C1-symmetric bicyclo[2.2.2]octa-2,5-diene (bod*) ligands in rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to enones and 1,2-addition to N-[(4-nitrophenyl)sulfonyl]imines

Article abstract of DOI:10.1002/hlca.201200369

A set of ten C₁-symmetric chiral bicyclo[2.2.2]octa-2,5-dienes (bod*) 2 (Fig. 1) were tested as ligands in Rh-catalyzed arylation reactions. The 1,4-addition of arylboronic acids to cyclohex-2-en-1-one, cyclopent-2-en-1-one, and tert-butyl cinn

Full text of DOI:10.1002/hlca.201200369

Helvetica Chimica Acta – Vol. 95 (2012)
1809
C1-Symmetric Bicyclo[2.2.2]octa-2,5-diene (bod*) Ligands in Rhodium-
Catalyzed Asymmetric 1,4-Addition of Arylboronic Acids to Enones and 1,2-
Addition to N-[(4-Nitrophenyl)sulfonyl]imines
by Rebecca Brçnnimanna), Sothys Chuna), and Roger Marti*a)
a
´
´
) Ecole dꢀIngenieurs et dꢀArchitectes de Fribourg, Institut de Chimie, Bd de Perolles 80,
CH-1705 Fribourg (phone: þ 41-26-4296703; fax: þ 41-26-4296600; e-mail: roger.marti@hefr.ch)
and
Stefan Abele*b)
b) Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil
(phone: þ 41-61-5656759; fax: þ 41-61-5658901; e-mail: stefan.abele@actelion.com)
Dedicated to Prof. Dieter Seebach on the occasion of his 75th birthday
A set of ten C1-symmetric chiral bicyclo[2.2.2]octa-2,5-dienes (bod*) 2 (Fig. 1) were tested as ligands
in Rh-catalyzed arylation reactions. The 1,4-addition of arylboronic acids to cyclohex-2-en-1-one,
cyclopent-2-en-1-one, and tert-butyl cinnamate proceeded smoothly with excellent enantioselectivities
(up to 99% ee; Tables 1 – 3). The challenging 1,2-addition of triphenylboroxine to N-[(4-nitrophenyl)-
sulfonyl]imines yielded the product in high yield and in good enantioselectivity (up to 92% ee; Table 4).
Generally, the use of C1-symmetric chiral bod* ligands bearing bulky substituents resulted in lower
enantioselectivities, whereas several electron-poor and electron-rich bod* ligands gave higher
enantioselectivities than the benchmark ligands reported in literature.
Introduction. – Chiral dienes have been established as an own class of chiral ligands
for asymmetric synthesis (for reviews on chiral diene ligands, see [1]). Based on the
pioneering work by Hayashi and co-workers [2a] and Carreira and co-workers [2b], a
multitude of different ligands are known today. However, the synthesis of enantiomeri-
cally pure chiral dienes remains a challenge – simple and inexpensive syntheses to
access the different types of ligands are still not available today1). Process research
chemists at Actelion Pharmaceuticals Ltd. have developed simple and scalable
syntheses of (1R,4R)-5-phenylbicyclo[2.2.2]oct-5-en-2-one (1) [3a][3b] (for a synthesis
of rac-5-phenylbicyclo[2.2.2]oct-5-en-2-one (rac-1) on a 180 kg scale, see [3c]). The
(1R,4R)-phenylbicyclo[2.2.2]oct-5-en-2-one (1) is a crystalline key intermediate, also
1
)
Costs according to the SigmaꢀAldrich catalogue: Hayashiꢀs (R,R)-Ph-bod* (2c): 743 CHF/500 mg;
Carreiraꢀs ligand (1R,4R,8R)-5-benzyl-2-isobutyl-8-methoxy-1,8-dimethylbicyclo[2.2.2]octa-2,5-
diene (¼(þ)-dolefin; III): 272.50 CHF/100 mg.
