Polymer supported trans-1-phenylsulfonylamino-2-isoborneolsulfonylaminocyclohexane ligand for the titanium catalyzed organozinc addition to ketones

Article abstract of DOI:10.1016/j.tetasy.2006.07.038

The catalytic enantioselective addition of different organozinc reagents, such as diethylzinc, or in situ generated phenylzinc derivatives to simple ketones was accomplished using titanium tetraisopropoxide and supported chiral ligands derived from trans-

Full text of DOI:10.1016/j.tetasy.2006.07.038

Tetrahedron: Asymmetry 17 (2006) 2054–2058
Polymer supported trans-1-phenylsulfonylamino-
2-isoborneolsulfonylaminocyclohexane ligand for the
titanium catalyzed organozinc addition to ketones
*
*
´
Vicente J. Forrat, Diego J. Ramon and Miguel Yus
Instituto de Sı´ntesis Orga´nica(ISO), Departamento de Quı´mica Orga´nica, Facultad de Ciencias, Universidad de Alicante,
Apdo. 99, E-03080 Alicante, Spain
Received 28 June 2006; accepted 31 July 2006
´
Dedicated to Professor Jose Antonio Abad on occasion of his retirement
Abstract—The catalytic enantioselective addition of different organozinc reagents, such as diethylzinc, or in situ generated phenylzinc
derivatives to simple ketones was accomplished using titanium tetraisopropoxide and supported chiral ligands derived from trans-1-
phenylsulfonylamino-2-isoborneolsulfonylamidocyclohexane, to give the corresponding tertiary alcohols with enantioselectivities up
to >99%. A simple and efficient procedure for the synthesis of the disulfonamide monomeric ligand and the corresponding polymeriza-
tion is described.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Although isoborneolsulfonamide ligands can be isolated
from the crude reaction by flash chromatography, its
recovery still remains difficult. In order to facilitate the sep-
aration of homogeneous ligands or catalysts from the reac-
tion mixture, they are usually immobilized on solid
supports.12 There are two main methods to immobilize a
chiral ligand on a support: (a) grafting of the desired ligand
onto a preformed support containing reactive groups and
(b) co-polymerization of a suitable functionalized ligand
with polymerizable monomers and cross-linkers. While
the latter offers many possibilities for generating and con-
trolling a specific environment around the ligand within
the polymer matrix (needing more synthetic efforts), the
former is often preferred since many suitable polymeric
supports are commercially available.
Nowadays, the catalytic enantioselective generation of
compounds with stereogenic tertiary carbon atoms can be
easily achieved in most cases.1 However, the related ap-
proach to compounds bearing quaternary stereocenters is
still an enormous challenge for synthetic organic chemistry.
Thus, every novel enantioselective procedure for the con-
struction of a fully substituted carbon center is of great
value,2 the simplest approach for the preparation of chiral
tertiary alcohols being the enantioselective 1,2-addition of
organometallic reagents3 to ketones.4
Recently, we have introduced isoborneolsulfonamide5 1 as
the first chiral ligand6 able to promote the catalytic enan-
tioselective addition of dialkylzinc reagents to simple ke-
tones7 in the presence of titanium tetraisopropoxide,8
other bisisoborneolsulfonamides improve the previous
results.9 Among all ligands tested, trans-1-arylsulfonyl-
amino-2-(isobornylsulfonylamino)cyclohexane derivatives
2 gave the best results,10 not only for the alkylation but
also for the arylation process.11
X
OH
S
NH
O2
O2S NH HN SO2
OH
1
2a: X = Me
2b: X = MeO
*
Corresponding authors. Tel.: +35 965 90 35 48; fax: +35 965 90 35 49
(M.Y.); e-mail addresses: djramon@ua.es; yus@ua.es
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.07.038

V. J. Forrat et al. / Tetrahedron: Asymmetry 17 (2006) 2054–2058
2055
Herein, we report for the first time the preparation and use
of heterogeneous chiral ligands of different polymers 3 sup-
