Enantioselective syntheses of (E)-γ,δ-disubstituted homoallylic alcohols via BF3·OEt2-catalyzed aldehyde allylboration and analysis of the origin of E-selectivity: A1,2 allylic strain vs. syn-pentane interaction

Article abstract of DOI:10.1016/j.tet.2019.04.019

Enantioselective allylboration of aldehydes with α-substituted β-methyl allylboronate was reported. By using BF₃·OEt₂ as the catalyst, γ,δ-disubstituted homoallylic alcohols were obtained in good yields with high E-selectivities and

Full text of DOI:10.1016/j.tet.2019.04.019

Accepted Manuscript
Enantioselective syntheses of (E)-γ,δ-disubstituted homoallylic alcohols via
BF ·OEt -catalyzed aldehyde allylboration and analysis of the origin of E-selectivity:
3
1,2
2
A
allylic strain vs. syn-pentane interaction
Jiaming Liu, Shang Gao, Ming Chen
PII:
S0040-4020(19)30418-1
https://doi.org/10.1016/j.tet.2019.04.019
TET 30264
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 March 2019
Revised Date: 5 April 2019
Accepted Date: 5 April 2019
Please cite this article as: Liu J, Gao S, Chen M, Enantioselective syntheses of (E)-γ,δ-disubstituted
homoallylic alcohols via BF ·OEt -catalyzed aldehyde allylboration and analysis of the origin
3
2
1,2
of E-selectivity: A
allylic strain vs. syn-pentane interaction, Tetrahedron (2019), doi: https://
doi.org/10.1016/j.tet.2019.04.019.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Leave this area blank for abstract info.
Enantioselective Syntheses of (E)-γ,δ-
Disubstituted Homoallylic Alcohols via
BF3ꢀOEt2-Catalyzed Aldehyde Allylboration and
Analysis of the Origin of E-selectivity: A1,2 Allylic
Strain vs. syn-Pentane Interaction
Jiaming Liu, Shang Gao and Ming Chen*
Auburn University, Auburn, AL 36849, USA.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Enantioselective Syntheses of (E)-γ,δ-Disubstituted Homoallylic Alcohols via
BF3 OEt2-Catalyzed Aldehyde Allylboration and Analysis of the Origin of E-
ꢀ
selectivity: A1,2 Allylic Strain vs. syn-Pentane Interaction
Jiaming Liu, Shang Gao and Ming Chen
Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA
ARTICLE INFO
ABSTRACT
Article history:
Received
Enantioselective allylboration of aldehydes with α-substituted β-methyl allylboronate was
reported. By using BF3 OEt2 as the catalyst, γ,δ-disubstituted homoallylic alcohols were obtained
ꢀ
Received in revised form
Accepted
in good yields with high E-selectivities and enantioselectivities. Transition state analysis
revealed that the disfavored transition state suffers from a syn-pentane interaction between the
BF3 catalyst and axially oriented α-substituent of the allylboron reagent. Such a syn-pentane
interaction is severe enough to overcome the A1,2 allylic strain between the β-methyl group and
the α-substituent of the boron reagent that is present in the favored competing transition state.
Consequently, the reaction proceeded with equatorial placement of the α-substituent to furnish γ-
methyl substituted homoallylic alcohols with high E-selectivity.
Available online
Keywords:
Asymmetric crotylboration; A1,2 allylic
strain; syn-pentane interaction
2009 Elsevier Ltd. All rights reserved.
isomer C as the predominant reaction product (Scheme 1).8
1. Introduction
These studies indicate the strong intrinsic pseudo axial
Enantioenriched γ-methyl substituted homoallylic alcohols are
common structural motifs in numerous biologically active
molecules, particularly in cembranoid and polyketide natural
products (Figure 1).1 The vast majority of prior reported
approaches, however, require a multi-step reaction sequence
to access these molecules.2-5 Methods that allow for stereo-
and enantioselective yet efficient synthesis of γ-methyl
substituted homoallylic alcohols would be highly valuable.
Asymmetric carbonyl allylation reaction is one of the most
adopted methods to synthesize homoallylic alcohols.6 In
principle, enantioenriched γ-methyl substituted homoallylic
alcohols could be prepared via asymmetric aldehyde allylation
with α-substituted β-methyl allylboronates (e.g., 1 in Scheme
1). The E-olefin geometry in the product would require the α-
substituent to occupy a pseudo equatorial position in the
chair-like transition state. However, such a requirement is
challenging in aldehyde addition with α, β-disubstituted
allylboronates. It has been shown by the Morken group that α-
alkyl-β-boryl-disubstituted allylboronate reagents reacted with
aldehydes to provide homoallylic alcohols with exclusive Z-
selectivity.7 Aggarwal and coworkers demonstrated that the
reaction of α, β-dimethyl crotylboronate A with benzaldehyde
gave a 1:9 mixture of homoallylic alcohols B and C with Z-
Figure 1. Selected natural products containing γ–methyl substituted
homoallylic alcohols.
———
Corresponding author e-mail: mzc0102@auburn.edu

2
Tetrahedron
preference of the α-substituent of α, β-disubstituted
alcohols bearing a trisubstituted olefin group (e.g., 2, Scheme
ACCEPTED MANUSCRIPT
allylboronates in transition state (e.g., TS-2) of the reaction of
1). We envisioned an alternative strategy to address the
such allylboron reagents (e.g., A) with aldehydes.
challenge of overcoming the intrinsic Z-selectivity of the
reaction. By using the combination of BF3 OEt2 catalyst and a
ꢀ
modified diol moiety, we were able to synthesize
enantioenriched γ-methyl substituted homoallylic alcohols 2
with high E-selectivity via reaction of aldehydes with α-alkyl-
β-methyl-disubstituted allylboronates (e.g., 1, Scheme 1).10
2. Results and Discussion
We started the studies by evaluating the intrinsic E/Z
selectivity of the reaction between benzaldehyde and reagent
1a (Scheme 2) in the absence of any catalyst. In initial
experiments, treatment of α,β-dimethyl substituted
allylboronate 1a with benzaldehyde in toluene at ambient
temperature for 12 h provided, surprisingly, a 1:2 mixture of
E- and Z-homoallylic alcohols 2a and 3a in 88% yield
(Scheme 2). The low E/Z selectivity is unexpected and quite
intriguing.11 Based on the studies reported by Aggarwal and
coworkers, we anticipated alcohol 3a would be the major
product from the reaction. Close examination of the two
competing transition states (TS-3 and TS-4) of the reaction
revealed that, in contrast to the pinacol moiety that has two
methyl groups in close proximity to the α-methyl group in
TS-1, the pinanediol unit in reagent 1a only has one methyl
group (Shown in orange in TS-3) and one H atom (Shown in
light blue in TS-3) pointing to the back face. Moreover, the
rigidity of pinanediol unit forces the methyl group of
pinanediol further away from the α-methyl group of reagent
1a, leaving only the H atom in close contact with the α-methyl
group. Therefore, the steric repulsion between the α-methyl
group and the pinanediol unit is significantly reduced
compared to TS-1 for reagent A. On the other hand, the
competing transition state TS-4 has very similar steric
interactions compared to TS-2 (Shown in red in TS-4).
