Catalytic enantioselective allylboration of propargylic aldehydes

Article abstract of DOI:10.1016/j.tet.2013.11.095

Homoallylic propargylic alcohols are important building blocks in natural product synthesis. This moiety can be transformed into various other structures by performing other known transformations, which can in turn lead to the synthesis of biologically us

Full text of DOI:10.1016/j.tet.2013.11.095

Tetrahedron 70 (2014) 678e683
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catalytic enantioselective allylboration of propargylic aldehydes
*
Urmibhusan Bhakta, Erin Sullivan, Dennis G. Hall
Department of Chemistry, 4-010 Centennial Centre for Interdisciplinary Science, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
a r t i c l e i n f o
a b s t r a c t
Article history:
Homoallylic propargylic alcohols are important building blocks in natural product synthesis. This moiety
can be transformed into various other structures by performing other known transformations, which can
in turn lead to the synthesis of biologically useful compounds. Herein, a methodology based on Lewis
acid assisted Brønsted acid catalysed allylboration of propargylic aldehydes is described. A detailed
optimization study followed by a thorough examination of substrate scope have been explored.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 30 September 2013
Received in revised form 22 November 2013
Accepted 25 November 2013
Available online 3 December 2013
Keywords:
Propargylic alcohols
Brønsted acid
Enantioselective catalysis
Crotylation
Homoallylic alcohols
1. Introduction
There are several enantioselective methods available for the
addition of allylic boron reagents3 and other allylmetal reagents4
Homoallylicpropargylicalcoholsareveryimportantend-products
and intermediates in natural product synthesis.1,2 Several character-
istic transformations of the alkyne unit, such as hydrometallation/
alkylation, catalytic hydrogenation, isomerization and many others
can lead to very important synthetic building blocks (Fig. 1).
onto aldehydes as a means to produce homoallylic alcohols.5
However, there have been only a few reported examples of addi-
tions onto propargylic aldehydes to provide the desired homoallylic
propargylic alcohols, and these methods often employ reagents
based on a stoichiometric chiral auxiliary.6 Some of these methods,
such as the one developed by Brown and co-workers, involve air-
sensitive allylic dialkyl boranes. Although it is a useful method,
use of unstable chiral reagents that need to be prepared and reacted
in situ without isolation, poses a limitation. On the other hand,
catalytic enantioselective variants with stable allylboronic esters
have recently been reported in the literature.7,8 In particular, Hu
and co-workers described a catalytic enantioselective allylboration
methodology for the synthesis of homoallylic propargylic alcohols
involving a chiral phosphoric acid as catalyst, but a detailed sub-
strate scope has not been presented.8b
Our group has developed a catalytic enantioselective allylbora-
tion methodology7 exploiting the concept of Lewis acid assisted
Brønsted acid catalysis.9 The development of a synthetic chiral diol
(vivol) provided a diol$SnCl4 catalyst that can be used in additions
of a wide range of allylic boronates to aliphatic aldehydes, yielding
homoallylic alcohols in >90% ee. This method is versatile and has
been employed in the synthesis of complex natural products.7e
Here, we report an asymmetric synthesis of homoallylic prop-
argylic alcohols by the addition of allylic boronates to propargylic
aldehydes under this condition (Scheme 1).
Fig. 1. Possibilities of synthetic manipulations of homoallylic propargylic alcohols.
* Corresponding author. Tel.: þ1 780 492 3141; fax: þ1 780 492 8231; e-mail
address: dennis.hall@ualberta.ca (D.G. Hall).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.095

U. Bhakta et al. / Tetrahedron 70 (2014) 678e683
679
Table 1
Our prior work:
F-Vivol-8 • SnCl = 1.3 : 1
Na CO
Optimization of the asymmetric allylboration of propargylic aldehyde using alde-
hyde 1a as model substrate
OH
OR
B
O
4 A mol. sieves
R
+
OR
R
H
toluene, – 78 °C, 12 h
ee upto 97 %
R = alkyl
Hu's prior work:
OH
SPINOL-phosphoric acid
(5 mol%)
O
OR
B
+
H
R
OR
toluene, – 78 °C
R
2 examples
86-98%, 98-99% ee
This work:
OH
O
OR
B
F-Vivol • SnCl
conditions
+
H
OR
R
R
Scheme 1. Catalytic asymmetric allylboration of propargylic aldehydes.
