Chiral bicyclo[3.3.0]octa-2,5-dienes as steering ligands in substrate-dependent rhodium-catalyzed 1,4-addition of arylboronic acids to enones

Article abstract of DOI:10.1002/adsc.200700232

The synthesis of disubstituted chiral diene ligands (3aR,6aR)- and (3aS,6aS)-10 with a pentalene backbone from the corresponding bicyclo[3.3.0]octa1,4-diones 7 is described. The latter were accessible by enzymatic resolution of the racemic diol rac-5 and

Full text of DOI:10.1002/adsc.200700232

FULL PAPERS
DOI: 10.1002/adsc.200700232
Chiral Bicyclo[3.3.0]octa-2,5-dienes as Steering Ligands in
A
Substrate-Dependent Rhodium-Catalyzed 1,4-Addition of
Arylboronic Acids to Enones
Sarah Helbig,a Sven Sauer,a Nicolai Cramer,a Sabine Laschat,a,* Angelika Baro,a
and Wolfgang Freya
a
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax : (+49)-711-685-64285; e-mail: sabine.laschat@oc.uni-stuttgart.de
Received: December 4, 2006; Revised: May 4, 2007
Dedicated to Prof. Peter Hofmann on the occasion of his 60th birthday.
Abstract: The synthesis of disubstituted chiral diene (3aR,6aR)- and (3aS,6aS)-10a were more selective
ligands (3aR,6aR)- and (3aS,6aS)-10 with a pentalene than the corresponding dibenzyldiene ligands 10b.
backbone from the corresponding bicyclo[3.3.0]octa- When acyclic enones 15 were employed this result,
N
1,4-diones 7 is described. The latter were accessible however, reversed. Ligands 10a were nearly inactive
by enzymatic resolution of the racemic diol rac-5 and whereas dibenzyldienes 10b afforded the addition
subsequent Swern oxidation. The efficiency of the li- products 16 with enantioselectivities up to 91%.
gands 10 in the rhodium-catalyzed 1,4-addition of
arylboronic acids 12 to cyclic and acyclic enones 11
and 15 could be demonstrated. In the case of cyclic Keywords: asymmetric catalysis; chirality; diene
enones 11 the enantiomeric diphenyldienes ligands; enones; rhodium; synthesis
Introduction
total synthesis of the tetramic acid lactam cylindra-
mide.[5] We anticipated that the convex roof shape of
In asymmetric catalysis alkenes such as ethylene, pro- dione 7[6] should lead to a diene ligand which bears
pene, 1,4-cyclooctadiene or norbornadiene and deriv- structural similarities with the known norbornadiene
atives thereof were mainly considered as weak li- ligands 1.[1f,5] Further motivation came from a report
gands, which do not allow stereochemical control in by Trauner that convex phenanthrene ligands resulted
contrast to P-, N-, O- and S-containing ligands as well in a chiral Pd(0) alkene complex with remarkable sta-
as N-heterocyclic carbenes. This situation changed
with the recent seminal work of Hayashi,[1] Carreira,[2]
and Grützmacher.[3] Their work confirmed the suc-
cessful application of chiral diene ligands 1, 2 based
on bicycloalkanes, or tropylidenephosphane
3
(Scheme 1), resulting in high selectivities,[4] for exam-
ple, in the Ir-catalyzed hydrogenation of imines[3d] and
allylic substitution,[2c] in the Rh-catalyzed 1,4-addition
of phenylboronic acid to enones[1h,l,2d] and fumar-
ates[1k] or in the Rh-catalyzed aryl transfer to sulfonyl-
imines.[1j]
In some cases, however, the synthetic access to the
ligands is rather tedious.[1h,k,l] Upon looking for alter-
native scaffolds which might be easily converted into
chiral diene ligands in both enantiomeric forms, we
turned our attention to C2-symmetrical bicyclo-
Scheme 1. Some chiral diene 1,2 and phosphane olefin li-
gands 3 reported by Hayashi, Carreira, and Grützmach-
[3.3.0]octa-1,4-dione 7 (Scheme 2), whose (3aR,6aR)-
enantiomer has been used as a building block in our er.[1–3]
Adv. Synth. Catal. 2007, 349, 2331 – 2337
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Sarah Helbig et al.
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Scheme 3. Preparation of chiral 3,6-disubstituted bicyclo-
[3.3.0]octa-2,5-dienes 10a,b.
antiomers 5 with DMSO and (COCl)2 afforded the
diones (3aR,6aR)- and (3aS,6aS)-7 with 98% ee and
>99% ee, respectively (Scheme 2).