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Helvetica Chimica Acta – Vol. 95 (2012)
available in its enantiomeric forms, for the preparation of chiral C1-symmetric
bicyclo[2.2.2]octa-2,5-diene (bod*) ligands 2 (Scheme)2).
Scheme
We now report the first application of these new bod* ligands 2 (Fig. 1) in four Rh-
catalyzed arylation reactions, comprising the 1,4-addition to enones and the 1,2-
addition to a N-[(4-nitrophenyl)sulfonyl]imine. Fig. 2 depicts the different types of
known chiral dienes that are mentioned in the text for comparison. At the outset, we
were interested to check the influence of the residue at the 2-position of the
bicyclo[2.2.2]octa-2,5-diene scaffold in these C1-symmetric dienes 2 on the enantiose-
lectivity. In all four test reactions, the commercially available C2-symmetric (R,R)-Ph-
bod* (2c) was used for comparison with our C1-symmetric dienes. Mono-substituted
chiral dienes of the type IV have shown similar enantioselectivities in Rh-catalyzed 1,4-
Fig. 1. Chiral dienes 2a – 2k, used as chiral ligands in the asymmetric addition reactions (Tables 1 – 4). All
dienes are solids, except for 2a and 2j [3a].
2
)
The 2-aryl-5-phenyl-substituted dienes are accessible from 1 by Grignard addition to the ketone,
followed by in situ elimination of the mesylate of the ensuing alcohol, whereas the 2-alkyl-5-phenyl
substituted dienes are synthesized by cross-coupling of the enol triflate derived from 1 (treatment
with lithium diisopropylamide (LDA)/(pyridin-2-yl)N(SO2CF3)2) with alkylmagnesium bromides,
see [3a].

Helvetica Chimica Acta – Vol. 95 (2012)
1811
Fig. 2. Types of chiral dienes that have been reported to give highest ee in the test reactions (Tables 1 – 4).
The C2-symmetric type-I dienes are obtained either by fractional crystallization of diastereoisomeric
dihydrazones of (R)-5-(1-phenylethyl)semioxamazides or by racemate resolution with chiral HPLC of
the C2-symmetric bicyclo[2.2.2]octane-2,5-dione [4]. The C2-symmetric type-II dienes are accessible by a
chemoenzymatic approach [5]. The C1-symmetric type-III and -IV dienes are derived from carvone
[6][7]. The C2-symmetric bicyclo[2.2.1]nona-2,6-diene ligands of type Vare obtained via a separation by
chiral HPLC [8]. The C1-symmetric ligands of type VI are obtained from (R)-a-phellandrene and
propiolic acid (¼ prop-2-ynoic acid) esters by a [4 þ 2] cycloaddition [9].
addition reactions as compared to disubstituted dienes. Hence, it was reckoned that C2-
symmetry was not mandatory for high enantioselectivities in these reactions [7]3).
Results and Discussion. – There is ample precedence for the asymmetric addition of
phenylboronic acid to cyclohex-2-en-1-one (3) and cyclopent-2-en-1-one (5) [4][6].
These two substrates were chosen for testing the chiral-diene ligands 2 in asymmetric
catalysis. Enantioselectivities of > 95% ee are reported for these substrates both with
C2-symmetric Hayashi bod* dienes I [4] and with one of Carreiraꢀs chiral dienes, i.e.,
(þ)-dolefin (III) [6]. Carnellꢀs type II ligand gave 99% ee [5]. Similarly, under slightly
different conditions, Darses reported an ee of 96 and 98% for cyclopentenone and
cyclohexenone with ligands of type IV [7].
Our results of the addition of phenylboronic acid to cyclohex-2-en-1-one (3) to give
ketone 4 by means of the new chiral dienes 2 are summarized in Table 1. The active
catalyst (3 mol-%) was prepared in situ by mixing the chiral ligand 2 with
[RhCl(C2H4)]2. A twofold excess of phenylboronic acid with respect to 3 was used in
dioxane and 50% aqueous KOH solution at 308 for 3 h [4]. In general, very good
enantioselectivities were achieved with all C1-symmetric chiral bod* dienes 2. The
highest ee (97%) was obtained with the mother bod* 2c and with 4-MeO-substituted
diaryldiene 2e. The result with 2c corresponds well with the result published by Hayashi
3
)
This is further corroborated by Carreiraꢀs seminal paper [2b].