Entries Catalyst
Solvent
Loading (%) Allylboronate Yield (%)d ee (%)c
2. Results and discussion
1
2
3
4
5
6
7
8
F-vivol-5 Toluene
F-vivol-7 Toluene
F-vivol-8 Toluene
F-vivol-12 Toluene
F-vivol-7 Toluene
F-vivol-8 Toluene
F-vivol-7 Toluene
F-vivol-8 Toluene
F-vivol-7 Toluene
F-vivol-8 Toluene
F-vivol-8 Toluene
F-vivol-8 Toluene
F-vivol-8 Toluene
F-vivol-8 Toluene
F-vivol-8 Toluene
F-vivol-8 Toluene
5
5
5
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2c
2d
2e
2f
2g
2h
2b
2b
2b
2b
2b
2b
2b
60
93
87
74
83
85
78
85
84
87
72
85
80
67
14
d
27
60
63
23
76
73
87
87
87
87
75
81
77
35
12
d
Using aldehyde 1a, a detailed optimization study was planned
with a focus on the varying nature of the chiral diol unit in the
catalyst, the catalyst loading, solvent, and different boronates
(Table 1). As observed in previous work from our group,7b we noted
a significant effect of the ring size of the chiral diol catalyst (F-vivol)
on the yield and enantioselectivity. A cyclooctyl ring unit on the
vivol catalyst provided optimal enantioselectivity when using
allylboronate 2a (entries 1e4). Increasing the catalyst loading to
a certain extent improved both the yield and enantioselectivity
(entries 5e6). The boronate unit of reagent 2 was found to have
a profound effect on the outcome of the reactions. Thus a boronate
made from a 1,3-diol, 2b, was found to be superior compared to 2a
(entry 8 vs entry 6). Placement of substituents on the six-mem-
bered boronate was found to be important. Although many boro-
nates with a spiro ring on C2 were evaluated (entries 12, 13, 16)
none of them performed better than boronate 2b with gem-di-
methyl unit. Reagent 2f with one methyl group on C2 exhibited
a poor selectivity (entry 14). Surprisingly, the reaction of allylbor-
onate 2h with a cyclopropyl ring on C2 (entry 16) did not proceed at
all despite its similarity to 2b. Solvent is known to have a strong
influence in allylboration reactions. Since carbonyl allylboration
involves charge separation at the transition state, polarity of the
solvent can exert a notable effect.10 In polar solvents, such as CH2Cl2
and mixtures of CH2Cl2 and toluene, the background racemic
reaction between the allylboronate and aldehyde is faster com-
pared to less polar arene solvents, which led to lower enantiose-
lectivities (entries 17, 18, 19). Lower selectivities were also observed
with solvents, such as fluorobenzene, xylene and trifluorotoluene
(entries 20e24). Looking at these results, toluene stood out as the
best solvent. Different Lewis acids (such as Yb(OTf)3, La(OTf)3, SnF4,
TiCl4, ZrCl4) were tried as alternatives to SnCl4 but none of them
were found to be more efficient. Finally we achieved our best re-
action conditions when using allylboronate 2b with 10% F-vivol-
8$SnCl4 as catalyst and toluene as the solvent.
5
10
10
10
10
20
20
10
10
10
10
10
10
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
F-vivol-8 Tol/CH2Cl2 (1:1) 10
78
82
74
68
65
58
85
81
81
75
72
64
53
83
F-vivol-8a Tol/CH2Cl2 (1:1) 10
F-vivol-8 CH2Cl2
F-vivol-8b Fluorobenzene 10
F-vivol-8b o-Xylene
10
F-vivol-8 Trifluorotoluene 10
F-vivol-8 Methyl
cyclopentane
F-vivol-8 Methyl
cyclohexane
10
10
24
10
2b
85
82
All reactions were performed in 0.56 mmol scale with respect to the aldehydes and
0.7 mmol of allylboronates.
a
Reaction was performed at ꢀ100 ꢁC.
b
Reaction was performed at ꢀ25 ꢁC.
c
Enantiomeric excesses were measured by chiral HPLC analysis.
d
Isolated yield.
relatively far from the alkyne substituent, the exact reason behind
this observation is, at this stage, unclear. Excellent selectivity and
yield were observed with 3-trimethylsilylpropynal (entry 5). This
substrate is important because easy removal of the TMS group can
afford a terminal alkyne that can be further transformed into many
other synthetic building blocks. The absolute stereochemistry of
products 3c, 3f and 3i was determined by comparing specific ro-
tation values with that of previously reported compounds (see
Supplementary data).
Because of the easy accessibility of E-crotyl boronates via the
method reported by Szabo11 from the corresponding crotyl alco-
hols, trans-crotylborations were also explored and were found to be
effective in affording very good yields and enantioselectivities
along with the usual, high levels of diastereoselectivity (Table 3).
Thus, crotylboration of aldehyde 1a afforded an excellent yield of
anti-propionate product 4a in high enantioselectivity (Table 3, en-
try 1). Other propargylic aldehydes 1b, 1c, 1g and 1h also provided
very good stereoselectivities (entries 2e5), demonstrating a broad
With the optimized conditions in hand, the versatility of this
method was explored with different aldehydes and allylic
boronates.
