A Catalytic Dual Isomerization/Allylboration Sequence for the Stereoselective Construction of Congested Secondary Homoallylic Alcohols

Article abstract of DOI:10.1021/acs.joc.0c00565

A catalytic sequence for the diastereo- and enantioselective preparation of homoallylic alcohols with an adjacent quaternary (stereo)center is reported. The one-pot process relies on the use of a single (achiral or chiral) iridium complex to catalyze the concomitant isomerization of primary allylic alcohols and homoallylboronates into (chiral) aldehydes and allylboronates, respectively. In the same flask, a chiral Br?nsted acid is added next to engage the isomerization products into a stereocontrolled allylboration reaction. Structural variations have been performed on both the allylic alcohols and the homoallylboronates. This mild process affords an array of stereochemically congested and complex chiral secondary homoallylic alcohols in high yield, excellent diastereoselectivity, and usually high enantioselectivity.

Full text of DOI:10.1021/acs.joc.0c00565

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Article
A Catalytic Dual Isomerization/Allylboration Sequence for the
Stereoselective Construction of Congested Secondary Homoallylic Alcohols
Yangbin Liu, and Clément Mazet
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00565 • Publication Date (Web): 26 Mar 2020
Downloaded from pubs.acs.org on March 27, 2020
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The Journal of Organic Chemistry
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A Catalytic Dual Isomerization/Allylboration Sequence for the
Stereoselective Construction of Congested Secondary Homoallylic
Alcohols
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Yangbin Liu, Clément Mazet*
Department of Organic Chemistry, University of Geneva, 30 quai Ernest Ansermet, 1211 Geneva, Switzerland.
ABSTRACT: A catalytic sequence for the diastereo- and enantioselective preparation of homoallylic alcohols with an
adjacent quaternary (stereo)center is reported. The one-pot process relies on the use of a single (achiral or chiral) iridium
complex to catalyze the concomitant isomerization of primary allylic alcohols and homoallylboronates into (chiral)
aldehydes and allylboronates respectively. In the same flask, a chiral Brønsted acid is added next to engage the isomerization
products into a stereocontrolled allylboration reaction. Structural variations have been performed on both the allylic
alcohols and the homoallylboronates. This mild process affords an array of stereochemically congested and complex chiral
secondary homoallylic alcohols in high yield, excellent diastereoselectivity and usually high enantioselectivity.
Over the last few years, Miura and Murakami have
■ INTRODUCTION
developed
a
series
of
very
elegant
Optically active homoallylic alcohols hold a prominent
position in the arsenal of structural subunits used for the
synthesis of biologically active polyketide natural
products.1 They also serve as a privileged platform for a
number of catalytic transformations.2 The stereoselective
isomerization/allylboration tandem processes to access
homoallylic alcohols and 3-boryl substituted homoallylic
alcohols with high levels of diastereo- and enantiocontrol
(Figure 1-B).14-16 Typically, an isomerization catalyst (Ir, Ru
or Pd) is employed for the in situ generation of the reactive
allylboronate derivative and is followed by the use of a
chiral phosphoric acid for the stereocontrolled
allylboration of aldehydes. These systems are particularly
effective and selective for alkenylboronates, 1,1- and 1,2-
diborylalkenes. Depending on the double bond geometry
of the precursor, borylated homoallylic alcohols or 1,2-
oxaborinan-3-enes are generated with excellent diastereo-
and enantioselectivity.15e Quite notably, the most recent
[Ru/Brønsted acid] and [Pd/Brønsted acid] combinations
provide access to -boryl substituted homoallylic alcohols
with a proximal gem-dimethyl carbon center (i.e. the
closest analogs to secondary homoallylic alcohols with an
adjacent quaternary stereocenter). Nonetheless, this is
achieved either without any stereocontrol or with only very
modest enantioinduction (Figure 1-B, right).15f These
results are a clear testimony of the difficulty associated
with the stereocontrolled installation of a secondary
alcohol adjacent to a congested quaternary center using
allylboration of carbonyl compounds as a C–C bond
forming strategy.
allylation of carbonyl compounds is
a particularly
straightforward and efficient synthetic method for the
preparation of chiral homoallylic alcohols. Nonetheless,
the majority of these allylation methods relies on the use
of stoichiometric chiral auxiliaries or reagents based on
main group metals which generates toxic waste.3 In this
context, the emergence of catalytic stereoselective
allylborations of carbonyls has opened new perspectives to
identify general and practical systems for the
stereocontrolled preparation of chiral homoallyl alcohols.
A specific focus has been placed on the development of
methods providing access to homoallylic alcohols with two
contiguous stereocenters using achiral -substituted
allylboronate in presence of a chiral catalysts (i.e. Lewis
acids or Brønsted acids).4 The six chiral structural motifs
that can be accessed by carbonyl allylation using -
substituted allyl boronic acids or allyl boronic esters are
depicted on Figure 1-A. Some of the most significant
advances have been realized using chiral Brønsted acids as
exemplified by the key contributions of Miyaura,5
Shibasaki,6 Hall,7 Antilla,8 Schaus,9 Kobayashi10 and Szabó.11
Remarkably, even chiral tertiary homoallylic alcohols with
an adjacent quaternary center are now accessible with high
levels of diastereo- and enantioinduction.12 Although
several catalytic enantioselective allylation methods
provide access to secondary homoallylic alcohols with a
neighboring quaternary stereocenter, to the best of our
knowledge, there is no report on their preparation based
on a catalytic allylboration of aldehydes.13
Over the past decade, our laboratory has reported
several examples of diastereo- and enantioselective
isomerizations of primary allylic alcohols into aldehydes.
The reaction is triggered by in situ generation of iridium-
hydrides and subsequent hydrometallation of the olefin
double bond (Figure 1-C).17 More recently, we also
disclosed a very general and selective Ir-catalyzed anti-
Markovnikov 3,4-hydroboration of branched 1,3-dienes
that affords homoallylboronates in high yields (Figure 1-
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Page 2 of 16
D).18 We wondered whether the [(P,N)Ir] catalysts used for
the isomerization
1
2
A)
Enantioselective allylboration of carbonyl compounds
3
4
5
6
Lewis acid catalyst
or
Brønsted acid catalyst
R4
R2 R4
HO
R3
2 or 3° alcohol
+
R1
Key patterns
B(OR)2
R3
non-stereogenic, 3 or 4° stereocenter
O
R2 R1
7
8
9
R4
R4
R4
OH
OH
OH
HO
R3
HO
R3
R1
3°/3°
Schaus (H+)
HO
R3
R3
R3
R3
R2 R1
R2 R1
R1
2°/3°
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2°/4°
3°/
3°/4°
2°/


Hall (Sn)
Antilla (H+)
Miyaura (Al), Hall (Sn), Antilla (H+),
Kobayashi (Zn), Miura-Murakami (H+)
not reported
Schaus (H+)
Szabo (H+)
Shibasaki (Cu)
B)
Sequential catalysis: isomerization/allylboration
Me Bpin
Bpin
Miura-Murakami (2013)
Miura-Murakami (2017)
Me
Bpin
Ar
Ar
O
P
O
Ir
[Ru] [Pd]
[
/PCy3]
or
O
O
P
O
(5 mol%)
cat.
O
91%, 96% ee
anti/syn 98:2
(15 examples)
M = Ru
67%, rac
(1 example)
M = Pd
98%, 20% ee
(1 example)
H
H
OH
OH
Ph
O
Ph
O
Ar
Ar
Ar = 2,4,6-(i-Pr)3C6H2
Ar = 2,4,6-(i-Pr)3C6H2
(R)-TRIP cat.
OH
OH
Me Bpin
(R)-TRIP (5 mol%)
Bpin
Me
Bpin
Ph
Ph
Me
Bpin
Me Me
Me
C)
D)
Ir-catalyzed hydroboration of 1,3-dienes
Ir-catalyzed isomerization of allylic alcohols
Ir
[(P,P) ] (5 mol%)
enantioselective (high ee)
diastereoselective (cat. controlled)
stereospecific (E)
R2
R2
Ir
[(P,N) ] (5 mol%)
4,3-selective
H-Bpin
>25 examples
R1
R
Bpin
R1
OH
R
O
E) This work:
Sequential selective catalysis: dual isomerization/allylboration
R2
R2
single catalyst
chiral Brønsted
acid catalyst
 dual isomerization
R2 OH
(achiral or chiral)
R1
Me
R1
OH
 sequential catalysis (one-pot)
 diastereoselective catalysis
 enantioselective catalysis
O
R1
H+
Ir
Me R
R
Bpin
 increased complexity (aldehydes)
R
Bpin
additional
stereocenter
2°/4°
Figure 1. (A) Enantioselective allylborations of carbonyls and representative key patterns of the homoallylic alcohols
accessible by this method. (B) Sequential isomerization/allylboration developed by Miura and Murakami. (C) iridium-
catalyzed isomerization of allylic alcohols. (D) Iridium-catalyzed hydroboration of 1,3-dienes. (D) Dual
isomerization/allylboration sequence.
of allylic alcohols would also prove competent for the
isomerization of homoallyboronates into allylboronates.
We anticipated that a dual isomerization of allylic alcohols
and homoallylboronates could be conducted concomitant-
-ly using a single catalyst to produce –in the same flask– an
aliphatic aldehyde and a 3,3-disubstituted allylboronate
that would subsequently react stereoselectively in the
presence of a chiral Brønsted acid. Successful realization of
this strategy would require the following challenges to be
compounds, the nature of the aldehyde component has not
been explored in great details and is often limited to
benzaldehyde derivatives. We have shown that chiral
aliphatic aldehydes can be obtained by iridium-catalyzed
isomerization, therefore we also envisioned that in its
ultimate version, our approach could produce chiral
secondary homoallylic alcohols possessing both a 
quaternary stereocenter and a ’ tertiary stereocenter set
by a Brønsted acid catalyst and by a chiral iridium catalyst
respectively (Figure 1-E).
overcome: (i) identify
a
single catalyst for the
isomerization of allylic alcohols and homoallylboronates;
(ii) produce stereoselectively (E)- or (Z)-allylboronates
because allylborations are stereospecific processes; (iii)
minimize non-stereoselective uncatalyzed allylboration;
(iv) impart excellent stereocontrol in the C–C bond
forming step; (v) meet the requirement for time resolution
and compatibility of all the reagents, catalysts and
intermediates to a single set of reaction conditions.
Moreover, we noticed that in allylborations of carbonyl
■ RESULTS AND DISCUSSION
To test the validity of our initial hypothesis and to evaluate
the possibility to operate under a single set of reaction
conditions, three independent experiments were
conducted at the outset of our investigations (Figure 2).
Isomerization of 3-phenylprop-2-enol (E)-1a was
performed in 1,2-dichloroethane at room temperature
using the Pfaltz-modified version of Crabtree’s catalyst to
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The Journal of Organic Chemistry
quantitatively deliver aldehyde 2a within 1 h (eq. (1)).19
that the strong uncatalyzed allylboration reaction could be
1
2
3
4
5
6
7
8
Gratifyingly, under identical conditions, isomerization of
homoallylboronate 3a furnished the desired allylboronate
4a, together with a small amount of vinylboronate (E)-5a
(eq. (2)). Reacting the independently synthesized aldehyde
2a and allylboronate 4a in 1,2-dichloroethane at room
temperature in the absence
outcompeted using the axially chiral phosphoric acid
catalyst(R)-TRIP by running the reaction at low
temperature. The highest enantioselectivity was obtained
at –30 °C (90% conv., 97% ee) (eq. (3)). 20 Our efforts were
next directed towards the identification of reaction
conditions where the two isomerizations processes and the
allylboration reaction could be conducted in the same
flask. Allylic alcohol (E)-1a and homoallylboronate 3a were
selected as model substrates. After extensive
investigations, we found that the order of addition of the
reagents, the reaction time, the temperature and the
relative stoichiometries were all important parameters to
achieve appreciable reactivity while imparting high levels
of stereocontrol (Table 1). When the reaction was
conducted in tandem with the iridium catalyst and the
Brønsted acid present at the beginning of the reaction,
using a stoichiometric amount of allylic alcohol 1a and
homoallylboronate 3a, homoallylic alcohol 6aa was
generated in 28% and 65% ee (Entry 1). When the
isomerizations and allylboration were performed in
sequence, the reactivity was increased significantly and an
appreciable level of enantiocontrol (90% ee) was achieved
at -20 °C using 2.0 equiv. of 3a (Entries 2-3). While
improved performances were obtained by conducting the
dual isomerization at 0 °C and the allylboration at -20 °C,
we also observed that the order of addition of the allylic
alcohol and the homoallylboronate impacted the
enantioselectivity of 6aa (Entries 4-5).21 We tentatively
attribute this phenomenon to a reduced contribution of
the uncatalyzed allylboration reaction which may itself
depend on the relative rate of isomerization of the two
BArF
Cy3
N
P
Ir
9
Ir
[
] (5.0 mol%)
H2 activation
(1)
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OH
O
1,2-DCE, 23 °C, 1 h
1a
conv. >99%
2a
(E)-
BArF
Cy3
N
P
Ir
Ir
[
] (5.0 mol%)
H2 activation
Me
Me
(2)
+
Me
Bpin
Me
Bpin
Me
Bpin
1,2-DCE, 23 °C, 1 h
3a
4a
5a
(E)-
95 % conv.
