysis using a chiral column (Chiralpak
IA 3ꢀ column, 22 °C, 0.75 mL/min, 800:1 Hexane:Isopropanol,
210 nm, = tminor 25.856 min, tmajor = 31.111 min). [α]D23: –41.8.
Methyl
(R,E)-2-(4-methoxyphenyl)-5-(4-
(trifluoromethyl)phenyl)pent-4-enoate, 14
To an oven dried 1 dram vial equipped with stirrer bar was
added
methyl
(R,E)-5-(benzyldimethylsilyl)-2-(4-
methoxyphenyl)pent-4-enoate (104 mg, 0.2 mmol, 1 equiv). The
vial was then capped and purged with N2 before adding THF
(0.36 mL, 0.56 M) and H2O (11 µL, 0.6 mmol, 3 equiv) and
cooling to 0 °C. Tetrabutylammonium fluoride (0.44 mL, 1 M in
THF, 0.44 mmol, 2.2 equiv,) was then added and the reaction
mixture was stirred at 0 °C for 5 minutes before the addition of 4-
iodobenzotrifluoride (44 µL, 0.3 mmol, 1.5 equiv) and Pd2dba3
(4.5 mg, 0.005 mmol, 2.5 mol%). The reaction mixture was then
warmed to rt and stirred for 24 h before being quenched with
H2O (2 mL) and extracted with Et2O (4 mL). The organics were
then dried and concentrated under vacuum before being purified
(R,E)-5-(Benzyldimethylsilyl)-2-(4-methoxyphenyl)pent-4-
enoic acid, 12
Prepared according to the General Procedure using 4-
methoxyphenyl acetic acid pentafluorophenyl ester (33 mg, 0.1
mmol,
1
equiv)
and
(Z)-3-(benzyldimethylsilyl)allyl

9
Angew. Chem., Int. Ed. 2015, 54, 12645. (c) Liu, K.; Hovey, T.;
Scheidt, K. A. Chem. Sci. 2014, 5, 4026. (d) Terrett, J. A.; Clift,
M. D.; MacMillan, D. W. C. J. Am. Chem. Soc. 2014, 136, 6858.
by column chromatography (silica gel, 10% Et2O/petroleum
ether) to afford the desired product as a yellow oil which
crystallized on standing (61 mg, 84% yield, 91:9 er). IR (film):
2957, 1733, 1613, 1512, 1327, 1254, 1156, 1106, 1068, 1032,
ACCEPTED MANUSCRIPT
(e) Krautwald, S.; Schafroth, M. A.; Sarlah, D.; Carreira, E. M. J.
Am. Chem. Soc. 2014, 136, 3020. (f) Lang, S. B.; O’Nele, K. M.;
Tunge, J. A. J. Am. Soc. Chem. 2014, 136, 13606. (g) Krautwald,
S.; Sarlah, D.; Schafroth, M. A.; Carreira, E. M. Science 2013,
340, 1065. (h) Bihelovic, F.; Matovic, R.; Vulovic, B.; Saicic, R.
N. Org. Lett. 2007, 9, 5063. (i) Ibrahem, I.; Cordova, A. Angew.
Chem., Int. Ed. 2006, 45, 1952.
1
975, 832, 800, 535. H NMR (CDCl3, 400 MHz): δ 7.52 (d, J =
8.1 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.7 Hz, 2H),
6.87 (d, J = 8.8 Hz, 2H), 6.45 (d, J = 15.8 Hz, 1H), 6.19 (dt, J =
15.6, 7.1 Hz, 1H), 3.79 (s, 3H), 3.68 – 3.64 (m, 4H), 3.00 – 2.87
(m, 1H), 2.70 – 2.50 (m, 1H). 13C NMR (CDCl3, 101 MHz): δ
5.
For reviews, see: (a) Morrill, L. C.; Smith, A. D. Chem. Soc. Rev.
2014, 43, 6214. (b) Paull, D. H.; Weatherwax, A.; Lectka, T.
2
174.1, 159.1, 140.9, 131.1, 130.5, 130.0, 129.2 (d, JC-F = 17.0
3
1
Tetrahedron 2009, 65, 6771.
Hz), 129.0, 126.3, 125.5 (d, JC-F = 3.9 Hz), 124.3 (d, JC-F
=
271.8 Hz), 114.3, 55.3, 52.2, 50.8, 37.1. 19F NMR (CDCl3, 376
MHz): δ –62.47 (s, 3F). HRMS: exact mass calculated for [M]+
C20H19F3O3 requires m/z 364.1281, found m/z 364.1285. HPLC
analysis using a chiral column (Chiralpak IA 3ꢀ column, 22 °C,
1.00 mL/min, 800:1 Hexane:Isopropanol, 210 nm, = tminor 19.925
min, tmajor = 22.425 min). [α]D23: –88.2.
6. For other examples of C1-ammonium enolates in combination
with transition metal catalysis, see: (a) Spoehrle, S. S.; West, T.
H.; Taylor, J. E.; Slawin, A. M. Z.; Smith, A. D. J. Am. Chem.
Soc. 2017, 139, 11895; (b) Jiang, Z.; Beiger, J. J; Hartwig, J. F. J.
