Catalytic enantioselective diboration of cyclic dienes. a modified ligand with general utility

Article abstract of DOI:10.1021/jo201321k

The enantioselective 1,4-diboration of cyclic dienes with a new taddol-derived phosphonite ligand occurs with excellent enantioselectivity. Oxidation delivers the derived 1,4-diol, whereas homologation can be used to deliver a chiral 1,6-diol.

Full text of DOI:10.1021/jo201321k

NOTE
pubs.acs.org/joc
Catalytic Enantioselective Diboration of Cyclic Dienes. A Modified
Ligand with General Utility
Kai Hong and James P. Morken*
Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, United States
S Supporting Information
b
ABSTRACT: The enantioselective 1,4-diboration of cyclic
dienes with a new taddol-derived phosphonite ligand occurs
with excellent enantioselectivity. Oxidation delivers the derived
1,4-diol, whereas homologation can be used to deliver a chiral
1,6-diol.
Scheme 1
he enantioselective 1,4-diboration of 1,3-dienes is a reaction
that provides 2-alkene-1,4-diols upon oxidative workup.1ꢀ3
T
This overall reaction does not have a generally effective comple-
ment in contemporary catalytic enantioselective methodology,
and it is important to gain a greater understanding of the
substrate scope.4 Previous examples from our laboratory sug-
gested that this transformation can be realized with Pt(0)
catalysis in the presence of a chiral TADDOL-derived phospho-
nite ligands. These studies included an example of an enantio-
selective 1,4-diboration of a prochiral cyclic diene (Scheme 1), a
reaction that delivers a new chiral carbocyclic product with good
efficiency. Using a chiral phosphonite ligand, this reaction was
found to be highly selective with n-alkyl-substituted substrates
such as 1a. However, further study of the scope of this reaction
revealed that with aryl or branched alkyl substituents on the
substrate enantioselection was severely diminished (vide infra).
In an effort to render this transformation more generally useful
for asymmetric synthesis, we have undertaken a systematic survey
of substituted TADDOL-derived phosphonites5 and report herein
that with an appropriately modified ligand structure significantly
improved generality is observed.
To identify a chiral phosphonite ligand structure that is
effective with a range of substrates, 2-butyl-1,3-cyclohexadiene
(1a) and 2-cyclohexyl-1,3-cyclohexadiene (2a) were chosen as
representative substrates and their diboration reactions were
surveyed with a range of taddol-derived phosphonite ligands.
As depicted in Table 1, with the ligand described in our preliminary
report (L2, entries 3 and 4), the diboration of n-butyl-substituted
substrate 1a occurred with excellent enantioselectivity; however,
the level of selectivity with cyclohexyl-substituted substrate 2a
was markedly inferior. In an effort to ameliorate this problem, the
size of the substituents on the aryl rings of the ligand backbone
was modified. Previous experience showed that the meta posi-
tions of the aryl rings are most consequential,1,6 and, indeed,
dramatic changes in enantioselection were noticed when the
methyl groups of the ligand (R) were replaced with either smaller
(ligand L1) or larger substituents (ligands L3 and L4). As
observed in Table 1, while the use of alkyl substituents on the
ligand backbone did not lead to a generally effective ligand
structure, use of aryl-substituted ligands was highly rewarding
and offered excellent levels of enantioselection for both sub-
strates (ligands L5 and L6, entries 9ꢀ12). Comparison of ligands
L5 and L6 showed that the more encumbered dioxolane
protecting group provided a subtle enhancement in stereoselec-
tion, and this ligand was chosen for further study. It is also
important to note that with only 1.2 equiv of ligand relative to
platinum, reduced selectivity was observed in the diboration of
1a (77:23 er). We attribute this outcome to incomplete pre-
complexation of the catalyst; precomplexation at 80 °C with 1.2
equiv of ligand returned selectivity to higher levels.
With a more generally effective ligand in hand, the catalytic
enantioselective diboration of a range of substituted cyclic dienes
was examined (Table 2).7,8 The standard set of reaction condi-
tions employed 6 mol % of ligand L6, 3 mol % of Pt(dba)3, and
1.05 equiv of B2(pin)2 in toluene solvent for 12 h at 60 °C. While
these conditions were effective for many substrates, it was found
that for the phenyl-substituted diene in entry 3, selectivity was
improved by executing the reaction at room temperature after
Received: July 12, 2011
Published: September 20, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo201321k J. Org. Chem. 2011, 76, 9102–9108
|

The Journal of Organic Chemistry
NOTE
Table 1. Evaluation of Ligands in the Pt-Catalyzed Enantio-
selective Diboration of 1 and 2a
was uncertain.12 To learn more about this process and about the
types of synthesis targets that might be accessed with these
structures, the sequence in Scheme 3 was carried out. Thus, after
diboration of diene 2a in toluene at 60 °C for 12 h, isovaler-
aldehyde (3 equiv) was added to the reaction mixture and the
concoction heated to 80 °C for 30 h. After oxidation, this reaction
furnished diol 14 in excellent yield and diastereo- and enantio-
meric purity.8 An exciting outcome of this sequence is that CꢀC
bond formation appeared to occur by association of the aldehyde
to putative intermediate allylboronate 13, followed by progres-
sion to the product through ts-1.13 Importantly, the chairlike
arrangement of the reacting array of atoms was maintained with
good fidelity and furnished the product in a predictable manner.
That the intermediate allylation product, prior to oxidation,
maps well onto cladiellin diterpene natural products portends
the use of this overall synthesis transform in complex molecule
synthesis.14
entry
diene
ligand
R
R1
% yieldb
erc
1
2
1a
2a
1a
2a
1a
2a
1a
2a
1a
2a
1a
2a
L1
L1
L2
L2
L3
L3
L4
L4
L5
L5
L6
L6
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
31
69
87
89
89
79
60
19
92
87
97
87
55:45
55:45
94:6
H
3
Me
Me
Et
4
75:25
82:18
56:44
61:39
52:48
94:6
5
6
Et
In conclusion, we have described the development of a Pt-
catalyzed diboration that bears general applicability to prochiral
substituted cyclohexadiene substrates.