4a
5a
/(E)- = 5.3:1
Ar
O
P
O
O
OH
Ar
Ar = 2,4,6-(i-Pr)3C6H2
(R)-TRIP (x mol%)
OH
Me
(3)
Ph
+
O
Ph
Me
Bpin
1,2-DCE (0.1 M), 20 h
Me Me
2a
4a
6aa
(S)-
6a
6a
(%)
Entry
(R)-TRIP (mol%) conv.
(%) ee
T (C)
1
2
3
23
23
0
10
10
85
rac.
89
90
90
30
97
Figure 2. Exploratory experiments (0.1 mmol scale).
1
Conversion and (E)/(Z) ratio determined by H NMR.
Enantiomeric excess determined by HPLC using a chiral
stationary phase.
Table 1. Reaction optimizationa
substrates into aldehyde 2a and allylboronate 4a.
Ar
O
O
P
BArF
Cy3
N
P
OH
O
Ir
Ar
Ar
Ar = 2,4,6-(i-Pr)3C6H2
O
O
Ir
[
] (5.0 mol%)
H2 activation
OH
(R)-TRIP (10 mol%)
P
BArF
Cy3
N
P
OH
+
O
R
OH
Ir
R
Me
Bpin
1,2-DCE (0.2 M)
20 C, 24 h
Me Me
6aa-ha
Ar
0 C, 35-90 min.
1a-h
3a
Ar = 2,4,6-(i-Pr)3C6H2
Ir
[
] (5.0 mol%)
H2 activation
OH
(R)-TRIP (10 mol%)
Allylic alcohol variations
+
Ph
OH
R
Me
Bpin
1,2-DCE (0.1 M) 1,2-DCE (0.1 M)
OH
O
Me Me
OH
T1 (C), t1 (min.)
T2 (C), t2 (h)
OH
6aa
1a
3a
(E)-
N
(x equiv.)
Me Me
Me Me
F3C
O
Me Me
1b
entrya
3a
T1
t1
T2
t2
Conv. 6
(%)b
ee 6
(%)c
65
6aa
6ba
6ca
(from (Z)-
)
86% yield, 93% ee
90% yield, 91% ee
86% yield, 90% ee
(x equiv.)
(˚C)
(min.)
-
(˚C)
23
(h)
28
6
OH
OH
OH
1
1.0
1.0
2.0
1.5
1.5
23
0
28
Me
2
60
60
40
40
0
65
66
Me Me
Me Me
Me Me
MeN
MeO
6da
6ea
6fa
3
-20
0
-20
-20
-20
20
24
24
42
90
73% yield, 95% ee
47% yield, 88% ee
68% yield, 88% ee
4d
5f
84(80)e
90(86)e
89
OH
OH
0
93
O
Me Me
Me Me
a
b
c
Reaction conditions: 1a (0.1 mmol), 3a (0.1-0.2 mmol).
6ga
6ha
1
80% yield, 94% ee
82% yield, 92% ee
Determined by H NMR using an internal standard.
Determined by HPLC using a chiral stationary phase. d 3a
Figure 3. Enantioselective allylborations starting from
various allylic alcohols 1a-h (0.1-0.2 mmol) and
homoallylboronate 3a (1.5 equiv.). Yield of isolated product
e
is added first. 1a is added after 30 min. Yield of isolated
product after purification by column chromatography in
parenthesis. f 1a is added first. 3a is added after 10 min.
after
purification
by
column
chromatography.
Enantiomeric excess determined by HPLC using a chiral
stationary phase.
of catalyst, afforded homoallylic alcohol 6aa in 85%
conversion in racemic form. After optimization, we found
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To probe the reaction scope under these optimized compatible with a variety of functionalities, including an
1
2
3
4
5
6
7
8
conditions, a series of (E)- and (Z)-configured allylic
alcohols was evaluated using 3a as common
homoallylboronate to afford chiral secondary homoallylic
alcohols with an adjacent quaternary center (Figure 3).22
The sequential catalytic system was found to be
imide (6ba), a trifluoromethyl (6ca), a methylether (6da),
an indole (6ea) and a benzyl ether (6ha). The allylboration
products were isolated in moderate to excellent yield and
consistently
Ar
O
O
P
O
BArF
Cy3P
Ir
OH
N
Ar
9
Ar = 2,4,6-(i-Pr)3C6H2
Ir
[
] (10 mol%)
OH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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28
29
30
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32
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40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(R)-TRIP (10-15 mol%)
H2 activation
+
R
OH
R1
Bpin
R
1,2-DCE or THF (0.2 M)
20 or 0 or 23 C
30-60 min.
1,2-DCE
30 or 20 or 0 C
48 h
Me R1
1a-b,i
Homoallylboronate variations
3b-g
6
OH
Me
OH
Me
OH
OH
Cl
Ph
Ph
Ph
Ph
Bpin
Ph
Bpin
Bpin
Me
Me
R
Cl
6ae
3d
3e
3b R = i-Bu
3c R = Ph
Ph
6ab
6ac
6ada
anti-
anti-
syn-
anti-
62% yield
Ph
i-Bu
78% yield
76% yield
19:1 dr, 60% ee
82% yield
19:1 dr, 72% ee
2.8:1 dr, 83% ee / 56% ee
1.3:1 dr, 55% ee / 84% ee
O
Ph
OH
OH
OH
OH
O
N
TBSO
Ph
Ph
Bpin
Bpin
Me
Me
Me
O
Me
O
Me
Me
Me
TBSO
6af
Me
1i
(from (Z)- )
3f
Me
6bg
Me
a
a
3g
Me
Me
6ag
1b
6ig
anti-
63% yield
1.3:1 dr, 73% ee / 88% ee
syn-
syn-
(from (Z)-
70% yield
10:1 dr, 85% ee
)
syn-
66% yield
19:1 dr, 90% ee
85% yield
10:1 dr, 86% ee
Figure 4. Diastereo- and enantioselective allylborations starting from various allylic alcohols 1a-b,i (0.1 mmol) and
homoallylboronates 3b-g (2.0 equiv.). Yield of isolated product after purification by column chromatography. Enantiomeric
excess determined by HPLC using a chiral stationary phase. Diastereomeric ratio determined by 1H NMR. a THF was used
for dual isomerization.
BArF
A)
We next explored the possibility to achieve high
diastereo- and enantioselectivity in reactions using
diversely substituted homoallylboronates 3b-g (Figure 4).
The catalyst loading in iridium and Brønsted acid was
increased to achieve appreciable reactivity. Time and
temperature were optimized for each step (See Supporting
Information for details). With 3b and 3c, two aryl
containing derivatives, the catalytic sequence proceeded
efficiently and gave anti-6ab and anti-6ac in high dr (19:1
in both cases) and promising level of enantioselectivity
(72% ee and 60% ee respectively). In contrast, with 3d, an
aliphatic derivative, syn-6ad was isolated as a 2.8:1 mixture
Cy3
N
P
Ir
Me
Ir
[
] (10.0 mol%)
H2 activation
Bpin
Bpin
1a
+
2a
+
1,2-DCE (0.1 M)
i-Bu
i-Bu
23 C, 45 min.
3b
4b/
(E)- (Z)-
4b
88% conv.
5.2:1
(81% conv.)
B)
BArF
Cy3
N
P
Ir
Me
Ir
[
] (10.0 mol%)
H2 activation
1a
+
2a
+
Ph
Ph
Bpin
THF (0.2 M)
Bpin
20 C, 30 min.
4d/
4d
(E)- (Z)-
3d
90% conv.
1:4
of diastereoisomers and with
enantioselectivity. Reduced levels of diastereoselection
were obtained with other alkyl substituted
homoallylboronates such as 3e and 3f, leading to nearly 1:1
a
slightly higher
(85% conv.)
C)
BArF
Cy3
P
Ir
N
Me
Ir
[
] (10.0 mol%)
H2 activation
Bpin
Me
Me
anti/syn mixtures. Quite unexpectedly, with 3g,
homoprenyl substituted homoallylboronate,
a
the
1a
+
2a
+
+
Me
Bpin
1,2-DCE (0.1 M)
20 C, 60 min.
Bpin
Me
Me
3g
Me
Me
4g
sequential process furnished quasi-exclusively syn-6ag
with excellent enantioselectivity (19:1 dr, 90% ee). Almost
identical catalytic performances were achieved when the
allylic alcohol was varied (syn-6bg: 10:1 dr, 85% ee; syn-6ig:
10:1 dr, 86% ee).23 To gain insight into the origin of this
contrasted results, three independent dual isomerizations
using 1a in conjunction with either 3b, 3d or 3g were
conducted under conditions identical to those developed
for the first step of the corresponding sequential process.
70% conv.
7g
(Z)-
1.1:1
(70% conv.)
Figure 5. Ir-catalyzed dual isomerization of 3b, 3d and 3f
in presence of 1a (0.1 mmol scale). Conversions determined
by 1H NMR using an internal standard.
high levels of enantioselectivity were obtained (88-95%
ee).
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1
The Journal of Organic Chemistry
Ar
O
P
O
The reactions were interrupted after 30-60 minutes and no
Brønsted acid was added so that only marginal amount of
A)
O
BArF
Me
Bpin
Cy3
N
P
OH
Ir
3a
2
3
4
5
6
7
8
9
allylboration products was generated (Figure 5). Whereas
isomerization of 3b gave 4b in an appreciable 5.2:1 (E)/(Z)
ratio, 3d afforded allylboronate 4d as a 1:4 mixture of
stereoisomers. Finally, a nearly equimolar amount of
geometrically pure allylboronate (Z)-4g and of 1,3-diene 7g
was obtained upon isomerization of 3g. Quite notably, in
all cases, the final dr measured for homoallylic alcohols 6
reflects the stereochemical preference of the transient
allylboronate 4. For aryl substituted homoallylboronate 3b,
the much higher selectivity measured in the final product
(19:1 vs 5.2:1) is due to the lower reactivity of (Z)-4b, as
deduced from quantitative analysis of the crude reaction
Ar
HO
H
+
Ar = 2,4,6-(i-Pr)3C6H2
OH
Ir
[
] (5.0 mol%)
H2 activation
Me
Me
(R)-TRIP (10 mol%)
Me
H
Me
H
H
THF (0.2 M)
0 C, 30 min.
1,2-DCE (0.1 M)
20 C, 48 h
Me
H
Me
H
H
H
1l
6la
HO
HO
Ar
40% yield, 19:1 dr
B)
O
O
P
BArF
Me
Bpin
Cy3
N
P
OH
O
Ir
3a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ar
HO
+
Ar = 2,4,6-(i-Pr)3C6H2
Me
Me
H
Ir
[
] (5.0 mol%)
H2 activation
(S)-TRIP (10 mol%)
Me
H
Me
H
OH
H
H
THF (0.2 M)
0 C, 45 min.
1,2-DCE (0.1 M)
20 C, 48 h
Me
H
Me
H
1
H
H
mixture by H NMR analysis. By contrast, the excellent
N3
1m
N3
6ma
64% yield, 19:1 dr
diastereo-differentiation obtained with 3g originates from
the ability of the iridium catalyst to produce (Z)-4g as a
single stereoisomer (along with the unreactive diene 7g).
Overall, these results are consistent with the stereospecific
nature of allylborations proceeding via a closed, cyclic
Figure 7. Dual isomerization/allylboration of steroid 1l
and 1m (0.05-0.1 mmol) using 3a (2.0 equiv.). Yield of
isolated product after purification by column
chromatography. Diastereomeric ratio determined by H
NMR using an internal standard.
1
Zimmerman-Traxler transition state.3a,4d-e
Ar
To illustrate the structural flexibility offered by our
approach, we demonstrated that an additional
stereocenter could be implemented using prochiral allylic
alcohols and a chiral iridium catalyst for the in situ
generation of -chiral aldehydes (Figure 6). The match
combination of (R)-[Ir]17d,17f,24 and (S)-TRIP catalysts
delivered (1R,3R)-6ja in good yield, high dr and excellent
enantioselectivity. By contrast, the association of (R)-[Ir]
and (R)-TRIP led only to a reduced yield and a lower
diastereomeric ratio in favor of the same isomer, thus
indicating that the two catalysts do not exert independent
stereocontrol. Using the optimal conditions, (1R,3R)-6ka
was isolated in 58% yield, 4.8:1 dr and 91% ee. Finally, the
secondary homoallylic alcohol (1R,3R,4R)-6jg –which is
characterized by the presence of both an  quaternary
stereocenter and a ’ tertiary stereocenter– was obtained
in 73% yield, 4.2:1.2:1 dr and 95% ee for the major
stereoisomer.