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Helvetica Chimica Acta – Vol. 95 (2012)
and co-workers [4]. Surprisingly, variation of the substituent at the para-position of the
diaryl-substituted dienes had no influence on the enantioselectivity: H- (2c), F- (2d),
MeO- (2e), PhO- (2f), or Ph-substituted (2h) diaryldienes gave similar results
independent of their electronic effect! The use of triphenylboroxine ((PhBO)3) as aryl
source gave an identical result (Entry 5). The two dienes with alkyl residues, 2a and 2b,
led to lower enantioselectivity – the same was observed for sterically demanding
ligands, like the 2-methylphenyl-substituted ligand 2i (Entry 12) or the naphthalen-1-yl
ligand 2j (Entry 13). This effect was also described in [4] with the C2-symmetric 2-
methylphenyl-bod* diene. Interestingly, the naphthalen-2-yl-substituted ligand 2k
performed much better than the naphthalen-1-yl-substituted ligand 2j, probably due to
less steric hindrance in the transition state [4][10]. The yields of adduct 4 isolated after
chromatography were in the range of 58 to 97% – Hayashi and co-workers reported
95% [4]. The yields were not further optimized.
Table 1. Enantioselective Addition of Phenylboronic Acid to Cyclohex-2-en-1-one (3), Catalyzed by
Chiral Rh/Diene 2 Complexes
Entry
Diene
Yield [%]a)
ee [%]b)
Entry
Diene
Yield [%]a)
ee [%]b)
1
2
3
4
5d)
6
7
2a
ent-2a
2b
2c
2c
75
72
65
90
94
70
86
92
ꢀ 92
92
8
9
2e
2f
2g
2h
2i
58
70
79
76
93
97
86
97
96
96
96
91
86
96
10
11
12
13
14
97 (96c))
97
ꢀ 97
96
ent-2c
2d
2j
2k
a) Yield of isolated 4 after chromatography. b) Determined by chiral HPLC (210 nm) of isolated 4.
c) Value reported by Hayashi and co-workers [4]. d) With (PhBO)3 instead of PhB(OH)2.
The same protocol was used for the addition of phenylboronic acid to cyclopent-2-
en-1-one (5) to give ketone 6 (Table 2). In general, very good enantioselectivities were
achieved with all C1-symmetric chiral dienes 2. Again, the best result (99% ee) was
achieved with the 4-MeO substituted diaryldiene 2e. With this Michael acceptor, the
bulky ligands 2i and 2j (Entries 11 and 12) showed very good enantioselectivities as
well, whereas the two alkyl-substituted bod* dienes 2a and 2b, and the [biphenyl]-4-yl-
substituted diene 2h gave slightly lower enantioselectivities. The yields of 1,4-adduct 6
were in the range of 53 to 95% after chromatography – slightly lower than for adduct 4.
Next, we studied the 1,4-addition of (4-methoxyphenyl)boronic acid to the acyclic
enone tert-butyl cinnamate (¼tert-butyl (2E)-3-phenylprop-2-enoate; 7) to give
propanoate 8 (Table 3). Some important drug substances are derived from chiral

Helvetica Chimica Acta – Vol. 95 (2012)
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Table 2. Enantioselective Addition of Phenylboronic Acid to Cyclopent-2-en-1-one (5), Catalyzed by
Rh/Diene 2 Complexes
Entry
Diene
Yield [%]a)
ee [%]b)
Entry
Diene
Yield [%]a)
ee [%]b)
1
2
3
4
5
6
7
2a
ent-2a
2b
2c
ent-2c
2d
95
87
73
63
71
75
73
94
ꢀ 93
95
8
9
10
11
12
13
2f
2g
2h
2i
2j
2k
80
55
65
53
60
77
98
97
94
97
97
98
98 (99c))
ꢀ 98
98
2e
99
a) Yield of isolated 6 after chromatography. b) Determined by chiral HPLC (210 nm) of isolated 6.