7
t-Bu
t-Bu
Ph
Ph
Ph
Ph
8
9
10
11
12
95:5
’ EXPERIMENTAL SECTION
96:4
Et
96:4
((4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis(di([1,10:30,
100-terphenyl]-50-yl)methanol) (15). Prepared from 1-bromo-3,
5-diphenylbenzene15 following literature procedures (495 mg, 62%
yield).5c 1H NMR (500 MHz, CDCl3): δ 1.14 (6H, s), 5.11 (2H, s),
7.32ꢀ7.40 (16H, m), 7.41ꢀ7.44 (8H, m), 7.52ꢀ7.54 (8H, m), 7.68ꢀ
7.70 (10H, m), 7.76 (4H, d, J = 1.7 Hz), 7.83 (2H, t, J = 1.7 Hz), 7.97 (4H,
d, J = 1.7 Hz). 13C NMR (100 MHz, CDCl3): δ 146.9, 143.9, 141.8, 141.4,
141.3, 141.1, 129.01, 128.96, 127.59, 127.57, 127.5, 126.6, 125.9, 125.7,
125.6, 110.3, 81.9, 78.8, 27.6. IR (neat): 3324.0 (br), 3034.5 (w), 1595.2
(m), 1497.5 (w), 1427.2 (w), 1239.8 (w), 1165.5 (w), 1049.1 (w), 879.7
(m), 759.2 (s), 742.1 (s), 696.3 (s), 614.2 (w) cmꢀ1. HRMS-(ESI+) for
a Reaction conditions: 1.05 equiv of B2(pin)2, precomplexation for 1 h at
rt, reaction time = 12 h, oxidation at rt for 4 h. b Yield of purified material.
c Enantiomer ratio was determined by GC or HPLC analysis on a chiral
stationary phase.
preactivating the catalyst at 60 °C for 20 min. Additionally,
substrates in entries 8 and 11 reacted sluggishly under the
standard conditions and required an increased catalyst loading
to achieve the yields depicted in Table 2. Notable features of the
substrate scope are that the reaction accommodates both alipha-
tic and aromatic substitution and that both small and large
substituents are tolerated. The example in entry 11 suggests that
seven-membered rings are processed selectively, even though
these substrates require added catalyst, and even then, the
cycloheptadiene provided moderated yields of reaction product.
Another notable point that this substrate survey revealed is that
protected alcohol and protected aldehyde functionality is well
tolerated.
One attractive feature of the diboration products is that the
organoboron group may be readily converted to a range of useful
functional groups or used in strategic CꢀC bond-forming
processes. While oxidation cleanly delivers hydroxylated end
products as depicted in Table 1, homologation can provide other
derivatives.9 While Matteson homologation reactions10 have
previously been applied to 1,2-bis(boronates) that arise from
alkene diboration,11 this transformation has not been applied to
2-alkene-1,4-bis(boronates) that would arise from diene dibora-
tion. To examine the efficacy of this process, the sequence in
Scheme 2 was examined. Thus, diene 6a was subjected to
catalytic diboration in the presence of the chiral catalyst, and
after 12 h of reaction, the solvent was removed in vacuo,
tetrahydrofuran was added, and the mixture was cooled to
ꢀ78 °C and treated with chloromethyllithium (2.2 equiv). Upon
oxidative workup, this sequence delivered the 1,6-diol reaction
product 12 in excellent yield and stereoselectivity.
C79H62O4Na [M + Na]: calcd 1097.4546, found 1097.4557. [α]20
+37.80 (c = 0.84, CHCl3, l = 50 mm).
:
D
(4R,5R)-2,2-Diethyl-1,3-dioxolane-4,5-diyl)bis(di([1,10:30,
100-terphenyl]-50-yl)methanol (16). Prepared from 1-bromo-3,
5-diphenylbenzene14 following literature procedures (3.75 g, 62%
yield).5c 1H NMR (500 MHz, CDCl3): δ 0.63 (6H, t, J = 7.4 Hz),
1.35ꢀ1.43 (4H, m), 4.60 (2H, br), 4.88 (2H, s), 7.29ꢀ7.33 (8H, m),
7.35ꢀ7.39 (16H, m), 7.51ꢀ7.53 (8H, m), 7.62ꢀ7.64 (8H, m),
7.68ꢀ7.69 (2H, m), 7.77ꢀ7.78 (6H, m), 7.91 (4H, d, J = 1.7 Hz).
13C NMR (125 MHz, CDCl3): δ 147.2, 143.8, 141.8, 141.4, 141.3,
141.0, 128.93, 128.92, 127.53, 127.51, 127.48, 127.47, 126.6, 125.8,
125.7, 125.6, 113.1, 81.4, 79.0, 30.1, 8.4. IR (neat): 3203.1 (br), 3035.4
(w), 2970.8 (w), 1595.5 (m), 1497.8 (w), 1426.7 (w), 1174.6 (w),
1031.1 (w), 897.7 (w), 759.2 (s), 740.8 (s), 727.5 (m), 696.5 (s), 614.1
(w) cmꢀ1. HRMS-(MALDI+) for C81H66O4Na [M + Na]: calcd
1125.4853, found 1125.4852. [α]20D: ꢀ22.80 (c = 1.01, CHCl3, l =
50 mm).
(3aR,8aR)-4,4,8,8-Tetra([1,10:30,100-terphenyl]-50-yl)-2,2-di-
methyl-6-phenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxa-
phosphepine (L5). Prepared from 15 in direct analogy to the
literature (384 mg, 70% yield).5c 1H NMR (500 MHz, CDCl3): δ
0.34 (3H, s), 1.59 (3H, s), 5.15 (1H, d, J = 8.6 Hz), 6.24 (1H, dd, J = 8.6
Hz, 4.6 Hz), 7.30ꢀ7.31 (6H, m), 7.34ꢀ7.47 (18H, m), 7.54ꢀ7.61
(15H, m), 7.67ꢀ7.70 (5H, m), 7.72ꢀ7.74 (2H, m), 7.81ꢀ7.85 (5H, m),
8.00 (4H, s), 8.24 (2H, m). 13C NMR (100 MHz, CDCl3): δ 147.9,
147.0, 146.9, 143.23, 143.22, 142.33, 142.31, 141.88, 141.82, 141.6,
141.5, 141.41, 141.40, 141.33, 141.31, 141.2, 140.9, 131.3, 130.3, 130.0,
129.1, 129.03, 128.97, 128.90, 128.83, 127.7, 127.63, 127.59, 127.54,
127.51, 127.4, 126.8, 126.2, 126.1, 125.8, 125.7, 125.6, 112.2, 84.63,
It was also considered that the 2-alkene-1,4-bis(boronates)
might engage in allylation reactions but the mode of regioselection
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The Journal of Organic Chemistry
NOTE
Table 2. Catalytic Enantioselective Diboration of Cyclic Dienesa
a Conditions: 1.05 equiv of B2(pin)2, precomplexation for 1 h at rt, reaction time = 12 h, oxidation at rt for 4 h. b Absolute configuration determined by
X-ray crystallography for 2b and 6b; by comparison to the literature for 1b (ref 1) and assumed by analogy for others. c Yield of purified material. Value is
an average of two experiments. d Enantiomer ratio was determined by GC or HPLC analysis on a chiral stationary phase. e Reaction at 60 °C for 20 min,
then ambient for 48 h. f Reaction employed 6 mol % of Pt(dba)3, 12 mol % of ligand L6 for 24 h. g Reaction with 10 mol % of Pt(dba)3, 20 mol % of ligand
L6 for 48 h.