O
P
O
BArF
O
O
Ph
N
OH
Ir
P
Ar
t-Bu t-Bu
Ar = 2,4,6-(i-Pr)3C6H2
Ir
(R)-[ ] (10.0 mol%)
Alk OH
Alk
(S)-TRIP (10 mol%)
H2 activation
+
R1
Bpin
Ar
Ar
OH
THF (0.2 M)
1,2-DCE (0.1 M)
0 to 23 C, 135 min. 20 or 23 C, 48 h
Me R1
6
1j-k
3a,g
(E)-
Match w/. (S)-TRIP
6ja
Mismatch w/. (R)-TRIP
6ja
OH
(1R,3R)-
(1R,3R)-
70% yield, 4.7:1 dr
45% yield, 1.5:1 dr
Me Me
95% ee / 96% ee
93% ee / 99% ee
Me
Me
OH
OH

'
6jg
(1R,3R,4R)-
73(48)% yielda
4.2:1.2:1 dr
95% ee
6ka
(1R,3R)-
Me Me
58% yield, 4.8:1 dr
Me
Me
MeO
91% ee /94% ee
Me
Figure 6. Dual isomerization/allylboration using prochiral
allylic alcohols (E)-1j-k together with 3a, 3g (0.1 mmol
scale). Yield of isolated product after purification by
column chromatography. Diastereomeric ratio determined
The effectiveness of the one-pot sequence was further
explored using stereochemically complex structures
reminiscent of naturally occurring compounds. Two
steroid-based allylic alcohols were subjected to catalysis
using Crabtree’s catalyst for the dual isomerization in THF
and (R)- or (S)-TRIP for the allylboration reaction after
switching solvent to 1,2-dichloroethane (Figure 7).
Substrate 1j gave secondary homoallylic alcohol 6la in 40%
yield as a single stereoisomer, indicating that the presence
of multiple vicinal stereocenters has essentially no
influence on the C–C bond forming event. Similarly and
consistent with our previous studies on the isomerization
of stereochemically complex allylic alcohols,17i 6ma was
isolated with an excellent 19:1 dr in 64% yield. As a side
note, the compatibility of the catalytic sequence with the
alcohol at C3 in 1l and the azide at C3 in 1m further
highlights the functional group tolerance of the protocol.
1
by H NMR using an internal standard. Enantiomeric
excess determined by HPLC using a chiral stationary
a
phase. In parenthesis, yield of stereochemically pure
(1R,3R,4s)-6jg after chromatography.
■ CONCLUSION
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The Journal of Organic Chemistry
Page 6 of 16
In summary, we have developed a catalytic sequence enantiomeric excesses (ee’s) were determined by HPLC,
1
2
3
4
5
6
7
8
combining an iridium catalyst and a Brønsted catalyst for
the diastereo- and enantioselective synthesis of chiral
SFC and GC analyses. HPLC analyses performed on a
Shimadzu CTO-20AA with column DAICEL OD-H, OJ-H,
AD-H and IC. GC analyses were performed on HP–6890,
column HYDRODEX DiMOM and HYDRODEX TBDM, 50
m. SFC analyses were performed on a Waters Acquity
UPC2 with columns OD-3, OJ-3, OZ-3, OB-H, AZ-3, AD,
AS-3, AY-H. Retention times (tR) are given in minutes. Thin
layer chromatography (TLC) was performed on plates of
silica precoated with 0.25 mm Kieselgel 60 F254 from
Merck. Flash chromatography was performed using silica
gel SiliaFlash® P60 (230-400 mesh) from Silicycle.
Commercial reagents, precatalysts and ligands were
purchased from Aldrich, Fluka, Acros or Strem and used
without purification unless otherwise noted.
secondary homoallylic alcohols bearing
a
vicinal
quaternary (stereo)center. The iridium catalyst exerts a
dual role as it performs the concomitant isomerization of
allylic alcohols into aldehydes and of homoallylboronates
into allylboronates. Subsequently, upon addition of a chiral
Brønsted acid catalyst to the same flask, the two products
of isomerization engage into a highly stereoselective
allylboration reaction. When an achiral iridium complex
and a chiral Brønsted acid catalyst were used together with
primary allylic alcohols and (3-methylbut-3-en-1-
yl)boronic ester, secondary homoallylic alcohols with a
proximal gem-dimethyl carbon center were obtained in
excellent yield and enantiomeric excess. Secondary
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General
procedure
for
the
dual
homoallylic alcohols bearing
a
vicinal quaternary
isomerization/allylboration sequence. The iridium
catalyst (0.01 mmol, 5 mol%) was introduced into a Schlenk
tube in a glove-box and dissolved in anhydrous and
degassed 1,2-DCE (0.9 mL). Next hydrogen gas was gently
bubbled directly through the solution (2-3 bubbles per
second) via a stainless-steel needle at room temperature.
The orange solution rapidly became light yellow color.
After 1-2 minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3a (60 mg, 0.3
mmol, 1.5 equiv.) was added immediately to the cold
solution in one portion. The rubber septum was replaced
with a polyethylene stopper and the reaction was stirred at
0 °C for 30 min. Then the appropriate allylic alcohol 1 (0.2
mmol, 1.0 equiv., in 0.2 mL of 1,2-DCE) was added to the
above solution at 0 °C for the indicated time. After that, the
stereocenter were generated in excellent dr and high ee for
homoallylboronates with an aryl or homoprenyl
derivatives. While the former led to anti-product, syn-
homoallylic alcohols were obtained with the latter.
Consistent with the stereospecific nature of allylboration
reactions, this phenomenon was found to originate from
the ability of the iridium catalyst to produce the
corresponding transient allylboronates with high (E)- or
(Z)-selectivity. Secondary homoallylic alcohols with an -
quaternary (stereo)center and a ’ stereocenter have been
prepared with high levels of diastereo- and enantiocontrol
using our catalytic sequence. Last, we demonstrated that
the protocol is applicable to stereochemically complex and
demanding environments using steroid-derived di- and
trisubstituted allylic alcohols. Current investigations are
directed towards the design of a more general system and
of its implementation in the synthesis of biologically and
pharmaceutically relevant products.
°
solution was cooled down to –20 C and the (R)-TRIP
catalyst (0.02 mmol, 10 mol%, in 0.1 mL of 1,2-DCE) was
added. After stirring at –20 °C for 24 h, the reaction mixture
was purified by column chromatography (pentane/diethyl
ether 9:1 to 5:1) to afford the corresponding homoallylic
alcohol 6. This compound was used for determination of
the enantiomeric excess.
■ EXPERIMENTAL SECTION
General Experimental Methods for Synthesis and
Chemical Characterization. All reactions were carried
out under an inert atmosphere of nitrogen using either
two-manifold vacuum/inert nitrogen lines or a M. Braun
glove-box. Solvents were dried over activated alumina
columns and further degassed by three successive "freeze-
pump-thaw" cycles if necessary. NMR spectra were
recorded on AMX-300, AMX-400 and AMX-500 Bruker
Synthesis of (S)-4,4-dimethyl-1-phenylhex-5-en-3-ol ((S)-
6aa). According to the general procedure: isomerization of
°
homoallylic boronate 3a (30 min, 0 C); isomerization of
°
allylic alcohol 1a (10 min, 0 C). Purification by column
chromatography (pentane/diethyl ether 9:1 to 5:1) to afford
(S)-6aa as a colorless oil (35 mg, 86% yield, 93% ee). Rf =
0.5 (pentane/diethyl ether 4:1). All spectroscopic and
spectrometric analyses were in agreement with the
literature.25 HPLC: 93% ee, chiral stationary column: AD-
H, mobile phase: hexane/iPrOH = 99/1, 1.0 mL/min, 210
1
Avance spectrometers at 298 K. H and 13C{1H} NMR
chemical shifts are given in ppm relative to SiMe4, with the
1
solvent resonance used as internal reference. H NMR
spectra were referenced to CDCl3 (7.26 ppm) and 13C{1H}
NMR spectra were referenced to CDCl3 (77.16 ppm).
Infrared spectra were obtained on a Perkin-Elmer 1650 FT-
IR spectrometer using neat samples on a diamond ATR
Golden Gate sampler. GC-MS analyses were performed on
GC–HP 6890, column Agilent–HP1 (30 m–ID 0.32 mm,
Film 0.25 μm) coupled with MS–HP 5973. HRMS were
obtained on a Xevo G2 TOF spectrometer (Ionization
mode: ESI positive polarity; Mobile phase: MeOH 100
μl/min). Mass spectrum is calibrated by the use of the MS
lockspray system (LeuEnk calibration solution). The
nm, 30 °C, tR (major) = 13.1 min, tR (minor) = 17.1 min. []20
D
= –40.7 (c 1.93, CH2Cl2).
Synthesis of (S)-2-(4-hydroxy-5,5-dimethylhept-6-en-1-
yl)isoindoline-1,3-dione ((S)-6ba). According to the general
procedure: isomerization of homoallylic boronate 3a (30
min, 0 °C); isomerization of allylic alcohol 1b (60 min, 0 °C).
Purification by column chromatography (pentane/diethyl
ether 6:1 to 3:1) to afford (S)-6ba as a colorless oil (51.7 mg,
90% yield, 91% ee). TLC: Rf = 0.3 (pentane/diethyl ether
4:1). 1H NMR (300 MHz, CDCl3)  (ppm) = 7.84 (dd, 3JHH
=
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Page 7 of 16
The Journal of Organic Chemistry
5.4, 3.1 Hz, 2H, H-11), 7.71 (dd, 3JHH = 5.5, 3.1 Hz, 2H, H-12),
5.80 (dd, JHH = 17.5, 10.9 Hz, 1H, H-2), 5.14 – 4.96 (m, 2H,
257.1509. IR (neat)  (cm-1): 3081, 2956, 2929, 2865, 1637,
1613, 1584, 1511, 1464, 1416, 1381, 1364, 1300, 1243, 1177, 1108,
1071, 1037, 1007, 914, 830, 770, 689. HPLC: 94.5% ee, chiral
stationary column: AD-H, mobile phase: hexane/iPrOH =
99/1, 1.0 mL/min, 210 nm, 30 °C, tR (major) = 23.3 min, tR
(minor) = 26.8 min. []20D = –33.3 (c 2.20, CH2Cl2).
3
1
2
3
4
5
6
7
8
H-1), 3.80 – 3.64 (m, 2H, H-8), 3.30 (dd, 3JHH = 10.6, 2.0 Hz,
1H, H-4), 2.03 – 1.85 (m, 1H, H-6), 1.79 – 1.65 (m, 1H, H-6),
1.64 – 1.53 (m, 2H, H-5 and O-H), 1.37 – 1.26 (m, 1H, H-5),
1.00 (s, 6H, H-7). 13C{1H} NMR (75 MHz, CDCl3)  (ppm) =
168.5 (C-9), 145.2 (CH-2), 133.9 (CH-12), 132.2 (C-10), 123.2
(CH-11), 113.6 (CH2-1), 77.8 (CH-4), 41.7 (C-3), 38.0 (CH2-8),
28.4 (CH2-5), 26.3 (CH2-6), 23.1 (CH3-7), 22.0 (CH3-7).
HRMS (ESI) m/z [M+H]+ Calcd for C17H21NO3: 288.1595;
Found: 288.1582. IR (neat)  (cm-1): 3082, 2960, 2871, 1772,
1703, 1639, 1615, 1467, 1439, 1396, 1364, 1188, 1172, 1117, 1070,
1047, 1008, 969, 913, 885, 795, 719, 692. HPLC: 91% ee, chiral
stationary column: AD-H, mobile phase: hexane/iPrOH =
95/5, 1.0 mL/min, 210 nm, 30 °C, tR (major) = 36.3 min, tR
(minor) = 27.9 min. []20D = –20.2 (c 2.93, CH2Cl2).