c) Value reported by Hayashi and co-workers [4].
diarylmethines of the type of 84). Carreira and co-workers reported enantioselectivites
of 93% ee with the carvon derived dienes of type III. To date, ligands of type I (bod*)
have not been tested with cinnamate 7 [11][12]5). Thus, the active catalyst (3 mol-%)
was prepared in situ by mixing chiral ligand 2 with [RhCl(C2H4)]2, and a twofold excess
of 4-methoxyphenylboronic acid with respect to 7 was used in the presence of 1.5m
aqueous KOH at 508 for 16 h. For this reaction, MeOH/H2O 10 :1 was found to be
superior to dioxane/H2O [11]. Gratifyingly, excellent enantioselectivities (98 – 99% ee)
were achieved with several bod* ligands 2, except for the ligands 2i and 2j carrying
bulky substituents (Entries 11 and 12) and the two aryl-alkyl-substituted dienes 2a and
2b (Entries 1 and 2). The use of less equiv. of (4-methoxyphenyl)boronic acid (Entry 4:
1.2 equiv. of boronic acid as compared to 2 equiv.) resulted in a slightly lower yield but a
similar enantioselectivity. The conversion 7 ! 8 could be easily determined by
1H-NMR spectroscopy by comparison the signals of the tert-butyl esters – in general
complete conversion was observed within 16 h. The yields after isolation by
chromatography were in the range of 56 to 97%6) – Carreira an co-workers reported
yields of 80 – 95% for the carvone derived ligands III [11]. In some cases, the
homocoupling product of (4-methoxyphenyl)boronic acid, the 4,4’-dimethoxy-1,1’-
biphenyl could be identified as a minor by-product.
4
)
)
For example, the antidepressant sertraline or the antimuscarinic drug tolterodine.
A recent paper by Hayashi and co-workers [12] describes the Rh-catalyzed 1,4-addition of sodium
tetraarylborates to b,b-disubstituted a,b-unsaturated esters with high ee. Even though bod* ligands
showed the highest eeꢀs, they have not further been employed in that work, probably due to
availability issues. Moreover, this reaction required 45 h at 608 for completion which makes
screening more cumbersome.
5
6
)
The explicit low yields in Entries 2 and 10 can be explained by un-optimized seperation during
column chromatography.

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 3. Enantioselective Addition of (4-Methoxyphenyl)boronic Acid to tert-Butyl Cinnamate (7),
Catalyzed by Rh/Diene 2 Complexes
Entry
Diene
Conversion [%]a)
Yield [%]b)
ee [%]c)
1
2
3
4d)
5
6
7
8
2a
2b
2c
> 95
60
> 95
90
> 95
70
> 95
75
95
92
91
99
20b)
78
2c
56
78
56
97
98
ent-2c
2d
2e
2f
ꢀ 97
99
99
98
79
9
2g
2h
2i
2j
2k
> 95
> 95
> 95
> 95
> 95
94
98
98
93
89
10
11
12
13
30b)
69
89
63
98
a
) Determined by H-NMR of the crude product. b) Yield of isolated 8 after chromatography. c) De-
1
termined by HPLC (230 nm) of isolated 8. d) With 1.2 instead of 2 equiv. of 4-MeOꢀC6H4B(OH)2.
Finally, N-[(4-nitrophenyl)sulfonyl]aldimine 9 was chosen as test substrate for the
1,2-addition of triphenylboroxine to afford chiral (diarylmethyl)amine derivative 10
(Table 4). This product is a precursor for the synthesis of notable pharmacologically
active substances7). N-[(4-Nitrophenyl)sulfonyl]imines are very challenging sub-
strates: Hayashiꢀs bod* ligands I gave a maximum ee of 90%. Highest enantioselec-
tivities (98% ee) were reported with bnd* ligands of type V [8] or with the
phellandrene derived ligands of type VI [9]. For this reaction, we prepared the active
catalyst separately prior to use in the various reactions. The enantioselectivities were
generally lower than those obtained with the preceding substrates: 88 – 92% ee were
obtained with five of the C1-symmetric dienes 2 (Entries 3, 5, and 7 – 9). This is in good
agreement with the result disclosed by Hayashi and co-workers for 2c (Entry 3).