84.59, 84.0, 83.9, 83.3, 83.1, 82.90, 82.85, 28.3, 25.1. 31P NMR (162 MHz,
CDCl3):δ156.7. IR (neat): 3034.2 (w), 1594.8 (m), 1497.2 (w), 1427.2 (w),
1160.3 (w), 1031.8 (m), 996.8 (m), 758.4 (s), 735.4 (s), 695.1 (s), 613.8
(w) cmꢀ1. HRMS (ESI+) for C85H65O4NaP [M + Na]: calcd 1203.4518,
found 1203.4495. [α]D20: ꢀ103.26 (c = 1.12, CHCl3, l = 50 mm).
literature (494 mg, 70% yield).5c 1H NMR (400 MHz, CDCl3): δ 0.28
(3H, t, J = 7.4 Hz), 0.72 (2H, q, J = 7.5 Hz), 0.82 (3H, t, J = 7.5 Hz),
1.71 (2H, q, J = 7.4 Hz), 5.26 (1H, d, J = 8.7 Hz), 6.02 (1H, dd, J =
8.7 Hz, 3.9 Hz), 7.28ꢀ7.43 (23H, m), 7.44ꢀ7.54 (8H, m), 7.58ꢀ7.63
(12H, m), 7.68ꢀ7.80 (6H, m), 7.89 (2H, d, J = 1.6 Hz), 7.93ꢀ7.98
(2H, m), 8.01 (2H, d, J = 1.6 Hz), 8.15 (2H, d, J = 1.6 Hz). 13C NMR
(100 MHz, CDCl3): δ 147.8, 147.22, 147.19, 143.32, 143.30, 142.59,
142.57, 141.9, 141.6, 141.5, 141.49, 141.47, 141.4, 141.3, 141.2, 140.9,
(3aR,8aR)-4,4,8,8-Tetra([1,10:30,100-terphenyl]-50-yl)-2,2-di-
ethyl-6-phenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxa-
phosphepine (L6). Prepared from 16 in direct analogy to the
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The Journal of Organic Chemistry
NOTE
Scheme 2
129.1, 128.5, 127.19, 127.15, 126.2, 122.1, 42.0, 22.65, 22.58. IR (neat):
3027.6 (w), 2930.4 (w), 2872.8 (w), 2821.6 (w), 1493.7 (w), 1452.6
(w), 1425.8 (w), 1164.5 (w), 1078.5 (w), 953.9 (m), 787.9 (w), 755.2
(w), 726.8 (s), 697.0 (s), 668.0 (m), 620.0 (m), 601.4 (m), 530.8 (w),
487.5 (w), 445.7 (w) cmꢀ1. HRMS (ESI+) for C13H15 [M + H]: calcd
171.1174, found 171.1168.
(2-(Cyclohexa-1,5-dien-1-yl)ethyl)benzene (5a). 234 mg, 85% yield.
1H NMR (400 MHz, CDCl3): δ 2.12 (4H, br), 2.34 (2H, t, J = 8.0 Hz),
2.70ꢀ2.74 (2H, m), 5.49 (1H, br), 5.86ꢀ5.92 (2H, m), 7.19ꢀ7.21 (3H,
m), 7.27ꢀ7.31 (2H, m). 13C NMR (MHz, CDCl3): δ 142.4, 135.4,
128.7, 128.4, 127.4, 127.1, 125.9, 120.8, 37.8, 35.2, 22.62, 22.57. IR
(neat): 3026.9 (m), 2930.4 (m), 2871.5 (w), 2821.2 (m), 1603.2 (w),
1495.6 (m), 1453.1 (m), 1437.7 (w), 1425.9 (w), 1164.7 (w), 1030.1
(w), 939.1 (w), 805.2 (m), 745.8 (s), 696.5 (s), 593.3 (m), 566.4 (m),
544.4 (m), 491.7 (m), 462.2 (w) cmꢀ1. HRMS(ESI+) forC14H17 [M+H]:
calcd 185.1330, found 185.1339.
Scheme 3
(3-(Cyclohexa-1,5-dien-1-yl)propyl)benzene (6a). 1.06 g, 58% yield.
1H NMR (400 MHz, CDCl3): δ 1.71ꢀ1.79 (2H, m), 2.06ꢀ2.13 (6H,
m), 2.61 (2H, t, J = 7.7 Hz), 5.50 (1H, br), 5.84 (2H, br), 7.16ꢀ7.20
(3H, m), 7.26ꢀ7.30 (2H, m). 13C NMR (100 MHz, CDCl3): δ 142.8,
135.7, 128.7, 128.4, 127.4, 127.0, 125.8, 120.6, 35.6, 35.3, 30.3, 22.7, 22.6.
IR (neat): 3026.8 (w), 2930.2 (m), 2856.4 (w), 2821.7 (w), 1495.5 (w),
1453.1 (w), 1029.7 (w), 941.3 (w), 805.7 (w), 740.8 (s), 696.4 (s), 589.0
(w), 544.4 (w), 494.2 (w), 467.7 (w) cmꢀ1. HRMS (ESI+) for C15H19
[M + H]: calcd 199.1487, found 199.1496.
1
20-Methyl-3,4-dihydro-1,10-biphenyl (7a). 225 mg, 88% yield. H
NMR (500 MHz, CDCl3): δ 2.20ꢀ2.25 (2H, m), 2.29ꢀ2.35 (5H, m),
5.71ꢀ5.73 (1H, m), 5.89ꢀ5.93 (1H, m), 5.96ꢀ5.99 (1H, m),
7.12ꢀ7.18 (4H, m). 13C NMR (125 MHz, CDCl3): δ 142.2, 137.4,
135.6, 130.3, 128.8, 128.0, 127.1, 126.2, 125.9, 124.6, 22.8, 22.2, 20.3. IR
(neat): 3035.2 (w), 2930.6 (w), 2822.3 (w), 1484.2 (w), 1453.7 (w),
997.5 (w), 823.7 (w), 756.3 (s), 734.4 (s), 611.0 (m), 501.2 (w), 453.5
(m) cmꢀ1. HRMS (ESI+) for C13H15 [M + H]: calcd 171.1174, found
171.1174.