porting trans-1-(phenylsulfanylamino)-2-(isobornylsulfon-
ylamino)cyclohexane moieties. We have chosen a styrene
co-polymerization strategy to immobilize our chiral ligand,
since this strategy has been used fruitfully in the heteroge-
nization of typical chiral ligands, among other, BINOL,13
NOBIN,14 TADDOL,15 bis(oxazolines),16 salens,17 1,2-
diamines,18 1,2-disulfonamides,19 and 1,2-hydr-oxysulfon-
amides.20
using a typical radical polymerization protocol in a suspen-
sion of polyvinyl alcohol (average molecular weights
85,000–146,000).24 In this way, we prepared four different
polymers changing only the amount of the cross-linker
and therefore their swelling properties (Scheme 2). All
polymers could be easily isolated from the reaction media
just by filtration and were purified by successive washes
with methanol and hexane. The chemical yield was practi-
cally quantitative and microanalysis showed the total
incorporation of monomer 4 to the formed polymer.25
2. Results and discussion
In order to follow this strategy, the styryl derivative 4 had
to be prepared (Scheme 1). Thus, the reaction of commer-
cially available sodium 4-vinylbenzenesulfonate 5 with
thionyl chloride under standard conditions21 gave the
expected sulfonyl chloride derivative, which was trapped
by reaction with (1R,2R)-trans-1,2-diaminocyclohexane 6
under classical biphasic conditions for amino acid protec-
tion.22 The final standard coupling reaction23 of the
in situ prepared amine with (1S)-(+)-10-camphorsulfonyl
chloride 7 yielded the corresponding ketone 8, which was
diastereoselectively reduced to monomer 4 with good
chemical yields and diastereoselectivities (de >80%).
Monomer 4 could be easily isolated in its pure form
(>99%) by column chromatography with a moderate over-
all yield.
n
+
+
O2S
NH HN
SO2
10
9
4
OH
AIBN
H2O /
m
OH
PhH / THF / 90 ºC / 2 d
1
99
n
Ph
i, SOCl2 / PhH / 80 ºC / 12 h
O2S
n
N
NH2
H
HN
ii,
3a: n = 32
3b: n = 8
3c: n = 1
3d: n = 0
S
O2
NH2
6 (1 equiv.)
HO
O
SO2
NH
SO3Na
CH2Cl2 / NaOH (2 M)
0 ºC / 5 h
Scheme 2.
NH
Polymeric ligands 3 were tested first in the enantioselective
addition of commercially available diethylzinc 11 to aceto-
phenone 12a in the presence of Ti(OPri)4. The reaction
gave the expected tertiary alcohol 13a at room tempera-
ture. Although the reaction rate was very slow, the enantio-
selectivity was excellent in all cases tested, minor (R)-
enantiomer could not be detected by chiral column GC-
analysis (Table 1, entries 1–4), independent of the polymer
used.
SO2
iii,
5
O
SO2Cl
7 (1.5 equiv.)
DMAP / Et3N
CH3CN
8
0 ºC / 24 h
The reuse of polymer 3c was studied by filtering and wash-
ing it with dry toluene under an argon atmosphere. We
found that after three uses, its activity decreased to nil
(compare entries 2, 5, and 6 in Table 1). In order to accel-
erate the reaction, we focused on the possibility of using
some faster alkoxide scavenger,26 and for that purpose,
the reaction was performed in the presence of an excess
amount of Et3B (Table 1, entry 7). Although the reaction
under these new conditions took place in only 9 days, it
is still far from the reaction times using the homogenous
ligands 2.10
NaBH4
EtOH
O2S NH HN
SO2
0 ºC / 24 h
OH
4 (41 %)
Scheme 1.
Once monomer 4 was obtained, the following step was the
co-polymerization with styrene 9 and divinylbenzene 10,

2056
V. J. Forrat et al. / Tetrahedron: Asymmetry 17 (2006) 2054–2058
Table 1.
Table 2.
Ti(OPri)4 (110 mol %)
O
Et2Zn
OH
O
OH
Ph
Ti(OPri)4
+ Et2Zn
+ BPh3
Polymer 3 (5 mol %)
PhMe / 25 ºC
Polymer 3
(5 mol %)
PhMe / 25 ºC
Br
Br
12a
11
13a
13b
14
12b
Entry
Polymer
Time (d)
Yielda (%)
eeb (%)
Entry
Polymer
Time (d)
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
3a
3b
3c
3d
3c
3c
3c
17
17
17
17
17d
17e
9f
16
>99
23 (17)c
56
>99 (>99)c
>99
1
2
3
4
5
6
3a
3b
3c
6
6
6
0.75
6
47
70
70
83
55
<5
71 (+)
73 (+)
83 (+)
86 (+)
82 (+)
—
36
17
<5
36
>99
>99
—
>99
3d
3cc
3cd
6
a Isolated yields after bulb-to-bulb distillation.