During our substrate scope study, we screened 11 propargylic
aldehydes with different steric and electronic characteristics (Table
2). The enantioselectivity and the yields ranged from excellent to
moderate depending on the substrate used. An interesting trend
was observed where the substrates with an aromatic group directly
attached to the alkyne provided lower enantioselectivities (entries
8e11) compared to the propargylic aldehydes substituted with an
aliphatic chain (entries 1e7). Because the aldehyde carbonyl is

680
U. Bhakta et al. / Tetrahedron 70 (2014) 678e683
Table 2
Table 3
Substrate scope study: enantioselective allylation of propargylic aldehydes
Substrate scope study: enantioselective E-crotylation of propargyl aldehydes
F-vivol-8 : SnCl4 = 1.3 : 1
F-vivol-8 : SnCl4 = 1.3 : 1
OH
Na2CO3
OH
Na2CO3
O
4 A mol. sieves
O
B
O
4 A mol. sieves
O
B
H
+
R
+
O
H
toluene, – 78 °C, 12 h
R
O
toluene, – 78 °C, 12 h
R
4
1
E-2c
R
1
2b
3
Entrya
Aldehyde
Product
Yield (%)b
88
ee (%)c,d
Entrya
Aldehyde
Product
Yield (%)b
88
ee (%)c
1
91
1
78
2
3
84
72
71
66
2
3
82
83
80
82
4
5
75
84
64
81
4
5
90
87
84
84
6
90
81
a
All reactions were performed in 0.56 mmol scale with respect to the aldehyde,
0.7 mmol of E-crotyl boronate with 10 mol % catalyst.
b
Isolated yields.
Enantiomeric excesses were measured by chiral HPLC.
>20:1 dr were observed with all of them.
c
7
8
74
80
81
69
d
acetate esters and then were subjected to gold/silver catalysed
€
cycloisomerization as first reported by Furstner and co-workers
(Scheme 2)13a to generate fused bicyclic rings, which are well-
known building blocks present in many natural products, such as
sesquisabinene.1g
9
77
58
AuCl(PPh ) (2 mol %)
O
AgSbF
(2 mol %)
O
O
10
11
79
80
50
55
K CO / MeOH
CH Cl , rt
Yield = 69 %
O
AuCl(PPh ) (2 mol %)
AgSbF
(2 mol %)
O
O
K CO / MeOH
CH Cl , rt
a
All reactions were performed in 0.56 mmol scale with respect to the aldehyde,
0.7 mmol of allylboronate with 10 mol % catalyst.
Yield = 71%
b
Isolated yields.
Enantiomeric excesses were measured by chiral HPLC.
c
Scheme 2. Cycloisomerization reaction catalysed by gold and silver.
substrate scope for this method. These results may be attributed to
the importance of the closed six-membered transition state12
through which allylboration reactions are proposed to proceed.
Molecular interactions between the catalyst and the larger crotyl
boronate may be amplified compared to the parent, unsubstituted
allylboronate.
Next we sought to examplify possible applications of the
homoallylic propargylic alcohols made using this catalytic enan-
tioselective allylboration methodology. Thus, two of the alcohol
products (3a and 4a) were transformed into the corresponding
3. Conclusion
In summary, we have presented a novel and useful catalytic
enantioselective method for the asymmetric synthesis of homo-
allylic propargylic alcohols, which are very important intermediates
in organic synthesis. A detailed and thorough optimization of re-
action conditions were followed by an elaborate evaluation of sub-
strate scope, which demonstrated the broad range of applicability
of this method. Moreover, for both simple allylation and E-

U. Bhakta et al. / Tetrahedron 70 (2014) 678e683
681
crotylboration of propargylic aldehydes, interesting outcomes were
revealed during optimization studies. The subtle role of solvent and
the structure of the boronic ester of the allylboronate will certainly
be an important guideline for future workdirected at other classes of
aldehyde substrates.
Tminor¼11.3 min; ½a D22
ꢄ
22.8 (c 1.30, CHCl3); Rf¼0.1 (hexanes/EtOAc
10:1); IR (film cast, CHCl3): 3375 (broad, m), 3076 (m), 3063 (m), 3027
(m), 2978 (w), 2924 (s), 2859 (m), 2226 (w),1641 (m),1496 (m),1453
(w),1032 (s), 698 (s) cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 7.33e7.29 (m,
2H), 7.24e7.21 (m, 3H), 5.90e5.80 (m,1H), 5.20e5.15 (m, 2H), 4.39 (tt,
J¼6.0, 2.0 Hz, 1H), 2.84 (t, J¼7.6 Hz, 2H), 2.52 (td, J¼7.6, 2.0 Hz, 2H),
4. Experimental section
2.45e2.41 (m, 2H), 1.94 (s, 1H); 13C NMR (125 MHz, CDCl3)
d 140.5,
133.2, 128.4, 128.3, 126.3, 118.7, 85.1, 81.4, 61.7, 42.4, 35.0, 20.8; EIMS
m/z 200.1 (Mþ, 0.2), 199.1 ([MꢀH]þ, 1), 182.1 (C14H14, 6), 159.1
(C11H11O, 73). EI HRMS calcd for C14H14þ ([MꢀH2O]þ) 182.1096,
found 182.1093.