1-(Cyclohexa-1,5-dien-1-yl)naphthalene (8a). 243 mg, 79% yield.
1H NMR (500 MHz, CDCl3): δ 2.31ꢀ2.37 (2H, m), 2.41ꢀ2.46 (2H,
m), 5.95 (1H, d, J = 4.3 Hz), 5.98 (1H, dt, J = 9.5 Hz, 4.4 Hz), 6.15 (1H,
d, J = 9.5 Hz), 7.34 (1H, d, J = 6.8 Hz), 7.43ꢀ7.49 (3H, m), 7.78 (1H, d,
J = 8.3 Hz), 7.84ꢀ7.88 (1H, m), 8.02ꢀ8.05 (1H, m). 13C NMR (125
MHz, CDCl3): δ 140.6, 136.5, 134.0, 131.6, 128.6, 128.5, 127.5, 126.3,
126.2, 125.9, 125.85, 125.81, 125.7, 125.6, 23.0, 22.2. IR (neat): 3035.4
(w), 2931.7 (w), 2819.5 (w), 1389.3 (w), 961.5 (w), 797.0 (m), 773.1
(s), 726.1 (m), 646.8 (m), 424.1 (w) cmꢀ1. HRMS (ESI+) for C16H15
[M + H]: calcd 207.1174, found 207.1172.
131.3, 130.3, 130.0, 129.05, 129.04, 129.01, 128.95, 128.8, 128.7,
127.6, 127.56, 127.54, 127.50, 127.4, 127.01, 126.97, 126.05, 125.96,
125.7, 125.6, 125.4, 116.1, 84.3, 84.2, 83.79, 83.77, 83.4, 83.3, 82.6,
82.4, 30.2, 27.9, 8.7, 8.6. 31P NMR (162 MHz, CDCl3): δ 157.6. IR
(neat): 3034.2 (w), 2970.8 (w), 1594.3 (w), 1426.6 (w), 1263.9 (w),
1170.4 (w), 1031.4 (w), 930.6 (m), 758.3 (m), 733.0 (s), 693.4 (s),
613.1 (m), 489.8 (w) cmꢀ1. HRMS (ESI+) for C87H69O4NaP
[M + Na] calcd 1231.4831, found 1231.4832. [α]20D: ꢀ87.30 (c = 0.51,
CHCl3, l = 50 mm).
Preparation of Cyclic Dienes by Kumada Coupling7. Mag-
nesium (292 mg, 12.0 mmol) and a single crystal of I2 were diluted with
diethyl ether (20 mL). Bromocyclohexane (1.23 mL, 10.0 mmol) was
slowly added. The stirred reaction was heated to 40 °C for 3 h and cooled
to room temperature. In a separate flask, NiCl2(dppe) (16 mg, 30 mmol),
cyclohexa-1,5-dien-1-yl diphenyl phosphate (1.00 g, 3.05 mmol), and
Et2O (10 mL) were cooled to 0 °C under N2. The Grignard reagent was
then added via syringe. Upon complete reaction (TLC analysis; 1ꢀ2 h),
saturated NH4Cl solution (10 mL) was added. Extraction with diethyl
ether (2 ꢁ 20 mL), drying, concentration, and purification by silica gel
chromatography (100% hexanes) afforded a colorless oil (331 mg, 68%
yield). A gravity column was required to separate the desired product
from 1,10-bi(cyclohexane), which can only be detected by NMR.
[1,10-Bi(cyclohexane)]-1,5-diene (2a). 331 mg, 68% yield. 1H NMR
(500 MHz, CDCl3): δ 1.09ꢀ1.19 (3H, m), 1.23ꢀ1.32 (2H, m),
1.66ꢀ1.77 (5H, m), 1.85 (1H, t, J = 11.6 Hz), 2.05ꢀ2.13 (4H, m),
5.44ꢀ5.46 (1H, m), 5.80ꢀ5.83 (1H, m), 5.88 (1H, dd, J = 11.2 Hz,
1.5 Hz). 13C NMR (125 MHz, CDCl3): δ 141.3, 126.9, 126.6, 118.1,
43.7, 32.2, 26.9, 26.6, 22.8, 22.6. IR (neat): 3033.1 (w), 2921.6 (s),
2850.2 (s), 2822.3 (w), 1447.7 (m), 1425.5 (w), 1165.1 (w), 998.9 (w),
948.2 (w), 891.6 (w), 806.6 (m), 736.8 (m), 687.7 (w), 592.2 (m), 570.2
(w), 518.7 (w) cmꢀ1. HRMS (ESI+) for C12H19 [M + H]: calcd
163.1487, found 163.1488. Rf = 0.78 (100% hexanes, stain in KMnO4).
(Cyclohexa-1,5-dien-1-ylmethyl)benzene (4a). (2.41 g, 77% yield.
1H NMR (500 MHz, CDCl3): δ 2.09ꢀ2.21 (4H, m), 3.37 (2H, s),
5.51ꢀ5.54 (1H, m), 5.76ꢀ5.84 (2H, m), 7.19ꢀ7.22 (3H, m),
7.27ꢀ7.31 (2H, m). 13C NMR (100 MHz, CDCl3): δ 140.2, 135.0,
2-(2-(Cyclohexa-1,5-dien-1-yl)ethyl)-1,3-dioxolane (10a). 867 mg,
55% yield. 1H NMR (500 MHz, CDCl3): δ 1.74ꢀ1.78 (2H, m),
2.05ꢀ2.11 (4H, m), 2.13ꢀ2.17 (2H, m), 3.82ꢀ3.89 (2H, m), 3.93ꢀ4.00
(2H, m), 4.87 (1H, t, J = 4.5 Hz), 5.50ꢀ5.52 (1H, m), 5.81ꢀ5.85 (2H, m).
13C NMR (125 MHz, CDCl3): δ 135.1, 127.2, 127.1, 120.5, 104.4, 65.1,
32.9, 30.1, 22.6, 22.5. IR (neat): 2929.4 (m), 2874.6 (m), 2822.5 (w),
1403.7 (m), 1131.9 (s), 1032.9 (s), 942.8 (s), 887.1 (m), 820.7 (w),
736.9(m), 591.7 (m), 551.3 (w) cmꢀ1. HRMS (ESI+) for C11H17O2
[M + H]: calcd 181.1229, found 181.1220.