b Determined by GLC using a b-CD column.
c In parentheses are results obtained without stirring.
d Reaction performed after one use of polymer.
e Reaction performed after two uses of polymer.
f Reaction performed in the presence of 1.6 equiv of Et3B.
a Isolated yields after column chromatography.
b Determined by HPLC using a Chiralcel-ODH column; the sign of the
predominant enantiomer is indicated in parentheses.
c Reaction performed after one use of polymer.
d Reaction performed after two uses of polymer.
Table 3.
After this partial success found for the enantioselective
ethylation of acetophenone, we turned our attention to
the zinc reagent reactivity. The idea was to improve the
reactivity of the zinc reagent in order to diminish the
reaction time. Recently, the preparation of ethyl phenyl
zinc reagent by transmetalation of diethylzinc with tri-
phenylboron has been described.27 This intermediate
showed a higher reactivity and enantioselectivity compared
with the related diethyl or diphenylzinc reagents.28 The
corresponding ethyl phenyl zinc intermediate was obtained
starting from commercially available triphenyl boron 14
and diethylzinc 11 by heating in toluene at 70 ꢁC. This
intermediate was reacted in situ with para-bromoacetophe-
none 12b in the presence of substoichiometric amounts of
polymeric ligands 3 and a small excess of titanium tetraiso-
propoxide to give the expected diaryl ethanol derivative
13b with good enantioselectivities (Table 2).
O
R2 OH
Et2Zn (720 mol %)
R1
R2
+ BPh3
R1
Ph
Ti(OPri)4 (130 mol %)
PhMe / 25 ºC
14
12
13
1
99
Ph
O2S
N
H
HN
S
O2
Polymer 3d
(5 mol %)
HO
Entry R1
R2
Time (d) No Yielda (%) eeb (%)
In the reaction shown in Table 2, we observed a different
behavior, depending on the solubility of polymeric ligand.
Thus, a decrease of the amount of the cross-linker im-
proved the chemical yield and enantioselectivity, with the
best results being obtained with the soluble polymer 3d in
only 18 h (entry 4). As in the previous case, the possible
reuse of ligand 3c was studied, we found a similar behavior
as in the case of using diethylzinc (compare entries 3, 5,
and 6).
1
2
3
4-BrC6H4
4-FC6H4
4-ClC6H4
Me 0.75
Me 0.75
Me 0.75
13b 83
13c 98
13d 99
86 (+)
87 (+)
88 (+)
90 (+)
88 (ꢀ)
84 (ꢀ)
71 (+)
38 (R)
80 (+)
71 (+)
—
4
4-F3CC6H4 Me 0.5
13e
13f
86
98
5
6
7
8
3-MeC6H4
4-MeC6H4
4-BrC6H4
Bun
Me 0.75
Me
Et
1
6
2
13g 80
13h 54
Me
13i
13e
13e
98
97
87
9
4-F3CC6H4 Me 0.75c
4-F3CC6H4 Me 3d
4-F3CC6H4 Me 5e
4-MeC6H4
4-MeC6H4
4-MeC6H4
10
11
12
13
14
Finally, we studied the catalytic enantioselective phenyl-
ation of different ketones using the soluble polymer 3d
(Table 3).29 The reaction gave good enantioselectivities for
methyl aryl ketones, practically independently of the elec-
tronic character of the aryl substituents (entries 1–6). These
results are in the range of those obtained using ligands 2,10
not only concerning the enantioselectivity or yield, but also
the reaction times. Increasing the size of the substituents of
ketone 12 (i.e., from methyl to ethyl) led to longer reaction
times with slightly worse enantioselectivities (entry 7). The
reaction with 2-hexanone gave a modest 38% ee (entry 8).
13e <5
13g 74
13g 84
13g <5
Me 1.5c
Me 3d
Me 5e
80 (ꢀ)
42 (ꢀ)
—
a Isolated yields after column chromatography.
b Determined by HPLC using Chiralcel columns; the absolute configura-
tion or the sign of the predominant enantiomer is indicated in
parentheses.
c Reaction performed after one use of polymer.
d Reaction performed after two uses of polymer.
e Reaction performed after three uses of polymer.