Scheme 2. Preparation of chiral bicyclo
via enzymatic resolution.
A
As outlined in Scheme 3, the disubstituted bicyclo-
AHCTREUNG
ACHTREUNG
Rh-catalyzed 1,4-addition of arylboronic acids to intermediates 8 in 90% and 84% yield, respectively.
enones.[8] Particular emphasis was spent on the influ- After dehydration with POCl3 in pyridine at 808C,[1f]
ence of the diene substituents on the substrate specif- ligands (3aR,6aR)- and (3aS,6aS)-10a were isolated in
icity. The results are described below.
50% and 62% yield. Deprotonation of diones
(3aR,6aR)- and (3aS,6aS)-7 with KHMDS[13] and sub-
sequent treatment with N-(2-pyridyl)triflimide[14] (2-
PyNTf2) in THF at ꢀ788C gave the bistriflates
(3aR,6aR)- and (3aS,6aS)-9 in 56–58% yield. The fol-
lowing Negishi coupling[15] was performed with
Results and Discussion
Ligand Synthesis
Fe
A
As depicted in Scheme 2, the bicyclo
ACHTREUNG
diones (3aR,6aR)- and (3aS,6aS)-7 were available manner, the chiral 3,6-dibenzylated bicyclo-
starting from cycloocta-1,5-diene 4 by a literature pro-
C
and vinyl acetate in methyl tert-butyl ether,[5,10,11] as a
key step, yielding the diol (1S,3aR,4S,6aR)-5 and the CH2Cl2 gave single crystals which were suitable for X-
diacetate (1R,3aS,4R,6aS)-6 in 19% and 46%, respec- ray crystal structure analysis.[16] Figure 1 clearly shows
tively. The diacetate 6 was separated by chromatogra- the roof-shape of the bicyclooctadiene with an angle
phy on SiO2 and deacetylated to the corresponding al- of 1158 for the convex bicyclic system. The double
cohol (1R,3aS,4R,6aS)-5 by treatment with Dowex 1” bonds between C-1/C-2 and C-5/C-6 are not parallel
8 in MeOH for 24 h. Swern oxidation[5,12] of both en- to each other but twisted by 288, thus being similar to
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Rhodium-Catalyzed 1,4-Addition of Arylboronic Acids to Enones
FULL PAPERS
Table 1. Rhodium-catalyzed addition of arylboronic acids
12a,b to cyclic enones 11a–c using ligands (3aR,6aR)-10a,b
and (3aS,6aS)-10a.
Entry Enone Ligand
Product Yield
[%][a]
%
Conf.[c]
ee[b]
1
11a
11a
11a
11b
11b
11b
11c
11c
11a
11b
11c
C
74
80
73
95
93
78
47
51
85
81
71
95
93
75
88
84
73
83
76
93
84
76
R
2
S
3
S
4
R
5
S
6
S
Figure 1. ORTEP plot of ligand 3,6-diphenylbicyclo-
[3.3.0]octa-2,5-diene (3aS,6aS)-10a.
ACHTREUNG
7
R
8
S
Hayashiꢁs 2,6-di(4-methylphenyl)bicyclo[3.3.1]nona-
N
9
S[d]
S[d]
S[d]
2,6-diene rhodium complex where a twist angle of 238
has been found.[1f]
10
11
Asymmetric Rh-Catalyzed 1,4-Addition
[a]
[b]
Yields are referred to isolated products.
Enantiomeric excess was determined by GC using chiral
stationary phases.
Assignment of the configuration by comparison of opti-
cal rotation values with literature data.[17,18]
In analogy to the assignment of products 13.
First the catalytic properties of the diene ligands 10
were investigated in the Rh-catalyzed 1,4-addition of
arylboronic acids 12a, b to the cyclic enones 11a–c
(Table 1). Treatment of cyclopentenone 11a with phe-
nylboronic acid 12a in the presence of 3 mol% Rh
and 3.3 mol% diphenyldiene ligand (3aS,6aS)-10a
and KOH (0.5 equivs.) in aqueous dioxane yielded
[c]
[d]
(R)-3-phenylcyclopentanone (R)-13a in 74% yield (entries 9–11). A considerable drop of the enantiose-
and 95% ee (entry 1). The enantiomeric ligand lectivity was observed when dibenzyldiene ligand
(3aR,6aR)-10a gave the corresponding (S)-configurat- (3aR,6aR)-10b was used under identical reaction con-
ed product in 80% yield and 93% ee (entry 2). The ditions (entries 3, 6).