1
2-Butylcyclohepta-1,3-diene (11a). 325 mg, 73% yield. H NMR
(500 MHz, CDCl3): δ 0.89 (3H, t, J = 7.3 Hz), 1.26ꢀ1.33 (2H, m),
1.35ꢀ1.41 (2H, m), 1.81ꢀ1.86 (2H, m), 2.01 (2H, t, J = 7.1 Hz), 2.22 (2H,
dt, J = 5.6 Hz, 5.6 Hz), 2.28 (2H, dt, J = 5.9 Hz, 5.4 Hz), 5.62 (1H, t, J = 5.9
Hz), 5.69 (1H, d, J = 11.7 Hz), 5.83 (1H, dt, J = 11.7 Hz, 5.1 Hz). 13C NMR
(100 MHz, CDCl3): δ 137.3, 133.5, 129.2, 128.6, 39.4, 31.88, 31.81, 30.1,
27.9, 22.5, 14.2. IR (neat): 2955.3 (m), 2924.5 (s), 2856.9 (m), 1437.1 (m),
1044.8 (w), 851.9 (w), 775.9 (w), 735.0 (m), 554.6 (m) cmꢀ1. HRMS
(ESI+) for C11H19 [M + H]: calcd 151.1487, found 151.1494.
Representative Procedure for Diene Diboration/Oxida-
tion. In the glovebox, Pt(dba)3 (13.5 mg, 15.0 mmol), ligand L6
9105
dx.doi.org/10.1021/jo201321k |J. Org. Chem. 2011, 76, 9102–9108

The Journal of Organic Chemistry
NOTE
(36.3 mg, 30.0 mmol), and toluene (5.0 mL, 0.1 M) were mixed. After
the mixture was stirred for 1 h, B2(pin)2 (133.3 mg, 0.525 mmol) and
[1,10-bi(cyclohexane)]-1,5-diene (2a, 81.1 mg, 0.50 mmol) were added.
The vessel was removed from the glovebox and stirred at 60 °C for 12 h.
The mixture was then cooled to 0 °C and slowly charged with
tetrahydrofuran (3 mL), 3 M NaOH (3 mL), and 30% H2O2
(1.5 mL). After stirring for 4 h at ambient temperature, the mixture
was cooled to 0 °C and treated with aqueous sodium thiosulfate (3 mL,
dropwise slowly). Extraction with ethyl acetate (3 ꢁ 20 mL), drying,
concentration, and purification (silica gel; hexane/ethyl acetate = 1:1 to
1:2) afforded a white solid (85.4 mg, 87% yield).
236.1651, found 236.1657. [α]20D: +9.82 (c = 0.62, CHCl3, l = 50 mm).
Mp: 114.5ꢀ116.0 °C. Enantiomer ratio determined by HPLC (Chiraldex
OD-R, 3% iPrOH/hexanes, 1 mL/min, 220 nm), major enantiomer 67.78
min, minor enantiomer 84.01 min, 95:5 er.
(1R,4S)-2-(3-Phenylpropyl)cyclohex-2-ene-1,4-diol (6b). 94.0 mg,
92% yield. Rf = 0.28 (hexanes/ethyl acetate = 1:2, stain in PMA).
1H NMR(500 MHz, CDCl3): δ1.64ꢀ1.72 (1H, m), 1.73ꢀ1.81(2H, m),
1.82ꢀ1.89 (3H, m), 2.10ꢀ2.16 (1H, m), 2.21ꢀ2.27 (1H, m),
2.58ꢀ2.68 (2H, m), 4.00ꢀ4.03 (1H, m), 4.15(1H, br), 5.57 (1H, br),
7.17ꢀ7.19 (3H, m), 7,26ꢀ7.29 (2H, m). 13C NMR (125 MHz, CDCl3):
δ 142.6, 142.5, 128.6, 128.5, 128.0, 126.0, 66.86, 66.82, 35.9, 33.4, 29.6,
29.4, 28.1. IR (neat): 3299.1 (br), 3025.2 (w), 2937.0 (s), 2859.7 (m),
1495.4 (m), 1453.1 (m), 1356.3 (w), 1287.8 (w), 1045.6 (m), 979.5
(m), 954.8 (m), 747.5 (m), 699.1 (s) cmꢀ1. HRMS (ESI+) for
(2S,5R)-[1,10-Bi(cyclohexan)]-6-ene-2,5-diol (2b). 85.4 mg, 87%
yield. Rf = 0.17 (hexane/ethyl acetate = 1:1, stain in phosphomolybdic
acid). 1H NMR (500 MHz, CDCl3): δ 1.01 (1H, dtd, J = 13.6 Hz, 11.9
Hz, 3.6 Hz), 1.11ꢀ1.20 (1H, m), 1.23ꢀ1.35 (3H, m), 1.61ꢀ1.82 (8H,
m), 1.83ꢀ1.89 (3H, m), 2.08 (1H, tt, J = 11.5 Hz, 3.1 Hz), 4.10 (1H, br),
4.16 (1H, br), 5.53 (1H, d, J = 2.7 Hz). 13C NMR (125 MHz, CDCl3): δ
147.8, 126.4, 67.4, 65.8, 41.3, 33.7, 31.9, 29.9, 27.7, 27.1, 26.8, 26.5. IR
(neat): 3300.3 (br), 2921.8 (s), 2850.4 (s), 1446.8 (m), 1285.9 (w),
1072.4 (m), 979.9 (m), 956.6 (w) cmꢀ1. HRMS (ESI+) for C12H24N1O2
[M + NH4]: calcd 214.1807, found 214.1818. [α]D: +9.78 (c = 0.92,
CHCl3, l = 50 mm). Mp: 115.1ꢀ117.0 °C. Enantiomer ratio determined
by GLC (diacetate derivative, Supelco β-dex, 180 °C, 20 psi), major
enantiomer 33.27 min, minor enantiomer 33.64 min, 96:4 er. Absolute
stereochemistry was determined by crystallography using anomalous
dispersion (Flack parameter = 0.11).
C15H19O1 [M + H ꢀ H2O]: calcd 215.1436, found 215.1443. [α]20
:
D
+31.37 (c = 0.91, CHCl3, l = 50 mm). Mp: 114.2ꢀ116.1 °C. Enantiomer
ratio determined by HPLC (diacetate derivative, Chiraldex OD-R, 1%
iPrOH/hexanes, 220 nm), major enantiomer 10.96 min, minor en-
antiomer 9.71 min, 96:4 er. Absolute stereochemistry was determined by
crystallography using anomalous dispersion (Flack parameter = ꢀ0.01).
(2R,5S)-20-Methyl-2,3,4,5-tetrahydro[1,10-biphenyl]-2,5-diol (7b).