4.1. General information and materials
All reactions were performed in standard, flame-dried glass-
ware under an inert atmosphere of nitrogen. Unless otherwise
specified, reagents were bought from commercial suppliers and
used without further purification. Solvents were dried either by
distillation or by using a solvent system purchased from MBRAUN.
Anhydrous Na2SO4 or MgSO4 were used as the drying agent after
aqueous workup. All substrates were purified by silica gel chro-
matography before use. Evaporation and concentration in vacuo
were accomplished at water aspirator pressure. Reaction products
were purified by column chromatography using silica gel-60
(230e400 mesh). Reactions were monitored by thin layer chro-
matography with precoated glass plates covered with 0.2 mm silica
gel. The spots were visualized by UV light, KMnO4 or anisaldehyde
stain. IR spectra were obtained with a Nicolet Magna-IR-750
spectrometer (cmꢀ1, cast film or neat). 1H, 11B, 13C NMR spectra
were obtained on a Varian Inova-300, 400 or Varian Unity-500
instruments, at 27 ꢁC in CDCl3. Residual solvent peaks (7.26 ppm
for 1H and 77.0 ppm for 13C) were employed as reference. Accuracy
for coupling constants (J-values) is estimated to be ꢂ0.2 Hz. EIMS
(m/z) was measured in a Kratos MS50 instrument. Optical rotation
was recorded using a Perkin Elmer 241 polarimeter using the So-
dium D line (589 nm) with a cell length of 10.002 cm. Optical pu-
rities of the products were measured by chiral HPLC using Chiralcel
OD or Chiralpak AS column.
4.2.2. 8-Phenylnon-1-en-5-yn-4-ol (3b). A 78% ee was determined
byHPLCanalysis(ChiralcelODcolumn,10%i-PrOHinhexanes, 0.5mL/
min,
l
¼254 nm, column temperature¼25 ꢁC), Tmajor¼11.9 min,
Tminor¼14.6 min; ½a D22
19.9 (c 1.30, CHCl3); Rf¼0.1 (hexanes/EtOAc
ꢄ
10:1); IR (film cast, CHCl3): 3359 (broad, m), 3078 (m), 3063 (m), 3026
(m), 2979 (w), 2939 (s), 2860 (m), 2229 (w), 1642 (m), 1603(m), 1496
(m), 1454 (m), 1431 (m), 1032 (s), 699 (s) cmꢀ1; 1H NMR (500 MHz,
CDCl3)
d
7.32e7.27 (m, 2H), 7.22e7.18 (m, 3H), 5.91 (ddt, J¼17.0, 10.0,
7.5 Hz, 1H), 5.23e5.17 (m, 2H), 4.43e4.44 (m, 1H), 2.72 (t, J¼7.5 Hz,
2H), 2.45e2.49 (m, 2H), 2.24 (td, J¼7.0, 2.0 Hz, 2H), 2.0 (d, J¼5.5 Hz,
1H), 1.84 (app. quintet, J¼7.0 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d
141.5,133.3,128.5,128.3,125.9,118.7, 85.4, 81.2, 61.8, 42.5, 34.8, 30.2,
18.1; EI HRMS calcd for C15H18ONa 237.1250, found 237.1247.
4.2.3. (4R)-Dec-1-en-5-yn-4-ol (3c). A 71% ee was determined by
HPLC analysis (Chiralcel OD column, 10% i-PrOH in hexanes, 0.5 mL/
min,
l
¼254 nm, column temperature¼25 ꢁC), Tmajor¼9.0 min,
Tminor¼16.9 min; ½a D22
ꢄ
27.6 (c 1.1, CHCl3). Spectral and analytical
properties of the product were in accordance with the literature.14a
4.2.4. 7,7-Dimethyloct-1-en-5-yn-4-ol (3d). A 66% ee was de-
termined by HPLC analysis (Chiralcel OD column, 15% i-PrOH in
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
4.2. General procedure
Tmajor¼13.10 min, Tminor¼8.0 min; ½a D22
32.8 (c 1.1, CHCl3); Rf¼0.1
ꢄ
(hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3347 (broad, m), 3078
In a flame-dried 10 mL round bottom flask equipped with
(m), 2969 (w), 2928 (s), 2867 (m), 2239 (w), 1642 (m), 1476 (m),
a
stirbar, the corresponding F-Vivol catalyst (0.056 mmol,
1457 (m), 1434 (m), 1362 (m), 1264 (s), cmꢀ1 1H NMR (500 MHz,
;
ꢀ
0.10 equiv), anhydrous Na2CO3 (0.2 equiv) and 4 A molecular sieves
(90 mg, pre dried under vacuum overnight and then stored in an
oven) were added. The flask was equipped with a rubber septum
and charged with nitrogen, then dry toluene (1.2 mL) was added.