enantioselectivities decreased with both (3aS,6aS)-
The most remarkable observation, however, was
and (3aR,6aR)-10a when cyclohexenone 11b and cy- made during 1,4-addition of boronic acids 12 to acy-
cloheptenone 11c were employed, while, with excep- clic enones 15 (Table 2).
tion of product 13c, good chemical yields were ob-
As can be seen in Table 2, diphenyl- and dibenzyl-
tained (entries 4, 5, 7, 8). The addition of tolylboronic substituted ligands 10a and 10b showed a strikingly
acid 12b in the presence of ligand (3aR,6aR)-10a pro- different activity. Whereas diphenyldiene ligand
ceeded with similar yields and enantioselectivities (3aS,6aS)-10a and its congener (3aR,6aR)-10a yielded
Adv. Synth. Catal. 2007, 349, 2331 – 2337
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Table 2. Rhodium-catalyzed addition of arylboronic acids
12a,b to acyclic enones 15a,b using ligands (3aR,6aR)- and
(3aS,6aS)-10a,b.
Conclusions
We have demonstrated that chiral bicyclo-
[3.3.0]octadiene ligands 10a and 10b which were
AHCTREUNG
easily accessible in optically pure form in a five (or
six) step sequence from cycloocta-1,5-diene 4, could
be used in the catalytic asymmetric 1,4-addition of ar-
ylboronic acids to enones. More importantly, the sub-
stitution pattern of the diene led to complementary
activity and substrate specificity of the catalyst.
Whereas diphenyldiene ligands 10a converted cyclic
enones 11a–c with good yields and high enantioselec-
tivities, it turned out to be almost completely inactive
towards acyclic enones 15a, b. In contrast, dibenzyl-
diene ligands 10b gave decreased selectivities for
cyclic enones 11 as compared to the diphenyldiene
counterpart 10a. For acyclic enones 15, however, li-
gands 10b produced good yields and selectivities.
Thus, it needs to be explored whether such comple-
mentary behaviour of ligands 10a, b is also observed
for other catalytic reactions.
Enone Ligand
Product Yield
[%][a]
%
[a]2D0
(c 1.0,
CH2Cl2)
ee[b]
15a
15a
15a
15a
15b
15b
15b
15b
15a
15b
C
16a
16a
<1[c]
<1[c]
71
1
-
0
-
(S)-
91
89
16
10
89
88
89
86
+29.1
ꢀ31.2
-
16a[d]
(R)-
59
16a[d]
(+)-
16b[e]
(ꢀ)-
16b[e]
<1[c]
1[c]
Experimental Section
-
General Remarks
(+)-16b 73
+63.4
ꢀ49.5
ꢀ30.0
ꢀ65.2
Melting points (uncorrected) were determined on a Büchi
SMP 20. Specific rotations were determined on a Perkin–
Elmer 241 polarimeter. IR spectra: Bruker Vektor22. Mass
spectra: Finnigan MAT 95, Varian MAT 711, and Bruker
Daltonics mircOTOFq. NMR spectra: Bruker Avance 300
and Avance 500. The spectra were recorded with TMS as in-
ternal standard. TLC: Silica gel 60 F254 (Merck). Column
chromatography: Fluka Kieselgel 60, grain size 40–63 mm.
GC: Fisons HRGC MEGA 8560 and Carlo Erba Strumenta-
zione HRGC 5300. Column and temperature programs are
given below.
(ꢀ)-16b 45[f]
(R)-
68
17a[g]
(ꢀ)-17b 58
[a]
Yields are referred to isolated products.
Enantiomeric excess was determined by GC using chiral
stationary phases.
Starting material 15a and 15b was recovered.
Assignment of the configuration by comparison of opti-
cal rotation values with literature data.[19]
According to the direction of rotation.
[b]
[c]
[d]
A
diones (7)
[e]
[f]
Compounds 7 were prepared as described in ref.[5] In order
to obtain enantiomerically pure (3aS,6aS)-7, the diacetate
(1R,3aS,4R,6aS)-6 obtained from enzymatic resolution with
96% ee was submitted to saponification followed by enzy-
matic acetylation and Swern oxidation.
72% yield with 6 mol% Rh catalyst.
In analogy to the assignment of derivative 16a.