Synthesis of (S)-4,4-dimethyl-1-(1-methyl-1H-indol-3-
yl)hex-5-en-3-ol ((S)-6ea). According to the general
procedure: isomerization of homoallylic boronate 3a (0.3
mmol, 30 min, 0 °C); isomerization of allylic alcohol 1e (0.2
9
°C). Purification by column
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
mmol, 10 min,
0
chromatography (pentane/diethyl ether 9:1 to 3:1) to afford
(S)-6ea as a colorless oil (24 mg, 47% yield, 88% ee). TLC:
1
Rf = 0.4 (pentane/diethyl ether 4:1). H NMR (400 MHz,
CDCl3)  (ppm) = 7.61 (d, 3JHH = 7.9 Hz, 1H, H-13), 7.29 (d,
3JHH = 8.2 Hz, 1H, H-11), 7.24 – 7.18 (m, 1H, H-12), 7.14 – 7.06
3
Synthesis
of
(S)-4,4-dimethyl-1-(4-(trifluoro-
(m, 1H, H-10), 6.86 (s, 1H, H-16), 5.82 (dd, JHH = 17.5, 10.8
methyl)phenyl)hex-5-en-3-ol ((S)-6ca). According to the
general procedure: isomerization of homoallylic boronate
3a (0.3 mmol, 30 min, 0 °C), isomerization of allylic alcohol
1c (0.2 mmol, 10 min, 0 °C). Purification by column
chromatography (pentane/diethyl ether 9:1 to 4:1) to afford
(S)-6ca as a colorless oil (47 mg, 86% yield, 90% ee). TLC:
Hz, 1H, H-2), 5.14 – 5.01 (m, 2H, H-1), 3.75 (s, 3H, H-15), 3.37
3
(dd, JHH = 10.5, 1.8 Hz, 1H, H-4), 3.08 – 2.98 (m, 1H, H-6),
2.84 – 2.74 (m, 1H, H-6), 2.02 – 1.92 (m, 1H, H-5), 1.68 – 1.60
(m, 1H, H-5), 1.57 (s, 1H, O-H), 1.00 (s, 6H, H-7). 13C{1H}
NMR (100 MHz, CDCl3)  (ppm) = 145.4 (CH-2), 137.1 (C-
14), 127.9 (C-9), 126.2 (CH-16), 121.5 (CH-12), 119.1 (CH-13),
118.6 (CH-10), 114.9 (C-8), 113.5 (CH2-1), 109.1 (CH-11), 78.0
(CH-4), 41.7 (C-3), 32.6 (CH3-15), 32.2 (CH2-5), 23.2 (CH3-7),
22.5 (CH2-6), 22.0 (CH3-7). HRMS (ESI) m/z [M+H]+ Calcd
for C17H23NO: 258.1853; Found: 258.1852. IR (neat)  (cm-1):
3456, 3055, 2926, 2855, 1637, 1615, 1555, 1471, 1417, 1377, 1324,
1247, 1203, 1152, 1070, 1044, 1011, 962, 915, 792, 738, 690.
HPLC: 88% ee, chiral stationary column: IC, mobile phase:
hexane/iPrOH = 95/5, 1.0 mL/min, 210 nm, 30 °C, tR (major)
1
Rf = 0.5 (pentane/diethyl ether 4:1). H NMR (300 MHz,
CDCl3)  (ppm) = 7.53 (d, 3JHH = 8.0 Hz, 2H, H-10), 7.32 (d,
3JHH = 8.0 Hz, 2H, H-9), 5.78 (dd, 3JHH = 17.5, 10.8 Hz, 1H, H-
2), 5.17 – 4.98 (m, 2H, H-1), 3.26 (dd, 3JHH = 10.7, 1.9 Hz, 1H,
H-4), 3.03 – 2.91 (m, 1H, H-6), 2.75 – 2.61 (m, 1H, H-6), 1.91
– 1.77 (m, 1H, H-5), 1.66 – 1.56 (m, 1H, H-5), 1.55 (s, 1H, O-
H), 1.00 (s, 6H, H-7). 13C{1H} NMR (75 MHz, CDCl3)  (ppm)
= 141.6 (q, 1JFC = 285, C-12), 145.1 (CH-2), 128.8 (CH-9), 128.2
2
3
= 9.6 min, tR (minor) = 16.2 min. []20 = –33.6 (c 1.40,
(q, JFC = 38, C-11), 125.2 (q, JFC = 8, CH-10), 113.9 (CH2-1),
77.2 (CH-4), 41.7 (C-3), 33.0 (CH2-6), 32.9 (CH2-5), 23.1
(CH3-7), 21.8 (CH3-7). 19F{1H} NMR (282 MHz, CDCl3) 
(ppm) = -62.29. HRMS (ESI) m/z [M+K]+ Calcd for
C15H19F3O: 311.1020; Found: 311.1015. IR (neat)  (cm-1): 2964,
2931, 2872, 1619, 1467, 1417, 1383, 1365, 1325, 1163, 1123, 1068,
1019, 919, 843, 824, 734, 689, 630. HPLC: 90% ee, chiral
stationary column: AD-H, mobile phase: hexane/iPrOH =
99/1, 1.0 mL/min, 210 nm, 30 °C, tR (major) = 11.2 min, tR
(minor) = 12.4 min. []20D = –46.5 (c 1.40, CH2Cl2).
D
CH2Cl2).
Synthesis of (S)-3,3-dimethylnon-1-en-4-ol ((S)-6fa).
According to the general procedure: isomerization of
°
homoallylic boronate 3a (30 min, 0 C); isomerization of
°
allylic alcohol 1f (60 min, 0 C). Purification by column
chromatography (pentane/diethyl ether 20:1 to 10:1) to
afford (S)-6fa as a colorless oil (23.2 mg, 68% yield, 88%
ee). TLC: Rf = 0.6 (pentane/diethyl ether 4:1). All
spectroscopic and spectrometric analyses were in
agreement with the literature.26 GC: HYDRODEX B-3P,
60°C-1°C/min-170°C, 20. M, H2, tR (major) = 33.5 min, tR
(minor) = 35.0 min. []20D = –2.9 (c 0.07, CH2Cl2).
Synthesis of (S)-1-(4-methoxyphenyl)-4,4-dimethylhex-5-
en-3-ol ((S)-6da). According to the general procedure:
isomerization of homoallylic boronate 3a (0.3 mmol, 30
min, 0 °C), isomerization of allylic alcohol 1d (0.2 mmol, 5
min, 0 °C). Purification by column chromatography
(pentane/diethyl ether 9:1 to 4:1) to afford (S)-6da as a
colorless oil (34 mg, 73% yield, 94.5% ee). TLC: Rf = 0.4
Synthesis of (S)-1-cyclohexyl-4,4-dimethylhex-5-en-3-ol
((S)-6ga). According to the general procedure:
isomerization of homoallylic boronate 3a (0.3 mmol, 30
min, 0 °C), isomerization of allylic alcohol 1g (0.2 mmol, 5
min, 0 °C). Purification by column chromatography
(pentane/diethyl ether 20:1 to 9:1) to afford (S)-6ga as a
colorless oil (34 mg, 80% yield, 94% ee). TLC: Rf = 0.7
1
(pentane/diethyl ether 4:1). H NMR (300 MHz, CDCl3) 
(ppm) = 7.13 (d, 3JHH = 8.6 Hz, 2H, H-10), 6.83 (d, 3JHH = 8.6
Hz, 2H, H-9), 5.80 (dd, 3JHH = 17.5, 10.9 Hz, 1H, H-2), 5.14 –
4.98 (m, 2H, H-1), 3.79 (s, 3H, H-12), 3.27 (d, 3JHH = 10.5, 1.8
Hz, 1H, H-4), 2.94 – 2.78 (m, 1H, H-6), 2.63 – 2.50 (m, 1H,
H-6), 1.87 – 1.72 (m, 1H, H-5), 1.62 – 1.46 (m, 2H, H-5 and O-
H), 1.00 (s, 6H, H-7). 13C{1H} NMR (75 MHz, CDCl3)  (ppm)
= 157.8 (C-11), 145.3 (CH-2), 134.4 (C-8), 129.4 (CH-10), 113.8
(CH-9), 113.5 (CH2-1), 77.5 (CH-4), 55.3 (CH3-12), 41.7 (C-3),
33.5 (CH2-5), 32.3 (CH2-6), 23.1 (CH3-7), 22.0 (CH3-7). HRMS
(ESI) m/z [M+Na]+ Calcd for C15H22O2: 257.1512; Found:
1
(pentane/diethyl ether 4:1). H NMR (300 MHz, CDCl3) 
(ppm) = 5.82 (dd, 3JHH = 17.5, 10.9 Hz, 1H, H-2), 5.15 – 4.96
(m, 2H, H-1), 3.25 – 3.14 (m, 1H, H-4), 1.74 – 1.41 (m, 8H),
1.27 – 1.11 (m, 6H), 1.00 (s, 6H, H-7), 0.94 – 0.80 (m, 2H).
13C{1H} NMR (75 MHz, CDCl3)  (ppm) = 145.6 (CH-2), 113.2
(CH2-1), 78.7 (CH-4), 41.8 (C-3), 37.8 (CH-8), 34.8, 33.7, 33.2,
28.7, 26.7, 26.5, 26.4, 23.2 (CH3-7), 22.1 (CH3-7). HRMS (ESI)
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 16
m/z [M+H-H2O]+ Calcd for C14H25O: 193.1946; Found:
193.1960. IR (neat)  (cm-1): 3389, 3082, 2921, 2851, 1638,
1450, 1415, 1380, 1304, 1279, 1127, 1072, 1006, 911, 688. Chiral
GC: HYDRODEX B-3P, 60°C-1°C/min-170°C, 20. M, H2, tR
(major) = 68.2 min, tR (minor) = 69.5 min. []20D = –27.2 (c
1.87, CH2Cl2).
(ppm) = 7.28 – 7.24 (m, 2H), 7.22 – 7.16 (m, 3H), 7.15 – 7.11
3
1
2
3
4
5
6
7
8
(m, 2H), 7.11 – 7.06 (m, 2H), 6.27 (dd, JHH = 17.7, 10.9 Hz,
1H, H-2), 5.27 (dd, 3JHH = 10.9, 1.3 Hz, 1H, H-1), 5.14 (dd, 3JHH
= 17.7, 1.3 Hz, 1H, H-1), 3.96 – 3.83 (m, 1H, H-4), 2.95 – 2.83
(m, 1H, H-6), 2.64 – 2.54 (m, 1H, H-6), 2.44 (d, 3JHH = 7.2 Hz,
2H, H-8), 1.90 – 1.80 (m, 1H, H-9), 1.75 – 1.47 (m, 3H, H-5
3
and O-H), 1.36 (s, 3H, H-7), 0.90 (d, JHH = 6.6 Hz, 6H, H-
Synthesis of (S)-8-(benzyloxy)-3,3-dimethyloct-1-en-4-ol
((S)-6ha). According to the general procedure:
isomerization of homoallylic boronate 3a (0.15 mmol, 30
min, 0 °C), isomerization of allylic alcohol 1h (0.1 mmol, 15
10). 13C{1H} NMR (100 MHz, CDCl3)  (ppm) = 143.3 (CH-2),
142.4 (C-Ar), 142.3 (C-Ar), 139.8 (C-Ar), 129.3 (CH-Ar), 128.5
(CH-Ar), 128.3 (CH-Ar), 126.5 (CH-Ar), 125.7 (CH-Ar), 114.6
(CH2-1), 76.6 (CH-4), 49.3 (C-3), 44.9 (CH2-8), 33.2 (CH2-6),
32.9 (CH2-5), 30.2 (CH-9), 22.5 (CH3-10), 22.4 (CH3-10), 19.6
(CH3-7). HRMS (ESI) m/z [M+Na]+ Calcd for C23H30O:
345.2189; Found: 345.2174. IR (neat)  (cm-1): 3479, 3085,
3026, 2955, 2926, 2868, 1634, 1604, 1511, 1497, 1455, 1415, 1384,
1282, 1168, 1057, 1018, 919, 845, 794, 747, 699, 667. HPLC:
72% ee, chiral stationary column: OJ-H, mobile phase:
hexane/iPrOH = 99/1, 1.0 mL/min, 210 nm, 30 °C, tR (major)
9
°
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
min, 0 C), (R)-TRIP catalyst (0.015 mmol, 15 mol%).
Purification by column chromatography (pentane/diethyl
ether 9:1 to 4:1) to afford (S)-6ha as a colorless oil (21.7 mg,
82% yield, 92% ee). TLC: Rf = 0.5 (pentane/diethyl ether
1
4:1). H NMR (400 MHz, CDCl3)  (ppm) = 7.31 – 7.23 (m,
4H), 7.22 – 7.18 (m, 1H), 5.73 (dd, 3JHH = 17.5, 10.8 Hz, 1H, H-
2), 5.05 – 4.93 (m, 2H, H-1), 4.43 (s, 2H, H-10), 3.46 – 3.36
3
(m, 2H, H-9), 3.17 (dd, JHH = 10.4, 1.8 Hz, 1H, H-4), 1.64 –
= 11.4 min, tR (minor) = 13.4 min. []20 = –4.9 (c 1.40,
D
1.51 (m, 3H, H-6 and H-8), 1.50 – 1.42 (m, 2H, H-5 and O-H),
1.37 – 1.27 (m, 1H, H-6), 1.22 – 1.16 (m, 1H, H-5), 0.92 (s, 6H,
H-7). 13C{1H} NMR (100 MHz, CDCl3)  (ppm) = 145.5 (CH-
2), 138.6 (C-Ar), 128.4 (CH-Ar), 127.7 (CH-Ar), 127.5 (C-Ar),
113.4 (CH2-1), 78.2 (CH-4), 72.9 (CH2-10), 70.4 (CH2-9), 41.7
(C-3), 31.2 (CH2-5), 29.7 (CH2-8), 23.8 (CH2-6), 23.1 (CH3-7),
22.0 (CH3-7). HRMS (ESI) m/z [M+Na]+ Calcd for C17H26O2:
285.1825; Found: 285.1832. IR (neat)  (cm-1): 3030, 2931,
2861, 1739, 1638, 1495, 1455, 1415, 1363, 1310, 1205, 1100, 1028,
1006, 911, 735, 697, 614. HPLC: 92% ee, chiral stationary
column: AD-H, mobile phase: hexane/iPrOH = 99/1, 1.0
mL/min, 210 nm, 30 °C, tR (major) = 22.7 min, tR (minor) =
20.7 min. []20D = –20.8 (c 1.13, CH2Cl2).