Consequently, the energy difference between transition states
TS-3 and TS-4 is much smaller than the difference between
TS-1 and TS-2. And the intrinsic pseudo axial preference of
the α-methyl group of reagent 1a is not nearly as strong as
that of reagent A in the transition state of the reaction with an
aldehyde. Therefore, the reaction of 1a with benzaldehyde
occurred with a much lower selectivity to give a 1:2 mixture
of 2a and 3a, slightly favoring Z-isomer 3a.
Scheme 1. Z or E-Selective Allylation with α-Substituted Methallylboronates
This Z-selectivity can be rationalized with the following
transition state analysis. As shown in Scheme 1, the reaction
of benzaldehyde with α, β-dimethyl substituted crotylboronate
A could proceed through two competing transition states, TS-
1 or TS-2, to give homoallylic alcohol B or C respectively.
However, TS-1 suffers from an A1,2 allylic strain between the β-
methyl group and the pseudo equatorially oriented α-methyl
group of the crotylboron reagent (Shown in red in TS-1).
Additionally, the unfavorable steric interaction between the α-
methyl group of reagent A and two methyl groups of the pinacol
moiety (Shown in orange in TS-1) is also developed in TS-1. By
contrast, the α-methyl group occupies a pseudo axial position in
TS-2 to minimize the A1,2 allylic strain with the β-methyl group
;
and only a minimal A1,3 allylic strain between the α-methyl
group and the vinyl H atom (Shown in blue in TS-2) is involved.
The steric interaction between the α-hydrogen atom (Shown in
blue in TS-2) and the methyl groups of pinacol moiety is also
negligible. As the result, the reaction of crotylboronate reagent
A with benzaldehyde proceeded through the lower energy
transition state TS-2 to give major product C with high Z-
selectivity. To overcome the strong intrinsic pseudo axial
preference of the α-methyl group of allylboron reagent in the
transition state is therefore the key challenge to achieve high E-
selectivity of the reaction.
An elegant solution to this problem was recently disclosed
by the Aggarwal group.8 By using a three-step reaction
sequence [(1) n-BuLi, (2) TFAA, (3) PhCHO], they were able
to obtain homoallylic alcohol B in 19:1 E-selectivity. 11B-
NMR studies showed that the reaction proceeded through an
allylborinate intermediate. By using this reaction sequence,
the steric repulsion between the α-methyl group of reagent A
and two methyl groups of the pinacol moiety is relieved. The
α-methyl group was positioned in the pseudo equatorial
position in the transition state to give E-homoallylic alcohol B
with high selectivity.9
Scheme 2. Allylboration of Benzaldehyde with Allylboronate 1a
To achieve high E-selectivity of the allylation reaction of
1a with aldehydes, studies with several acid catalysts
including Lewis acid and Brønsted acid were performed.12,13
As shown in Table 1, the reaction with 10 mol % of BF3
as the catalyst in CH2Cl2 at −78 ºC for 5 h provided a 11:1
ꢀ
OEt2
In connection with a current project on natural product
synthesis, we were interested in preparation of E-homoallylic

3
mixture of 2a and 3a in 79% yield, with E-isomer 2a as the
10 mol % of BF3 OEt2, reactions of several representative
ꢀ
ACCEPTED MANUSCRIPT
major component of the mixture (entry 2). The enantiomeric
excess of alcohol 2a was determined to be 93% ee by using
modified Mosher ester analysis.14 Reactions with other Lewis
acid such as Sc(OTf)3 and Cu(OTf)2 gave much lower E-
selectivities (entries 3 and 4).15 Reactions with either one of
the four phosphoric acids13 listed in Table 1 as the catalyst did
not improve the E-selectivity (entries 5-8). Therefore, we
decided to explore the scope of aldehyde that participates in
aldehydes with allylboronates 1b-d occurred to give products
2p-x in 76-92% yields with 12-20:1 E-selectivities and 85-
92% ee (Table 4). Again, the absolute configuration and the
enantiomeric excess of the secondary hydroxyl group in the
homoallylic alcohol products were determined by modified
Mosher ester analysis;14 the geometry of olefin group in
alcohols 2 was determined to be E by nOe studies.
this reaction with 10 mol % of BF
ꢀ
3 OEt2 as the catalyst.
Table 2. Scope of the Aldehyde for Reactions with 1a a-d
Table 1. Reaction Optimization with Allylboronate 1a a
(a) Reaction conditions: allylboronate 1a (0.12 mmol, 1.2 equiv), PhCHO
(0.1 mmol, 1.0 equiv), catalyst (10 mol % or 5 mol %) CH2Cl2 (0.3 mL). (b)
1
The Z/E ratios were determined by H NMR analysis of the crude reaction
products. (c) Yields of isolated products are listed. (d) Enantioselectivities
were determined by modified Mosher ester analysis. (e) The reaction was
conducted at 25 °C in CH2Cl2. (f) The reactions were conducted at −78 °C in
CH2Cl2. (g) The reactions were conducted at −40 °C in toluene with 5 mol %
of chiral phosphoric acid as the catalyst.
(a) Reaction conditions: allylboronate 1a (0.12 mmol, 1.2 equiv), RCHO (0.1
mmol, 1.0 equiv), BF3ꢀOEt2 (10 mol %), CH2Cl2 (0.3 mL), −78 °C, 5 h. (b)
1
The Z/E ratios were determined by H NMR analysis of the crude reaction
products. (c) Yields of isolated products are listed. (d) Enantioselectivities
were determined by modified Mosher ester analysis.
The scope of aldehyde that participates in the BF3 OEt2-
ꢀ
catalyzed allylboration with allylboronates 1a is summarized
in Table 2. Reactions with aromatic aldehydes with a
substituent at the para-position gave product 2a-h in 73-86%
yields, 10-17:1 E/Z selectivities and 90-94% ee regardless of
the electronic and steric properties of the substituents. The
reactions of 1a with ortho- or meta-substituted aromatic
aldehydes furnished alcohols 2i-l in 77-93% yields, 9-16:1
E/Z selectivities and 91-93% ee. Other aldehydes such as α,β-
unsaturated aldehydes or aliphatic aldehydes also reacted with
1a to furnish 2m-o in 71-78% yields, 12-15:1 E/Z selectivities
and 88-91% ee. The absolute configuration and enantiomeric
excess of E-homoallylic alcohols 2a-o were determined by
using modified Mosher ester analysis.14 The E-olefin
geometry was determined by nOe studies.