V. J. Forrat et al. / Tetrahedron: Asymmetry 17 (2006) 2054–2058
2057
´
Res. Devel. Org. Chem. 1998, 2, 489–523; (b) Ramon, D. J.;
Yus, M. Chem. Rev. 2006, 106, 2126–2208.
The last part of this study was focused on the possible
recovery and reuse of the soluble polymer 3d. In this case,
the crude reaction mixture, obtained after typical aqueous
work-up, extraction and solvent elimination, was treated
with methanol and filtered in order to isolate polymer 3d
as an amorphous solid, from the methanolic phase contain-
ing the tertiary alcohol. The yield of recovered polymer 3d
was in the range of 75–90%. Unfortunately, the activity of
the polymer decreased rapidly after a few reuses (compare
entries 4 and 9–11, as well as 6 and 12–14). The reason for
this decrease is still unclear since transmission electron
microscopy experiments of twofold recovered polymer 3d
did not show the expected presence of titanium occluded
in the polymer.30
´
9. For recent results from our group, see: (a) Yus, M.; Ramon,
D. J.; Prieto, O. Tetrahedron: Asymmetry 2002, 13, 2291–
2293; (b) Yus, M.; Ramon, D. J.; Prieto, O. Tetrahedron:
´
´
Asymmetry 2003, 14, 1103–1114; (c) Prieto, O.; Ramon, D. J.;
Yus, M. Tetrahedron: Asymmetry 2003, 14, 1955–1957; (d)
Yus, M.; Ramon, D. J.; Prieto, O. Eur. J. Org. Chem. 2003,
´
2745–2748.
´
10. (a) Forrat, V. J.; Ramon, D. J.; Yus, M. Tetrahedron:
Asymmetry 2005, 16, 3341–3344; (b) Forrat, V. J.; Prieto, O.;
Ramon, D. J.; Yus, M. Chem. Eur. J. 2006, 12, 4431–
´
4445.
11. For reviews on asymmetric arylation processes, see: (a) Bolm,
C.; Hildebrand, J. P.; Muniz, K.; Hermanns, N. Angew.
˜
Chem., Int. Ed. 2001, 40, 3284–3308; (b) Schmidt, F.;
Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev.
2006, 35, 454–470.
3. Conclusion
12. For reviews, see: (a) Gladysz, J. A. Chem. Rev. 2002, 102,
3215–3216, thematic issue on recoverable catalysts and
In conclusion, we have described an easy and simple
synthesis of polymers bearing chiral trans-1-phenylsulfon-
ylamino-2-isoborneolsulfonylaminocyclo-hexane moiety.
These ligands have been shown to be good promoters for
the heterogeneous and homogenous catalytic enantioselec-
tive alkylation and arylation of ketones. Work is currently
in progress in order to anchor the above chiral moiety to
other polymeric materials, improving the possible recovery
and reuse.
´
reagents; (b) Corma, A.; Garcıa, H. Chem. Rev. 2003, 103,
4307–4365; (c) Dai, L.-X. Angew. Chem., Int. Ed. 2004, 43,
5726–5729; (d) Itsuno, S.; Haraguchi, N.; Arakawa, Y.
Recent Res. Devel. Org. Chem. 2005, 9, 27–47.
13. See for instance: (a) Sellner, H.; Faber, C.; Rheiner, P. B.;
Seebach, D. Chem. Eur. J. 2000, 6, 3692–3705; (b) Sasai, H.;
Jayaprakash, D. Tetrahedron Lett. 2001, 12, 2589–2595; (c)
Herres, S.; Hesemann, P.; Moreau, J. J. E. Eur. J. Org. Chem.
2003, 99–105; (d) Hesemann, P.; Moreau, J. J. E. C. R. Chim.
2003, 6, 199–207; (e) Sekiguti, T.; Iizuka, Y.; Takizawa, S.;
Jayaprakash, D.; Arai, T.; Sasai, H. Org. Lett. 2003, 5, 2647–
2650.
Acknowledgements
14. Mandoli, A.; Pini, D.; Orlandi, S.; Mazzini, F.; Salvadori, P.
Tetrahedron: Asymmetry 1998, 9, 1479–1482.