CH2Cl2).
Synthesis of (3S,4S)-4-([1,1'-biphenyl]-4-yl)-4-methyl-1-
phenylhex-5-en-3-ol (anti-6ac). The iridium catalyst (0.01
mmol, 10 mol%) was introduced into a Schlenk tube in a
glove-box and dissolved in anhydrous and degassed 1,2-
DCE (0.9 mL). Next hydrogen gas was gently bubbled
directly through the solution (2-3 bubbles per second) via
a stainless-steel needle at room temperature. The orange
solution rapidly became light yellow color. After 1-2
minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3c (0.2 mmol,
2.0 equiv.) was added immediately to the cold solution in
one portion. The rubber septum was replaced with a
Synthesis of (3S,4S)-4-(4-isobutylphenyl)-4-methyl-1-
phenylhex-5-en-3-ol (anti-6ab). The iridium catalyst (0.01
mmol, 10 mol%) was introduced into a Schlenk tube in a
glove-box and dissolved in anhydrous and degassed 1,2-
DCE (0.9 mL). Next hydrogen gas was gently bubbled
directly through the solution (2-3 bubbles per second) via
a stainless-steel needle at room temperature. The orange
solution rapidly became light yellow color. After 1-2
minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3b (0.2 mmol,
2.0 equiv.) was added immediately to the cold solution in
one portion. The rubber septum was replaced with a
polyethylene stopper and the reaction was stirred at room
temperature for 15 min. Then the appropriate allylic
alcohol 1a (0.1 mmol, 1.0 equiv., in 0.2 mL of 1,2-DCE) was
added to the above solution at room temperature for 30
min. After that, the solution was cooled down to 0 °C and
the (R)-TRIP catalyst (0.01 mmol, 10 mol%, in 0.1 mL of 1,2-
DCE) was added. After stirring at 0 °C for 48 h, the reaction
mixture was purified by column chromatography
(pentane/diethyl ether 9:1 to 5:1) to afford the
corresponding homoallylic alcohol anti-6ab. This
compound was used for determination of the enantiomeric
excess Purification by column chromatography
(pentane/diethyl ether 9:1 to 4:1) to afford 6ab as a colorless
oil (25 mg, 78% yield, 19:1 dr, 72% ee). TLC: Rf = 0.5
°
polyethylene stopper and the reaction was stirred at 0 C
for 15 min. Then the appropriate allylic alcohol 1a (0.1
mmol, 1.0 equiv., in 0.2 mL of 1,2-DCE) was added to the
°
above solution at 0 C for 30 min. After that, the solution
°
was cooled down to 0 C and the (R)-TRIP catalyst (0.01
mmol, 10 mol%, in 0.1 mL of 1,2-DCE) was added. After
stirring at 0 °C for 48 h, the reaction mixture was purified
by column chromatography (pentane/diethyl ether 9:1 to
5:1) to afford the corresponding homoallylic alcohol anti-
6ac. This compound was used for determination of the
enantiomeric
excess.
Purification
by
column
chromatography (pentane/diethyl ether 9:1 to 4:1) to afford
6ac as a colorless oil (26 mg, 76% yield, 19:1 dr, 60% ee).
1
TLC: Rf = 0.5 (pentane/diethyl ether 4:1). H NMR (400
MHz, CDCl3)  (ppm) = 7.62 – 7.53 (m, 4H), 7.48 – 7.42 (m,
2H), 7.41 – 7.33 (m, 3H), 7.32 – 7.26 (m, 2H), 7.22 – 7.14 (m,
3
3
3H), 6.31 (dd, JHH = 17.7, 10.9 Hz, 1H, H-2), 5.31 (dd, JHH
=
3
10.9, 1.2 Hz, 1H, H-1), 5.19 (dd, JHH = 17.6, 1.3 Hz, 1H, H-1),
3.98 (d, JHH = 9.2 Hz, 1H, H-4), 2.97 – 2.87 (m, 1H, H-6),
3
2.67 – 2.59 (m, 1H, H-6), 1.75 – 1.60 (m, 3H, H-5 and O-H),
1.42 (s, 3H, H-7). 13C{1H} NMR (100 MHz, CDCl3)  (ppm) =
144.4 (C-Ar), 143.1 (CH-2), 142.2 (C-Ar), 140.7 (C-Ar), 139.2
(C-Ar), 128.8 (CH-Ar), 128.6 (CH-Ar), 128.4 (CH-Ar), 127.3
(CH-Ar), 127.3 (CH-Ar), 127.2 (CH-Ar), 127.0 (CH-Ar), 125.8
(CH-Ar), 115.0 (CH2-1), 76.5 (CH-4), 49.5 (C-3), 33.2 (CH2-
6), 33.0 (CH2-5), 19.7 (CH3-7). HRMS (ESI) m/z [M+Na]+
1
(pentane/diethyl ether 4:1). H NMR (400 MHz, CDCl3) 
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The Journal of Organic Chemistry
= 10.5 min, tR (minor) = 14.7 min. []20 = –16.9 (c 0.83,
Calcd for C25H26O: 365.1876; Found: 365.1888. IR (neat) 
D
(cm-1): 3580, 3028, 2927, 1602, 1487, 1454, 1397, 1264, 1059,
1007, 919, 840, 766, 736, 698. SFC: 60% ee, chiral stationary
column: OB, mobile phase: 20% MeOH, 2.0 mL/min, 254
CH2Cl2).
1
2
3
4
5
6
Synthesis of ((3S,4R)-7-chloro-4-methyl-1-phenyl-4-
vinylheptan-3-ol (anti-6ae). The iridium catalyst (0.01
mmol, 10 mol%) was introduced into a Schlenk tube in a
glove-box and dissolved in anhydrous and degassed 1,2-
DCE (0.9 mL). Next hydrogen gas was gently bubbled
directly through the solution (2-3 bubbles per second) via
a stainless-steel needle at room temperature. The orange
solution rapidly became light yellow color. After 1-2
minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3e (0.2 mmol,
2.0 equiv.) was added immediately to the cold solution in
one portion. The rubber septum was replaced with a
nm, 30 °C, tR (major) = 7.1 min, tR (minor) = 6.1 min. []20
= 13.3 (c 1.11, CH2Cl2).
D
Synthesis of (3S,4S)-4-methyl-4-phenethyl-1-phenylhex-5-
en-3-ol (syn-6ad). The iridium catalyst (0.01 mmol, 10
mol%) was introduced into a Schlenk tube in a glove-box
and dissolved in anhydrous and degassed THF (0.5 mL).
Next hydrogen gas was gently bubbled directly through the
solution (2-3 bubbles per second) via a stainless-steel
needle at room temperature. The orange solution rapidly
became light yellow color. After 1-2 minutes, bubbling was
cased and the solution was degassed by two successive
freeze-pump-thaw cycles. After the second cycle, the
homoallylic boronate 3d (0.2 mmol, 2.0 equiv.) was added
immediately to the cold solution in one portion. The
rubber septum was replaced with a polyethylene stopper
and the reaction was stirred at –20 °C for 15 min. Then the
appropriate allylic alcohol 1a (0.1 mmol, 1.0 equiv., in 0.2
mL of THF) was added to the above solution at –20 °C for
15 min. After that, the solvent THF was removed slowly
under vacuum. Then the mixture was cooled down to –30
°C and the (R)-TRIP catalyst (0.015 mmol, 15 mol%, in 1.0
mL of 1,2-DCE) was added. After stirring at –30 °C for 48 h,
the reaction mixture was purified by column
chromatography (pentane/diethyl ether 9:1 to 4:1) to afford
the corresponding homoallylic alcohol syn-6ad. This
compound was used for determination of the enantiomeric
excess. Purification by column chromatography
(pentane/diethyl ether 9:1 to 4:1) to afford 6ad as a colorless
oil (24 mg, 82% yield, 2.8:1 dr, 83% ee/ 56% ee). TLC: Rf =
0.4 (pentane/diethyl ether 4:1). 1H NMR (300 MHz, CDCl3)
 (ppm) = 7.36 – 7.29 (m, 4H), 7.28 – 7.15 (m, 6H), 5.94 –
5.74 (m, 1H, H-2), 5.37 – 5.25 (m, 1H, H-1), 5.22 – 5.10 (m, 1H,
H-1), 3.46 – 3.36 (m, 1H, H-4), 3.04 – 2.90 (m, 1H, H-6), 2.72
– 2.61 (m, 1H, H-6), 2.60 – 2.47 (m, 2H, H-9), 2.00 – 1.86 (m,
1H, H-5), 1.77 – 1.62 (m, 3H, H-5 and H-8), 1.52 – 1.38 (m, 1H,
O-H), 1.14 (s, 2.3H, syn-isomer H-7), 1.10 (s, 0.8H, anti-
isomer H-7). 13C{1H} NMR (75 MHz, CDCl3)  (ppm) =
143.90 (syn, CH-2), 143.13 (anti, CH-2), 143.03 (syn, C-Ar),
142.94 (anti, C-Ar), 142.38 (anti, C-Ar), 142.26 (syn, C-Ar),
128.53 (syn, CH-Ar), 128.41 (syn, CH-Ar), 128.38 (syn, CH-
Ar), 128.33 (syn, CH-Ar), 125.84 (syn, CH-Ar), 125.82 (anti,
CH-Ar), 125.75 (anti, CH-Ar), 125.71 (syn, CH-Ar), 115.81
(anti, CH2-1), 115.21 (syn, CH2-1), 77.39 (syn, CH-4), 76.41
(anti, CH-4), 45.27 (anti, C-3), 45.03 (syn, C-3), 39.62 (anti,
CH2-8), 39.56 (syn, CH2-8), 33.80 (syn, CH2-5), 33.29 (anti,
CH2-5), 33.26 (syn, CH2-6), 32.93 (anti, CH2-6), 30.68 (anti,
CH2-9), 30.56 (syn, CH2-9), 17.81 (syn, CH3-7), 16.7 (anti,
CH3-7). HRMS (ESI) m/z [M+Na]+ Calcd for C21H26O:
317.1876; Found: 317.1886. IR (neat)  (cm-1): 3452, 3063,
3027, 2928, 2862, 1634, 1604, 1496, 1455, 1414, 1377, 1301, 1154,
1032, 1007, 916, 740, 699. HPLC: chiral stationary column:
IC, mobile phase: hexane/iPrOH = 99/1, 1.0 mL/min, 210
nm, 30 °C, for major diastereoisomer: tR (major) = 13.1 min,
tR (minor) = 20.0 min, for minor diastereoisomer: tR (major)
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
°
polyethylene stopper and the reaction was stirred at 0 C
for 30 min. Then the appropriate allylic alcohol 1a (0.1
mmol, 1.0 equiv., in 0.2 mL of 1,2-DCE) was added to the
°
above solution at 0 C for 10 min. Then the mixture was
°
cooled down to –30 C and the (R)-TRIP catalyst (0.015
mmol, 15 mol%, in 0.1 mL of 1,2-DCE) was added. After
stirring at –30 °C for 48 h, the reaction mixture was purified
by column chromatography (pentane/diethyl ether 9:1 to
4:1) to afford the corresponding homoallylic alcohol anti-
6ae. This compound was used for determination of the
enantiomeric
excess.
Purification
by
column
chromatography (pentane/diethyl ether 9:1 to 4:1) to afford
6ae as a colorless oil (16.5 mg, 62% yield, 1.3:1 dr, 55% ee/
84% ee). TLC: Rf = 0.5 (pentane/diethyl ether 4:1). 1H NMR
(400 MHz, CDCl3)  (ppm) = 7.35 – 7.27 (m, 2H), 7.25 – 7.15
(m, 3H), 5.77 – 5.61 (m, 1H, H-2), 5.26 – 5.16 (m, 1H, H-1),
5.10 – 5.00 (m, 1H, H-1), 3.54 – 3.46 (m, 2H, H-10), 3.35 – 3.28
(m, 1H, H-4), 2.98 – 2.87 (m, 1H, H-6), 2.66 – 2.56 (m, 1H,
H-6), 1.91 – 1.79 (m, 1H, H-5), 1.72 – 1.44 (m, 6H), 0.99 (s,
1.3H, syn-isomer H-7), 0.96 (s, 1.7H, anti-isomer H-7).