[g]
only trace amounts of the corresponding 1,4-addition
products 16a and 16b in racemic form, the corre-
sponding dibenzyldienes (3aS,6aS)- and (3aR,6aR)-
10b gave the target products 16a, b in good yields and
enantioselectivities of 88–91%. When tolylboronic
acid 12b was employed in the presence of dibenzyl-
diene ligand (3aR,6aR)-10b comparable results were
obtained.[20]
A
(8)
CeCl3·7H2O (2.1 g, 5.6 mmol) was heated under vacuum at
1408C for 2 h and cooled. Then THF (10 mL) was added
and the suspension stirred for 1 h at room temperature. The
suspension was cooled to ꢀ788C, PhLi (3.1 mL, 5.6 mmol,
1.8M in dibutyl ether) was added and the reaction mixture
stirred for a further 1 h. After addition of a solution of
(3aR,6aR)-7 (276 mg, 2 mmol) in THF (2 mL), the reaction
mixture was warmed to ꢀ408C over 6 h. The reaction was
quenched with water (20 mL), the layers were separated,
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Rhodium-Catalyzed 1,4-Addition of Arylboronic Acids to Enones
FULL PAPERS
and the aqueous layer was extracted with EtOAc (3”
50 mL). The combined organic layers were dried (MgSO4),
and the solvent was removed under vacuum. Chromatogra-
phy of the residue on SiO2 [PE/EtOAc, 4:1!0:1, Rf (PE/
EtOAc 5:1)=0.6] afforded 8 as a white solid; yield 531 mg
(90%); mp 1928C; [a]D20: ꢀ53.7 (c 1.0, CH2Cl2). FT-IR
ꢀ788C, and the reaction mixture stirred for 3 h. Then a satu-
rated solution of NaHCO3 (10 mL) was added. The aqueous
layer was extracted with pentane (2”50 mL), the combined
organic layers were washed with a solution of 5% NaOH-
H2O, dried (MgSO4) and concentrated. Chromatogaphy on
SiO2 (PE/EtOAc, 25:1, Rf =0.4) afforded triflate 9 as a col-
orless oil; yield: 675 mg (56%); [a]2D0: ꢀ45.2 (c 1.0, CH2Cl2).
˜
(ATR): n=3326 (s), 2966 (m), 2925 (m), 1734 (m), 1494
˜
(m), 1459 (m), 1444 (m), 1372 (m), 1297 (m), 1249 (m), 1154
FT-IR (ATR): n=2936 (m), 2871 (m), 1964 (m), 1659 (s),
(m), 1071 (m), 1037 (m), 927 (m), 756 (s), 697 (s) cmꢀ1
;
1420 (vs), 1331 (s) cmꢀ1; H NMR (500 MHz, CDCl3): d=
1
1H NMR (300 MHz, CDCl3): d=1.73–1.85 (m, 2H, 3-Ha, 6-
Ha), 2.08–2.39 (m, 6H, 2-H, 3-Hb, 5-H, 6-Hb), 2.94–3.07 (m,
2H, 3a-H, 6a-H), 3.64 (s, 2H, OH), 7.22–7.39 (m, 2H, p-H),
7.31–7.39 (m, 4H, o-H), 7.49–7.54 (m, 4H, m-H); 13C NMR
(62.5 MHz, CDCl3): d=20.9 (C-3, C-6), 45.1 (C-2, C-5), 55.4
(C-3a, C-6a), 81.3 (C-1, C-4), 125.3 (o-C), 126.9 (p-C), 128.3
(m-C), 145.0 (i-C); GC-MS (EI): m/z (%)=295 (1) [M+ +
H], 276 (15) [M+ꢀH2O], 258 (80) [M+ꢀ2H2O], 230 (20),
156 (40), 143 (50), 129 (45), 115 (43), 105
[M+ꢀ2H2Oꢀ2C6H5 +H], 90 (50), 77 (25) [C6H5]; ESI-MS:
m/z=317.1517 [M+], calcd. for C20H22NaO2 317.1512; anal.
calcd. for C20H22O2 (294.38): C 81.60, H 7.53; found: C
81.37, H 7.63.