15. See for instance: (a) Seebach, D.; Marti, R. E.; Hintermann,
T. Helv. Chim. Acta 1996, 79, 1710–1740; (b) Rheiner, P. B.;
Sellner, H.; Seebach, D. Helv. Chim. Acta 1997, 80, 2027–
2032; (c) Sellner, H.; Seebach, D. Angew. Chem., Int. Ed.
1999, 38, 1918–1920; (d) Altava, B.; Burguete, I.; Fraile, J.
This work was generously supported by the current Span-
´
ish Ministerio de Educacion y Ciencia (Project CTQ2004-
01261), the Generalitat Valenciana (Projects GV05/157
and CTIDB/2002/318) and University of Alicante (UA).
V.J.F. thanks the UA for a fellowship.
´
M.; Garcıa, J. I.; Luis, S. V.; Mayoral, J. A.; Vicent, M. J.
Angew. Chem., Int. Ed. 2000, 39, 1503–1506; (e) Degni, S.;
´
Wilen, C.-E.; Leino, R. Org. Lett. 2001, 3, 2551–2554; (f)
References
Sellner, H.; Rheiner, P. B.; Seebach, D. Helv. Chim. Acta
2002, 85, 352–387.
1. (a) Stereoselective Synthesis (Houben-Weyl); Helmchen, G.,
Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Thieme:
Stuttgart, 1996; Vols. 1–10; (b) Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Berlin, 1999; Vols. 1–3.
´
´
´
16. (a) Diez-Barra, E.; Fraile, J. M.; Garcıa, J. I.; Garcıa-
´
Verdugo, E.; Herrerıas, C. I.; Luis, S. V.; Mayoral, J. A.;
´
´
Sanchez-Verdu, P.; Tolosa, J. Tetrahedron: Asymmetry 2003,
14, 773–778; (b) Mandoli, A.; Orlandi, S.; Pini, D.; Salvadori,
P. Tetrahedron: Asymmetry 2004, 15, 3233–3244.
2. (a) Fuji, K. Chem. Rev. 1993, 93, 2037–2066; (b) Corey, E. J.;
17. See for instance: (a) Canali, L.; Sherrington, D. C.; Deleuze,
H. React. Funct. Polym. 1999, 40, 155–168; (b) Heckel, A.;
Seebach, D. Helv. Chim. Acta 2002, 85, 913–926; (c) Sellner,
´
´
Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388–401;
´
(c) Ramon, D. J.; Yus, M. Curr. Org. Chem. 2004, 8, 149–183;
(d) Quaternary Stereocenters—Challenges and Solutions for
Organic Synthesis; Christoffers, J., Baro, A., Eds.; Wiley-
VCH: Weinheim, 2005.
H.; Hametner, K.; Gunther, D.; Seebach, D. J. Catal. 2003,
215, 87–93.
18. Itsuno, S.; Tsuji, A.; Takahashi, M. J. Polym. Sci. Part A:
Polym. Chem. 2004, 42, 4556–4562.
¨
´
3. Yus, M.; Ramon, D. J. Recent Res. Dev. Org. Chem. 2002, 6,
297–378.
19. Halm, C.; Kurth, M. J. Angew. Chem., Int. Ed. 1998, 37, 510–
512.
´
4. Ramon, D. J.; Yus, M. In Ref. 2d, pp 207–241.
´
5. (a) Ramon, D. J.; Yus, M. Tetrahedron: Asymmetry 1997, 8,
20. See for instance: (a) Itsuno, S.; Watanabe, K.; Ito, K.; El-
Shehawy, A. A.; Sarhan, A. A. Angew. Chem., Int. Ed. 1997,
36, 109–110; (b) El-Shehawy, A. A.; Abdelaal, M. Y.;
Watanabe, K.; Ito, K.; Itsuno, S. Tetrahedron: Asymmetry
1997, 8, 1731–1734; (c) Itsuno, S.; El-Shehawy, A. A.; Sarhan,
A. A. React. Funct. Polym. 1998, 37, 283–287; (d) Itsuno, S.;
Watanabe, K.; Watanabe, K.; Matsumoto, T.; Kuroda, S.;
Yokoi, A.; El-Shehawy, A. A. J. Chem. Soc., Perkin Trans. 1
1999, 2011–2016; (e) Itsuno, S.; Watanabe, K.; El-Shehawy,
A. A. Adv. Synth. Catal. 2001, 343, 89–94.
´
2479–2496; For a review, see: (b) Yus, M.; Ramon, D. J. Pure
Appl. Chem. 2005, 77, 2111–2119.