76.6 mg, 75% yield. Rf = 0.26 (hexanes/ethyl acetate = 1:2, stain in
PMA). 1H NMR (500 MHz, CDCl3): δ 1.83ꢀ1.92 (1H, m), 1.93ꢀ2.00
(3H, m), 2.30 (3H, s), 4.28ꢀ4.33 (1H, m), 4.34ꢀ4.36 (1H, m), 5.75
(1H, d, J = 3.2 Hz), 7.12ꢀ7.22 (4H, m). 13C NMR (100 MHz, CDCl3):
δ 143.3, 139.4, 136.0, 131.6, 130.6, 129.2, 127.8, 125.9, 67.5, 66.5, 28.3,
28.0, 20.1. IR (neat): 3277.4 (br), 2944.8 (m), 2899.3 (m), 1483.5 (m),
1439.7 (m), 1290.4 (w), 1269.6 (w), 1042.6 (s), 980.8 (s), 954.0 (s),
842.1 (w), 764.3 (m), 656.8 (s), 606.0 (s), 445.5 (m) cmꢀ1. HRMS
(ESI+) for C13H15O1 [M + H ꢀ H2O]: calcd 187.1123, found 187.1122.
[α]20D: +90.55 (c = 0.98, CHCl3, l = 50 mm). Mp: 116.2ꢀ119.0 °C.
Enantiomer ratio determined by GLC (diacetate derivative, Supelco
β-dex, 160 °C, 20 psi), major enantiomer 98.20 min, minor enantiomer
99.65 min, 96:4 er.
(2S,5R)-2,3,4,5-Tetrahydro[1,10-biphenyl]-2,5-diol (3b). 59.9 mg,
63% yield. Rf = 0.21 (hexanes/ethyl acetate = 1:2, stain in PMA).
1H NMR (500 MHz, CDCl3): δ1.77ꢀ1.85 (1H, m), 1.87ꢀ1.94 (1H, m),
1.98ꢀ2.07 (2H, m), 4.35(1H, br), 4.67 (1H, br), 6.13 (1H, dd, J = 2.9
Hz, 0.7 Hz), 7.29ꢀ7.32 (1H, m), 7.35ꢀ7.39 (2H, m), 7.49ꢀ7.52 (2H,
m). 13C NMR (125 MHz, CDCl3): δ 141.2, 138.9, 130.9, 128.9, 128.1,
126.6, 67.5, 65.4, 29.3, 27.4. IR (neat): 3222.8 (br), 2938.0 (w), 1490.1
(w), 1441.9 (w), 1307.2 (w), 1047.1 (s), 969.6 (s), 950.3 (m), 760.1
(m), 697.3 (s), 508.4 (m), 485.0 (m) cmꢀ1. HRMS (ESI+) for
(1R,4S)-2-(Naphthalen-1-yl)cyclohex-2-ene-1,4-diol (8b). 33.9 mg,
94% yield. Rf = 0.21 (hexanes/ethyl acetate = 1:2, stain in PMA).
1H NMR(500 MHz, CDCl3): δ1.94ꢀ2.02 (1H, m), 2.04ꢀ2.11(3H, m),
4.42 (1H, br), 4.52 (1H, br), 5.92 (1H, d, J = 2.9 Hz), 7.36 (1H, dd, J =
7.1 Hz, 1.0 Hz), 7.45ꢀ7.51 (3H, m), 7.82 (1H, d, J = 8.3 Hz), 7.86ꢀ7.89
(1H, m), 7.93ꢀ7.95 (1H, m). 13C NMR (125 MHz, CDCl3): δ 142.0,
137.7, 134.0, 133.4, 131.9, 128.7, 128.3, 126.4, 126.3, 126.2, 125.53,
125.51, 68.0, 66.9, 28.5, 27.9. IR (neat): 3273.1 (br), 2898.9 (m), 1440.8
(w), 1272.2 (w), 1051.3 (m), 981.8 (m), 801.8 (s), 778.3 (s), 667.5 (m),
597.4 (m) cmꢀ1. HRMS (ESI+) for C16H15O [M + H ꢀ H2O] calcd
223.1123, found: 223.1134; [α]D20: +26.13 (c = 0.15, CHCl3, l = 50
mm); mp: 176.5ꢀ179.2 °C. Enantiomer ratio determined by HPLC
(dibenzoate derivative, Chiraldex OD-R, 1% iPrOH/hexanes, 1.0 mL/
min, 220 nm), major enantiomer 18.86 min, minor enantiomer 22.62
min, 96:4 e.r.
(1R,4S)-2-(2-(benzyloxy)ethyl)cyclohex-2-ene-1,4-diol (9b). (34.3 mg,
92% yield) Rf = 0.17 (hexanes: ethyl acetate =1:2, stain in PMA); 1H NMR
(500 MHz, CDCl3): δ 1.69ꢀ1.76 (2H, m), 1.80ꢀ1.85 (2H, m), 2.30ꢀ
2.36 (1H, m), 2.47ꢀ2.52 (1H, m), 3.56ꢀ3.60 (1H, m), 3.62ꢀ3.66 (1H,
m), 3.99 (1H, br), 4.13 (1H, br), 4.52 (1H, d, J = 12.0 Hz), 4.55 (1H, d, J =
12.0 Hz), 5.59 (1H, d, J = 2.8 Hz), 7.28ꢀ7.37 (5H, m); 13C NMR (125
MHz, CDCl3): δ 141.5, 137.7, 129.8, 128.7, 128.11, 128.09, 73.5, 70.4,
66.95, 66.90, 35.3, 28.6, 28.1; IR (neat): 3343.2 (br), 2927.7 (s), 2857.1
(s), 1453.9 (m), 1360.3 (m), 1275.2 (w), 1074.6 (s), 980.3 (s), 737.7 (s),
698.2 (s), 608.1 (w); HRMS (ESI+) for C15H19O2 [M + HꢀH2O]: calcd
231.1385, found: 231.1379; [α]D20: ꢀ5.41 (c = 0.53, CHCl3, l = 50 mm).
Enantiomer ratio determined by HPLC (Chiraldex OD-R, 3% iPrOH/
hexanes, 1.0 mL/min, 220 nm), major enantiomer 74.35 min, minor
enantiomer 67.69 min, 94:6 e.r.
C12H13O2 [M + H ꢀ H2O]: calcd 173.0966, found 173.0966. [α]20
:
D
+64.49 (c = 0.83, CHCl3, l = 50 mm). Mp: 137.0ꢀ139.0 °C. Enantiomer
ratio determined by GLC (diacetate derivative, Supelco β-dex, 180 °C,
20 psi), major enantiomer 48.65 min, minor enantiomer 49.65 min,
93:7 er.
(1S,4R)-2-Benzylcyclohex-2-ene-1,4-diol (4b). 96.0 mg, 94% yield.