The mixture was stirred for 2 min and SnCl4 (1.0 M in CH2Cl2,
CDCl3)
d
5.89 (ddt, J¼17.1, 10.2, 7.1 Hz, 1H), 5.21e5.14 (m, 2H), 4.40
(t, J¼6.1 Hz, 1H), 2.44 (m, 2H), 1.99 (br s, 1H), 1.22 (s, 9H); 13C NMR
(125 MHz, CDCl3)
d 133.4, 118.5, 94.2, 79.0, 61.7, 42.6, 30.9, 27.3; EI
HRMS calcd for C10H15ONa, 174.2200 found 174.2202.
38.5
m
L, 0.0385 mmol, 0.078 equiv) was added. After stirring for
4.2.5. 7-Cyclopentylhept-1-en-5-yn-4-ol (3e). A 64% ee was de-
termined by HPLC analysis (Chiralcel OD column, 10% i-PrOH in hex-
5 min at rt the reaction was cooled to ꢀ78 ꢁC where it was main-
tained for 15 min. Allylboronic acid ester (0.8 mmol, 1.4 equiv) was
added dropwise, followed 30 min later by the addition of the al-
dehyde (0.56 mmol, 1.0 equiv). The reaction was stirred at ꢀ78 ꢁC
until TLC analysis no longer showed presence of the aldehyde
starting material. DIBAL-H (1.5 M in toluene, 2.0 equiv) was cooled
to ꢀ78 ꢁC and cannulated into the reaction flask, maintain the re-
action at ꢀ78 ꢁC. After all the remaining aldehyde was reduced (ca.
30e50 min), the excess DIBAL-H was quenched by the addition of
10% HCl (4.0 mL). The reaction was slowly warmed to rt over 1 h and
stirred for an additional 30 min. The reaction mixture was then
extracted with Et2O (5ꢃ10 mL) and the combined organic extracts
were extracted with saturated aq NaCl, dried over Na2SO4, filtered
and concentrated in vacuo. Column chromatography (silica gel,
5e30% EtOAc in hexanes) gave the corresponding product.
Crotylboration was also carried out in the same way and in the
same scale.
anes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
Tmajor¼17.2 min, Tminor¼9.0 min; ½a D22
34.3 (c 2.2, CHCl3); Rf¼0.1
ꢄ
(hexanes/EtOAc10:1);IR(filmcast, CHCl3):3351(broad,m),3078(m),
3011 (m), 2980 (w), 2914 (m), 2866 (w), 2240 (m),1641 (m),1429 (m),
1358 (m),1052 (s),1030 (s), 813 (m) cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
5.87 (ddt, J¼17.0, 10.4, 7.2 Hz, 1H), 5.19e5.13 (m, 2H), 4.40e4.38 (m,
1H), 2.46e2.41 (m, 2H), 2.20 (dd, J¼7.0, 2.0 Hz, 2H) 2.06e1.96 (m, 2H),
1.80e1.72 (m, 2H), 1.66e1.48 (m, 4H), 1.30e1.20 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 132.9, 118.1, 84.9, 80.2, 61.4, 42.2, 38.5, 31.5, 24.8,
24.0; EI HRMS calcd for C12H17ONa 200.2520 found 200.2551.
4.2.6. (4R)-1-Trimethylsilylhex-1-en-5-yn-4-ol (3f). A 81% ee was
determined by HPLC analysis (Chiralcel OD column, 10% i-PrOH in
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
Tmajor¼16.85 min, Tminor¼8.97 min; ½a D22
ꢄ
56.9 (c 6.4, CHCl3);
Spectral and analytical properties of the product were in ac-
cordance with the literature.14b
4.2.1. 8-Phenyloct-1-en-5-yn-4-ol (3a). A 87% ee was determined by
HPLC analysis (Chiralcel OD column, 50% i-PrOH in hexanes, 0.5 mL/
4.2.7. 1-Cyclohexylhex-5-en-1-yn-3-ol (3g). A 81% ee was de-
termined by HPLC analysis (Chiralcel OD column, 10% i-PrOH in
min,
l
¼254 nm, column temperature¼25 ꢁC), Tmajor¼7.8 min,

682
U. Bhakta et al. / Tetrahedron 70 (2014) 678e683
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
7.0 Hz, 1H), 5.29e5.24 (m, 2H), 4.65e4.61 (m, 1H), 2.57e2.54 (m,
2H), 2.2 (br s, 1H); 13C NMR (125 MHz, CDCl3)
1C), 133.6 (d, J¼8.5 Hz, 2C), 132.9, 119.1, 118.6 (d, J¼3.4 Hz, 2C), 115.5
(d, J¼22 Hz, 2C), 89.1, 84.1, 62.0, 42.2; EI HRMS calcd for C12H11FONa
213.0686, found 213.0690.