2.51 (ddd, J=17.4, 5.2, 2.6 Hz, 2H, 3-Ha, 6-Ha), 2.62–2.68
(m, 2H, 3-Hb, 6-Hb), 3.62–3.65 (m, 2H, 3a-H, 6a-H), 5.58–
5.66 (m, 2H, 2-H, 5-H); 13C NMR (125 MHz, CDCl3): d=
30.3 (C-3, C-6), 44.1 (C-3a, C-6a), 115.3 (C-2, C-5), 118.6 (q,
J=2.6, SO2CF3), 149.0 (C-1, C-4) ppm; GC-MS (CI, CH4):
m/z (%)=402 (1) [M+], 269 (9) [M+ꢀCF3O2S], 162 (2), 135
(6), 119 (12), 99 (6), 91 (19), 77 (8), 69 (36) [CF3], 64 (17)
[SO2], 55 (100); HR-MS (CI, CH4): m/z=401.9647 [M+],
calcd. for C10H8F6O6S2: 401.9666.
A
rahydropentalen-1-yl trifluoromethanesulfonate (9): Yield:
58%; [a]20: +47.1 (c 1.0, CH2Cl2). The spectroscopic data
are in accDordance with those of (3aR,6aR)-9.
A
(8):
Yield: 84%; [a]2D0: +54.1 (c 1.0, CH2Cl2). The spectroscopic
data are in accordance with those of (3aR,6aR)-8.
A
(10b)
BnMgCl (0.5 mL, 1 mmol, 2M in THF) was slowly added to
A
a solution of (3aR,6aR)-9 (210 mg, 0.52 mmol) and Fe(acac)3
A
lene (10a)
(37 mg, 0.10 mmol, 5 mol%) in THF (5 mL) at 08C, and the
reaction mixture stirred for 15 min. The reaction was then
quenched at 08C with a saturated solution of NH4Cl. The
aqueous layer was extracted with CH2Cl2 (3”20 mL), the
combined extracts were dried (MgSO4), and concentrated.
Chromatography on SiO2 (PE/Et2O, 500:1, Rf =0.2) afforded
10b as a colorless oil; yield: 111 mg (75%); [a]2D0: ꢀ49.5 (c
To a solution of (3aR,6aR)-8 (264 mg, 0.90 mmol) in pyri-
dine (1 mL) at room temperature was added POCl3
(495 mL), and the reaction mixture refluxed for 12 h. After
cooling to room temperature, the reaction was quenched
with water (10 mL) and extracted with CH2Cl2 (3”20 mL).
The combined extracts were washed with a 2M solution of
NaOH, dried (MgSO4) and concentrated. Chromatography
on SiO2 (PE/Et2O, 500:1, Rf =0.1) afforded 10a as a white
solid; yield: 132 mg (50%); [a]2D0: ꢀ406 (c 1.0, CH2Cl2). FT-
˜
1.0, CH2Cl2). FT-IR (ATR): n=3025 (m), 2902 (m), 2844
(m), 1601 (s), 1493 (m), 1452 (m), 1155 (s), 1072 (m), 1029
(m), 819 (m), 752 (m), 696 (s), 614 (m) cmꢀ1 1H NMR
;
(500 MHz, CDCl3): d=2.25–2.32 (m, 2H, 3-Ha, 6-Ha), 2.40–
2.49 (m, 2H, 3-Hb, 6-Hb), 3.17–3.22 (m, 2H, 3a-H, 6a-H),
3.26 (dd, J=15.4, 1.4 Hz, 2H, 7-Ha, 8-Ha), 3.47 (d, J=
15.4 Hz, 2H, 7-Hb, 8-Hb), 5.13–5.16 (m, 2H, 2-H, 5-H), 7.08–
7.14 (m, 8H, o-H, m-H) 7.17–7.29 (m, 2H, p-H); 13C NMR
(125 MHz, CDCl3): d=35.9 (C-3, C-6), 36.0 (C-7, C-8), 49.8
(C-3a, C-6a), 123.3 (C-2, C-5), 125.9 (C-p), 128.2 (C-m),
129.0 (C-o), 140.0 (C-i), 145.9 (C-1, C-4); GC-MS (CI, CH4):
m/z (%)=286 (40) [M+], 195 (74) [M+ꢀC7H7], 178 (8), 167
(22), 153 (8), 129 (10), 117 (26), 91 (100) [C7H7], 77 (8)
[C6H5], 65 (14), 51 (6); HR-MS (CI, CH4): m/z=286.1722
[M+], calcd. for C22H22: 286.1721.