Rf = 0.23 (hexanes/ethyl acetate = 1:2, stain in PMA). 1H NMR (500 MHz,
CDCl3): δ 1.65ꢀ1.76 (4H, m), 1.79ꢀ1.88 (2H, m), 3.43 (1H, d, J =
15.1 Hz), 3.52 (1H, d, J = 15.1 Hz), 3.95 (1H, br), 4.18 (1H, br),
5.58 (1H, br), 7.20ꢀ7.23 (3H, m), 7.28ꢀ7.31 (2H, m). 13C NMR
(100 MHz, CDCl3): δ 142.3, 139.2, 129.7, 129.3, 128.7, 126.5, 66.9,
66.2, 40.5, 29.3, 28.0. IR (neat): 3313.5 (br), 2939.6 (m), 2867.3 (w),
1493.6 (w), 1453.1 (m), 1278.4 (w), 1070.6 (m), 1030.2 (m), 980.3
(m), 962.0 (m), 755.7 (w), 700.7 (s) cmꢀ1. HRMS (ESI+) for C13H20O2N
[M + NH4]: calcd 222.1494, found 222.1489. [α]20D: +100.80 (c = 0.92,
CHCl3, l = 50 mm). Mp: 114.8ꢀ116.6 °C. Enantiomer ratio determined
by HPLC (Chiraldex OD-R, 3% iPrOH/hexanes, 1 mL/min, 220 nm),
major enantiomer 45.91 min, minor enantiomer 63.95 min, 94:6 er.
(1R,4S)-2-Phenethylcyclohex-2-ene-1,4-diol (5b). 50.0 mg, 91%
yield. Rf = 0.18 (hexanes/ethyl acetate = 1:2, stain in PMA). 1H NMR
(500 MHz, CDCl3): δ 1.64ꢀ1.71 (1H, m), 1.74ꢀ1.80 (1H, m),
1.81ꢀ1.89 (2H, m), 2.41 (1H, ddd, J = 14.9 Hz, 10.1 Hz, 6.4 Hz),
2.48 ꢀ2.54 (1H, m), 2.74 (1H, ddd, J = 13.7 Hz, 9.8 z, 6.4 Hz), 2.83 (1H,
dd, J = 13.7 Hz, 10.1 Hz, 5.7 Hz), 4.04 (1H, br), 4.15 (1H, br),
7.17ꢀ7.20 (3H, m), 7.26ꢀ7.30 (2H, m). 13C NMR (125 MHz, CDCl3):
δ 142.3, 142.0, 128.62, 128.57, 128.4, 126.2, 67.1, 66.8, 35.5, 34.6, 29.4,
28.1. IR (neat): 3300.4 (br), 2935.0 (s), 2858.3 (m), 1495.8 (w), 1453.6
(m), 1276.4 (w), 1042.3 (m), 979.1 (m), 954.8 (m), 873.4 (w), 749.0
(m), 699.3 (s) cmꢀ1. HRMS (ESI+) for C14H22O2N [M + NH4]: calcd
9106
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The Journal of Organic Chemistry
NOTE
(1R,4S)-2-(2-(1,3-dioxolan-2-yl)ethyl)cyclohex-2-ene-1,4-diol (10b).
(90.0 mg, 84% yield) Rf = 0.23 (100% ethyl acetate, stain in PMA);
1H NMR (500 MHz, CDCl3): δ1.63ꢀ1.75 (2H, m), 1.76ꢀ1.89 (4H, m),
2.18ꢀ2.31 (2H, m), 3.81ꢀ3.87 (2H, m), 3.92ꢀ3.97 (2H, m), 3.98 (1H,
br), 4.10 (1H, br), 4.87 (1H, t, J = 4.7 Hz), 5.55 (1H, br); 13C NMR (125
MHz, CDCl3): δ 141.9, 128.1, 104.4, 66.69, 66.66, 65.07, 65.04, 32.0, 29.3,
28.1, 27.9; IR (neat): 3353.7 (br), 2937.5 (w), 2878.1 (s), 1443.1 (w),
1408.9 (m), 1265.6 (w), 1135.1 (s), 1044.3 (s), 977.8 (s), 955.6 (s), 895.6
(m), 644.4 (w); HRMS (ESI+) for C11H17O3 [M + HꢀH2O]: calcd
197.1178, found: 197.1169; [α]D20: +15.91 (c = 0.95, CHCl3, l = 50 mm).
Enantiomer ratio determined by HPLC (dibenzoate derivative, Chiraldex
OD-R, 3% iPrOH/hexanes, 1.0 mL/min, 220 nm), major enantiomer
24.53 min, minor enantiomer 14.52 min, 95:5 e.r.
(1R,4S)-2-butylcyclohept-2-ene-1,4-diol (11b). (14.7 mg, 32% yield)
Rf = 0.26 (hexanes: ethyl acetate =3:2, stain in PMA); 1H NMR (500 MHz,
CDCl3): δ 0.91 (3H, t, J = 7.2 Hz), 1.29ꢀ1.36 (2H, m), 1.37ꢀ1.43
(2H, m), 1.55ꢀ1.69 (3H, m), 1.84ꢀ1.93 (2H, m), 2.08 (2H, td, J = 7.6
Hz, 1.2 Hz), 2.28ꢀ2.37 (1H, m), 4.12 (1H, d, J = 6.6 Hz), 4.26 (1H, ddd,
J = 6.9 Hz, 6.8 Hz, 1.5 Hz), 5.71 (1H, d, J = 6.8 Hz); 13C NMR (100
MHz, CDCl3): δ 149.7, 129.5, 72.3, 68.2, 37.9, 34.5, 33.8, 30.6, 22.6,
19.5, 14.2; IR (neat): 3315.0 (br), 2924.3 (s), 2856.1 (m), 1647.7 (w),
1453.7 (m), 1272.8 (w), 1059.3 (s), 1028.1 (s), 937.1 (m), 654.6 (w);
HRMS (ESI+) for C11H19O [M + H ꢀ H2O]: calcd 167.1436, found
167.1430. [α]20D: +6.28 (c = 0.53, CHCl3, l = 50 mm). Enantiomer ratio
determined by HPLC (dibenzoate derivative, Chiraldex OD-R, 1%
iPrOH/hexanes, 0.25 mL/min, 220 nm), major enantiomer 28.34
min, minor enantiomer 31.49 min, 96:4 er.
((1R,4S)-2-(3-Phenylpropyl)cyclohex-2-ene-1,4-diyl)dimethanol (12).