Transition state analysis of the origin of BF3 OEt2-
ꢀ
catalyzed, E-selective allylboration with 1 is outlined in
Scheme 3. It is conceivable that, to minimize steric interaction
with the angular methyl group (shown in orange in TS-5),
Lewis acid BF3 should coordinate to the oxygen atom distal to
the angular methyl group. Consequently, pseudo axial
placement of the α-substituent R1 of allylboronate 1 will
develop an unfavorable 1,3-syn-pentane interaction between
R1 and the BF3 catalyst (Shown in red in TS-6). By contrast,
such a 1,3-syn-pentane interaction is absent in TS-5 where the
α-substituent R1 of the allylboron reagent 1 was oriented in a
pseudo equatorial position. Although an A1,2 allylic strain
between the β-methyl group and the α-substituent R1 is
present (Shown in red in TS-5), such a steric interaction is
relatively weak compared to the 1,3-syn-pentane interaction in
Asymmetric allylboration of aldehydes with several α-
substituted β-methyl allylboronates (1b-d) were conducted
and the results are summarized in Table 3. In the presence of

4
Tetrahedron
ACCEPTED MANUSCRIPT
TS-6. Additionally, the steric interaction between the α-
syn-pentane interaction between the BF3 catalyst and axially
substituent R1 and one methyl group of pinanediol unit is
negligible owning to the rigid bicyclic structure of pinanediol
unit. Therefore, the reaction proceeded predominantly through
the lower energy transition state TS-5 with equatorial
placement of the α-substituent of the allylboron reagent to
furnish γ-methyl-δ-alkyl-disubstituted homoallylic alcohols 2
with high E-selectivity.
oriented α-substituent of the allylboron reagent. Although an
A1,2 allylic strain between the β-methyl group and the α-
substituent of the boron reagent is present in the favored
transition state, it is not as severe as the unfavorable syn-
pentane interactions in the competing transition state.
Consequently, the reaction proceeded
placement of the α-substituent to furnish γ-methyl-δ-alkyl-
with equitorial
disubstituted homoallylic alcohols with high E-selectivity.
Table 3. Scope of the Aldehyde for Reactions with
Allylboronates 1b-d a-d
4. Experimental
General Experimental Details. All reaction solvents were
purified before use. Tetrahydrofuran, dichloromethane,
diethyl ether, 1,2-dichloroethane and toluene were purified by
passing through a solvent column composed of activated A-1
alumina. Unless indicated otherwise, all reactions were
conducted under an atmosphere of argon using flame-dried or
oven-dried (120 ˚C) glassware. The term “concentrated under
reduced pressure” refers to the removal of solvents and other
volatile materials using a rotary evaporator with the water
bath temperature below 30 ˚C, followed by the removal of
residual solvents at high vacuum (< 0.5 mbar). Enantiomeric
excesses were determined by the Mosher method.
Proton nuclear magnetic resonance (1H NMR) spectra were
acquired on commercial instruments (400 or 600 MHz) at
Auburn University NMR facility. Carbon-13 nuclear magnetic
resonance (13C NMR) spectra were acquired at 101 and 151
MHz. The proton signal for the residual non-deuterated
solvent (δ 7.26 for CHCl3) was used as an internal reference
1
for H NMR spectra. For 13C NMR spectra, chemical shifts
are reported relative to the δ 77.36 resonance of CHCl3.
Coupling constants are reported in Hz. Optical rotations were
measured using a quartz cell with 1 mL capacity and a 10 cm
path length. High-resolution mass spectra were recorded on a
commercial high-resolution mass spectrometer via the Micro
Mass/Analytical Facility.
(a) Reaction conditions: allylboronate 1 (0.12 mmol, 1.2 equiv), RCHO (0.1
mmol, 1.0 equiv), BF3ꢀOEt2 (10 mol %), CH2Cl2 (0.3 mL), −78 °C, 5 h. (b)
1
The Z/E ratios were determined by H NMR analysis of the crude reaction
products. (c) Yields of isolated products are listed. (d) Enantioselectivities
were determined by modified Mosher ester analysis.
Analytical thin layer chromatography (TLC) was
performed on Kieselgel 60 F254 glass plates precoated with a
0.25 mm thickness of silica gel. The TLC plates were
visualized with UV light and/or by staining with Hanessian
solution (ceric sulfate and ammonium molybdate in aqueous
sulfuric acid) or KMnO4. Column chromatography was
generally performed using Kieselgel 60 (230-400 mesh) silica
gel, typically using a 50-100:1 weight ratio of silica gel to
crude product.
General procedure for the syntheses of homoallylic
alcohols 2: To a reaction flask containing a stirring bar and
freshly activated 4 Å MS (30 mg) was added allylboronate 1
(0.12 mmol) and dichloromethane (1 mL). The mixture was
cooled in a −78 ˚C cold bath and stirred for 15 min, followed
by the addition of BF3·OEt2 (0.1 M in CH2Cl2, 0.1 mL). After
stirring for another 5 min at −78 ˚C, freshly distilled aldehyde
(0.1 mmol, if it is a liquid) was added slowly to the reaction
mixture via a microliter syringe. The mixture was kept at −78
˚C and stirred until complete consumption of the aldehyde.
Then 3 N NaOH (1.0 mL) was added to the reaction mixture
followed by slow addition of 30% H2O2 (0.5 mL). The
reaction was stirred vigorously for 2 h. Brine (1 mL) and
CH2Cl2 (0.5 mL) were added, the organic layer was separated
and the aqueous layer was extracted with Et2O (3 x 1 mL).
The combined organic extracts were dried over anhydrous
magnesium sulfate, filtered, and concentrated under reduced
pressure. Purification of the crude product was performed by
Scheme 3. Transition State Analyses for E-Selective Allylboration with α-
Substituted Methallylboronates 1.
3. Conclusion
In summary, we developed a stereo- and enantioselective
synthesis γ-methyl-δ-alkyl-disubstituted homoallylic alcohols
via BF3 OEt2-catalyzed allylboration of aldehydes with α-
ꢀ
alkyl-β-methyl disubstituted allylboronates. Transition state
analysis revealed that the disfavored transition state suffers a

5
flash chromatography (gradient elution with hexane and Et2O)
provided the product 2.