13C{1H} NMR (100 MHz, CDCl3)  (ppm) = 143.48 (anti, CH-
2), 142.94 (syn, CH-2), 142.30 (anti, C-Ar), 142.17 (syn, C-Ar),
128.53 (anti, CH-Ar), 128.52 (syn, CH-Ar), 128.44 (syn, CH-
Ar), 128.42 (anti, CH-Ar), 125.88 (syn, CH-Ar), 125.86 (anti,
CH-Ar), 115.88 (anti, CH2-1), 115.24 (syn, CH2-1), 77.37 (syn,
CH-4), 76.50 (anti, CH-4), 45.84 (syn, CH2-10), 45.78 (anti,
CH2-10), 44.76 (anti, C-3), 44.57 (syn, C-3), 34.39 (anti, CH2-
9), 34.37 (syn, CH2-9), 33.71 (CH2-5), 33.24 (anti, CH2-6),
32.93 (syn, CH2-6), 27.58 (anti, CH2-8), 27.49 (syn, CH2-8),
17.57 (syn, CH3-7), 16.85 (anti, CH3-7). HRMS (ESI) m/z
[M+Na]+ Calcd for C16H23ClO: 289.1330; Found: 289.1313. IR
(neat)  (cm-1): 3427, 3027, 2955, 2862, 1636, 1604, 1496,
1454, 1415, 1376, 1308, 1156, 1034, 1007, 967, 917, 748, 699,
649. HPLC: chiral stationary column: AD-H, mobile phase:
hexane/iPrOH = 99/1, 1.0 mL/min, 210 nm, 30 °C, for major
diastereoisomer: tR (major) = 20.8 min, tR (minor) = 24.1
min, for minor diastereoisomer: tR (major) = 26.3 min, tR
(minor) = 33.6 min.
Synthesis of (3S,4R)-7-((tert-butyldimethylsilyl)oxy)-4-
methyl-1-phenyl-4-vinylheptan-3-ol (anti-6af). The iridium
catalyst (0.01 mmol, 10 mol%) was introduced into a
Schlenk tube in a glove-box and dissolved in anhydrous
and degassed 1,2-DCE (0.9 mL). Next hydrogen gas was
gently bubbled directly through the solution (2-3 bubbles
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The Journal of Organic Chemistry
Page 10 of 16
per second) via
a stainless-steel needle at room 2.0 equiv.) was added immediately to the cold solution in
1
2
3
4
5
6
7
8
temperature. The orange solution rapidly became light
yellow color. After 1-2 minutes, bubbling was cased and the
solution was degassed by two successive freeze-pump-
thaw cycles. After the second cycle, the homoallylic
boronate 3f (0.2 mmol, 2.0 equiv.) was added immediately
to the cold solution in one portion. The rubber septum was
replaced with a polyethylene stopper and the reaction was
one portion. The rubber septum was replaced with a
polyethylene stopper and the reaction was stirred at –20 °C
for 30 min. Then the appropriate allylic alcohol 1a (0.1
mmol, 1.0 equiv., in 0.2 mL of 1,2-DCE) was added to the
above solution at –20 °C for 30 min. Then the mixture was
°
cooled down to –30 C and the (R)-TRIP catalyst (0.015
mmol, 15 mol%, in 0.1 mL of 1,2-DCE) was added. After
stirring at –30 °C for 48 h, the reaction mixture was purified
by column chromatography (pentane/diethyl ether 20:1 to
9:1) to afford the corresponding homoallylic alcohol syn-
°
stirred at –20 C for 30 min. Then the appropriate allylic
alcohol 1a (0.1 mmol, 1.0 equiv., in 0.2 mL of 1,2-DCE) was
9
added to the above solution at –20 °C for 30 min. Then the
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
°
mixture was cooled down to –20 C and the (R)-TRIP
6ag.
Purification
by
column
chromatography
catalyst (0.015 mmol, 15 mol%, in 0.1 mL of 1,2-DCE) was
added. After stirring at –20 °C for 48 h, the reaction mixture
was purified by column chromatography (pentane/diethyl
ether 9:1 to 4:1) to afford the corresponding homoallylic
alcohol anti-6af. This compound was deprotected using
TBAF (1.0 M in THF) for determination of the enantiomeric
excess (vide infra). Purification by column chromatography
(pentane/diethyl ether 9:1 to 4:1) to afford 6af as a colorless
oil (23 mg, 63% yield, 1.3:1 dr, 73% ee/ 88% ee). TLC: Rf = 0.5
(pentane/diethyl ether 20:1 to 9:1) to afford syn-6ag as a
colorless oil (18 mg, 66% yield, 19:1 dr, 90% ee). TLC: Rf =
0.7 (pentane/diethyl ether 4:1). 1H NMR (400 MHz, CDCl3)
 (ppm) = 7.32 – 7.26 (m, 2H), 7.23 – 7.16 (m, 3H), 5.69 (dd,
3JHH = 17.6, 10.9 Hz, 1H, H-2), 5.16 (dd, 3JHH = 10.9, 1.4 Hz, 1H,
3
H-1), 5.11 – 5.05 (m, 1H, H-10), 5.02 (dd, JHH = 17.6, 1.5 Hz,
1H, H-1), 3.35 – 3.29 (m, 1H, H-4), 2.95 – 2.87 (m, 1H, H-6),
2.66 – 2.56 (m, 1H, H-6), 1.90 – 1.81 (m, 3H, H-5 and H-9),
1.67 (s, 3H, H-12), 1.57 (s, 3H, H-13), 1.56 – 1.50 (m, 1H, H-5),
1.42 – 1.35 (m, 3H, H-8 and O-H), 1.01 (s, 3H, H-7). C{1H}
1
13
(pentane/diethyl ether 4:1). H NMR (400 MHz, CDCl3) 
(ppm) = 7.31 – 7.26 (m, 2H), 7.24 – 7.15 (m, 3H), 5.78 – 5.62
(m, 1H, H-2), 5.23 – 5.11 (m, 1H, H-1), 5.08 – 4.98 (m, 1H, H-
1), 3.60 – 3.52 (m, 2H, H-10), 3.38 – 3.28 (m, 1H, H-4), 2.98 –
2.88 (m, 1H, H-6), 2.66 – 2.56 (m, 1H, H-6), 1.88 – 1.77 (m,
1H, H-5), 1.74 – 1.72 (br, 0.45H, O-H), 1.63 – 1.56 (m, 1.5H,
H-5 and O-H), 1.46 – 1.31 (m, 4H, H-8 and H-9), 0.98 (s,
1.3H, syn-isomer H-7), 0.94 (s, 1.7H, anti-isomer H-7), 0.89
(s, 9H, H-12), 0.06 (s, 6H, H-11). 13C{1H} NMR (100 MHz,
CDCl3)  (ppm) = 144.08 (anti, CH-2), 143.37 (syn, CH-2),
142.49 (anti, C-Ar), 142.41 (syn, C-Ar), 128.53 (CH-Ar),
128.36 (CH-Ar), 125.76 (CH-Ar), 115.26 (anti, CH2-1), 114.73
(syn, CH2-1), 76.93 (syn, CH-4), 76.21 (anti, CH-4), 63.82
(syn, CH2-10), 63.76 (anti, CH2-10), 44.73 (anti, C-3), 44.51
(syn, C-3), 33.63, 33.34, 33.31, 33.28, 32.84, 27.37 (anti, CH2-
8), 27.19 (syn, CH2-8), 26.00 (CH3-12), 18.41 (C-13), 18.00,
16.83, -5.25 (CH3-11). HRMS (ESI) m/z [M+Na]+ Calcd for
C22H38O2Si: 385.2534; Found: 385.2520. IR (neat)  (cm-1):
3476, 2953, 2930, 2858, 1638, 1604, 1496, 1460, 1388, 1254,
1068, 1006, 937, 915, 836, 776, 748, 699. HPLC: The
compound anti-6af was deprotected using TBAF (1.0 M in
THF) for determination of the enantiomeric excess. Chiral
stationary column: OD-H, mobile phase: hexane/iPrOH =
96/4, 1.0 mL/min, 210 nm, 30 °C, for the major
diastereoisomer: tR (major) = 28.2 min, tR (minor) = 25.4
min, for the minor diastereoisomer: tR (major) = 75.1 min,
tR (minor) = 68.6 min.
NMR (100 MHz, CDCl3)  (ppm) = 143.3 (CH-2), 142.4 (C-
Ar), 131.4 (C-11), 128.5 (CH-Ar), 128.4 (CH-Ar), 125.8 (CH-
Ar), 124.8 (CH-10), 114.9 (CH2-1), 77.4 (CH-4), 44.9 (C-3),
37.3 (CH2-8), 33.8 (CH2-5), 33.3 (CH2-6), 25.7 (CH3-12), 22.6
(CH2-9), 17.8 (CH3-13), 17.6 (CH3-7). HRMS (ESI) m/z
[M+Na]+ Calcd for C19H28O: 295.2033; Found: 295.2044. IR
(neat)  (cm-1): 3414, 3083, 3027, 2967, 2925, 2858, 1637,
1604, 1496, 1454, 1415, 1377, 1072, 1040, 1006, 915, 838, 748,
699. HPLC: Chiral stationary column: AD-H, mobile phase:
hexane/iPrOH = 99/1, 1.0 mL/min, 210 nm, 30 °C, tR (major)
= 12.8 min, tR (minor) = 17.7 min. []20 = –33.8 (c 1.00,
D
CH2Cl2).
Synthesis
of
2-((4S,5S)-4-hydroxy-5,9-dimethyl-5-
vinyldec-8-en-1-yl)isoindoline-1,3-dione (syn-6bg). The
iridium catalyst (0.01 mmol, 10 mol%) was introduced into
a Schlenk tube in a glove-box and dissolved in anhydrous
and degassed THF (0.5 mL). Next hydrogen gas was gently
bubbled directly through the solution (2-3 bubbles per
second) via a stainless-steel needle at room temperature.
The orange solution rapidly became light yellow color.
After 1-2 minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3g (0.4 mmol,
4.0 equiv.) was added immediately to the cold solution in
one portion. The rubber septum was replaced with a
polyethylene stopper and the reaction was stirred at –20 °C
for 15 min. Then the appropriate allylic alcohol (Z)-1b (0.1
mmol, 1.0 equiv., in 0.2 mL of THF) was added to the above
Synthesis of (3S,4S)-4,8-dimethyl-1-phenyl-4-vinylnon-7-
en-3-ol (syn-6ag). The iridium catalyst (0.01 mmol, 10
mol%) was introduced into a Schlenk tube in a glove-box
and dissolved in anhydrous and degassed 1,2-DCE (0.9
mL). Next hydrogen gas was gently bubbled directly
through the solution (2-3 bubbles per second) via a
stainless-steel needle at room temperature. The orange
solution rapidly became light yellow color. After 1-2
minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3g (0.2 mmol,
°
solution at –20 C for 15 min. After that, the solvent THF
was removed slowly under vacuum. Then the mixture was
°
cooled down to –20 C and the (R)-TRIP catalyst (0.015
mmol, 15 mol%, in 1.0 mL of 1,2-DCE) was added. After
stirring at –20 °C for 48 h, the reaction mixture was purified
by column chromatography (pentane/diethyl ether 6:1 to
2:1) to afford the corresponding homoallylic alcohol syn-
6bg.
Purification
by
column
chromatography
(pentane/diethyl ether 6:1 to 2:1) to afford syn-6bg as a
ACS Paragon Plus Environment

Page 11 of 16
The Journal of Organic Chemistry
colorless oil (25 mg, 70% yield, 10:1 dr, 85% ee). TLC: Rf =
0.3 (pentane/diethyl ether 4:1). 1H NMR (400 MHz, CDCl3)
(CH-Ar), 128.1 (CH-Ar), 127.3 (CH-Ar), 127.1 (CH-Ar), 124.7
1
2
3
4
5
6
7
8
(CH-10), 114.9 (CH2-1), 77.7 (CH-4), 65.0 (CH2-14), 44.9 (C-
3), 37.4 (CH2-8), 28.2 (CH2-6), 26.4 (CH2-5), 25.7 (CH3-12),
22.7 (CH2-9), 17.8 (CH3-13), 17.6 (CH3-7). HRMS (ESI) m/z
[M+Na]+ Calcd for C27H34O3: 429.2401; Found: 429.2393. IR
(neat)  (cm-1): 3520, 2964, 2924,2338, 2233, 2178, 2160,
2045, 2019, 1988, 1715, 1610, 1565, 1487, 1450, 1406, 1380, 1276,
1181, 1116, 1007, 971, 914, 856, 784, 748, 698. HPLC: Chiral
stationary column: OD-H, mobile phase: hexane/iPrOH =
98/2, 1.0 mL/min, 210 nm, 30 °C, tR (major) = 23.2 min, tR
(minor) = 38.3 min. []20D = –12.7 (c 1.49, CH2Cl2).