IR (ATR): n=2904 (m), 2837 (m), 1494 (m), 1444 (m), 747
(s), 694 (s) cmꢀ1; H NMR (500 MHz, CDCl3): d=2.42 (ddd,
J=17.8, 5.9, 3.0 Hz, 2H, 3-Ha, 6-Ha), 2.88–2.97 (m, 2H, 3-
Hb, 6-Hb), 4.03–4.10 (m, 2H, 3a-H, 6a-H), 6.00–6.04 (m, 2H,
2-H, 5-H), 7.18–7.26 (m, 2H, p-H), 7.27–7.37 (m, 4H, o-H),
7.41–7.47 (m, 4H, m-H); 13C NMR (125 MHz, CDCl3): d=
38.6 (C-3, C-6), 48.3 (C-3a, C-6a), 124.4 (C-2, C-5), 126.3
(C-m), 126.9 (C-p), 128.4 (C-o), 135.9 (C-i), 145.1 (C-1, C-
4); MS (CI, CH4): m/z (%)=258 (100) [M+], 243 (19), 230
(17), 215 (11), 202 (7), 178 (11), 167 (28), 154 (31), 141 (15),
128 (12), 117 (88), 102 (8), 91 (28), 77 (9) [C6H5]; HR-MS
(CI, CH4): m/z= 258.1409 [M+], calcd. for C20H18: 258.1409.
(3aS,6aS)-2,5-Dibenzyl-1,3a,4,6a-tetrahydropentalene
(10b): Yield: 76%; [a]D20: +52.8 (c 1.0, CH2Cl2). The spectro-
scopic data are in accordance with those of (3aR,6aR)-10b.
(10a): Yield: 62%; [a]20: +396 (c 1.0, Et2O). The spectro-
scopic data are in accoDrdance with those of (3aR,6aR)-10a.
AHCTREUNG
AHCTREUNG
A
and (3aS,6aS)-9 (100 mg, 0.25 mmol) at room temperature,
reaction time 16 h; yield: 62%; [a]2D0: +379.5 (c 1.0, Et2O).
3,3a,6,6a-tetrahydropentalen-1-yl Trifluoromethane-
sulfonate (9)
A solution of KHMDS (1.32 g, 6.64 mmol) in THF (12 mL)
was slowly added to a solution of (3aR,6aR)-7 (400 mg,
3.00 mmol) and N-(2-pyridyl)-bis(trifluoromethanesulfon-
imide) (2-PyNTf2) (2.49 g, 6.96 mmol) in THF (12 mL) at
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Sarah Helbig et al.
FULL PAPERS
(R)-4-Phenylpentan-2-one (16a): Rf =0.3; [a]20: ꢀ31.2 (c
1.0, CH2Cl2) [with (3aR,6aR)-10b]; GC: 1 min atD408C, then
28C minꢀ1 gradient to 2008C, tR1 =27.15 min (major enantio-
mer), tR2 =27.71 min.
General Procedure for the Rhodium-Catalyzed
Asymmetric 1,4-Addition of Arylboronic Acids 12 to
Enones 11 and 15
(S)-4-Phenylpentan-2-one (16a): [a]2D0: +29.1 (c 1.0,
CH2Cl2) [with (3aS,6aS)-10b]; GC: tR2 =27.71 min.
(ꢀ)-4-(2-Furyl)-4-phenylbutan-2-one (16b): Rf =0.28;
[a]2D0: ꢀ49.5 (c 1.0, CH2Cl2) [with (3aR,6aR)-10b]. FT-IR
A solution of [RhCl(C2H4)2]2 (3 mol% Rh) and the respec-
A
tive ligand 10 (3.3 mol%) in degassed dioxane (2 mL) was
stirred at room temperature for 15 min. Then a degassed
1M solution of KOH (0.5 equivs.) was added, and the mix-
ture stirred for a further 10 min. After addition of the re-
spective enones 11 or 15 (1 equiv.) and arylboronic acids 12
(2 equivs.), the reaction mixture was stirred at 508C for 2 h.
The reaction was then quenched with a saturated solution of
NH4Cl (5 mL), and the aqueous layer was extracted with
Et2O (3”20 mL). The combined organic layers were dried
(MgSO4) and the solvent removed under vacuum. The crude
products 13, 14 or 16, 17 were purified by chromatography
on SiO2 with PE/EtOAc (10:1). GC: cyclic products 13a,b,
14a,b: column Bondex un a (20 m”0.25 mm), 0.4 bar H2;
cyclic products 13c, 14c: column Bondex un b (20 m”
0.25 mm); acyclic products 16a,b, 17a,b: column Amidex C
(0.5% mono-2-undecamethylenepermethyl-b-cyclodextrin,
1.2% N-(4-trimethylenoxybenzoyl)-l-valine bornylamide)
(20 m”0.25 mm), 0.35 bar H2.