= 8.6 Hz, 2H), 5.42 (q, J = 6.5 Hz, 1H), 4.85 (d, J = 9.9 Hz,
ACCEPTED MANUSCRIPT
1H), 2.43 (d, J = 13.6 Hz, 1H), 2.30 (d, J = 1.5 Hz, 1H), 2.24
(dd, J = 13.5, 10.2 Hz, 1H), 1.71 (s, 3H), 1.66 (d, J = 6.6 Hz,
3H). 13C NMR (151 MHz, CDCl3) δ 152.0, 147.4, 131.8,
126.7, 125.1, 124.0, 70.3, 51.0, 15.9, 14.0. HRMS (ESI+): m/z
for C12H15NO3Na [M+Na]+ calcd. 244.0950, found: 244.0956.
(S,E)-3-methyl-1-phenylpent-3-en-1-ol (2a)
Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2a as
colorless oil in 79% yield (14 mg, 11:1 dr). The enantiomeric
excess was determined to be 93% ee by Mosher ester
(S,E)-methyl-4-(1-hydroxy-3-methylpent-3-en-1-
analysis; [α]D25 = −53.3
̊
(c 0.30, CHCl3); 1H NMR (600 MHz,
yl)benzoate (2f) Prepared according to the general procedure.
The crude mixture was purified by column chromatography to
give compound 2f as colorless oil in 85% yield (20 mg, 14:1
dr). The enantiomeric excess was determined to be 93% ee by
CDCl3) δ 7.35 − 7.41 (m, 4H), 7.27 − 7.29 (m, 1H), 5.41 (q,
J = 6.5 Hz, 1H), 4.76 (dt, J = 10.0, 2.4 Hz, 1H), 2.41 (d, J =
13.0 Hz, 1H), 2.31 (dd, J = 13.5, 10.1 Hz, 1H), 2.16 (d, J =
1.6 Hz, 1H), 1.70 (s, 3H), 1.65 (d, J = 6.7 Hz, 3H). 13C NMR
(151 MHz, CDCl3) δ 144.5, 132.7, 128.7, 127.7, 126.0, 123.8,
71.3, 50.9, 16.0, 14.0. HRMS (EI+): m/z for C12H16O [M]+
calcd. 176.1201, found: 176.1202.
25
1
Mosher ester analysis; [α]D = −60.6 ̊ (c 0.75, CHCl3); H
NMR (600 MHz, CDCl3) δ 8.01 (d, J = 8.2 Hz, 2H), 7.44 (d, J
= 8.1 Hz, 2H), 5.40 (q, J = 6.1 Hz, 1H), 4.80 (d, J = 9.3 Hz,
1H), 3.91 (s, 3H), 2.41 (d, J = 13.4 Hz, 1H), 2. 17 – 2. 34 (m,
2H), 1.69 (s, 3H), 1.65 (d, J = 6.4 Hz, 3H). 13C NMR (151
MHz, CDCl3) δ 167.4, 149.7, 132.2, 130.0, 129.3, 125.9,
124.4, 70.8, 52.5, 50.9, 15.9, 14.0. HRMS (EI+): m/z for
C14H16O2 [M-H2O]+ calcd. 216.1150, found: 216.1141.
(S,E)-1-(4-isopropylphenyl)-3-methylpent-3-en-1-ol (2b)
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2b as colorless oil in 73% yield (16 mg, 17:1 dr).
The enantiomeric excess was determined to be 90% ee by
(S,E)-1-(4-bromophenyl)-3-methylpent-3-en-1-ol
(2g)
25
1
Mosher ester analysis; [α]D = −44.3
̊
(c 0.37, CHCl3); H
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2g as colorless oil in 82% yield (21 mg, 12:1 dr).
The enantiomeric excess was determined to be 92% ee by
NMR (600 MHz, CDCl3) δ 7.30 (d, J = 7.9 Hz, 2H), 7.21 (d, J
= 7.8 Hz, 2H), 5.42 (q, J = 6.3 Hz, 1H), 4.73 (dd, J = 9.9, 2.5
Hz, 1H), 2.90 (hept, J = 6.7 Hz, 1H), 2.40 (d, J =13.4 Hz, 1H),
2.32 (dd, J = 13.4, 10.3 Hz, 1H), 2.14 (br, 1H), 1.70 (s, 3H),
1.65 (d, J = 5.9 Hz, 3H), 1.24 (d, J = 6.9 Hz, 6H). 13C NMR
(151 MHz, CDCl3) δ 148.3, 141.9, 132.9, 126.7, 126.0, 123.6,
71.1, 50.8, 34.1, 24.39, 24.38, 15.9, 14.0. HRMS (EI+): m/z
for C15H22O [M]+ calcd. 218.1671, found: 218.1679.
25
1
Mosher ester analysis; [α]D = −59.5 ̊ (c 0.90, CHCl3); H
NMR (600 MHz, CDCl3) δ 7.46 (d, J = 8.2 Hz, 2H), 7.25 (d, J
= 8.3 Hz, 2H), 5.39 (q, J = 6.3 Hz, 1H), 4.71 (dd, J = 9.7, 2.5
Hz, 1H), 2.37 (d, J = 13.5 Hz, 1H), 2.23 (dd, J = 13.1, 10.2
Hz, 1H), 2.20 (br, 1H), 1.68 (s, 3H), 1.64 (d, J = 6.6 Hz, 3H).
13C NMR (151 MHz, CDCl3) δ 143.5, 132.3, 131.7, 127.8,
124.3, 121.3, 70.6, 50.9, 15.9, 14.0. HRMS (EI+): m/z for
C12H13Br [M-H2O]+ calcd. 236.0201, found: 236.0199.
(S,E)-1-([1,1'-biphenyl]-4-yl)-3-methylpent-3-en-1-ol (2c)
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2c as white solid in 83% yield (21 mg, 10:1 dr).
The enantiomeric excess was determined to be 90% ee by
(S,E)-3-methyl-1-(4-(trifluoromethoxy)phenyl)pent-3-
en-1-ol (2h) Prepared according to the general procedure. The
crude mixture was purified by column chromatography to
give compound 2h as colorless oil in 81% yield (21 mg, 11:1
dr). The enantiomeric excess was determined to be 91% ee by
25
1
Mosher ester analysis; [α]D = −45.0 ̊ (c 1.00, CHCl3); H
NMR (600 MHz, CDCl3) δ 7.58 − 7.61 (m, 4H), 7.39 – 7.51
(m, 4H), 7.34 − 7.37 (m, 1H), 5.44 (q, J = 6.1 Hz, 1H), 4.81 (d,
J = 9.6 Hz, 1H), 2.46 (d, J = 13.5 Hz, 1H), 2.35 (dd, J = 13.2,
10.4 Hz, 1H), 2.22 (d, J = 1.3 Hz, 1H), 1.73 (s, 3H), 1.67 (d, J
= 6.4 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 143.6, 141.2,
140.5, 132.7, 129.1, 127.5, 127.44, 127.41, 126.5, 123.9, 71.0,
50.9, 16.0, 14.0. HRMS (ESI+): m/z for C18H20ONa [M+Na]+
calcd 275.1409, found: 275.1412.