Likewise, the bulky 2-methylphenyl- and naphthalen-1-yl-substituted ligands 2i and 2j
(Entries 10 and 11), respectively, gave the lowest enantioselectitivities (ca. 70% ee),
and the aryl-alkyl substituted dienes 2a and 2b showed significantly lower selectivities
than the aryl-aryl substituted dienes. Interestingly, a heteroaryl substituted C1-
symmetric diene ligand, the thienyl-substituted diene 2g, gave the best result (92%
7
)
For example, the antihistamine cetirizine or the anti-emetic meclozine.

Helvetica Chimica Acta – Vol. 95 (2012)
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Table 4. Enantioselective Addition of Triphenylboroxine to N-[(4-Nitrophenyl)sulfonyl]aldimine 9,
Catalyzed by Rh/Diene 2 Complexes (Ns ¼ nosyl ¼ (4-nitrophenyl)sulfonyl)
Entry
Diene
Yield [%]a)
ee [%]b)
Entry
Diene
Yield [%]a)
ee [%]b)
1
2
3
4
5
6
2a
2b
2c
ent-2c
2d
87
88
69
85
90
94
81
78
7
8
9
10
11
12
2f
2g
2h
2i
2j
2k
82
93
92
93
98
95
88
92
89
69
68
87
88 (89c))
ꢀ 88
89
2e
84
c
a) Yield of isolated 10 after chromatography. b) Determined by HPLC (210 nm) of isolated 10. ) Value
reported by Hayashi and co-workers [8].
ee). The yields of isolated amine 10 were in the region of 69 – 98%, which correspond
quite well with the yields of 88 – 99% reported in [8].
Conclusions. – In summary, C1-symmetric bicyclo[2.2.2]octa-2,5-diene ligands 2
were successfully tested in Rh-catalyzed arylation reactions of different substrates with
phenylboronic acids. The highest enantioselectivities reported so far with benchmark
diene ligands were achieved or exceeded with several dienes 2 when applied to the
addition to cyclohex-2-en-1-one, cyclopent-2-en-1-one, and tert-butyl cinnamate
(Tables 1 – 3). The C1-symmetric 4-fluorophenyl-, 4-methoxyphenyl-, 4-phenoxyphen-
yl-, and 2-thienyl-substituted dienes 2d, 2e, 2f, and 2g, respectively, gave similar
enantioselectivities as Hayashiꢀs ꢃmother diene ligandꢀ Ph-bod* 2c. The aryl-alkyl-
substituted C1-symmetric dienes 2a and 2b showed generally slightly lower selectivities
than the aryl-aryl-substituted dienes. The 2-methylphenyl- and naphthalen-1-yl-
substituted dienes 2i and 2j, respectively, with sterically demanding residues gave
consistently lower selectivities – except for the 1,4-addition to cyclopent-2-en-1-one (5)
where all C1-symmetric aryl-aryl-substituted ligands gave high ee (> 97%). The
thienyl-substituted diene 2g was the best chiral diene for the arylation of N-[(4-
nitrophenyl)sulfonyl]aldimine 9, albeit with lower enantioselectivity (92% ee) than the
best ligand reported by Hayashi and co-workers [8][9] for this reaction (98% ee with
bnd*-diene ligands).
The isolated yields of pure products of the 1,4-additions to enones were typically in
the range of 53 – 97% (Tables 1 – 3), i.e., slightly lower than for the 1,2-addition to
imine 9 (69 – 98%, Table 4). It must be mentioned that these are un-optimized yields,
and in this work, all reactions were performed by a scale-up of 10 compared to the
experimental procedures reported in [4][6][8].