3
3
 (ppm) = 7.84 (dd, JHH = 5.4, 3.1 Hz, 2H), 7.71 (dd, JHH
5.5, 3.0 Hz, 2H), 5.78 – 5.64 (m, 1H, H-2), 5.14 (dd, JHH
=
=
3
10.9, 1.5 Hz, 1H, H-1), 5.11 – 5.05 (m, 1H, H-10), 5.04 – 4.97
(m, 1H, H-1), 3.71 (t, 3JHH = 7.3 Hz, 2H, H-14), 3.36 – 3.29 (m,
1H, H-4), 1.98 – 1.91 (m, 1H, H-6), 1.90 – 1.83 (m, 2H, H-9),
1.75 – 1.68 (m, 1H, H-6), 1.66 (s, 3H, H-12), 1.64 – 1.57 (m, 2H,
H-5 and O-H), 1.56 (s, 3H, H-13), 1.41 – 1.34 (m, 2H, H-8), 1.31
– 1.25 (m, 1H, H-5), 0.99 (s, 3H, H-7, syn-isomer), 0.95 (s,
9
13
0.3H, H-7, anti-isomer). C{1H} NMR (100 MHz, CDCl3) 
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(ppm) = 168.6 (C-15), 143.2 (CH-2), 134.0 (CH-Ar), 132.1 (C-
Ar), 131.5 (C-11), 124.7 (CH-10), 123.3 (CH-Ar), 115.0 (CH2-1),
77.8 (CH-4), 45.0 (C-3), 38.0 (CH2-14), 37.3 (CH2-8), 28.7
(CH2-6), 26.5 (CH2-5), 25.8 (CH3-12), 22.7 (CH2-9), 17.7
(CH3-13), 17.5 (CH3-7). HRMS (ESI) m/z [M+H-H2O]+ Calcd
for C22H29NO3: 338.2110; Found: 338.2108. IR (neat)  (cm-1):
3527, 2928, 2179, 2119, 2040, 2013, 1976, 1959, 1772, 1708,
1439, 1398, 1369, 1188, 1045, 913, 720. HPLC: Chiral
stationary column: OD-H, mobile phase: hexane/iPrOH =
96/4, 1.0 mL/min, 210 nm, 30 °C, tR (major) = 17.9 min, tR
(minor) = 40.4 min. []20D = –7.7 (c 0.98, CH2Cl2).
Synthesis
of
((1R,3R)-1-cyclohexyl-4,4-dimethyl-1-
phenylhex-5-en-3-ol (6ja). The iridium catalyst (R)-[Ir]
(0.01 mmol, 10 mol%) was introduced into a Schlenk tube
in a glove-box and dissolved in anhydrous and degassed
THF (0.5 mL). Next hydrogen gas was gently bubbled
directly through the solution (2-3 bubbles per second) via
a stainless-steel needle at room temperature. The orange
solution rapidly became light yellow color. After 5 minutes,
bubbling was cased and the solution was degassed by two
successive freeze-pump-thaw cycles. After the second
cycle, the homoallylic boronate 3a (0.2 mmol, 2.0 equiv.)
was added immediately to the cold solution in one portion.
The rubber septum was replaced with a polyethylene
stopper and the reaction was stirred at 0 °C for 15 min. Then
the appropriate allylic alcohol 1j (0.1 mmol, 1.0 equiv., in
0.2 mL of THF) was added to the above solution at room
temperature for 2 h. After that, the solvent THF was
removed slowly under vacuum. Then the mixture was
Synthesis of (4S,5S)-4-hydroxy-5,9-dimethyl-5-vinyldec-
8-en-1-yl [1,1'-biphenyl]-4-carboxylate (syn-6ig). The
iridium catalyst (0.01 mmol, 10 mol%) was introduced into
a Schlenk tube in a glovebox and dissolved in anhydrous
and degassed THF (0.5 mL). Next hydrogen gas was gently
bubbled directly through the solution (2-3 bubbles per
second) via a stainless-steel needle at room temperature.
The orange solution rapidly became light yellow color.
After 1-2 minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3g (0.4 mmol,
4.0 equiv.) was added immediately to the cold solution in
one portion. The rubber septum was replaced with a
polyethylene stopper and the reaction was stirred at –20 °C
for 15 min. Then the appropriate allylic alcohol (Z)-1i (0.1
mmol, 1.0 equiv., in 0.2 mL of THF) was added to the above
°
cooled down to –20 C and the (S)-TRIP catalyst (0.01
mmol, 10 mol%, in 1.0 mL of 1,2-DCE) was added. After
stirring at –20 °C for 48 h, the reaction mixture was purified
by column chromatography (pentane/diethyl ether 15:1 to
8:1) to afford the corresponding homoallylic alcohol 6ja.
Purification by column chromatography (pentane/diethyl
ether 15:1 to 8:1) to afford 6ja as a colorless oil (20 mg, 70%
yield, 4.7:1 dr, 95% ee/ 96% ee). TLC: Rf
(pentane/diethyl ether 4:1). H NMR (400 MHz, CDCl3) 
= 0.8
1
°
(ppm) = 7.33 – 7.26 (m, 2H), 7.21 – 7.09 (m, 3H), 5.82 (dd,
solution at –20 C for 15 min. After that, the solvent THF
3JHH = 17.5, 10.9 Hz, 0.2H, H-2, anti-isomer), 5.68 (dd, 3JHH
=
was removed slowly under vacuum. Then the mixture was
°
17.5, 10.8 Hz, 1H, H-2, syn-isomer), 5.07 – 4.95 (m, 2H, H-1),
2.84 (dd, 3JHH = 10.5, 4.8 Hz, 1H, H-4), 2.67 – 2.59 (m, 1H, H-
6), 1.93 – 1.86 (m, 1H), 1.81 – 1.65 (m, 3H), 1.63 – 1.57 (m, 2H),
1.46 – 1.30 (m, 3H), 1.27 – 1.02 (m, 4H), 0.91 (s, 6H, H-7), 0.83
cooled down to –30 C and the (R)-TRIP catalyst (0.015
mmol, 15 mol%, in 1.0 mL of 1,2-DCE) was added. After
stirring at –30 °C for 48 h, the reaction mixture was purified
by column chromatography (pentane/diethyl ether 9:1 to
5:1) to afford the corresponding homoallylic alcohol syn-
– 0.74 (m, 1H). C{1H} NMR (100 MHz, CDCl3)  (ppm) =
13
6ig.
Purification
by
column
chromatography
major syn-6ja isomer; 145.5 (C-Ar), 143.9 (CH-2), 128.8
(CH-Ar), 128.0 (CH-Ar), 125.9 (CH-Ar), 113.2 (CH2-1), 75.3
(CH-4), 48.4 (CH-6), 43.80, 41.5 (C-3), 34.1, 31.4, 31.2, 26.6,
22.90 (CH3-7), 22.05 (CH3-7). HRMS (ESI) m/z [M+Na]+
Calcd for C20H30O: 309.2189; Found: 309.2175. IR (neat) 
(cm-1): 3481, 3027, 2925, 2853, 2029, 1637, 1493, 1450, 1380,
1061, 1032, 912, 758, 702. HPLC: Chiral stationary column:
OD-H, mobile phase: hexane/iPrOH = 99/1, 0.5 mL/min,
210 nm, 30 °C, for major diastereoisomer: tR (major) = 9.2
min, tR (minor) = 10.5 min, for minor diastereoisomer: tR
(major) = 11.3 min, tR (minor) = 12.4 min. []20D = 32.1 (c 1.00,
CH2Cl2).
(pentane/diethyl ether 9:1 to 5:1) to afford syn-6ig as a
colorless oil (34.4 mg, 85% yield, 10:1 dr, 86% ee). TLC: Rf =
0.3 (pentane/diethyl ether 4:1). 1H NMR (300 MHz, CDCl3)
 (ppm) = 8.18 – 7.99 (m, 2H), 7.71 – 7.58 (m, 4H), 7.55 – 7.31
3
(m, 3H), 5.74 (dd, JHH = 17.6, 10.9 Hz, 1H, H-2), 5.21 – 5.14
(m, 1H, H-1), 5.14 – 4.98 (m, 2H, H-1 and H-10), 4.37 (t, 3JHH
= 6.5 Hz, 2H, H-14), 3.42 – 3.31 (m, 1H, H-4), 2.14 – 2.02 (m,
1H, H-6), 1.98 – 1.86 (m, 2H, H-6 and H-9), 1.86 – 1.70 (m,
2H, H-9 and O-H), 1.67 (s, 3H, H-12), 1.58 (s, 3H, H-13), 1.51
– 1.33 (m, 4H, H-5 and H-8), 1.04 (s, 3H, H-7, syn-isomer),
0.99 (s, 0.3H, H-7, anti-isomer). 13C{1H} NMR (75 MHz,
CDCl3)  (ppm) = 166.6 (C-15), 145.6 (C-Ar), 143.3 (CH-2),
140.1 (C-Ar), 131.5 (C-11), 130.1 (CH-Ar), 129.2 (C-Ar), 128.9
Synthesis
of
(4R,6R)-6-(4-methoxyphenyl)-3,3,7-
trimethyloct-1-en-4-ol (6ka). The iridium catalyst (R)-[Ir]
ACS Paragon Plus Environment

The Journal of Organic Chemistry
(0.01 mmol, 10 mol%) was introduced into a Schlenk tube
Page 12 of 16
°
polyethylene stopper and the reaction was stirred at 0 C
1
2
3
4
5
6
7
8
in a glove-box and dissolved in anhydrous and degassed
THF (0.5 mL). Next hydrogen gas was gently bubbled
directly through the solution (2-3 bubbles per second) via
a stainless-steel needle at room tempera-ture. The orange
solution rapidly became light yellow color. After 5 minutes,
bubbling was cased and the solution was degassed by two
successive freeze-pump-thaw cycles. After the second
cycle, the homoallylic boronate 3a (0.2 mmol, 2.0 equiv.)
was added immediately to the cold solution in one portion.
The rubber septum was replaced with a polyethylene
stopper and the reaction was stirred at 0 °C for 15 min.
Allylic alcohol 1b (0.1 mmol, 1.0 equiv., in 0.2 mL of THF)
was added to the above solution at room temperature for 2
h. After that, the solvent THF was removed slowly under
vacuum. Then the mixture was cooled down to –20 °C and
the (S)-TRIP catalyst (0.01 mmol, 10 mol%, in 1.0 mL of 1,2-
DCE) was added. After stirring at –20 °C for 48 h, the
reaction mixture was purified by column chromatography
(pentane/diethyl ether 9:1 to 4:1) to afford the
corresponding homoallylic alcohol 6ka. Purification by
column chromatography (pentane/diethyl ether 9:1 to 4:1)
to afford 6ka as a colorless oil (16 mg, 58% yield, 4.8:1 dr,
91% ee/ 94% ee). TLC: Rf = 0.6 (pentane/diethyl ether 4:1).