˜
(ATR): n=2361 (m), 2342 (m), 1715 (s), 1586 (m), 1504
(m), 1494 (m), 1453 (m), 1413 (m), 1359 (s), 1158 (s), 1079
(m), 1009 (s), 936 (m), 922 (m), 808 (m), 731 (m), 698 (s),
1
577 (m), 535 (m), 509 (s) cmꢀ1; H NMR (300 MHz, CDCl3):
d=2.09 (s, 3H, 1-H), 3.00 (dd, J=7.3, 16.7 Hz, 1H, 3-Ha),
3.23 (dd, J=7.5, 16.7 Hz, 1H, 3-Hb), 4.59 (dd, J=7.5, 7.3 Hz,
1H, 4-H), 5.99 (d, J=3.3 Hz, 1H, 3’-H), 6.27 (dd, J=1.9,
3.1 Hz, 1H, 4’-H), 7.19–7.32 (m, 6H, aryl-H, 5’-H);
13C NMR (125 MHz, CDCl3): d=30.4 (C-1), 40.2 (C-4), 48.4
(C-3), 105.7 (C-4’), 110.2 (C-3’), 126.9 (C-p), 127.7 (C-m),
128.6 (C-o), 141.6 (C-5’), 141.7 (C-i), 156.5 (C-2’), 206.2 (C-
2); MS (EI): m/z (%)=215 (8) [M+ +H], 214 (50) [M+], 171
(12) [C12H11O], 157 (100) [C11H9O], 128 (20), 115 (9), 103
(18), 77 (6) [C6H6], 43 (17); ESI-MS: m/z=237.0886 [M+
Na]+, calcd. for C14H14NaO2: 237.0884. GC: 10 min at
1008C, then 28C minꢀ1 gradient to 1608C, 10 min at 1608C,
According to this protocol the following addition products
were obtained. The spectroscopic data of 13, 14 and 16a,
17a are in accordance with those in the literature.[17,21]
(S)-3-Phenylcyclopentanone (13a): Rf =0.25; [a]2D0: ꢀ101.7
(c 1.0, CH2Cl2) [with (3aR,6aR)-10a], [a]2D0: ꢀ73.5 (c 1.0,
CH2Cl2) [with (3aR,6aR)-10b]; GC: 108C minꢀ1 gradient
from 408C to 1208C, 3 min at 1208C, then 28C minꢀ1 gradi-
ent to 2008C, tR1 =17.04 min, tR2 =17.39 min (major enantio-
mer).
then 108C minꢀ1 gradient to 2008C, tR1 =29.91 min, tR2
=
30.35 min (major enantiomer).
(+)-4-(2-Furyl)-4-phenylbutan-2-one (16b): [a]2D0: +63.4 (c
1.0, CH2Cl2) [with (3aS,6aS)-10b]; GC: tR1 =29.91 min.
(R)-4-(4-Methylphenyl)pentan-2-one (17a): Rf =0.25;
[a]2D0: ꢀ30.0 (c 1.0, CH2Cl2) [with (3aR,6aR)-10b]; GC: 1 min
at 408C, then 28C minꢀ1 gradient to 2008C, tR1 =31.85 min
(major enantiomer), tR2 =32.17 min.
(R)-3-Phenylcyclopentanone (13a): [a]2D0: +96.4 (c 1.0,
CH2Cl2) [with (3aS,6aS)-10a]; GC: tR1 =17.04 min.
(ꢀ)-4-(2-Furyl)-4-(4-methylphenyl)butan-2-one
(17b):
Rf =0.25; [a]2D0: ꢀ65.2 (c 1.0, CH2Cl2) [with (3aR,6aR)-10b].