25
1
Mosher ester analysis; [α]D = −32.1 ̊ (c 0.95, CHCl3); H
NMR (600 MHz, CDCl3) δ 7.40 (d, J = 8.4 Hz, 2H), 7.19 (d, J
= 8.0 Hz, 2H), 5.41 (q, J = 6.2 Hz, 1H), 4.75 (d, J = 9.5 Hz,
1H), 2.39 (d, J = 13.5 Hz, 1H), 2.26 (dd, J = 13.0, 10.3 Hz,
1H), 2.23 (d, J = 1.0 Hz, 1H), 1.70 (s, 3H), 1.65 (d, J = 6.4
Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 148.6, 143.2, 132.3,
127.4, 124.3, 121.3, 120.7 (q, J = 257 Hz), 70.5, 51.0, 15.9,
14.0. HRMS (EI+): m/z for C13H15O2F3 [M]+ calcd. 260.1024,
found: 260.1026.
(S,E)-4-(1-hydroxy-3-methylpent-3-en-1-yl)benzonitrile
(2d) Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2d as colorless oil in 79% yield (16 mg, 17:1 dr).
(S,E)-1-(2-fluorophenyl)-3-methylpent-3-en-1-ol
(2i)
The enantiomeric excess was determined to be 92% ee by
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2i as colorless oil in 93% yield (18 mg, 9:1 dr).
The enantiomeric excess was determined to be 91% ee by
1
Mosher ester analysis; [α]D25 = −68.3
̊
(c 0.29, CHCl3); H
NMR (600 MHz, CDCl3) δ 7.64 (d, J = 7.4 Hz, 2H), 7.48 (d, J
= 7.6 Hz, 2H), 5.40 (q, J = 6.0 Hz, 1H), 4.79 (d, J = 9.7 Hz,
1H), 2.40 (d, J = 13.5 Hz, 1H), 2.28 (br, 1H), 2.22 (dd, J =
13.4, 11.3 Hz, 1H), 1.70 (s, 3H), 1.65 (d, J = 6.1 Hz, 3H). 13C
NMR (151 MHz, CDCl3) δ 149.9, 132.5, 131.9, 126.7, 124.9,
119.4, 111.2, 70.4, 50.9, 15.9, 14.0. HRMS (EI+): m/z for
C13H13N [M-H2O]+ calcd. 183.1048, found: 183.1054.
Mosher ester analysis; [α]D25 = −7.5 (c 0.34, CHCl3); 1H
̊
NMR (600 MHz, CDCl3) δ 7.52 (dd, J = 7.1, 7.0 Hz, 1H),
7.22 – 7.26 (m, 1H), 7.15 (dd, J = 7.1, 7.2 Hz, 1H), 7.00 –
7.03 (m, 1H), 5.40 (q, J = 6.2 Hz, 1H), 5.08 (d, J = 9.2 Hz,
1H), 2.48 (d, J = 13.4 Hz, 1H), 2.26 (dd, J = 13.2, 10.4 Hz,
1H), 2.16 (br, 1H), 1.71 (s, 3H), 1.64 (d, J = 6.2 Hz, 3H). 13
C
(S,E)-3-methyl-1-(4-nitrophenyl)pent-3-en-1-ol
(2e)
NMR (151 MHz, CDCl3) δ 159.9 (d, J = 245 Hz), 132.6,
131.5 (d, J = 12.8 Hz), 128.9 (d, J = 8.2 Hz), 127.3 (d, J = 4.5
Hz), 124.5 (J = 3.3 Hz), 124.0, 115.4 (J = 21.7 Hz), 65.3,
49.4, 15.9, 14.0. HRMS (EI+): m/z for C12H15OF [M]+ calcd.
194.1107, found: 194.1099.
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2e as white solid in 86% yield (19 mg, 11:1 dr).
The enantiomeric excess was determined to be 94% ee by
25
1
Mosher ester analysis; [α]D = −54.9
̊ (c 0.60, CHCl3); H
NMR (600 MHz, CDCl3) δ 8.21 (d, J = 8.6 Hz, 2H), 7.55 (d, J

6
Tetrahedron
ACCEPTED MANUSCRIPT
(S,E)-3-methyl-1-(3-nitrophenyl)pent-3-en-1-ol
(2j)
= 6.1 Hz, 1H), 3.61 – 3.82 (m, 1H), 2.81 – 2.88 (m, 1H), 2.64
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2j as colorless oil in 77% yield (17 mg, 16:1 dr).
The enantiomeric excess was determined to be 93% ee by
– 2.77 (m, 1H), 2.22 (dd, J = 13.3, 2.3 Hz, 1H), 2.05 (dd, J =
13.3, 9.7 Hz, 1H), 1.70 – 1.88 (m, 3H), 1.61 – 1.63 (m, 6H).
13C NMR (151 MHz, CDCl3) δ 142.6, 132.9 128.8, 128.7,
126.1, 123.2, 68.0, 48.4, 39.1, 32.5, 16.1, 13.9. HRMS (ESI+):
m/z for C14H20ONa [M+Na]+ calcd . 227.1411, found:
227.1412.
25
1
Mosher ester analysis; [α]D = −48.9 ̊ (c 0.85, CHCl3); H
NMR (600 MHz, CDCl3) δ 8.26 (s, 1H), 8.05 – 8.20 (m, 1H),
7.72 (d, J = 7.6 Hz, 1H), 7.52 (dd, J = 7.9, 7.9 Hz, 1H), 5.43
(q, J = 6.1 Hz, 1H), 4.85 (d, J = 9.7 Hz, 1H), 2.44 (d, J = 13.5
Hz, 1H), 2.33 (d, J = 1.5 Hz, 1H), 2.26 (dd, J = 13.3, 10.4 Hz,
1H), 1.72 (s, 3H), 1.66 (d, J = 6.5 Hz, 3H). 13C NMR (151
MHz, CDCl3) δ 148.5, 146.6, 132.2, 131.8, 129.6, 125.0,
122.6, 121.1, 70.2, 51.0, 15.9, 14.0. HRMS (EI+): m/z for
C12H15NO3 [M]+ calcd. 221.1052, found: 221.1072.