Although one aryl residue of 2 is fixed (Ph), this array of stable C1-symmetric diene
ligands 2 displays differences in reactivity and selectivity and allows for a systematic

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Helvetica Chimica Acta – Vol. 95 (2012)
screening of reaction conditions [13] with more complex substrates. The availability of
the common precursor (1R,4R)-5-phenylbicyclo[2.2.2]oct-5-en-2-one (1) on a multi-kg
scale is an important asset for the simple and expeditious synthesis of a large variety of
novel ligands.
´
We thank Rene Vogelsanger and Lara Rentsch for valuable analytical support. S. A. acknowledges
continuous support by Dr. Thomas Wetter.
Experimental Part
General. All reactions were performed under Ar in dried glassware and anh. solvents, except for
reactions with aq. reagents. All chemicals and solvents were reagent-grade and used as supplied, unless
stated otherwise. Anal. TLC: pre-coated Merck silica gel 60 F254 plates (SiO2; 0.25 mm). Column
chromatography (FC): Fluka SiO2 60 (230 – 400 mesh). HPLC: normal-phase Daicel-Chiralpak anal.
columns (4.6 ꢁ 250 mm; 5 mm) of the AS-H or AD-H type, Chiralpak-AY-3 anal. column (4.6 ꢁ 100 mm;
3 mm), or Chiralcel-OD-H anal. column (4.6 – 250 mm; 5 mm). M.p.: Bꢀchi-510 melting-point apparatus;
uncorrected. Optical rotations ([a]2D0 ): Perkin-Elmer 241 polarimeter; enantiomer excesses (ee) by
HPLC analyses; tR in min. 1H- and 13C-NMR Spectra: Bruker-Avance instrument; at 300 (1H) and
75 MHz (13C).
(3R)-3-Phenylcyclohexanone (4). A soln. of [RhCl(C2H4)2]2 (14 mg, 0.072 mmol Rh, 0.03 equiv. of
Rh), chiral ligand 2 (0.08 mmol, 0.033 equiv.), and phenylboronic acid (600 mg, 4.92 mmol, 2 equiv.) in
1,4-dioxane (10 ml) was stirred at r.t. for 5 min. To this mixture was added cyclohex-2-en-1-one (3;
2.46 mmol, 1 equiv.) and aq. 1.5m KOH (1.25 mmol, 0.85 ml, 0.50 equiv.). The mixture was stirred at 308
for 3 h. Then the mixture was filtered over a pad of SiO2, the pad washed with Et2O, and the solvent was
evaporated. Purification by FC (SiO2, hexane/AcOEt 3 :1 (Rf 0.56)) yielded 4 as a liquid. Anal. data:
corresponding to literature data [13]. HPLC (Chiral-Pak AS-H, heptane/i-PrOH 90 :10, 0.8 ml minꢀ1
,
210 nm): tR(minor) 13.4, tR(major) 14.4, 97% ee, Entry 8, Table 1. [a]2D0 ¼ þ23.1 (c ¼ 1.1 CHCl3), ((R)-
enantiomer [14]: [a]D20 ¼ þ20.9 (c ¼ 1.0, CHCl3), 99% ee).
(3R)-3-Phenylcyclopentanone (6). As described for 4, with cyclopent-2-en-1-one (5; 2.46 mmol,
1 equiv.). Purification by FC (SiO2, hexane/AcOEt 4 :1 (Rf 0.7)) yielded 6 as liquid. Anal. data:
corresponding to literature data [13]. HPLC (Chiralpak AY-3, heptane/i-PrOH (0.05% Et2NH) 90 :10,
0.8 ml minꢀ1, 220 nm): tR(major) 4.3, tR(minor) 5.4; 97% ee, Entry 12, Table 2. [a]2D0 ¼ þ86.6 (c ¼ 2.5,
CHCl3) ((R)-enantiomer [14]: [a]2D0 ¼ þ87.3 (c ¼ 1.0, CHCl3), 99% ee).