Pt(dba)3 (6.7 mg, 7.5 mmol), phosphonite ligand (L6) (18.1 mg, 15.0
mmol), and toluene (2.5 mL, 0.1 M) were mixed under Ar and stirred for 1
h. Then, B2(pin)2 (66.7 mg, 262.5 mmol) and (3-(cyclohexa-1,5-dien-1-
yl)propyl)benzene (49.6 mg, 0.25 mmol) were added. After stirring at
60 °C for 12 h, the volatiles were removed. THF (2.5 mL) was added, the
flask cooled to ꢀ78 °C, and bromochloromethane (35.7 mL, 0.55 mmol)
and n-BuLi (0.19 mL, 0.55 mmol) added sequentially. After 10 min, the
cooling bath was removed and the contents stirred for 12 h. Then, THF
(2 mL), 3 M NaOH (2 mL) and 30% H2O2 (1 mL) were added, slowly, at
0 °C, and the mixture was allowed to stir for 4 h at ambient. After cooling to
0 °C, saturated aqueous sodium thiosulfate was added (2 mL, dropwise
slowly). Extraction with ethyl acetate (3 ꢁ 20 mL), drying, concentration,
and purification by silica gel chromatography (hexanes/ethyl acetate = 1:1)
afforded a colorless oil (57.3 mg, 88% yield). Rf = 0.24 (hexanes/ethyl
acetate = 1:1, stain in PMA). 1H NMR (500 MHz, CDCl3): δ 1.45ꢀ1.53
(1H, m), 1.59ꢀ1.76 (3H, m), 1.77ꢀ1.88 (1H, m), 1.89ꢀ1.95 (1H, m),
2.02ꢀ2.13 (2H, m), 2.23 (1H, br), 2.32 (1H, br), 2.55ꢀ2.67 (2H, m),
3.50ꢀ3.59 (3H, m), 3.66 (1H, dd, J = 10.6 Hz, 2.8 Hz), 5.49 (1H, br),
7.17ꢀ7.20 (3H, m), 7.26ꢀ7.30 (2H, m). 13C NMR (125 MHz, CDCl3):
δ 142.6, 139.7, 128.6, 128.5, 125.9, 125.6, 67.3, 64.5, 39.8, 38.8, 35.9, 35.3,
30.2, 24.5, 22.0. IR (neat): 3314.4 (br), 2935.6 (w), 2862.4 (w), 1451.8
(w), 1028.7 (m), 734.2 (w), 697.4 (s), 488.5 (w) cmꢀ1. HRMS (ESI+) for
C17H25O2 [M + H] calcd 261.1855, found 261.1864. [α]20D: +8.09 (c =
0.82, CHCl3, l = 50 mm). Enantiomer ratio determined by HPLC
(Chiraldex AD-H, 5% iPrOH/hexanes, 1.0 mL/min, 220 nm), major
enantiomer 39.48 min, minor enantiomer 34.56 min, 95:5 er.
to 0 °C and charged with THF (3 mL), 3 M NaOH (3 mL), and 30%
H2O2 (3 mL). The reaction was stirred for 4 h at ambient tempera-
ture and then cooled to 0 °C and saturated aqueous sodium
thiosulfate (3 mL, dropwise slowly) added dropwise. Extraction
(ethyl acetate, 3 ꢁ 20 mL), drying, concentration, and purification
on silica gel (100% dichloromethane, then hexanes/ethyl acetate =
4:1) afforded a white solid (114.6 mg, 86% yield). Rf = 0.18 (hexanes/
1
ethyl acetate = 5:1, stain in PMA). H NMR (500 MHz, CDCl3):
δ 0.79ꢀ0.89 (1H, m), 0.93 (3H, d, J = 6.6 Hz), 0.96 (3H, d, J =
6.6 Hz), 1.14ꢀ1.19 (1H, m), 1.23ꢀ1.34 (4H, m), 1.60ꢀ1.73 (5H,
m), 1.79ꢀ1.97 (5H, m), 2.01ꢀ2.08 (1H, m), 2.25ꢀ2.33 (2H, m),
4.12 (1H, ddd, J = 9.0 Hz, 4.4 Hz, 4.4 Hz), 4.31 (1H, ddd, J = 7.3 Hz,
3.2 Hz, 3.2 Hz), 5.51 (1H, br). 13C NMR (100 MHz, CDCl3): δ
141.1, 120.7, 70.4, 69.5, 45.7, 44.6, 41.9, 34.7, 31.0, 28.3, 27.2, 27.0,
26.8, 25.0, 23.9 22.3, 21.7; IR (neat): 3311.0 (br), 2922.7 (s), 2850.4
(m), 1448.1 (m), 1261.2 (w), 1068.9 (m), 1045.3 (m), 845.9 (w),
755.2 (m), 568.4 (w). HRMS (ESI+) for C17H29O [M + H ꢀ H2O]:
calcd 249.2218, found 249.2210. [α]20D: +24.83 (c = 0.60, CHCl3, l =
50 mm). Mp: 78.0ꢀ82.1 °C. Enantiomer ratio determined by GLC
(Supelco β-dex, 150 °C, 20 psi), major enantiomer 242.57 min, minor
enantiomer 246.66 min, 95:5 er. Absolute stereochemistry was
determined by crystallography using anomalous dispersion (Flack
parameter = 0.0).
’ ASSOCIATED CONTENT
S
Supporting Information. Compound characterization
b
(spectra). This material is available free of charge via the Internet
at http://pubs.acs.org/.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: morken@bc.edu.
’ ACKNOWLEDGMENT
Support by the NIGMS (GM-59417) and the NSF (DBI-
06195766, BC Mass Spectrometry Center) is gratefully acknow-
ledged. AllyChem is acknowledged for a generous donation of
B2(pin)2.
’ REFERENCES
(1) Burks, H. E.; Kliman, L. T.; Morken, J. P. J. Am. Chem. Soc. 2009,
131, 9134.
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(2R,3S)-2-((S)-1-Hydroxy-3-methylbutyl)[1,10-bi(cyclohexan)]-
6-en-3-ol (14). In a glovebox, a stir bar, Pt(dba)3 (13.5 mg, 15.0 mmol),
phosphonite ligand (L6) (36.3 mg, 30.0 mmol), and toluene (5.0 mL,
0.1 M) were added to a vial. After the mixture was stirred for 1 h,
B2(pin)2 (133.3 mg, 0.525 mmol) and [1,10-bi(cyclohexane)]-1,
5-diene (81.1 mg, 0.50 mmol) were added. The vial was sealed,
removed from the glovebox, and stirred at 60 °C for 12 h. After the
mixture was cooled to room temperature, isovaleraldehyde was
added (129.2 mg, 1.50 mmol) under nitrogen atmosphere. The vial
was sealed again and stirred at 80 °C for 30 h. The mixture was cooled
9107
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The Journal of Organic Chemistry
NOTE
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