Tmajor¼19.9 min, Tminor¼10.4 min; ½a D22
ꢄ
58.7 (c 1.15, CHCl3); Rf¼0.1
d
163.5 (d, J¼250 Hz,
(hexanes/EtOAc 10:1), IR (film cast, CHCl3): 3338 (broad, m), 3077
(w), 3006 (w), 2979 (w), 2930 (s), 2854 (s), 2229 (w), 1642 (m),
1448 (m), 1338 (w), 1035 (s), 861 (s) cmꢀ1 1H NMR (500 MHz,
;
CDCl3)
d
5.87 (ddt, J¼17.0, 10, 7.5 Hz, 1H), 5.18e5.13 (m, 2H), 4.40
(ddd, J¼11.5, 6, 2 Hz, 1H), 2.46e2.41 (m, 2H), 2.40e2.34 (m, 1H),
1.97e1.94 (m, 1H), 1.80e1.73 (m, 2H), 1.71e1.64 (m, 2H), 1.51e1.47
(m, 1H), 1.44e1.37 (m, 2H), 1.31e1.24 (m, 3H); 13C NMR (125 MHz,
4.3. Characterization of enantioselective crotylboration
products
CDCl3)
d
133.4, 118.5, 90, 80.5, 61.8, 42.6, 32.6, 28.9, 25.8, 24.8; EI
4.3.1. Methyl-7-phenyloct-5-en-1-yn-3-ol (4a). A 91% ee was de-
termined by HPLC analysis (Chiralcel OD column, 40% i-PrOH in
HRMS calcd for C15H18ONa 201.1257, found 201.1244.
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
4.2.8. 1-Cyclopropylhex-5-en-1-yn-3-ol (3h). A 81% ee was de-
termined by HPLC analysis (Chiralcel OD column, 10% i-PrOH in
Tmajor¼7.63 min, Tminor¼11.26 min; ½a D22
ꢄ
24.2 (c 1.3, CHCl3); IR (film
cast, CHCl3): 3400 (broad, m), 3064 (s), 2965 (s), 2928 (m), 2861 (s),
2229 (m), 1640 (s), 1603 (s), 1496 (s), 1454 (s), 1440 (m), 1429 (m),
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
Tmajor¼24.4 min, Tminor¼13.4 min; ½a D22
ꢄ
71.1 (c 1.05, CHCl3); Rf¼0.1
1419 (m) cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 7.28e7.34 (m, 2H),
(hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3351 (broad, m), 3078
7.24e7.2 (m, 3H), 5.84e5.74 (m, 1H), 5.18e5.12 (m, 2H), 4.22e4.17
(m, 1H), 2.85 (t, 7.6 Hz, 2H), 2.55 (dt, J¼7.2, 1.6 Hz, 2H), 2.45e2.37
(m, 1H), 1.92 (d, J¼5.2 Hz, 1H), 1.1 (d, J¼6.8 Hz, 3H); 13C NMR
(m), 3011 (m), 2980 (w), 2914 (m), 2866 (w), 2240 (m), 1641 (m),
1429 (m), 1358 (m), 1052 (s), 1030 (s), 813 (m) cmꢀ1 1H NMR
;
(500 MHz, CDCl3)
d
5.88e5.8 (m, 1H), 5.16e5.11 (m, 2H), 4.36e4.32
(125 MHz, CDCl3) d 140.5, 139.5, 128.4, 128.3, 126.3, 116.5, 85.7, 80.3,
(m, 1H), 2.41e2.38 (m, 2H), 2.04e2.02 (m, 1H), 1.25e1.2 (m, 1H),
66.3, 44.5, 35.0, 20.9, 15.2; EI HRMS calcd for C15H18ONa 237.1250,
found 237.1245.
0.72e0.76 (m, 2H), 0.66e0.63 (m, 2H); 13C NMR (125 MHz, CDCl3)
d
133.3, 118.5, 88.9, 75.7, 61.7, 42.5, 8.2, ꢀ0.6; EI HRMS calcd for
C9H12ONa 159.0785, found 159.0777.