´
6. (a) Ramon, D. J.; Yus, M. Tetrahedron Lett. 1998, 39, 1239–
´
1242; (b) Ramon, D. J.; Yus, M. Tetrahedron 1998, 54, 5651–
5666.
´
7. For an overview, see: Ramon, D. J.; Yus, M. Angew. Chem.,
Int. Ed. 2004, 116, 286–289.
8. For reviews on enantioselective reactions promoted by
´
titanium derivatives, see: (a) Ramon, D. J.; Yus, M. Recent

2058
V. J. Forrat et al. / Tetrahedron: Asymmetry 17 (2006) 2054–2058
´
21. Yus, M.; Ramon, D. J.; Prieto, O. Tetrahedron: Asymmetry
mixtures of hexane/ethyl acetate with decreasing ratios,
yielding the monomer 4. This monomer 4 (0.496 g, 1 mmol)
was dissolved in benzene (12 mL) and THF (4 mL) at 25 ꢁC
under an argon atmosphere. To this solution was successively
2002, 13, 1573–1579.
22. See for instance: (a) Fischer, E.; Lifschitz, W. Chem. Ber.
1915, 48, 360–378; (b) McChesney, E. W.; Swann, W. K. J.
Am. Chem. Soc. 1937, 59, 116–118; (c) Baganz, H.; Baganz,
H. Arch. Pharm. 1957, 290, 567–571; (d) Greene, T. W.;
Wuts, P. G. M. In Protective Groups in Organic Synthesis,
3rd ed.; John Wiley and Sons: New York, 1999; pp 603–
607.
23. Prieto, O.; Ramon, D. J.; Yus, M. Tetrahedron: Asymmetry
2000, 11, 1629–1644.
24. (a) Gomez, C.; Ruiz, S.; Yus, M. Tetrahedron Lett. 1998, 39,
added styrene
9 (11.35 mL, 99 mmol), AIBN (0.128 g,
0.78 mmol), divinylbenzene (for amounts see Scheme 2). This
solution was slowly added over an aqueous solution at 0 ꢁC,
obtained in turn by heating polyvinyl alcohol (0.2 g) in water
(50 mL) at 40 ꢁC for 30 min and final filtration. The resulting
mixture was heated at 90 ꢁC for 2 days. Polymers 3 were
obtained just after filtration, washing with portions of water,
methanol and hexane, and final drying over reduced pressure
´
´
25
´
1397–1400; (b) Gomez, C.; Ruiz, S.; Yus, M. Tetrahedron
1999, 55, 7017–7026; (c) Yus, M.; Gomez, C.; Candela, P.
Tetrahedron Lett. 2001, 42, 3977–3979; (d) Alonso, F.;
(0.1 Torr) during 24 h {3d: ½aꢁD ¼ þ1:9 (c 1.4, PhMe)}.
´
26. For recent uses of boron compounds as alkoxide scavengers,
see: (a) Yu, C.-M.; Kim, J.-M.; Shin, M.-S.; Cho, D.
Tetrahedron Lett. 2003, 44, 5487–5490; (b) Xia, G.; Shib-
atomi, K.; Yamamoto, H. Synlett 2004, 2437–2439.
´
Candela, P.; Gomez, C.; Yus, M. Adv. Synth. Catal. 2003,
´
345, 275–279; (e) Candela, P.; Gomez, C.; Yus, M. Russ. J.
Org. Chem. 2004, 40, 795–801.
25. General procedure for the synthesis of polymers 3: To a
27. For examples on the enantioselective phenylation of alde-
hydes after boron/zinc transmetalation, see: (a) Rudolph, J.;
Schmidt, F.; Bolm, C. Adv. Synth. Catal. 2004, 346, 867–872;
(b) Rudolph, J.; Hermanns, N.; Bolm, C. J. Org. Chem. 2004,
69, 3997–4000; (c) Bolm, C.; Zani, L.; Rudolph, J.; Schiffers,
I. Synthesis 2004, 2173–2180; (d) Bolm, C.; Schmidt, F.; Zani,
solution of sodium 4-vinylbenzenesulfonate
5 (2.47 g,
12 mmol) in benzene (80 mmol) were added SOCl2 (5.2 mL,
72 mmol) and a few drops of DMF. The resulting solution
was refluxed for 12 h and all the volatiles were removed under
reduced pressure (0.1 Torr) to yield the corresponding sulfo-
nyl chloride derivative. This compound was soluble in
CH2Cl2 (32 mL) and this solution was slowly added
(20 min) to a mixture of (1R,2R)-1,2-diaminocyclohexane 6
(1.37 g, 12 mmol) in CH2Cl2 and aqueous NaOH solution
(2 M, 16 mL) at 0 ꢁC. After 4 h, allowing the temperature to
rise to 25 ꢁC, the mixture was treated with HCl (2 M,
3 · 60 mL). The resulting acidic aqueous phase was basified
with NaOH (6 M) and extracted with CH2Cl2 (3 · 60 mL).