1H NMR (400 MHz, CDCl3)  (ppm) = 7.04 – 7.01 (m, 2H),
6.85 – 6.81 (m, 2H), 5.82 (dd, 3JHH = 17.5, 10.9 Hz, 0.2H, H-2,
for 15 min. Then the appropriate allylic alcohol 1j (0.1
mmol, 1.0 equiv., in 0.2 mL of THF) was added to the above
solution at room temperature for 2 h. After that, the
solvent THF was removed slowly under vacuum. Then (S)-
TRIP catalyst (0.01 mmol, 10 mol%, in 1.0 mL of 1,2-DCE)
was added. After stirring at room temperature for 48 h, the
reaction mixture was purified by column chromatography
(pentane/diethyl ether 20:1 to 15:1) to afford the
corresponding homoallylic alcohol 6jg. Purification by
column chromatography (pentane/diethyl ether 20:1 to
15:1) to afford pure syn-6jg as a colorless oil (13 mg, 48%
yield, 95% ee). TLC: Rf = 0.6 (pentane/diethyl ether 8:1). 1H
NMR (400 MHz, CDCl3)  (ppm) = 7.30 – 7.27 (m, 1H), 7.21
– 7.15 (m, 1H), 7.21 – 7.15 (m, 1H), 7.12 – 7.07 (m, 2H), 5.57
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
(dd, JHH = 17.6, 10.9 Hz, 1H, H-2), 5.15 – 5.09 (m, 1H, H-1),
5.06 – 5.00 (m, 1H, H-10), 4.99 – 4.92 (m, 1H, H-1), 2.87 (dd,
3
3JHH = 10.7, 6.4 Hz, 1H, H-4), 2.61 (ddd, JHH = 11.6, 7.6, 3.6
Hz, 1H, H-6), 1.92 – 1.88 (m, 1H), 1.81 – 1.67 (m, 5H), 1.65 (s,
3H, H-12), 1.62 – 1.57 (m, 2H), 1.52 (s, 3H, H-13), 1.43 – 1.36
(m, 2H), 1.31 – 1.20 (m, 4H), 1.11 – 1.03 (m, 2H), 0.96 – 0.88
(m, 4H), 0.82 – 0.74 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3)
 (ppm) = 143.9 (C-Ar), 143.6 (CH-2), 131.3 (C-11), 128.8 (CH-
Ar), 128.0 (CH-Ar), 125.9 (CH-Ar), 124.9 (CH-10), 114.4
(CH2-1), 75.1 (CH-4), 48.5 (CH-6), 44.7 (C-3), 43.7 (CH-14),
37.1, 34.4, 31.4, 31.2, 26.60, 26.58, 26.56, 25.7 (CH3-12), 22.6,
17.6 (CH3-7 and CH3-13). HRMS (ESI) m/z [M+Na]+ Calcd
for C25H38O: 377.2815; Found: 377.2799. IR (neat)  (cm-1):
3471, 2924, 2853, 2370, 2304, 2032, 2009, 1493, 1450, 1376,
1271, 1006, 913, 757, 702, 647. HPLC: Chiral stationary
column: IA, mobile phase: hexane/iPrOH = 99/1, 1.0
mL/min, 210 nm, 23 °C, tR (major) = 9.1 min, tR (minor) = 7.0
min. []20D = 20.0 (c 0.64, CH2Cl2).
3
anti-isomer), 5.69 (dd, JHH = 17.5, 10.9 Hz, 1H, H-2, syn-
isomer), 5.07 – 4.96 (m, 2H, H-1), 3.80 (s, 3H, H-10), 2.86
(dd, 3JHH = 10.5, 1.7 Hz, 1H, H-4), 2.55 (td, 3JHH = 7.8, 3.8 Hz,
1H, H-6), 1.77 – 1.68 (m, 2H, H-5 and H-8), 1.66 – 1.58 (m,
1H, H-5), 1.34 (br, 1H, O-H), 0.97 – 0.85 (m, 9H, H-7 and H-
9), 0.71 (d, JHH = 6.8, 3H, H-9). 13C{1H} NMR (100 MHz,
3
CDCl3)  (ppm) = major syn-6ka isomer; 157.7 (C-Ar), 145.5
(CH-2), 135.7 (C-Ar), 129.5 (CH-Ar), 113.4 (CH-Ar), 113.2
(CH2-1), 75.3 (CH-4), 55.2 (CH3-10), 48.4 (CH-6), 41.5 (C-3),
34.5 (CH2-5), 34.1 (CH-8), 22.9 (CH3-7), 22.1 (CH3-9), 21.0
(CH3-9), 20.7 (CH3-7). IR (neat) n (cm-1): 3481, 3027, 2925,
2853, 2029, 1637, 1493, 1450, 1380, 1061, 1032, 912, 758, 702.
HRMS (ESI) m/z [M+Na]+ Calcd for C18H28O2: 299.1982;
Found: 299.1997. IR (neat)  (cm-1): 3474, 2958, 2872, 2168,
2029, 1964, 1612, 1511, 1467, 1383, 1246, 1179, 1038, 914, 826,
804, 748. HPLC: Chiral stationary column: AD-H, mobile
phase: hexane/iPrOH = 99/1, 1.0 mL/min, 210 nm, 30 °C, for
major diastereoisomer: tR (major) = 10.3 min, tR (minor) =
11.1 min, for minor diastereoisomer: tR (major) = 9.5 min, tR
(minor) = 13.8 min. []20D = 41.2 (c 0.73, CH2Cl2).
Synthesis of (6la). The iridium catalyst (0.005 mmol, 5
mol%) was introduced into a Schlenk tube in a glove-box
and dissolved in anhydrous and degassed THF (0.5 mL).
Next hydrogen gas was gently bubbled directly through the
solution (2-3 bubbles per second) via a stainless-steel
needle at room temperature. The orange solution rapidly
became light yellow color. After 1-2 minutes, bubbling was
cased and the solution was degassed by two successive
freeze-pump-thaw cycles. After the second cycle, the
homoallylic boronate 3a (0.2 mmol, 2.0 equiv.) was added
immediately to the cold solution in one portion. The
rubber septum was replaced with a polyethylene stopper
°
and the reaction was stirred at 0 C for 15 min. Then the
Synthesis of (1R,3R,4R)-1-cyclohexyl-4,8-dimethyl-1-
phenyl-4-vinylnon-7-en-3-ol (syn-6jg). The iridium catalyst
(R)-[Ir] (0.01 mmol, 10 mol%) was introduced into a
Schlenk tube in a glove-box and dissolved in anhydrous
and degassed THF (0.5 mL). Next hydrogen gas was gently
bubbled directly through the solution (2-3 bubbles per
second) via a stainless-steel needle at room temperature.
The orange solution rapidly became light yellow color.
After 5 minutes, bubbling was cased and the solution was
degassed by two successive freeze-pump-thaw cycles. After
the second cycle, the homoallylic boronate 3g (0.2 mmol,
2.0 equiv.) was added immediately to the cold solution in
one portion. The rubber septum was replaced with a
appropriate allylic alcohol 1l (0.1 mmol, 1.0 equiv., in 0.4
mL of THF) was added to the above solution at 0 °C for 15
min. After that, the solvent THF was removed slowly under
vacuum. Then the mixture was cooled down to –20 °C and
the (R)-TRIP catalyst (0.01 mmol, 10 mol%, in 1.0 mL of 1,2-
°
DCE) was added. After stirring at –20 C for 48 h, the
reaction mixture was purified by preparative TLC
(pentane/acetone 4:1) to afford the corresponding
homoallylic alcohol 6la. Purification by preparative TLC
(pentane/acetone 4:1) to afford 6la as a white solid (16 mg,
1
40% yield, 19:1 dr). TLC: Rf = 0.3 (pentane/acetone 4:1). H
NMR (400 MHz, CDCl3)  (ppm) = 5.81 (dd, 3JHH = 17.5, 10.8
3
Hz, 1H, H-2), 5.35 (dd, JHH = 5.0, 2.6 Hz, 1H, H-8), 5.12 –
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The Journal of Organic Chemistry
4.99 (m, 2H, H-1), 3.52 (tt, 3JHH = 10.8, 4.8 Hz, 1H, H-10), 3.22
■ AUTHOR INFORMATION
(dd, 3JHH = 10.2, 1.8 Hz, 1H, H-4), 2.34 – 2.20 (m, 2H), 2.02 –
1.92 (m, 1H), 1.88 – 1.70 (m, 5H), 1.63 – 1.38 (m, 10H), 1.26 –
1.08 (m, 5H), 1.03 – 0.92 (m, 12H), 0.59 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3)  (ppm) = 145.5 (CH-2), 140.8 (C-9), 121.7
(CH-8), 113.4 (CH2-1), 79.1 (CH-4), 71.8 (CH-10), 56.1, 51.2,
50.5, 42.3, 42.1, 41.8, 37.9, 37.3, 36.6, 32.0, 31.9, 31.7, 30.6,
28.6, 28.0, 24.7, 23.3, 21.9, 20.9, 19.5, 12.4. HRMS (ESI) m/z
[M+Na]+ Calcd for C27H44O2: 423.3234; Found: 423.3225. IR
(neat)  (cm-1): 3580, 3283, 2931, 2862, 2359, 2052, 1639,
1450, 1415, 1376, 1251, 1195, 1060, 1034, 1006, 977, 954, 914,
878, 838, 799, 739, 690. []20D = –47.0 (c 0.80, CH2Cl2).
1
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Corresponding Author
* clement.mazet@unige.ch
■ ACKNOWLEDGMENT
We thank the University of Geneva for financial support.
Stéphane Rosset is acknowledged for assistance in the
synthesis of (R)-TRIP and for measuring HRMS analyses.
Daniele Fiorito is acknowledged for running preliminary
experiments.
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■ REFERENCES
Synthesis of (6ma). The iridium catalyst (0.0025 mmol, 5
mol%) was introduced into a Schlenk tube in a glove-box
and dissolved in anhydrous and degassed THF (0.5 mL).
Next hydrogen gas was gently bubbled directly through the
solution (2-3 bubbles per second) via a stainless-steel
needle at room temperature. The orange solution rapidly
became light yellow color. After 1-2 minutes, bubbling was
cased and the solution was degassed by two successive
freeze-pump-thaw cycles. After the second cycle, the
homoallylic boronate 3a (0.1 mmol, 2.0 equiv.) was added
immediately to the cold solution in one portion. The
rubber septum was replaced with a polyethylene stopper
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°
and the reaction was stirred at 0 C for 15 min. Then the
appropriate allylic alcohol 1m (0.05 mmol, 1.0 equiv., in 0.2
mL of THF) was added to the above solution at rt for 30
min. After that, the solvent THF was removed slowly under
vacuum. Then the mixture was cooled down to –20 °C and
the (S)-TRIP catalyst (0.005 mmol, 10 mol%, in 0.5 mL of
°
1,2-DCE) was added. After stirring at –20 C for 48 h, the
reaction mixture was purified by column chromatography
(pentane/diethyl ether 9:1 to 5:1) to afford the
corresponding homoallylic alcohol 6ma. Purification by
column chromatography (pentane/diethyl ether 9:1 to 5:1)
to afford 6ma as a colorless oil (16 mg, 64% yield, 19:1 dr).
1
TLC: Rf = 0.5 (pentane/diethyl ether 4:1). H NMR (400
MHz, CDCl3)  (ppm) = 7.26 – 7.21 (m, 2H), 7.19 – 7.13 (m,
3
3H), 5.61 (dd, JHH = 17.5, 10.8 Hz, 1H, H-2), 5.36 –5.32 (m,
1H, H-8), 5.05 – 4.92 (m, 2H, H-1), 3.19 – 3.11 (m, 1H, H-10),
2.80 – 2.69 (m, 2H, H-6 and H-4), 2.27 – 2.21 (m, 2H), 2.00
– 1.90 (m, 2H), 1.82 – 1.46 (m, 9H), 1.40 – 1.29 (m, 2H), 1.16
– 1.04 (m, 3H), 1.01 – 0.93 (m, 2H), 0.90 – 0.82 (m, 9H), 0.82
– 0.74 (m, 1H), 0.68 (s, 3H), 0.53 (td, 3JHH = 12.7, 4.9 Hz, 1H),
3
0.32 (dt, JHH = 12.9, 3.5 Hz, 1H). 13C{1H} NMR (100 MHz,
CDCl3)  (ppm) = 145.4 (CH-2), 144.8 (C-Ar), 139.9 (C-9),
128.7 (CH-Ar), 128.0 (CH-Ar), 125.9 (CH-Ar), 122.4 (CH-8),
113.1 (CH2-1), 74.5 (CH-4), 61.1 (CH-10), 56.5, 56.2, 50.0, 44.5
(CH-6), 42.5, 41.3, 38.4, 38.1, 37.5, 37.2, 36.5, 31.8, 31.8, 28.3,
27.9, 24.1, 22.9, 22.0, 20.8, 19.2, 12.3. HRMS (ESI) m/z
[M+Na]+ Calcd for C33H47N3O: 524.3612; Found: 524.3600.
IR (neat)  (cm-1): 3482, 3026, 2939, 2868, 2094, 1721, 1636,
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■ ASSOCIATED CONTENT
Supporting Information. Experimental procedures,
characterization of all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
anti-3-butenediols
via
Allene
Hydroboration-Aldehyde
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(21) For a relevant and related example, see: Maligres, P. E.; Li,
J.; Krska, S. W.; Schreier, J. D.; Raheem, I. T. C-O Cross-Coupling
of Activated Aryl and Heteroaryl Halides with Aliphatic Alcohols.
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(22) For alternative prenylation methods: (a) Brown, H. C.;
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and (−)-artemisia alcohol in exceptionally high enantiomeric
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ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 16
SYNOPSIS TOC
1
2
3
R2
dual isomerization
allylboration
 dual isomerization

 diastereoselective catalysis
 enantioselectve catalysis
 1, 2 or 3 stereocenters
R2 OH
R1
R
OH
4
5
6
7
8
9
sequential catalysis (one-pot)
Ir
H+
R1
Me R
single catalyst
(achiral or chiral)
chiral Brønsted
acid catalyst
Bpin
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ACS Paragon Plus Environment