(S)-3-Phenylcyclohexanone (13b): Rf =0.3; [a]2D0: ꢀ15.0 (c
1.0, CH2Cl2) [with (3aR,6aR)-10a]; [a]2D0: ꢀ14.1 (c 1.0,
CH2Cl2) [with (3aR,6aR)-10b]; GC: 108C minꢀ1 gradient
from 408C to 1208C, 3 min at 1208C, then 28C minꢀ1 gradi-
˜
FT-IR (ATR): n=2361 (m), 1715 (s), 1588 (m), 1513 (m),
1415 (m), 1358 (m), 1158 (s), 1112 (m), 1009 (m), 966 (s),
884 (m), 802 (s), 732 (s), 547 (m), 518 (m), 505 (m) cmꢀ1
;
1H NMR (300 MHz, CDCl3): d=2.08 (s, 3H, 1-H), 2.29 (s,
3H, CH3), 2.98 (dd, J=7.4, 16.7 Hz, 1H, 3-Ha), 3.21 (dd, J=
7.4, 16.7 Hz, 1H, 3-Hb), 4.55 (dd, J=7.4, 7.4 Hz, 1H, 4-H),
5.96–5.99 (m, 1H, 3’-H), 6.27 (dd, J=1.8, 3.1 Hz, 1H, 4’-H),
7.07–7.15 (m, 4H, aryl-H), 7.28 (dd, J=0.7, 1.8, 1H, 5’-H);
13C NMR (125 MHz, CDCl3): d=20.9 (CH3), 30.3 (C-1),
48.4 (C-3), 49.8 (C-4), 105.5 (C-4’), 110.1 (C-3’), 127.6 (C-
m), 129.2 (C-o), 136.3 (C-p), 138.6 (C-5’), 141.7 (C-i), 156.5
(C-2’), 206.2 (C-2); MS (EI): m/z (%)=229 (8) [M+ +H],
228 (40) [M+], 185 (6), 171 (100) [C12H11O], 141 (7), 128
(12), 117 (10), 115 (7), 77 (2) [C6H6], 43 (5); ESI-MS: m/z=
251.1043 [M+Na]+, calcd. for C15H16NaO2: 251.1046. GC:
3 min at 1008C, then 1.58C minꢀ1 gradient to 1608C, then
ent to 1508C, then 108C minꢀ1 gradient to 2008C, tR1
19.57 min, tR2 =20.02 min (major enantiomer).
=
(R)-3-Phenylcyclohexanone (13b): [a]2D0: +8.4 (c 1.0,
CH2Cl2) [with (3aS,6aS)-10a]; GC: tR1 =19.57 min.
(S)-3-Phenylcycloheptanone (13c): Rf =0.3; [a]2D0: ꢀ43.0 (c
1.0, CH2Cl2) [with (3aR,6aR)-10a]; GC: 0.58C minꢀ1 gradi-
ent from 808C to 1308C, then 108C minꢀ1 gradient to
2008C, tR1 =83.88 min (major enantiomer), tR2 =84.88 min.
(R)-3-Phenylcycloheptanone (13c): [a]2D0: +41.4 (c 1.0,
CH2Cl2) [with (3aS,6aS)-10a]; GC: tR2 =84.88 min.
(S)-3-(4-Methylphenyl)cyclopentanone (14a): Rf =0.2;
[a]2D0: ꢀ89.0 (c 1.0, CH2Cl2) [with (3aR,6aR)-10a]; GC: 108C
minꢀ1 gradient from 408C to 1208C, 3 min at 1208C, then
28C minꢀ1 gradient to 2008C, tR1 =22.17 min, tR2 =22.45 min
(major enantiomer).
108C minꢀ1 gradient to 2008C,
tR1 =34.99 min, tR2 =
35.32 min (major enantiomer).
(S)-3-(4-Methylphenyl)cyclohexanone (14b): Rf =0.23;
[a]2D0: ꢀ19.8 (c 1.0, CH2Cl2) [with (3aR,6aR)-10a]; GC: 108C
minꢀ1 gradient from 408C to 1208C, 3 min at 1208C, then
28C minꢀ1 gradient to 2008C, tR1 =24.13 min, tR2 =24.62 min
(major enantiomer).
Acknowledgements
(S)-3-(4-Methylphenyl)cycloheptanone (14c): Rf =0.28;
[a]2D0: ꢀ29.0 (c 1.0, CH2Cl2) [with (3aR,6aR)-10a]; GC: 0.58C
minꢀ1 gradient from 808C to 1308C, then 108C minꢀ1 to
2008C, tR1 =85.67 min (major enantiomer), tR2 =86.54 min.
This work was supported by the Deutsche Forschungsgemein-
schaft, the Ministerium für Wissenschaft, Forschung und
Kunst des Landes Baden-Württemberg, and the Fonds der
Chemischen Industrie (fellowship for N.C.).
2336
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2331 – 2337

Rhodium-Catalyzed 1,4-Addition of Arylboronic Acids to Enones
FULL PAPERS
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