(S,E)-1-cyclohexyl-3-methylpent-3-en-1-ol (2o) Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2o as
colorless oil in 71% yield (13 mg, 12:1 dr). The enantiomeric
excess was determined to be 91% ee by Mosher ester
analysis; [α]D25 = −7.5
̊
(c 0.34, CHCl3); H NMR (600 MHz,
1
CDCl3) δ 5.32 (q, J = 7.8 Hz, 1H), 3.41 (ddd, J = 9.6, 5.4, 2.4
Hz, 1H), 2.23 (d, J = 13.2 Hz, 1H), 1.95 (dd, J = 13.2, 10.8
Hz, 1H), 1.86 (d, J = 12.7 Hz, 1H), 1.55 – 1.80 (m, 11H), 1.30
– 1.36 (m, 1H), 0.97 – 1.28 (m, 5H). 13C NMR (151 MHz,
CDCl3) δ 133.4, 123.0, 72.4, 45.0, 43.6, 29.3, 28.7, 26.9, 26.7,
26.5, 15.9, 13.9. HRMS (EI+): m/z for C12H22O [M]+ calcd.
182.1671, found: 182.1682.
(S,E)-1-(3-bromophenyl)-3-methylpent-3-en-1-ol
(2k)
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2k as colorless oil in 78% yield (20 mg, 14:1 dr).
The enantiomeric excess was determined to be 91% ee by
25
1
Mosher ester analysis; [α]D = −31.2 ̊ (c 0.75, CHCl3); H
NMR (600 MHz, CDCl3) δ 7.54 (s, 1H), 7.39 (d, J = 7.8 Hz,
1H), 7.28 (d, J = 7.6 Hz, 1H), 7.21 (dd, J = 7.8, 7.7 Hz, 1H),
5.40 (q, J = 6.2 Hz, 1H), 4.71 (dd, J = 10.1, 1.7 Hz, 1H), 2.39
(d, J = 13.5 Hz, 1H), 2.25 (dd, J =13.3, 10.3 Hz , 1H), 2.22
(br, 1H), 1.69 (s, 3H), 1.65 (d, J = 6.7 Hz, 3H). 13C NMR (151
MHz, CDCl3) δ 147.1, 132.5, 130.9, 130.5, 129.4, 124.9,
124.6, 123.0, 70.7, 51.2, 16.2, 14.3. HRMS (EI+): m/z for
C12H15OBr [M]+ calcd. 254.0306, found: 254.0314.
(S,E)-3-methyl-1-phenylhex-3-en-1-ol (2p) Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2p as
colorless oil in 89% yield (17 mg, 16:1 dr). The enantiomeric
excess was determined to be 88% ee by Mosher ester
analysis; [α]D25 = −33.5 (c 0.92, CHCl3); 1H NMR (600 MHz,
̊
CDCl3) δ 7.34 – 7.40 (m, 4H), 7.20 – 7.31 (m, 1H), 5.32 (t, J
= 6.5 Hz, 1H), 4.75 (dd J = 9.9, 1.8 Hz, 1H), 2.40 (d, J = 13.1
Hz, 1H), 2.29 (dd, J = 13.1, 10.4 Hz, 1H), 2.19 (br, 1H), 2.06
(dt, J = 6.5, 7.5 Hz, 2H), 1.69 (s, 3H), 0.97 (t, J = 7.5 Hz, 3H).
13C NMR (151 MHz, CDCl3) δ 144.4, 131.9, 131.2, 128.7,
127.7, 126.0, 71.2, 50.9, 21.7, 16.2, 14.7. HRMS (EI+): m/z
for C13H18O [M]+ calcd. 190.1358, found: 190.1347.
(S,E)-1-(3-fluorophenyl)-3-methylpent-3-en-1-ol
(2l)
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2l as colorless oil in 88% yield (17 mg, 12:1 dr).
The enantiomeric excess was determined to be 91% ee by
25
1
Mosher ester analysis; [α]D = −45.4 ̊ (c 0.19, CHCl3); H
(S,E)-3-methyl-1-(4-nitrophenyl)hex-3-en-1-ol
(2q)
NMR (600 MHz, CDCl3) δ 7.28 – 7.32 (m, 2H), 7.10 – 7.13
(m, 2H), 6.93 – 6.96 (m, 1H), 5.40 (q, J = 6.1 Hz, 1H), 4.74
(d, J = 9.6 Hz, 1H), 2.40 (d, J = 13.4 Hz, 1H), 2.26 (dd, J =
13.3, 10.4 Hz, 1H), 2.20 (br, 1H), 1.69 (s, 3H), 1.65 (d, J =
6.2 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 163.2 (d J =
245.6 Hz), 147.2 (d, J = 6.9 Hz), 132.3, 130.1 (d, J = 8.2 Hz),
124.3, 121.6 (d, J = 2.7 Hz), 114.4 (d, J = 21.2 Hz), 112.9 (d,
J = 21.9 Hz), 70.6, 50.9, 15.9, 14.0. HRMS (EI+): m/z for
C12H15OF [M]+ calcd. 194.1107, found: 194.1104
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2q as colorless oil in 85% yield (20 mg, 20:1 dr).
The enantiomeric excess was determined to be 92% ee by
25
1
Mosher ester analysis; [α]D = −43.8 ̊ (c 1.11, CHCl3); H
NMR (600 MHz, CDCl3) δ 8.21 (d, J = 8.7 Hz, 2H), 7.55 (d, J
= 8.5 Hz, 2H), 5.33 (t, J = 6.4 Hz, 1H), 4.85 (d, J = 9.1 Hz,
1H), 2.43 (d, J = 13.4 Hz, 1H), 2.32 (br, 1H), 2.22 (dd, J =
13.1, 10.4 Hz, 1H), 2.07 (dt, J = 6.5, 7.5 Hz, 2H), 1.71 (s,
3H), 0.98 (t, J = 7.5 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ
151.9, 147.4, 133.0, 130.3, 126.7, 124.0, 70.2, 51.0, 21.7,
16.1, 14.6. HRMS (EI+): m/z for C13H15NO2 [M-H2O]+ calcd.