4.3.2. Methyl-8-phenylnon-1-en-5-yn-4-ol (4b). A 80% ee was de-
termined by HPLC analysis (Chiralcel OD column, 10% i-PrOH in
4.2.9. (3S)-1-Phenylhex-5-en-1-yn-3-ol (3i). A 69% ee was de-
termined by HPLC analysis (Chiralcel OD column, 50% i-PrOH in
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
Tmajor¼11.3 min, Tminor¼12.7 min; ½a D22
ꢄ
15.3 (c 1.8, CHCl3); IR (film
hexanes, 0.5 mL/min,
l
¼210 nm, column temperature¼25 ꢁC),
cast, CHCl3): 3371 (broad, m), 3064 (s), 2964 (s), 2932 (m), 2862 (s),
2238 (m), 1640 (s), 1602 (s), 1496 (s), 1454 (s), 1430 (m), 1419 (m)
Tmajor¼7.3 min, Tminor¼9.3 min; ½a D22
ꢄ
26.0 (c 0.36, CHCl3). Spectral
and analytical properties of the product were in accordance with
cmꢀ1 1H NMR (500 MHz, CDCl3)
; d 7.35e7.19 (m, 5H), 5.91 (ddd,
the literature.6h
J¼17.9, 10.4, 7.5 Hz, 1H), 5.24e5.15 (m, 2H), 4.26 (m, 1H), 2.76 (t,
J¼7.5 Hz, 2H), 2.52e2.44 (m,1H), 2.28 (td, J¼7.0, 2.0 Hz, 2H),1.91 (br
s, 1H), 1.87 (m, 2H), 1.18 (d, J¼6.8 Hz, 3H); 13C NMR (125 MHz,
4.2.10. 1-(4-Methylphenyl)hex-5-en-1-yn-3-ol (3j). A 58% ee was
determined by HPLC analysis (Chiralcel OD column, 50% i-PrOH in
CDCl3) d 141.6, 139.6, 128.5, 128.3, 125.9, 116.5, 86.0, 80.1, 66.4, 44.7,
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
34.8, 30.3, 18.2, 15.3; EI HRMS calcd for C16H20ONa 251.1406, found
251.1402.
Tmajor¼6.9 min, Tminor¼8.3 min; ½a D22
22.6 (c 1.2, CHCl3); Rf¼0.1
ꢄ
(hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3375 (broad, m), 3078
(s), 3029 (s), 2980 (s), 2921 (m), 2860 (s), 2202 (m), 1666 (m), 1643
4.3.3. Methyl-1-trimethylsilylhex-1-en-5-yn-4-ol (4c). A 81% ee was
(m), 1606 (m), 1510 (s), 1440 (m), 1038 (s), 817 (s) cmꢀ1
;
1H NMR
determined by Mosher ester analysis; ½a D22
ꢀ0.38 (c 4.1, CHCl3);
ꢄ
(500 MHz, CDCl3)
7.0 Hz, 1H), 5.25e5.19 (m, 2H), 4.64 (t, J¼6.0 Hz, 1H), 2.58e2.55 (m,
2H), 2.3 (s, 3H), 2.0 (br s, 1H); 13C NMR (125 MHz, CDCl3)
138.5,
d
7.32 (m, 2H), 7.11 (m, 2H), 5.96 (ddt, J¼17.0, 10.5,
Rf¼0.1 (hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3367 (broad, m),
3080 (w), 2963 (w), 2933 (s), 2173 (w), 1641 (m), 1456 (m), 1251 (s),
d
1030 (s), cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
¼5.83 (ddd, J¼17.1, 10.5,
133.1, 131.6, 129.0, 119.4, 118.9, 88.7, 85.3, 62.1, 42.3, 21.4; EI HRMS
calcd for C13H14ONa 209.0937, found 209.0939.
7.7 Hz, 1H), 5.21e5.15 (m, 2H), 4.20 (t, J¼5.5 Hz, 1H), 2.49e2.44 (m,
1H), 1.90 (d, J¼6 Hz, 1H), 1.15 (d, J¼6.8 Hz, 3H), 0.19 (s, 9H); 13C NMR
(125 MHz, CDCl3)
HRMS calcd for C10H17ONa 204.3227, found 204.3218.
d
139.2, 116.7, 105.0, 90.5, 66.6, 44.4,15.3, ꢀ0.1; EI
4.2.11. 1-(4-Methoxyphenyl)hex-5-en-1-yn-3-ol (3k). A 50% ee was
determined by HPLC analysis (Chiralcel OD column, 50% i-PrOH in
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
4.3.4. Methyl-1-cyclohexylhex-5-en-1-yn-3-ol (4d). A 84% ee was
determined by HPLC analysis (Chiralcel OD column, 1.5% i-PrOH in
Tmajor¼10.9 min, Tminor¼7.4 min; ½a D22
16.1 (c 1.4, CHCl3); Rf¼0.1
ꢄ
(hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3384 (broad, m), 3075
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
(m), 3006 (m), 2935 (m), 2913 (m), 2837 (m), 2228 (m), 1642 (m),
Tmajor¼29.9 min, Tminor¼26.2 min; ½a D22
49.3 (c 1.2, CHCl3); Rf¼0.1
ꢄ
1606 (s), 1463 (m), 1441 (m), 1031 (s), 1030 (s), 831 (m) cmꢀ1
;
1H
(hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3366 (broad, m), 3078
NMR (500 MHz, CDCl3)
d
7.37 (m, 2H), 6.83 (d, 2H), 5.96 (ddt, J¼17.2,
(w), 2932 (w), 2854 (s), 2232 (w), 1640 (m), 1449 (m), 1348 (w), 1024
10.0, 7.2 Hz, 1H), 5.26e5.20 (m, 2H), 4.65e4.62 (m, 1H), 3.80 (s, 3H),
(s), cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
5.83 (ddd, J¼17.4, 10.2, 7.5 Hz,
2.58e2.55 (m, 2H), 2.13 (br s, 1H); 13C NMR (100 MHz, CDCl3)
1H), 5.19e5.11 (m, 2H), 4.22 (t, J¼4.4 Hz, 1H), 2.48e2.38 (m, 2H),1.90
(d, J¼4.8 Hz, 1H), 1.83e1.75 (m, 2H), 1.74e1.66 (m, 2H), 1.55e1.40 (m,
3H), 1.36e1.27 (m, 3H), 1.13 (d, J¼7.0 Hz, 3H); 13C NMR (125 MHz,
d
159.3, 132.8, 118.5, 114.2, 113.6, 113.5, 87.6, 84.7, 61.7, 54.9, 41.9; EI
HRMS calcd for C13H14O2Na 225.0886, found 225.0885.