Am. Chem. Soc. 2017, 139, 87; (c) Lu, X.; Ge, L.; Cheng, C.;
Chen, J.; Cao, W.; Wu, X. Chem. Eur. J. 2017, 23, 7689; (d)
Song, J.; Zhang, Z.-J.; Gong, L.-Z. Angew. Chem. Int. Ed. 2017,
56, 5212.
7. For selected examples of silicon-substituted electrophiles in allylic
functionalization, see: (a) Hirao, T.; Enda, J.; Ohshiro, Y.; Agawa,
T. Tetrahedron Lett. 1981, 22, 3079. (b) Trost, B. M.; Self, C. R.
J. Am. Chem. Soc. 1983, 105, 5942. (c) Trost, B. M.; Lautens, M.
Organometallics 1983, 2, 1687. (d) Tsuji, J.; Yuhara, M.; Minato,
M.; Yamada, H.; Sato, F.; Kobayashi, Y. Tetrahedron Lett. 1988,
29, 343. (e) Romero, D. L.; Fritzen, E. L. Tetrahedron Lett. 1997,
38, 8659. (f) Chavhan, S. W.; Cook, M. J. Chem. Eur. J. 2014, 20,
4891. (g) Branchadell, V.; Moreno-Mañas, M.; Pleixats, R.
Organometallics 2002, 21, 2407.
8. Fleming, I.; Dunoguès, J.; Smithers, R. The Electrophilic
Substitution of Allylsilanes and Vinylsilanes. Organic Reactions.
2004, 37, 257-575.
9. Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
10. (a) Denmark, S. E.; Liu, J. H.-C. Angew. Chem. Int. Ed. 2010, 49,
2978; (b) Sore, H. F.; Galloway, W. R. J. D.; Spring. D. R. Chem.
Soc. Rev. 2012, 41, 1845; (c) Nakao, Y.; Hiyama, T. Chem. Soc.
Rev., 2011, 40, 4893.
Methyl (R)-2-(4-methoxyphenyl)-5-oxopentanoate 15
To an oven dried 2 dram vial equipped with stirrer bar was
added methyl (R,E)-2-(4-methoxyphenyl)-5-(trimethylsilyl)pent-
4-enoate (146 mg, 0.5 mmol, 1 equiv) and DCM (2.5 mL, 0.2M).
mCPBA (140 mg, 0.6 mmol, 1.2 equiv) was then added and the
reaction mixture was stirred at rt for 18 h. The reaction mixture
was then quenched with sat. sodium sulfite (2 mL) diluted with
DCM (10 mL) and washed with sat. sodium bicarbonate (10 mL).
The organics were then dried and concentrated under vacuum
before being dissolved in THF (2 mL) and stirred with aq. H2SO4
(2 mL, 3.6 M) for 1 h at rt. The reaction mixture was then diluted
with H2O (5 mL), extracted with Et2O (10 mL), washed with sat.
sodium bicarbonate (10 mL) and brine (10 mL). The organics
were then dried and concentrated under vacuum to afford the
desired product as a colorless oil (72 mg, 61% yield). IR (film):
3018, 2954, 2932, 2838, 1730, 1611, 1513, 1249, 1215, 1164,
11. Ramesh, R.; Reddy, D. S. J. Med. Chem. 2017, DOI:
10.1021/acs.jmedchem.7b00718.
1
1034, 753. H NMR (CDCl3, 400 MHz): δ 9.70 (t, J = 1.3 Hz,
12. (a) Liu, P.; Yang, X.; Birman, V. B.; Houk, K. N. Org. Lett. 2012,
14, 3288; (b) Bumbu, V. D.; Birman, V. B. J. Am. Chem. Soc.
2011, 133, 13902; (c) Yang, X.; Lu, G.; Birman, V. B. Org. Lett.
2010, 12, 892; (d) Birman, V. B.; Li, X. Org. Lett. 2006, 8, 1351.
13. Running the reaction with (S)-BTM afforded the (S) configured
product. In order to rule out an asymmetric protonation process,
the (R) product was resubmitted to the reaction conditions with the
opposite (S)-enantiomer of BTM. No change in er was observed
by HPLC analysis.
1H), 7.19 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.7 Hz, 2H), 3.79 (s,
3H), 3.65 (s, 3H), 3.55 (t, J = 7.5 Hz, 1H), 2.43 – 2.36 (m, 2H),
2.35 – 2.26 (m, 1H), 2.14 – 2.03 (m, 1H). 13C NMR (CDCl3, 101
MHz): δ 201.4, 174.2, 159.1, 130.2, 129.1, 114.3, 55.4, 52.2,
49.6, 41.6, 25.8. HRMS: exact mass calculated for [M]+
C13H16O4 requires m/z 236.1043, found m/z 236.1048. [α]D23: –
34.6.
14. (a) Ilardi, E. A.; Stivala, C. E., Zakarian, A. Org Lett. 2008, 10,
1727; (b) Stamos, D. P.; Taylor, A. G.; Kishi, Y. Tetrahedron Lett.
1987, 48, 8647.
Acknowledgements
15. McLaughlin, M. J.; McAdam, C. A.; Cook, M. J. Org. Lett. 2015,
17, 10.
16. The er of product 15 could not be determined due to degradation
under HPLC conditions.
We gratefully acknowledge Indiana University, NIH
(R01GM121573) and ACS-PRF (55734-DNI) for generous
financial support.
Supporting Information
The supporting information related to this article, including
full experimental details, characterization data and associated
spectra can be found at
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