217.1103, found: 217.1097
(S,1Z,5E)-2-bromo-5-methyl-1-phenylhepta-1,5-dien-3-
ol (2m) Prepared according to the general procedure. The
crude mixture was purified by column chromatography to
give compound 2m as white solid in 75% yield (21 mg, 15:1
dr). The enantiomeric excess was determined to be 91% ee by
(R,E)-5-methyl-1-phenyloct-5-en-3-ol (2r) Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2r as
colorless oil in 92% yield (20 mg, 20:1 dr). The enantiomeric
excess was determined to be 85% ee by Mosher ester
25
1
Mosher ester analysis; [α]D = −14.8 ̊ (c 1.10, CHCl3); H
NMR (600 MHz, CDCl3) δ 7.59 – 7.60 (m, 2H), 7.35 – 7.38
(m, 2H), 7.30 – 7.33 (m, 1H), 7.10 (s, 1H), 5.43 (q, J = 6.3
Hz, 1H), 4.36 (dt, J = 8.3, 4.2 Hz, 1H), 2.57 (dd, J = 13.3, 2.9
Hz, 1H), 2.37 (dd, J = 13.4, 8.7 Hz, 1H), 2.24 (d, J = 4.3 Hz,
1H), 1.70 (s, 3H), 1.64 (d, J = 6.5 Hz, 3H). 13C NMR (151
MHz, CDCl3) δ 135.5, 131.7, 129.8, 129.4, 128.5, 128.3,
127.9, 124.2, 74.9, 47.0, 16.1, 14.0. HRMS (EI+): m/z for
C14H17OBr [M]+ calcd. 280.0463, found: 280.0472.
25
1
analysis; [α]D = 43.1 ̊ (c 0.6, CHCl3); H NMR (600 MHz,
CDCl3) δ 7.28 – 7.30 (m, 2H), 7.18 – 7.22 (m, 3H), 5.27 (t, J
= 6.4 Hz, 1H), 3.67 – 3.71 (m, 1H), 2.76 – 2.92 (m, 1H), 2.58
– 2.76 (m, 1H), 2.21 (d, J = 13.0 Hz, 1H), 1.95 – 2.09 (m,
3H), 1.74 – 1.81 (m, 3H), 1.61 (s, 3H), 0.96 (t, J = 7.5 Hz,
3H). 13C NMR (151 MHz, CDCl3) δ 142.6, 131.4, 131.3,
128.8, 128.7, 126.1, 67.9, 48.3, 39.1, 32.5, 21.6, 16.2, 14.7.
HRMS (EI+): m/z for C15H20 [M-H2O]+ calcd. 200.1565,
found: 200.1560.
(R,E)-5-methyl-1-phenylhept-5-en-3-ol (2n) Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2n as
colorless oil in 78% yield (16 mg, 12:1 dr). The enantiomeric
excess was determined to be 88% ee by Mosher ester
(S,E)-3-methyl-1-phenylhept-3-en-1-ol (2s) Prepared
according to the general procedure. The crude mixture was
1
analysis; [α]D25 = 10.6
̊
(c 0.90, CHCl3); H NMR (600 MHz,
CDCl3) δ 7.26 – 7.30 (m, 2H), 7.18 – 7.22 (m, 3H), 5.33 (q, J

7
purified by column chromatography to give compound 2s as
colorless oil in 83% yield (17 mg, 20:1 dr). The enantiomeric
excess was determined to be 92% ee by Mosher ester
3H), 1.59 – 1.65 (m, 1H), 0.88 (t, J = 6.4 Hz, 3H), 0.87 (t, J
ACCEPTED MANUSCRIPT
= 6.2 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 151.9, 147.4,
131.5, 130.2, 126.8, 124.0, 70.3, 51.1, 37.5, 29.0, 22.8, 22.7,
16.4. HRMS (ESI+): m/z for C15H21NO3Na [M+Na]+ calcd.
286.1419, found: 286.1395.
analysis; [α]D25 = −22.4 (c 0.76, CHCl3); 1H NMR (600 MHz,
̊
CDCl3) δ 7.34 – 7.40 (m, 4H), 7.26 – 7.28 (m, 1H), 5.32 (t, J
= 6.8 Hz, 1H), 4.75 (d, J = 8.5 Hz, 1H), 2.42 (d, J = 13.3 Hz,
1H), 2.31 (dd, J = 13.1, 10.3 Hz, 1H), 2.18 (br, 1H), 2.00 –
2.04 (m, 2H), 1.69 (s, 3H), 1.35 – 1.39 (m, 2H), 0.89 (t, J =
7.3 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 144.4, 131.9,
130.1, 128.7, 127.7, 126.1, 71.2, 51.0, 30.4, 23.2, 16.3, 14.2.
HRMS (EI+): m/z for C14H18 [M-H2O]+ calcd. 186.1409,
found: 186.1410.
(R,E)-5,8-dimethyl-1-phenylnon-5-en-3-ol (2x) Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2x as
colorless oil in 85% yield (21 mg, 15:1 dr). The enantiomeric
excess was determined to be 86% ee by Mosher ester
25
1
analysis; [α]D = 3.4 ̊ (c 0.93, CHCl3); H NMR (600 MHz,
CDCl3) δ 7.26 – 7.30 (m, 2H), 7.18 – 7. 22 (m, 3H), 5.28 (t, J
= 6.7 Hz, 1H), 3.69 – 3.70 (m, 1H), 2.83 (dt, J = 14.7, 8.0 Hz,
1H), 2.69 (dt, J = 14.2, 8.3 Hz, 1H), 2.24 (d, J = 12.9 Hz, 1H),
2.06 (dd, J = 12.5, 10.1 Hz, 1H), 1.91 (dd, J = 6.8, 6.8 Hz,
2H), 1.73 – 1.78 (m, 4H), 1.71 (s, 3H), 0.88 (d, J = 6.5 Hz,
3H), 0.87 (d, J = 6.5 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ
142.6, 132.6, 128.8, 128.7, 128.5, 126.1, 67.9, 48.6, 39.1,
37.5, 32.5, 29.1, 22.8, 22.7, 16.5. HRMS (ESI+): m/z for
C17H26ONa [M+Na]+ calcd. 269.1881, found: 269.1881.
(S,E)-3-methyl-1-(4-nitrophenyl)hept-3-en-1-ol
(2t)
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2t as colorless oil in 76% yield (19 mg, 20:1 dr).
The enantiomeric excess was determined to be 89% ee by
25
1
Mosher ester analysis; [α]D = −43.8 ̊ (c 0.74, CHCl3); H
NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.6 Hz, 2H), 7.54 (d, J
= 8.5 Hz, 2H), 5.33 (t, J = 7.0 Hz, 1H), 4.85 (dd, J = 9.7, 3.4
Hz, 1H), 2.45 (dd, J = 13.4, 2.8 Hz, 1H), 2.29 (br, 1H), 2.25
(dd, J = 13.5, 10.0 Hz, 1H), 2.04 (dt, J = 14.4, 7.2 Hz, 2H),
1.71 (s, 3H), 1.34 – 1.43 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H). 13
C
Acknowledgments
NMR (101 MHz, CDCl3) δ 152.0, 147.5, 131.2, 131.0, 126.8,
124.0, 70.4, 51.0, 30.5, 23.1, 16.3, 14.2. HRMS (EI+): m/z for
C14H17NO2 [M–H2O]+ calcd. 231.1259, found: 231.1247.