CDCl3) d 139.6, 116.3, 90.6, 79.4, 66.4, 44.7, 32.6, 28.9, 25.8, 24.7, 15.2;
4.2.12. 1-(4-Fluorophenyl)hex-5-en-1-yn-3-ol (3l). A 55% ee was
determined by HPLC analysis (Chiralcel OD column, 50% i-PrOH in
EI HRMS calcd for C13H20ONa 215.1406, found 215.1400.
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
4.3.5. Methyl-1-cyclopropylhex-5-en-1-yn-3-ol (4e). A 84% ee was
determined by HPLC analysis (Chiralcel OD column, 1.5% i-PrOH in
Tmajor¼9.3 min, Tminor¼10.9 min; ½a D22
15.6 (c 1.4, CHCl3), Rf¼0.1
ꢄ
(hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3363 (broad, m), 3078
(s), 2980 (s), 2921 (m), 2860 (s), 2232 (m), 1642 (s), 1602 (s), 1507
(s), 1232 (s), 1440 (m), 1031 (m), 835 (s) cmꢀ1; 1H NMR (500 MHz,
hexanes, 0.5 mL/min,
l
¼254 nm, column temperature¼25 ꢁC),
Tmajor¼16.5 min, Tminor¼18.4 min; ½a D22
56.3 (c 1.0, CHCl3); Rf¼0.1
ꢄ
(hexanes/EtOAc 10:1); IR (film cast, CHCl3): 3318 (broad, m), 3081
CDCl3)
d
7.45e7.41 (m, 2H), 7.05e7.0 (m, 2H), 5.98 (ddt, J¼17.0, 10.5,
(m), 3011 (m), 2970 (w), 2931 (m), 2248 (m), 1601 (m), 1540 (s),

U. Bhakta et al. / Tetrahedron 70 (2014) 678e683
683
1444 (m), 1313 (m), 1221 (s), 1051 (s), 1027 (s), cmꢀ1
;
1H NMR
Walts, A. E.; Hoong, L. K. J. Am. Chem. Soc. 1985, 107, 8186; (g) Reetz, M. Pure
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4. For selected examples of other enantioselective aldehyde allylation methods,
see: (a) Riediker, M.; Duthaler, R. O. Angew. Chem., Int. Ed. Engl. 1989, 28, 494;
(b) Furuta, K.; Mouri, M.; Yamamoto, H. Synlett 1991, 561; (c) Panek, J. S.; Yang,
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(500 MHz, CDCl3)
d
5.81 (ddd, J¼16.9, 10.6, 7.6 Hz, 1H), 5.17e5.12
(m, 2H), 4.17 (dd, J¼6.2, 1.5 Hz, 1H), 2.45e2.37 (m, 1H), 1.87 (br s,
1H), 1.27 (dddd, J¼12.5, 9.0, 5.0, 2.0 Hz, 1H), 1.11 (d, J¼6.8 Hz, 3H),
0.78 (s, 2H), 0.70e0.67 (m, 2H); 13C NMR (125 MHz, CDCl3)
d 139.5,
116.4, 89.6, 74.7, 66.3, 44.7, 15.2, 8.2, ꢀ0.6; EI HRMS calcd for
C
10H14ONa 173.0937, found 173.0931.
Acknowledgements
Acknowledgement for financial support of this research is made
to the Natural Sciences and Engineering Research Council (NSERC)
of Canada and the University of Alberta.
Supplementary data
5. For general reviews on carbonyl allylation, see: (a) Yamamoto, Y.; Asao, N.
Chem. Rev. 1993, 93, 2207; (b) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763;
(c) Denmark, S. E.; Almstead, N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.;
Wiley-VCH: Weinheim, Germany, 2000; p 299.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.11.095.
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