tert-Butyl (3R)-3-(4-Methoxyphenyl)-3-phenylpropanoate (¼1,1-Dimethylethyl (bR)-4-Methoxy-b-
phenylbenzenepropanoate; 8). [RhCl(C2H4)]2 (2.8 mg, 0.014 mmol Rh, 0.3 equiv. Rh) and diene 2
(0.016 mmol, 0.3 equiv.) were dissolved in MeOH (1.6 ml). The soln. was stirred for 15 min, followed by
the addition of aq. 1.5m KOH (0.245 mmol, 165 ml, 0.5 equiv.). After stirring for 15 min, 4-
MeOC6H4B(OH)2 (149 mg, 0.98 mmol, 2 equiv.) was added, followed by tert-butyl cinnamate (7;
100 mg, 116 ml, 0.49 mmol, 1 equiv.), and the mixture was stirred at 508 for 16 h (reaction monitoring by
1H-NMR by comparing the tert-butyl signal of 7 (d(H) 1.55) with that of 8 (d(H)1.27). Then, sat. NH4Cl
soln. was added, the aq. layer extracted with Et2O (3ꢁ), and the combined org. layer washed with brine,
dried (MgSO4), and concentrated to give the crude product. Purification by FC (SiO2, Et2O/cyclohexane
1:20 (Rf 0.20)) yielded 8 as an off-white solid. M.p. 70 – 71.58 ([11]: 70 – 718). Anal. data: corresponding
to literature data [11]. HPLC (Chiralpak AD-H, heptane/i-PrOH (0.05% Et2NH) 90 :10, 0.8 ml minꢀ1
,
230 nm): tR(minor) 6.1, tR(major) 7.1; 99% ee, Entry 7, Table 3. [a]2D0 ¼ ꢀ1.06 (c ¼ 0.94, MeOH) ((S)-
enantiomer [11]): [a]2D6 ¼ þ1.6 (c ¼ 0.96, MeOH), 93% ee).
N-[(S)-(4-Chlorophenyl)phenylmethyl]-4-nitrobenzenesulfonamide (10). A soln. of [RhCl(C2H4)2]2
(13.5 mg, 0.07 mmol Rh, 0.09 equiv.) and chiral diene 2 (0.03 mmol, 0.037 equiv.) in CH2Cl2 (1 ml) was
stirred at r.t. for 1 h. The mixture was first filtered on a pad of Celite, then through a pad of SiO2 (eluent
CH2Cl2, then THF). The solvents were evaporated to afford the [Rh(diene)] complex as an orange solid
that was directly used as catalyst for the arylation reaction. The [Rh(diene)] complex (ca. 0.03 equiv.)
was dissolved in 1,4-dioxane (2.3 ml) and aq. 3.1m KOH (0.155 mmol, 50 ml, 0.2 equiv.) was added. After

Helvetica Chimica Acta – Vol. 95 (2012)
1817
5 min, this soln. was added to a suspension of N-[(4-nitrophenyl)sulfonyl]imine 9 (prepared according to
[15]; 250 mg, 0.77 mmol, 1 equiv.) and triphenylboroxine (290 mg, 0.92 mmol, 1.2 equiv.) in 1,4-dioxane
(3.9 ml). The mixture was stirred at 608 for 6 h. Then, it was passed through a pad of SiO2 (pre-treated
with MeOH, eluent: AcOEt). The filtrate was evaporated, and the residue was subjected to FC (SiO2,
cyclohexane/AcOEt 2 :1 (Rf 0.48)): 10 as an off-white solid. M.p. 180 – 1838 ([16]: 180.7 – 181.58). Anal.
data: corresponding to literature data [17]. HPLC (Chiralcel OD-H, heptane/EtOH 1:1, 0.8 ml minꢀ1
,
210 nm): tR(major) 5.7, tR(minor) 7.9; 92% ee, Entry 8, Table 4. [a]2D0 ¼ þ2.1 (c ¼ 1.16, CHCl3) ((S)-
enantiomer [17]: [a]2D0 ¼ þ3.3 (c ¼ 0.94, CHCl3), 98.5% ee).
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Received July 17, 2012