Financial support provided by Auburn University is gratefully
acknowledged
.
(R,E)-5-methyl-1-phenylnon-5-en-3-ol (2u) Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2u as
colorless oil in 77% yield (18 mg, 19:1 dr). The enantiomeric
excess was determined to be 85% ee by Mosher ester
References
1. (a) Zampella, A.; D’Auria, M. V.; Minale, L.; Debitus, C.;
Roussakis, C. J. Am. Chem. Soc. 1996, 118, 11085. (b)
Sone, H.; Kigoshi, H.; Yamada, K. J. Org. Chem. 1996,
61, 8956. (c) Tanaka, J.; Higa, T. Tetrahedron Lett. 1996,
37, 5535. (d) Iwashima, M., Matsumoto, Y., Takahashi,
H., and Iguchi, K. J. Nat. Prod. 2000, 63, 1647. (e)
Cutignano, A.; Bruno, I.; Bifulco, G.; Casapullo, A.;
Debitus C.; Gomez-Paloma, L.; Riccio, R. Eur. J. Org.
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Zhou, G.-X.; Masuno, M. N.; Molinski, T. F. J. Am.
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Y.; Zhang, K. J. Nat. Prod. 2011, 74, 1526. (h) Liu, X.;
Sun, C.; Mlynarski, S.; Morken, J. P. Org. Lett. 2018, 20,
1898. For recent reviews: (i) Ellis, J. M.; Crimmins, M. T.
Chem. Rev. 2008, 108, 5278. (j) Craig, R. A.; Stoltz, B.
M. Chem. Rev. 2017, 117, 7878.
2. (a) Evans, D. A.; Hu, J.; Burch, J. D.; Jaeschke, G. J. Am.
Chem. Soc. 2002, 124, 5654. (b) Trost, B. M.; Gunzner, J.
L.; Dirat, O.; Rhee, Y. H. J. Am. Chem. Soc. 2002, 124,
10396. (c) Paterson, I.; Davies, R. D. M.; Heimann, A. C.;
Marquez, R.; Meyer, A. Org. Lett. 2003, 5, 4477. (d)
Carpenter, J.; Northrup, A. B.; Chung, D.; Wiener, J. J.
M.; Kim, S.-G.; MacMillan, D. W. C. Angew. Chem., Int.
Ed. 2008, 47, 3568. (e) Hoye, T. R.; Danielson, M. E.;
May, A. E.; Zhao, H. J. Org. Chem. 2010, 75, 7052.
25
1
analysis; [α]D = 10.0 ̊ (c 0.20, CHCl3); H NMR (400 MHz,
CDCl3) δ 7.24 – 7.34 (m, 2H), 7.17 – 7.23 (m, 3H), 5.27 (t, J
= 7.0 Hz, 1H), 3.68 – 3.74 (m, 1H), 2.83 (dt, J = 14.3, 8.0 Hz,
1H), 2.70 (dt, J = 13.8, 8.0 Hz, 1H), 2.23 (dd, J = 13.2, 2.4
Hz, 1H), 1.98 – 2.07 (m, 3H), 1.66 – 1.85 (m, 3H), 1.62 (s,
3H), 1.33 – 1.42 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 142.6, 132.2, 129.3, 128.8, 128.7, 126.1,
68.1, 48.5, 39.1, 32.5, 30.4, 23.2, 16.4, 14.2. HRMS (EI+): m/z
for C16H22 [M-H2O]+ calcd. 214.1722, found: 214.1723
(S,E)-3,6-dimethyl-1-phenylhept-3-en-1-ol (2v) Prepared
according to the general procedure. The crude mixture was
purified by column chromatography to give compound 2v as
colorless oil in 82% yield (18 mg, 12:1 dr). The enantiomeric
excess was determined to be 92% ee by Mosher ester
analysis; [α]D25 = −28.6 (c 0.40, CHCl3); 1H NMR (600 MHz,
̊
CDCl3) δ 7.33 – 7.40 (m, 4H), 7.26 – 7.28 (m, 1H), 5.33 (t, J
= 6.8 Hz, 1H), 4.64 – 4.86 (m, 2H), 2.43 (d, J = 13.3 Hz, 1H),
2.33 (dd, J = 13.0, 10.2 Hz, 1H), 2.17 (br, 1H), 1.93 (dd, J =
6.9, 6.9 Hz 2H), 1.68 (s, 3H), 1.59 – 1.65 (m, 1H), 0.88 (d, J =
7.1 Hz, 3H), 0.87 (d, J = 7.1 Hz, 3H). 13C NMR (151 MHz,
CDCl3) δ 144.4, 132.4, 129.1, 128.7, 127.7, 126.1, 71.3, 51.1,
37.5, 29.1, 22.8, 22.7, 16.4. HRMS (EI+): m/z for C15H20 [M-
H2O]+ calcd. 200.1565, found: 200.1555.
3. (a) Park, P. K.; O’Malley, S. J.; Schmidt, D. R.; Leighton,
J. L. J. Am. Chem. Soc. 2006, 128, 2796. (b) Hanson, P.
R.; Chegondi, R.; Nguyen, J.; Thomas, C. D.; Waetzig, J.
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(S,E)-3,6-dimethyl-1-(4-nitrophenyl)hept-3-en-1-ol (2w)
Prepared according to the general procedure. The crude
mixture was purified by column chromatography to give
compound 2w as colorless oil in 84% yield (22 mg, 15:1 dr).
The enantiomeric excess was determined to be 91% ee by
25
1
Mosher ester analysis; [α]D = −66.7 ̊ (c 0.80, CHCl3); H
NMR (600 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 2H), 7.55 (d, J
= 8.3 Hz, 2H), 5.34 (t, J = 6.5 Hz, 1H), 4.85 (dd, J =10.0, 3.1
Hz, 1H), 2.45 (d, J = 13.3 Hz, 1H), 2.31 (br, 1H), 2.26 (dd, J
= 13.0, 10.1 Hz, 1H), 1.94 (dd, J = 6.8, 6.7 Hz, 2H), 1.70 (s,

8
Tetrahedron
ACCEPTED MANUSCRIPT
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