The organic layers were dried over Na2SO4, filtered, and the
solvents were removed under reduced pressure (15 Torr). The
resulting crude product was dissolved in CH3CN (50 mL)
at 0 ꢁC, and to this new solution were added subsequently
Et3N (7.6 mL, 54 mmol), 4-dimethylaminopyridine (0.73 g,
6 mmol) and (1S)-(+)-10-camphorsulfonyl chloride 7 (4.52 g,
18 mmol). The resulting mixture was stirred for 24 h
allowing the temperature to rise to 25 ꢁC. The reaction was
quenched by the addition of NaOH (3 M, 30 mL) and
extracted with ethyl acetate (4 · 30 mL). The resulting
organic layer was dried over Na2SO4, filtered, and the
solvents were removed under reduced pressure (15 Torr).
The resulting crude product 8 was dissolved in ethanol
(50 mL) at 0 ꢁC and treated with NaBH4 (1.82 g, 4.8 mmol).
After 24 h, allowing the temperature to rise to 25 ꢁC, ethanol
was removed under reduced pressure (15 Torr) and the
residue was treated with HCl (2 M, 25 mL) and extracted
with ethyl acetate (4 · 30 mL). The resulting organic layer
was dried over Na2SO4, filtered, and the solvents were
removed under reduced pressure (15 Torr). The residue was
purified by column chromatography using silica gel and
¨
L. Tetrahedron: Asymmetry 2005, 16, 1367–1376; (e) Ozc¸u-
bukc¸u, S.; Schmidt, F.; Bolm, C. Org. Lett. 2005, 7, 1407–
1409; (f) Rudolph, R.; Lormann, M.; Bolm, C.; Dahmen, S.
Adv. Synth. Catal. 2005, 347, 1361–1368; (g) Dahmen, S.;
Lormann, M. Org. Lett. 2005, 7, 4597–4600.
28. (a) Rudolph, J.; Rasmussen, T.; Bolm, C.; Norrby, P.-O.
Angew. Chem. Int. Ed. 2003, 42, 3002–3005; (b) Fontes, M.;
`
`
Verdaguer, X.; Sola, L.; Pericas, M. A.; Riera, A. J. Org.
Chem. 2004, 69, 2532–2543; (c) Rudolph, J.; Bolm, C.;
Norrby, P.-O. J. Am. Chem. Soc. 2005, 127, 1548–1552.
29. General procedure for the enantioselective phenylation of
ketones: A solution of Et2Zn (1.1 M in toluene, 6.5 mL,
7.2 mmol) was slowly added to a pressure tube charged with
triphenylborane 14 (0.39 g, 1.6 mmol) at 0 ꢁC under an argon
atmosphere. The resulting solution was warmed to 70 ꢁC for
16 h. Then, the mixture was cooled to 0 ꢁC and transferred to
a Schlenk tube. To this mixture were added the corresponding
polymer 3 (0.5 g, 0.05 equiv of isobornyl structure), Ti(OPri)4
(0.39 mL, 1.3 mmol) and ketone 12 (1 mmol). The reaction
mixture was stirred at 25 ꢁC (see Table 3) and quenched by
successive addition of methanol (1 mL) and a saturated
solution of NH4Cl (15 mL). The mixture was filtered through
Celite and the resulting mixture was extracted with ethyl
acetate (3 · 10 mL). The resulting organic layer was dried
over Na2SO4, filtered, and the solvent removed under reduced
pressure (15 Torr). The residue was purified by column
chromatography using silica gel and mixtures of hexane/ethyl
acetate with decreasing ratios, to yield the corresponding
alcohol 13.
30. We thank a referee for calling our attention to this possibility.